@article {pmid39915243, year = {2025}, author = {Zhao, S and Lin, H and Li, W and Xu, X and Wu, Q and Wang, Z and Shi, J and Chen, Y and Ye, L and Xi, L and Chen, L and Yuan, M and Su, J and Gao, A and Jin, J and Ying, X and Wang, X and Ye, Y and Sun, Y and Zhang, Y and Deng, X and Shen, B and Gu, W and Ning, G and Wang, W and Hong, J and Wang, J and Liu, R}, title = {Post sleeve gastrectomy-enriched gut commensal Clostridia promotes secondary bile acid increase and weight loss.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2462261}, doi = {10.1080/19490976.2025.2462261}, pmid = {39915243}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Bile Acids and Salts/metabolism ; *Weight Loss ; Mice ; *Gastrectomy ; Humans ; Male ; *Clostridium/metabolism/genetics ; *Mice, Inbred C57BL ; *Obesity/microbiology/metabolism/surgery ; Receptors, G-Protein-Coupled/metabolism/genetics ; Fecal Microbiota Transplantation ; Female ; Adult ; Feces/microbiology ; Symbiosis ; Bariatric Surgery ; Adipose Tissue/metabolism ; }, abstract = {The gut microbiome is altered after bariatric surgery and is associated with weight loss. However, the commensal bacteria involved and the underlying mechanism remain to be determined. We performed shotgun metagenomic sequencing in obese subjects before and longitudinally after sleeve gastrectomy (SG), and found a significant enrichment in microbial species in Clostridia and bile acid metabolizing genes after SG treatment. Bile acid profiling further revealed decreased primary bile acids (PBAs) and increased conjugated secondary bile acids (C-SBAs) after SG. Specifically, glycodeoxycholic acid (GDCA) and taurodeoxycholic acid (TDCA) were increased at different follow-ups after SG, and were associated with the increased abundance of Clostridia and body weight reduction. Fecal microbiome transplantation with post-SG feces increased SBA levels, and alleviated body weight gain in the recipient mice. Furthermore, both Clostridia-enriched spore-forming bacteria and GDCA supplementation increased the expression of genes responsible for lipolysis and fatty acid oxidation in adipose tissue and reduced adiposity via Takeda G-protein-coupled receptor 5 (TGR5) signaling. Our findings reveal post-SG gut microbiome and C-SBAs as contributory to SG-induced weight loss, in part via TGR5 signaling, and suggest SBA-producing gut microbes as a potential therapeutic target for obesity intervention.}, } @article {pmid39912727, year = {2025}, author = {Ma, X and Li, M and Zhang, Y and Xu, T and Zhou, X and Qian, M and Yang, Z and Han, X}, title = {Akkermansia muciniphila identified as key strain to alleviate gut barrier injury through Wnt signaling pathway.}, journal = {eLife}, volume = {12}, number = {}, pages = {}, pmid = {39912727}, issn = {2050-084X}, support = {32172765//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Wnt Signaling Pathway ; *Akkermansia/physiology ; *Gastrointestinal Microbiome/physiology ; Mice ; Swine ; *Enterotoxigenic Escherichia coli/physiology ; *Fecal Microbiota Transplantation ; Intestinal Mucosa/microbiology/metabolism ; Escherichia coli Infections/microbiology/therapy ; Disease Models, Animal ; Bacteroides fragilis/physiology ; Organoids ; }, abstract = {As the largest mucosal surface, the gut has built a physical, chemical, microbial, and immune barrier to protect the body against pathogen invasion. The disturbance of gut microbiota aggravates pathogenic bacteria invasion and gut barrier injury. Fecal microbiota transplantation (FMT) is a promising treatment for microbiome-related disorders, where beneficial strain engraftment is a significant factor influencing FMT outcomes. The aim of this research was to explore the effect of FMT on antibiotic-induced microbiome-disordered (AIMD) models infected with enterotoxigenic Escherichia coli (ETEC). We used piglet, mouse, and intestinal organoid models to explore the protective effects and mechanisms of FMT on ETEC infection. The results showed that FMT regulated gut microbiota and enhanced the protection of AIMD piglets against ETEC K88 challenge, as demonstrated by reduced intestinal pathogen colonization and alleviated gut barrier injury. Akkermansia muciniphila (A. muciniphila) and Bacteroides fragilis (B. fragilis) were identified as two strains that may play key roles in FMT. We further investigated the alleviatory effects of these two strains on ETEC infection in the AIMD mice model, which revealed that A. muciniphila and B. fragilis relieved ETEC-induced intestinal inflammation by maintaining the proportion of Treg/Th17 cells and epithelial damage by moderately activating the Wnt/β-catenin signaling pathway, while the effect of A. muciniphila was better than B. fragilis. We, therefore, identified whether A. muciniphila protected against ETEC infection using basal-out and apical-out intestinal organoid models. A. muciniphila did protect the intestinal stem cells and stimulate the proliferation and differentiation of intestinal epithelium, and the protective effects of A. muciniphila were reversed by Wnt inhibitor. FMT alleviated ETEC-induced gut barrier injury and intestinal inflammation in the AIMD model. A. muciniphila was identified as a key strain in FMT to promote the proliferation and differentiation of intestinal stem cells by mediating the Wnt/β-catenin signaling pathway.}, } @article {pmid39911724, year = {2025}, author = {Dutta, SK and Firnberg, E and Verma, S and Phillips, L and Nair, PP}, title = {Detection of Human Y Chromosome and the SRY Gene in Fecal Samples of Female Patients Following Fecal Microbiota Transplantation.}, journal = {Gastro hep advances}, volume = {4}, number = {2}, pages = {100568}, pmid = {39911724}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: We have postulated that fecal microbiota transplantation (FMT) is associated with transfer of microbiota from the donor and engraftment of intestinal epithelial cells in the recipient's colonic mucosa enabling the restoration of a stable microbial environment.

METHODS: We analyzed the presence of human Y chromosome (ChrY) and sex-determining region Y (SRY) gene within total human DNA extracted from fecal samples collected from 30 donors and 22 recurrent Clostridium difficile infection (RCDI) patients before and up to 24 months after FMT. A next-generation sequencing data analysis pipeline was applied to quantify the percentage of reads aligning to human ChrY. SRY gene detection was also performed by quantitative polymerase chain reaction and droplet digital polymerase chain reaction.

RESULTS: A significantly higher percentage of ChrY reads were identified in fecal samples of male donors as compared to female donor (P < .0001). Fecal samples collected from female RCDI patients who received FMT from male donors showed a significantly (P < .05) higher percentage of ChrY reads compared to female samples without male FMT donors. Four female patients with RCDI who received FMT from male donors showed a very large percent ChrY increase post-FMT even several months after FMT. SRY gene signal was detected by droplet digital polymerase chain reaction in 7 of the 11 fecal samples collected from the male donor pool but none from the female pool.

CONCLUSION: These observations clearly demonstrate the presence of ChrY and SRY gene signal in stool samples collected from male patients. The presence of increased ChrY in the stool samples of female RCDI patients after FMT from a male donor suggests possible engraftment of exfoliated intestinal epithelial cells in a subset of these patients.}, } @article {pmid39910418, year = {2025}, author = {Li, L and Mo, Q and Wan, Y and Zhou, Y and Li, W and Li, W}, title = {Antimicrobial peptide AP2 ameliorates Salmonella Typhimurium infection by modulating gut microbiota.}, journal = {BMC microbiology}, volume = {25}, number = {1}, pages = {64}, pmid = {39910418}, issn = {1471-2180}, support = {No. 82003436//Young Scientists Fund of the National Natural Science Foundation of China/ ; No. 2011BAD26B02//the 'twelfth five-year-plan' in National Support Program for Science and Technology for rural development in China/ ; No. 31472128//Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Salmonella typhimurium/drug effects/pathogenicity ; Mice ; *Cecum/microbiology ; *Salmonella Infections/microbiology/drug therapy ; RNA, Ribosomal, 16S/genetics ; Mice, Inbred C57BL ; Cytokines/metabolism ; Antimicrobial Peptides/pharmacology ; Feces/microbiology ; Administration, Oral ; Salmonella Infections, Animal/drug therapy/microbiology ; Antimicrobial Cationic Peptides/pharmacology ; Fecal Microbiota Transplantation ; Bacteria/drug effects/classification/genetics ; Female ; }, abstract = {BACKGROUND: Endogenous antimicrobial peptides and proteins are essential for shaping and maintaining a healthy gut microbiota, contributing to anti-inflammatory responses and resistance to pathogen colonization. Salmonella enterica subsp. enterica serovar Typhimurium (ST) infection is one of the most frequently reported bacterial diseases worldwide. Manipulation of the gut microbiota through exogenous antimicrobial peptides may protect against ST colonization and improve clinical outcomes.

RESULTS: This study demonstrated that oral administration of the antimicrobial peptide AP2 (2 µg /mouse), an optimized version of native apidaecin IB (AP IB), provided protective effects against ST infection in mice. These effects were evidenced by reduced ST-induced body weight loss and lower levels of serum inflammatory cytokines. A 16 S rRNA-based analysis of the cecal microbiota revealed that AP2 significantly modulated the gut microbiota, increasing the relative abundance of Bifidobacterium while decreasing that of Akkermansia at the genus level. Furthermore, the transplantation of fecal microbiota from AP2-treated donor mice, rather than from Control mice, significantly reduced cecal damage caused by ST and decreased the concentration of ST by one order of magnitude after infection.

CONCLUSIONS: These findings reveal a novel mechanism by which exogenous antimicrobial peptides mitigate Salmonella Typhimurium infection through the modulation of gut microbiota.}, } @article {pmid39909032, year = {2025}, author = {Zhu, X and Hu, M and Huang, X and Li, L and Lin, X and Shao, X and Li, J and Du, X and Zhang, X and Sun, R and Tong, T and Ma, Y and Ning, L and Jiang, Y and Zhang, Y and Shao, Y and Wang, Z and Zhou, Y and Ding, J and Zhao, Y and Xuan, B and Zhang, H and Zhang, Y and Hong, J and Fang, JY and Xiao, X and Shen, B and He, S and Chen, H}, title = {Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses.}, journal = {Cell metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmet.2024.12.013}, pmid = {39909032}, issn = {1932-7420}, abstract = {Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but remains effective in only a subset of patients. Emerging evidence suggests that the gut microbiome and its metabolites critically influence ICB efficacy. In this study, we performed a multi-omics analysis of fecal microbiomes and metabolomes from 165 patients undergoing anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) therapy, identifying microbial and metabolic entities associated with treatment response. Integration of data from four public metagenomic datasets (n = 568) uncovered cross-cohort microbial and metabolic signatures, validated in an independent cohort (n = 138). An integrated predictive model incorporating these features demonstrated robust performance. Notably, we characterized five response-associated enterotypes, each linked to specific bacterial taxa and metabolites. Among these, the metabolite phenylacetylglutamine (PAGln) was negatively correlated with response and shown to attenuate anti-PD-1 efficacy in vivo. This study sheds light on the interplay among the gut microbiome, the gut metabolome, and immunotherapy response, identifying potential biomarkers to improve treatment outcomes.}, } @article {pmid39908366, year = {2025}, author = {Wu, F and Lin, S and Luo, H and Wang, C and Liu, J and Zhu, X and Pang, Y}, title = {Noncontact microbiota transplantation by core-shell microgel-enabled nonleakage envelopment.}, journal = {Science advances}, volume = {11}, number = {6}, pages = {eadr7373}, pmid = {39908366}, issn = {2375-2548}, mesh = {*Microgels/chemistry ; *Gastrointestinal Microbiome ; Humans ; Fecal Microbiota Transplantation/methods ; Animals ; Probiotics ; Gelatin/chemistry ; Bacteria/metabolism ; }, abstract = {Transplantation of beneficial bacteria to specific microbiota has been widely exploited to treat diseases by reshaping a healthy microbial structure. However, direct exposure of exogenous bacteria in vivo suffers from low bioavailability and infection risk. Here, we describe a noncontact microbiota transplantation system (NMTS) by core-shell microgel-enabled nonleakage envelopment. Bacteria are encapsulated into the core of core-shell microgels via two-step light-initiated emulsion polymerization of gelatin methacrylate. NMTS is versatile for biocontainment of diverse strains, showing near complete encapsulation and negligible influence on bacterial activity. As a proof-of-concept study on probiotic transplantation to the gut microbiota, NMTS demonstrates the shielding effect to protect sealed bacteria from intraluminal insults of low pH and bile acid, the toughness to prevent bacterial leakage during entire gastrointestinal passage and reduce infection risk, and the permeability to release beneficial metabolites and reconstruct a balanced intestinal microbial structure, proposing a contactless fashion for advanced microbiota transplantation.}, } @article {pmid39908176, year = {2025}, author = {}, title = {Correction to: A Randomized Controlled Trial of Efficacy and Safety of Fecal Microbiota Transplant for Preventing Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {80}, number = {1}, pages = {242-243}, doi = {10.1093/cid/ciaf032}, pmid = {39908176}, issn = {1537-6591}, } @article {pmid39907559, year = {2025}, author = {Ding, Q and Xue, J and Li, N and Hu, Z and Song, J}, title = {Fecal microbiota transplantation alleviates radiation enteritis by modulating gut microbiota and metabolite profiles.}, journal = {Biomolecules & biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2025.11835}, pmid = {39907559}, issn = {2831-090X}, abstract = {This study investigates the safety and underlying mechanisms of fecal microbiota transplantation (FMT) in treating radiation enteritis (RE). A rat model of RE was established with six groups: NC, RT, H-FMT, modified FMT (M-FMT), L-FMT, and BTAC. The therapeutic effects of FMT were assessed using the Disease Activity Index (DAI), histological analysis, and biochemical tests, including ink-propelling, xylitol exclusion, and enzyme-linked immunosorbent assay (ELISA). Gut microbiota alterations and fecal metabolism were analyzed via 16S rDNA sequencing and targeted metabolomics. The results demonstrated that FMT, particularly in the M-FMT group, effectively alleviated RE by reducing DAI scores, histological damage, and inflammatory markers while enhancing enzyme activity, superoxide dismutase (SOD) levels, and intestinal absorption. FMT also modulated gut microbiota composition, increasing beneficial species, such as Blautia wexlerae and Romboutsia timonensis while decreasing Enterococcus ratti. Metabolomics analysis revealed that FMT influenced niacin, nicotinamide, and starch metabolism, with notable changes in pantothenic acid and fatty acid levels. Spearman correlation analysis further indicated that these microbial shifts were associated with improved metabolic profiles. Overall, FMT mitigates RE by regulating gut microbiota and metabolites, with pantothenic acid and fatty acids emerging as potential therapeutic targets. Further research is needed to explore the underlying mechanisms in greater detail.}, } @article {pmid39906503, year = {2025}, author = {Song, Q and Zhang, K and Li, S and Weng, S}, title = {Trichosanthes kirilowii Maxim. Polysaccharide attenuates diabetes through the synergistic impact of lipid metabolism and modulating gut microbiota.}, journal = {Current research in food science}, volume = {10}, number = {}, pages = {100977}, pmid = {39906503}, issn = {2665-9271}, abstract = {Polysaccharide, a chain of sugars bound by glycosidic bonds, have a wide range of physiological activities, including hypoglycemic activity. In present study, we established T2DM mice models to explore the effects and mechanism of Trichosanthes kirilowii Maxim polysaccharide (TMSP1) on high-fat diet/streptozotocin (HF-STZ) induced diabetes mice. The results showed that high-fat diet significantly increased the oral glucose tolerance test (OGTT), viscera index, oxidative stress, impaired glucose tolerance, decreased body weight, immune response and short-chain fatty acid (SCFAs) content, and disrupted the balance of intestinal flora structure. However, after 6 weeks of TMSP1 intervention decreased lipid accumulation, ameliorated gut microbiota dysbiosis by increasing SCFAs-producing bacteria and mitigated intestinal inflammation and oxidative stress. Moreover, TMSP1 significantly restored the integrity of the intestinal epithelial barrier and mucus barrier. The results of fecal microbiota transplantation confirmed that TMSP1 exerted hypoglycemic effect through regulating intestinal flora to a certain extent. Collectively, the findings revealed TMSP1 intervention inhibits hyperglycemia by improving gut microbiota disorder, lipid metabolism, and inflammation. Hence, TMSP1 may be an effective measure to ameliorate HF-STZ induced diabetes.}, } @article {pmid39905483, year = {2025}, author = {Lin, Z and Feng, Y and Wang, J and Men, Z and Ma, X}, title = {Microbiota governs host chenodeoxycholic acid glucuronidation to ameliorate bile acid disorder induced diarrhea.}, journal = {Microbiome}, volume = {13}, number = {1}, pages = {36}, pmid = {39905483}, issn = {2049-2618}, mesh = {Animals ; *Chenodeoxycholic Acid/analogs & derivatives/metabolism ; Mice ; *Diarrhea/microbiology ; *Gastrointestinal Microbiome ; Swine ; *Bile Acids and Salts/metabolism ; Limosilactobacillus reuteri/metabolism ; Fecal Microbiota Transplantation ; Intestinal Mucosa/metabolism/microbiology ; Apoptosis ; Indoles/metabolism ; Glucuronides/metabolism ; Humans ; Disease Models, Animal ; Male ; Mice, Inbred C57BL ; Sirtuin 1/metabolism ; Receptors, Cytoplasmic and Nuclear ; }, abstract = {BACKGROUND: Disorder in bile acid (BA) metabolism is known to be an important factor contributing to diarrhea. However, the pathogenesis of BA disorder-induced diarrhea remains unclear.

METHODS: The colonic BA pool and microbiota between health piglets and BA disorder-induced diarrheal piglets were compared. Fecal microbiota transplantation and various cell experiments further indicated that chenodeoxycholic acid (CDCA) metabolic disorder produced CDCA-3β-glucuronide, which is the main cause of BA disorder diarrhea. Non-targeted metabolomics uncovered the inhibition of the BA glucuronidation by Lactobacillus reuteri (L. reuteri) is through deriving indole-3-carbinol (I3C). In vitro, important gene involved in the reduction of BA disorder induced-diarrhea were screened by RNA transcriptomics sequencing, and activation pathway of FXR-SIRT1-LKB1 to alleviate BA disorder diarrhea and P53-mediated apoptosis were proposed in vitro by multifarious siRNA interference, CO-IP, immunofluorescence, and so on, which mechanism was also verified in a variety of mouse models.

RESULTS: Here, we reveal for the first time that core microbiota derived I3C represses gut epithelium glucuronidation, particularly 3β-glucuronic CDCA production, which reaction is mediated by host UDP glucuronosyltransferase family 1 member A4 (UGT1A4) and necessary of BA disorder induced diarrhea. Mechanistically, L. reuteri derived I3C activates aryl hydrocarbon receptor to decrease UGT1A4 transcription and CDCA-3β-glucuronide content, thereby upregulating FXR-SIRT1-LKB1 signal. LKB1 binds with P53 based on protein interaction, ultimately resists to apoptosis and diarrhea. Moreover, I3C assists CDCA to attain the ameliorative effects of FXR activation in BA disorder diarrhea, through reversion of abnormal metabolism pathway, improving the outcomes of CDCA supplement.

CONCLUSION: These findings uncover the crucial interplay between gut epithelial cells and microbes, highlighting UGT1A4-mediated conversion of CDCA-3β-glucuronide as a key target for ameliorating BA disorder-induced diarrhea. Video Abstract.}, } @article {pmid39725357, year = {2025}, author = {Ju, C and Liu, R and Ma, Y and Dong, H and Xu, R and Hu, H and Hao, D}, title = {Targeted microbiota dysbiosis repair: An important approach to health management after spinal cord injury.}, journal = {Ageing research reviews}, volume = {104}, number = {}, pages = {102648}, doi = {10.1016/j.arr.2024.102648}, pmid = {39725357}, issn = {1872-9649}, mesh = {*Spinal Cord Injuries/microbiology/therapy ; Humans ; *Dysbiosis ; *Gastrointestinal Microbiome/physiology ; *Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation/methods ; }, abstract = {Current research primarily focuses on the pathological mechanisms of spinal cord injury (SCI), seeking to promote spinal cord repair and restore motorial and sensory functions by elucidating mechanisms of cell death or axonal regeneration. However, SCI is almost irreversible, and patients often struggle to regain mobility or self-care abilities after injuries. Consequently, there has been significant interest in modulating systemic symptoms following SCI to improve patients' quality of life. Neuron axonal disconnection and substantial apoptotic events following SCI result in signal transmission loss, profoundly impacting various organ and systems, including the gastrointestinal tract. Dysbiosis can lead to severe bowel dysfunction in patients, substantially lowering their quality of life and significantly reducing life expectancy of them. Therefore, researches focusing on the restoration of the gut microbiota hold promise for potential therapeutic strategies aimed at rehabilitation after SCI. In this paper, we explore the regulatory roles that dietary fiber, short-chain fatty acids (SCFAs), probiotics, and microbiota transplantation play in patients with SCI, summarize the potential mechanisms of post-SCI dysbiosis, and discuss possible strategies to enhance long-term survival of SCI patients. We aim to provide potential insights for future research aimed at ameliorating dysbiosis in SCI patients.}, } @article {pmid39904968, year = {2025}, author = {Ashiqueali, SA and Hayslip, N and Chaudhari, DS and Schneider, A and Zhu, X and Rubis, B and Seavey, CE and Alam, MT and Hussein, R and Noureddine, SA and Golusinska-Kardach, E and Pazdrowski, P and Yadav, H and Masternak, MM}, title = {Fecal microbiota transplant from long-living Ames dwarf mice alters the microbial composition and biomarkers of liver health in normal mice.}, journal = {GeroScience}, volume = {}, number = {}, pages = {}, pmid = {39904968}, issn = {2509-2723}, support = {R56AG074499/NH/NIH HHS/United States ; R56AG069676/NH/NIH HHS/United States ; R56AG064075/NH/NIH HHS/United States ; RF1AG071762/NH/NIH HHS/United States ; R21AG072379/NH/NIH HHS/United States ; U01AG076928/NH/NIH HHS/United States ; W81XWH-18-PRARP AZ180098//U.S. Department of Defense/ ; 22A17//Florida Department of Health/ ; 22A17//Florida Department of Health/ ; HORIZON 2020-MSCA-RISE//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; HORIZON 2020-MSCA-RISE//HORIZON EUROPE Marie Sklodowska-Curie Actions/ ; }, abstract = {Aging is associated with intestinal dysbiosis, a condition characterized by diminished microbial biodiversity and inflammation. This leads to increased vulnerability to extraintestinal manifestations such as autoimmune, metabolic, and neurodegenerative conditions thereby accelerating mortality. As such, modulation of the gut microbiome is a promising way to extend healthspan. In this study, we explore the effects of fecal microbiota transplant (FMT) from long-living Ames dwarf donors to their normal littermates, and vice versa, on the recipient gut microbiota and liver transcriptome. Importantly, our previous studies highlight differences between the microbiome of Ames dwarf mice relative to their normal siblings, potentially contributing to their extended lifespan and remarkable healthspan. Our findings demonstrate that FMT from Ames dwarf mice to normal mice significantly alters the recipient's gut microbiota, potentially reprogramming bacterial functions related to healthy aging, and changes the liver transcriptome, indicating improved metabolic health. Particularly, the microbiome of Ames dwarf mice, characterized by a higher abundance of beneficial bacterial families such as Peptococcaceae, Oscillospiraceae, and Lachnospiraceae, appears to play a crucial role in modulating these effects. Alongside, our mRNA sequencing and RT-PCR validation reveals that FMT may contribute to the significant downregulation of p21, Elovl3, and Insig2, genes involved with cellular senescence and liver metabolic pathways. Our data suggest a regulatory axis exists between the gut and liver, highlighting the potential of microbiome-targeted therapies in promoting healthy aging. Future research should focus on functional validation of altered microbial communities and explore the underlying biomolecular pathways that confer geroprotection.}, } @article {pmid39904603, year = {2025}, author = {Lou, F and Yan, L and Luo, S and Dong, Y and Xu, J and Kang, N and Wang, H and Liu, Y and Pu, J and Yang, B and Cannon, RD and Xie, P and Ji, P and Jin, X}, title = {Dysbiotic oral microbiota-derived kynurenine, induced by chronic restraint stress, promotes head and neck squamous cell carcinoma by enhancing CD8[+] T cell exhaustion.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-333479}, pmid = {39904603}, issn = {1468-3288}, abstract = {BACKGROUND: Chronic restraint stress (CRS) is a tumour-promoting factor. However, the underlying mechanism is unknown.

OBJECTIVE: We aimed to investigate whether CRS promotes head and neck squamous cell carcinoma (HNSCC) by altering the oral microbiota and related metabolites and whether kynurenine (Kyn) promotes HNSCC by modulating CD8[+] T cells.

DESIGN: 4-nitroquinoline-1-oxide (4NQO)-treated mice were exposed to CRS. Germ-free mice treated with 4NQO received oral microbiota transplants from either CRS or control mouse donors. 16S rRNA gene sequencing and liquid chromatography-mass spectrometry were performed on mouse saliva, faecal and plasma samples to investigate alterations in their microbiota and metabolites. The effects of Kyn on HNSCC were studied using the 4NQO-induced HNSCC mouse model.

RESULTS: Mice subjected to CRS demonstrated a higher incidence of HNSCC and oral microbial dysbiosis than CRS-free control mice. Pseudomonas and Veillonella species were enriched while certain oral bacteria, including Corynebacterium and Staphylococcus species, were depleted with CRS exposure. Furthermore, CRS-altered oral microbiota promoted HNSCC formation, caused oral and gut barrier dysfunction, and induced a host metabolome shift with increased plasma Kyn in germ-free mice exposed to 4NQO treatment. Under stress conditions, we also found that Kyn activated aryl hydrocarbon receptor (AhR) nuclear translocation and deubiquitination in tumour-reactive CD8[+] T cells, thereby promoting HNSCC tumourigenesis.

CONCLUSION: CRS-induced oral microbiota dysbiosis plays a protumourigenic role in HNSCC and can influence host metabolism. Mechanistically, under stress conditions, Kyn promotes CD8[+] T cell exhaustion and HNSCC tumourigenesis through stabilising AhR by its deubiquitination.}, } @article {pmid39903739, year = {2025}, author = {Men, J and Li, H and Cui, C and Ma, X and Liu, P and Yu, Z and Gong, X and Yao, Y and Ren, J and Zhao, C and Song, B and Yin, K and Wu, J and Liu, W}, title = {Fecal bacteria transplantation replicates aerobic exercise to reshape the gut microbiota in mice to inhibit high-fat diet-induced atherosclerosis.}, journal = {PloS one}, volume = {20}, number = {2}, pages = {e0314698}, pmid = {39903739}, issn = {1932-6203}, mesh = {Animals ; *Diet, High-Fat/adverse effects ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Atherosclerosis/microbiology/etiology ; Male ; Mice ; *Physical Conditioning, Animal ; *Mice, Inbred C57BL ; Disease Models, Animal ; Lipids/blood ; }, abstract = {Aerobic exercise exerts a significant impact on the gut microbiota imbalance and atherosclerosis induced by a high-fat diet. However, whether fecal microbiota transplantation, based on aerobic exercise, can improve atherosclerosis progression remains unexplored. In this study, we utilized male C57 mice to establish models of aerobic exercise and atherosclerosis, followed by fecal microbiota transplantation(Fig 1a). Firstly, we analyzed the body weight, somatotype, adipocyte area, and aortic HE images of the model mice. Our findings revealed that high-fat diet -induced atherosclerosis mice exhibited elevated lipid accumulation, larger adipocyte area, and more severe atherosclerosis progression. Additionally, we assessed plasma lipid levels, inflammatory factors, and gut microbiota composition in each group of mice. high-fat diet -induced atherosclerosis mice displayed dyslipidemia along with inflammatory responses and reduced gut microbiota diversity as well as abundance of beneficial bacteria. Subsequently performing fecal microbiota transplantation demonstrated that high-fat diet -induced atherosclerosis mice experienced weight loss accompanied by reduced lipid accumulation while normalizing their gut microbiota profile; furthermore it significantly improved blood lipids and inflammation markers thereby exhibiting notable anti- atherosclerosis effects. The findings suggest that aerobic exercise can modify gut microbiota composition and improve high-fat diet-induced atherosclerosis(Fig 1b). Moreover, these beneficial effects can be effectively transmitted through fecal microbiota transplantation, offering a promising therapeutic approach for managing atherosclerosis.}, } @article {pmid39902926, year = {2025}, author = {Rahman, R and Fouhse, JM and Ju, T and Fan, Y and Bhardwaj, T and Brook, RK and Nosach, R and Harding, J and Willing, BP}, title = {The impact of wild-boar-derived microbiota transplantation on piglet microbiota, metabolite profile, and gut proinflammatory cytokine production differs from sow-derived microbiota.}, journal = {Applied and environmental microbiology}, volume = {}, number = {}, pages = {e0226524}, doi = {10.1128/aem.02265-24}, pmid = {39902926}, issn = {1098-5336}, abstract = {Colonization of co-evolved, species-specific microbes in early life plays a crucial role in gastrointestinal development and immune function. This study hypothesized that modern pig production practices have resulted in the loss of co-evolved species and critical symbiotic host-microbe interactions. To test this, we reintroduced microbes from wild boars (WB) into conventional piglets to explore their colonization dynamics and effects on gut microbial communities, metabolite profiles, and immune responses. At postnatal day (PND) 21, 48 piglets were assigned to four treatment groups: (i) WB-derived mixed microbial community (MMC), (ii) sow-derived MMC, (iii) a combination of WB and sow MMC (Mix), or (iv) Control (PBS). Post-transplantation analyses at PND 48 revealed distinct microbial communities in WB-inoculated piglets compared with Controls, with trends toward differentiation from Sow but not Mix groups. WB-derived microbes were more successful in colonizing piglets, particularly in the Mix group, where they competed with Sow-derived microbes. WB group cecal digesta enriched with Lactobacillus helveticus, Lactobacillus mucosae, and Lactobacillus pontis. Cecal metabolite analysis showed that WB piglets were enriched in histamine, acetyl-ornithine, ornithine, citrulline, and other metabolites, with higher histamine levels linked to Lactobacillus abundance. WB piglets exhibited lower cecal IL-1β and IL-6 levels compared with Control and Sow groups, whereas the Mix group showed reduced IFN-γ, IL-2, and IL-6 compared with the Sow group. No differences in weight gain, fecal scores, or plasma cytokines were observed, indicating no adverse effects. These findings support that missing WB microbes effectively colonize domestic piglets and may positively impact metabolite production and immune responses.IMPORTANCEThis study addresses the growing concern over losing co-evolved, species-specific microbes in modern agricultural practices, particularly in pig production. The implementation of strict biosecurity measures and widespread antibiotic use in conventional farming systems may disrupt crucial host-microbe interactions that are essential for gastrointestinal development and immune function. Our research demonstrates that by reintroducing wild boar-derived microbes into domestic piglets, these microbes can successfully colonize the gut, influence microbial community composition, and alter metabolite profiles and immune responses without causing adverse effects. These findings also suggest that these native microbes can fill an intestinal niche, positively impacting immune activation. This research lays the groundwork for future strategies to enhance livestock health and performance by restoring natural microbial populations that produce immune-modulating metabolites.}, } @article {pmid39901991, year = {2025}, author = {Hemachandra, S and Rathnayake, SN and Jayamaha, AA and Francis, BS and Welmillage, D and Kaur, DN and Zaw, HK and Zaw, LT and Chandra, HA and Abeysekera, ME}, title = {Fecal Microbiota Transplantation as an Alternative Method in the Treatment of Obesity.}, journal = {Cureus}, volume = {17}, number = {1}, pages = {e76858}, pmid = {39901991}, issn = {2168-8184}, abstract = {Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for various health conditions, particularly obesity and metabolic disorders. This review examines the mechanisms underlying FMT, including its role in restoring gut microbiota diversity and enhancing immunomodulatory functions, which are essential for maintaining overall health. Recent studies indicate that FMT can significantly improve body weight and metabolic parameters, suggesting its potential as an alternative or complementary treatment to current obesity therapies. However, the effectiveness of FMT depends on several factors, including the composition of the donor microbiota, recipient characteristics, and concomitant medications or dietary interventions. Despite its great promise, challenges such as standardized protocols, donor screening, and the need for a deeper understanding of gut microbiota dynamics remain key hurdles. Future research should focus on elucidating the specific microbial compositions necessary for optimal therapeutic outcomes and exploring personalized FMT approaches tailored to individual patient profiles. This evolving field presents exciting opportunities for innovative strategies in obesity treatment, warranting further investigation and clinical application.}, } @article {pmid39901521, year = {2025}, author = {Kappel, SS and Sangild, PT and Zachariassen, G and Andersen, JH and Rasmussen, KK and Jeppesen, PB and Aunsholt, L}, title = {Protein and energy digestibility in preterm infants fed fortified human milk.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.70000}, pmid = {39901521}, issn = {1536-4801}, support = {//Innovation Fund Denmark (NEOCOL grant 6150-00004B)./ ; }, abstract = {OBJECTIVES: The objective of the present study is to determine whether the apparent nutrient digestibility differs between very preterm infants fortified with bovine colostrum (BC) compared to those fortified with a conventional fortifier (CF), building on previous findings that BC was associated with looser stools and reduced need for laxatives in very preterm infants (VPI).

METHODS: We conducted a 24-h digestibility balance study in 10 VPIs to assess the retention of protein, energy, and wet-weight following the intake of fortified human milk and collection of faecal excretions. Infants (n = 5) were matched by gestational age and birthweight.

RESULTS: In the 10 infants, the mean gestational age and birthweight were 28 ± 1 weeks and 899 ± 182 g, respectively. Infants fortified with BC had a higher faecal energy loss compared with infants fortified with CF (BC: 178 [range 111-205] vs. CF: 153 [96-235] kJ/kg, p < 0.05). No differences (p > 0.05) were found for wet-weight intake (421 [360-427] vs. 494 [328-500] kJ/kg), relative absorption of protein (60 [33-75] vs. 50 [33-75]%) or absolute protein absorption (249 [159-310) vs. 281 [210-347]).

CONCLUSION: Nutrient absorption was similar between groups although higher energy loss indicates reduced overall digestibility of BC versus CF, however, with a large variation within each group. Studies on more infants are required to confirm these results. A 24-h digestibility balance study can successfully be used to assess nutrient and energy retention in preterm infants.}, } @article {pmid39900090, year = {2025}, author = {Tay, SW and Low, AHL}, title = {Is faecal microbiota transplantation ready for prime time in systemic sclerosis?.}, journal = {The Lancet. Rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2665-9913(24)00376-X}, pmid = {39900090}, issn = {2665-9913}, } @article {pmid39843757, year = {2025}, author = {Pitashny, M and Kesten, I and Shlon, D and Hur, DB and Bar-Yoseph, H}, title = {The Future of Microbiome Therapeutics.}, journal = {Drugs}, volume = {85}, number = {2}, pages = {117-125}, pmid = {39843757}, issn = {1179-1950}, mesh = {Humans ; *Microbiota ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation/methods ; Phage Therapy/methods ; Synthetic Biology/methods/trends ; }, abstract = {The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy. Advancements in technology are paving the way for the development of novel microbiome therapeutics, across a wide range of indications. In this narrative review, we provide an overview of state-of-the-art technologies in late-stage development, examining their advantages and limitations. By covering a spectrum, from fecal-derived products to live biotherapeutics, phage therapy, and synthetic biology, we illuminate the path toward the future of microbiome therapeutics.}, } @article {pmid39900089, year = {2025}, author = {Fretheim, H and Barua, I and Bakland, G and Dhainaut, A and Halse, AK and Carstens, MN and Didriksen, H and Midtvedt, Ø and Lundin, KEA and Aabakken, L and Sarna, VK and Zaré, HK and Khanna, D and Distler, O and Midtvedt, T and Bækkevold, ES and Olsen, IC and Domanska, D and Pesonen, ME and Molberg, Ø and Hoffmann-Vold, AM}, title = {Faecal microbiota transplantation in patients with systemic sclerosis and lower gastrointestinal tract symptoms in Norway (ReSScue): a phase 2, randomised, double-blind, placebo-controlled trial.}, journal = {The Lancet. Rheumatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2665-9913(24)00334-5}, pmid = {39900089}, issn = {2665-9913}, abstract = {BACKGROUND: Gastrointestinal tract involvement is highly prevalent in systemic sclerosis, with few treatment options. We assessed the efficacy and safety of faecal microbiota transplantation using standardised anaerobic cultivated human intestinal microbiome (ACHIM) as a novel treatment option for patients with systemic sclerosis and symptomatic lower gastrointestinal tract involvement.

METHODS: In this phase 2, randomised, double-blind, placebo-controlled trial done at four university hospitals in Norway, we enrolled adults aged 18-85 years with systemic sclerosis and moderate-to-severe lower gastrointestinal tract symptoms (bloating or diarrhoea). Participants were randomly assigned 1:1 to intestinal infusions of placebo or ACHIM at weeks 0 and 2, stratified by worst symptom (bloating or diarrhoea). The primary endpoint was change in worst lower gastrointestinal tract symptom (bloating or diarrhoea) from week 0 to week 12, measured using the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract 2.0 scoring system in the intention-to-treat population. Safety was assessed at weeks 0, 2, 4, 6, and 12 in all participants who received at least one infusion. A person with lived experience of systemic sclerosis was involved in the study planning and conduct. This trial was registered at ClinicalTrials.gov, NCT04300426.

FINDINGS: Between Sept 24, 2020, and Jan 14, 2022, 67 participants were enrolled and randomly allocated to placebo (n=34) or ACHIM (n=33). Mean age was 58·91 years (SD 11·59). 62 (93%) of 67 participants were women, five (7%) were men, and 50 (75%) were anti-centromere antibody positive. Change in worst lower gastrointestinal tract symptom from week 0 to week 12 did not differ between participants who received ACHIM (-0·13, 95% CI -0·37 to 0·11) and participants who received placebo (-0·33, -0·57 to -0·09; average marginal effect 0·20, 95% CI -0·12 to 0·52; p=0·22). Adverse events, mostly mild and short-lived gastrointestinal tract symptoms, were reported by 16 (48%) of 33 participants in the ACHIM group and 19 (56%) of 34 in the placebo group. During gastroscopy, one participant had a duodenal perforation.

INTERPRETATION: Faecal microbiota transplantation with ACHIM was well tolerated in participants with systemic sclerosis but did not result in an improvement in lower gastrointestinal tract symptoms.

FUNDING: KLINBEFORSK.

TRANSLATION: For the Norwegian translation of the abstract see Supplementary Materials section.}, } @article {pmid39899452, year = {2025}, author = {Chaki, T and Horiguchi, Y and Tachibana, S and Sato, S and Hirahata, T and Nishihara, N and Kii, N and Yoshikawa, Y and Hayamizu, K and Yamakage, M}, title = {Gut Microbiota Influences Developmental Anesthetic Neurotoxicity in Neonatal Rats.}, journal = {Anesthesia and analgesia}, volume = {}, number = {}, pages = {}, doi = {10.1213/ANE.0000000000007410}, pmid = {39899452}, issn = {1526-7598}, abstract = {BACKGROUND: Anesthetic exposure during childhood is significantly associated with impairment of neurodevelopmental outcomes; however, the causal relationship and detailed mechanism of developmental anesthetic neurotoxicity remain unclear. Gut microbiota produces various metabolites and influences the brain function and development of the host. This relationship is referred to as the gut-brain axis. Gut microbiota may influence developmental anesthetic neurotoxicity caused by sevoflurane exposure. This study investigated the effect of changes in the composition of gut microbiota after fecal microbiota transplantation on spatial learning disability caused by developmental anesthetic neurotoxicity in neonatal rats.

METHODS: Neonatal rats were allocated into the Control (n = 10) and Sevo (n = 10) groups in Experiment 1 and the Sevo (n = 20) and Sevo+FMT (n = 20) groups in Experiment 2, according to the randomly allocated mothers' group. The rats in Sevo and Sevo+FMT groups were exposed to 2.1% sevoflurane for 2 hours on postnatal days 7 to 13. Neonatal rats in the Sevo+FMT group received fecal microbiota transplantation immediately after sevoflurane exposure on postnatal days 7 to 13. The samples for fecal microbiota transplantation were obtained from nonanesthetized healthy adult rats. Behavioral tests, including Open field, Y-maze, Morris water maze, and reversal Morris water maze tests, were performed to evaluate spatial learning ability on postnatal days 26 to 39.

RESULTS: Experiment 1 revealed that sevoflurane exposure significantly altered the gut microbiota composition. The relative abundance of Roseburia (effect value: 1.01) and Bacteroides genus (effect value: 1.03) increased significantly after sevoflurane exposure, whereas that of Lactobacillus (effect value: -1.20) decreased significantly. Experiment 2 revealed that fecal microbiota transplantation improved latency to target (mean ± SEM; Sevo group: 9.7 ± 8.2 seconds vs, Sevo+FMT group: 2.7 ± 2.4 seconds, d=1.16, 95% confidence interval: -12.7 to -1.3 seconds, P = .019) and target zone crossing times (Sevo group: 2.4 ± 1.6 vs, Sevo+FMT group: 5.4 ± 1.4, d=1.99, 95% confidence interval: 2.0-5.0, P < .001) in the reversal Morris water maze test. Microbiota analysis revealed that the α-diversity of gut microbiota increased after fecal microbiota transplantation. Similarly, the relative abundance of the Firmicutes phylum (effect value: 1.44), Ruminococcus genus (effect value: 1.69), and butyrate-producing bacteria increased after fecal microbiota transplantation. Furthermore, fecal microbiota transplantation increased the fecal concentration of butyrate and induced histone acetylation and the mRNA expression of brain-derived neurotrophic factor in the hippocampus, thereby suppressing neuroinflammation and neuronal apoptosis.

CONCLUSIONS: The alternation of gut microbiota after fecal microbiota transplantation influenced spatial learning ability in neonatal rats with developmental anesthetic neurotoxicity. Modulation of the gut microbiota may be an effective prophylaxis for developmental anesthetic neurotoxicity in children.}, } @article {pmid39897551, year = {2025}, author = {Yu, C and Sun, R and Yang, W and Gu, T and Ying, X and Ye, L and Zheng, Y and Fan, S and Zeng, X and Yao, S}, title = {Exercise ameliorates osteopenia in mice via intestinal microbial-mediated bile acid metabolism pathway.}, journal = {Theranostics}, volume = {15}, number = {5}, pages = {1741-1759}, pmid = {39897551}, issn = {1838-7640}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; Mice ; *Fecal Microbiota Transplantation/methods ; *Bone Diseases, Metabolic/metabolism/therapy ; *Bile Acids and Salts/metabolism ; Female ; *Physical Conditioning, Animal/physiology ; Ovariectomy ; Mice, Inbred C57BL ; Disease Models, Animal ; Osteoporosis/metabolism/therapy ; RNA, Ribosomal, 16S/genetics ; Bone and Bones/metabolism ; Metabolomics/methods ; }, abstract = {Rationale: Physical exercise is essential for skeletal integrity and bone health. The gut microbiome, as a pivotal modulator of overall physiologic states, is closely associated with skeletal homeostasis and bone metabolism. However, the potential role of intestinal microbiota in the exercise-mediated bone gain remains unclear. Methods: We conducted microbiota depletion and fecal microbiota transplantation (FMT) in ovariectomy (OVX) mice and aged mice to investigate whether the transfer of gut ecological traits could confer the exercise-induced bone protective effects. The study analyzed the gut microbiota and metabolic profiles via 16S rRNA gene sequencing and LC-MS untargeted metabolomics to identify key microbial communities and metabolites responsible for bone protection. Transcriptome sequencing and RNA interference were employed to explore the molecular mechanisms. Results: We found that gut microbiota depletion hindered the osteogenic benefits of exercise, and FMT from exercised osteoporotic mice effectively mitigated osteopenia. Comprehensive profiling of the microbiome and metabolome revealed that the exercise-matched FMT reshaped intestinal microecology and metabolic landscape. Notably, alterations in bile acid metabolism, specifically the enrichment of taurine and ursodeoxycholic acid, mediated the protective effects on bone mass. Mechanistically, FMT from exercised mice activated the apelin signaling pathway and restored the bone-fat balance in recipient MSCs. Conclusion: Our study underscored the important role of the microbiota-metabolic axis in the exercise-mediated bone gain, heralding a potential breakthrough in the treatment of osteoporosis.}, } @article {pmid39897545, year = {2025}, author = {Hou, W and Cao, Y and Wang, J and Yin, F and Wang, J and Guo, N and Wang, Z and Lv, X and Ma, C and Chen, Q and Yang, R and Wei, H and Li, J and Wang, R and Qin, H}, title = {Single-cell nanocapsules of gut microbiota facilitate fecal microbiota transplantation.}, journal = {Theranostics}, volume = {15}, number = {5}, pages = {2069-2084}, pmid = {39897545}, issn = {1838-7640}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Nanocapsules ; *Fecal Microbiota Transplantation/methods ; Mice ; Colitis/therapy/microbiology ; Disease Models, Animal ; Phosphatidylcholines/chemistry ; Fibroins ; Mice, Inbred C57BL ; Male ; }, abstract = {Rationale: Fecal microbiota transplantation (FMT) is advantageous for treating intractable diseases via the microbiota-gut-organ axis. However, invasive administration of gut microbiota via nasal feeding tubes limits the widespread application of FMT. Here, we attempted to develop a novel strategy to deliver gut microbiota using nanocapsules. Methods: Single-cell nanocapsules were fabricated within 1 h by layer-by-layer assembly of silk fibroin and phosphatidylcholine to generate a protective nanoshell on the cell surface of complicated microbiota. The physical properties of the microbiota nanocapsules were analyzed. The protective effects of nanocapsules on the gastrointestinal tract were analyzed both in vitro and in vivo. The efficacy of FMT assisted by single-cell nanocapsules (NanoFMT) was evaluated using the inflammatory response, gut microbiota balance, and histopathological analysis in animal model. Results: The nanocapsules achieved a good coating ratio for a single type of microbe and complex microbiota, resulting in a remarkable increase in the survival rate of microbes in the gastrointestinal tract. NanoFMT improved the diversity and abundance of the gut microbiota better than common FMT in germ-free mice. Moreover, NanoFMT alleviated intestinal inflammation and positively reversed the microbiota balance in a mouse model of colitis compared with common FMT, assisted by the inherent anti-inflammatory effects of silk fibroin and phosphatidylcholine. Conclusions: Considering its rapid preparation, convenient delivery, and perfect therapeutic effect, we anticipate that NanoFMT may be a promising clinical candidate for next-generation FMT treatment.}, } @article {pmid39896755, year = {2025}, author = {Zhao, B and Zhou, H and Lin, K and Xu, J and Zhou, B and Xie, D and Ma, J and Yang, L and Su, C and Yang, L}, title = {Antimicrobial peptide DP7 alleviates dextran sulfate sodium (DSS)-induced colitis via modifying gut microbiota and regulating intestinal barrier function.}, journal = {MedComm}, volume = {6}, number = {2}, pages = {e70085}, pmid = {39896755}, issn = {2688-2663}, abstract = {Inflammatory bowel diseases (IBDs), such as Crohn's disease (CD) and ulcerative colitis (UC), represent a growing global health concern. Restoring the balance of the gut microbiota, a crucial factor in intestinal health, offers potential for treating IBD. DP7, a novel antimicrobial peptide with potent antibacterial activity, was investigated for its anti-inflammatory effects in a dextran sulfate sodium (DSS)-induced UC mouse model. DP7 significantly ameliorated key disease parameters, including disease activity index, weight loss, and shortened colon length, while preserving colonic epithelial integrity and reducing inflammatory infiltration. Further analysis revealed potential targets of DP7, highlighting the significant role of Muribaculaceae bacteria during inflammatory states. To further explore the role of the gut microbiota in DP7's efficacy, fecal microbiota transplantation (FMT) was performed using feces from DP7-treated mice. FMT successfully ameliorated colitis in recipient mice, providing further evidence for the crucial role of the gut microbiome in IBD treatment and DP7's ability to modulate the gut microbiota for therapeutic benefit. Moreover, our findings suggest that DP7's modulation of the immune system is intricately linked to the complex microbial environment. Our findings demonstrate that DP7 effectively mitigates inflammation, attenuates barrier dysfunction, and shapes the gut microbiota, suggesting its potential as a therapeutic agent for UC.}, } @article {pmid39896483, year = {2025}, author = {Gray, SM and Wood, MC and Mulkeen, SC and Ahmed, S and Thaker, SD and Chen, B and Sander, WR and Bibeva, V and Zhang, X and Yang, J and Herzog, JW and Zhang, S and Dogan, B and Simpson, KW and Sartor, RB and Montrose, DC}, title = {Dietary protein source mediates colitis pathogenesis through bacterial modulation of bile acids.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.24.634824}, pmid = {39896483}, issn = {2692-8205}, abstract = {Evidence-based dietary recommendations for individuals with inflammatory bowel diseases (IBD) are limited. Red meat consumption is associated with increased IBD incidence and relapse in patients, suggesting that switching to a plant-based diet may limit gut inflammation. However, the mechanisms underlying the differential effects of these diets remain poorly understood. Feeding diets containing plant- or animal-derived proteins to murine colitis models revealed that mice given a beef protein (BP) diet exhibited the most severe colitis, while mice fed pea protein (PP) developed mild inflammation. The colitis-promoting effects of BP were microbially-mediated as determined by bacterial elimination or depletion and microbiota transplant studies. In the absence of colitis, BP-feeding reduced abundance of Lactobacillus johnsonii and Turicibacter sanguinis and expanded Akkermansia muciniphila , which localized to the mucus in association with decreased mucus thickness and quality. BP-fed mice had elevated primary and conjugated fecal bile acids (BAs), and taurocholic acid administration to PP-fed mice worsened colitis. Dietary psyllium protected against BP-mediated inflammation, restored BA-modulating commensals and normalized BA ratios. Collectively, these data suggest that the protein component of red meat may be responsible, in part, for the colitis-promoting effects of this food source and provide insight into dietary factors that may influence IBD severity.}, } @article {pmid39895632, year = {2025}, author = {Gazzaniga, FS and Kasper, DL}, title = {The gut microbiome and cancer response to immune checkpoint inhibitors.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {3}, pages = {}, pmid = {39895632}, issn = {1558-8238}, mesh = {*Gastrointestinal Microbiome/drug effects/immunology ; Humans ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; Animals ; *Neoplasms/immunology/drug therapy/microbiology/therapy ; Mice ; *Fecal Microbiota Transplantation ; Immunotherapy ; }, abstract = {Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy, yet only a fraction of patients respond. Remarkably, gut bacteria impact the efficacy of ICIs in fighting tumors outside of the gut. Certain strains of commensal gut bacteria promote antitumor responses to ICIs in a variety of preclinical mouse tumor models. Patients with cancer who respond to ICIs have a different microbiome compared with that of patients who don't respond. Fecal microbiota transplants (FMTs) from patients into mice phenocopy the patient tumor responses: FMTs from responders promote response to ICIs, whereas FMTs from nonresponders do not promote a response. In patients, FMTs from patients who have had a complete response to ICIs can overcome resistance in patients who progress on treatment. However, the responses to FMTs are variable. Though emerging studies indicate that gut bacteria can promote antitumor immunity in the absence of ICIs, this Review will focus on studies that demonstrate relationships between the gut microbiome and response to ICIs. We will explore studies investigating which bacteria promote response to ICIs in preclinical models, which bacteria are associated with response in patients with cancer receiving ICIs, the mechanisms by which gut bacteria promote antitumor immunity, and how microbiome-based therapies can be translated to the clinic.}, } @article {pmid39895628, year = {2025}, author = {Si, W and Zhao, X and Li, R and Li, Y and Ma, C and Zhao, X and Bugno, J and Qin, Y and Zhang, J and Liu, H and Wang, L}, title = {Lactobacillus rhamnosus GG induces STING-dependent IL-10 in intestinal monocytes and alleviates inflammatory colitis in mice.}, journal = {The Journal of clinical investigation}, volume = {135}, number = {3}, pages = {}, pmid = {39895628}, issn = {1558-8238}, mesh = {Animals ; *Interleukin-10/immunology/genetics/metabolism ; *Lacticaseibacillus rhamnosus/immunology ; Mice ; *Colitis/immunology/therapy/pathology/microbiology ; *Membrane Proteins/genetics/immunology/metabolism ; *Monocytes/immunology/metabolism ; Signal Transduction/immunology ; Probiotics/administration & dosage/pharmacology ; Protein Serine-Threonine Kinases/metabolism/genetics/immunology ; Gastrointestinal Microbiome/immunology ; Transcription Factor RelA/metabolism/genetics/immunology ; Mice, Knockout ; Fecal Microbiota Transplantation ; }, abstract = {Preclinical and clinical observations indicate that the probiotic Lactobacillus rhamnosus GG (LGG) can modulate colonic inflammation. However, the underlying mechanisms have not been explored in depth. Here, we demonstrate that oral administration of live LGG alleviated inflammatory colitis by increasing IL-10 expression in intestinal Ly6C+ monocytes. Mechanistically, LGG induced IL-10 production via the stimulator of IFN genes (STING)/TBK1/NF-κB (RELA) signaling pathway in intestinal Ly6C+ monocytes, enhancing their immune-suppressive function. Elevated IL-10 subsequently activated IL-10 signaling in Ly6C+ monocytes, resulting in an IL-10-based autocrine regulatory loop and inhibition of proinflammatory cytokine production. Furthermore, LGG shifted the gut microbial community and its metabolic functions, leading to intestinal immune responses against colitis. Fecal microbiota transplantation from LGG-colonized mice alleviated immune checkpoint blockade-associated colitis. Our findings highlight the importance of STING signaling in IL-10-dependent antiinflammatory immunity and establish an empirical basis for developing oral administration of live LGG as an efficient and safe therapeutic strategy against inflammatory colitis.}, } @article {pmid39180326, year = {2025}, author = {Feuerstadt, P and Chopra, T and Knapple, W and Van Hise, NW and Dubberke, ER and Baggott, B and Guthmueller, B and Bancke, L and Gamborg, M and Steiner, TS and Van Handel, D and Khanna, S}, title = {PUNCH CD3-OLS: A Phase 3 Prospective Observational Cohort Study to Evaluate the Safety and Efficacy of Fecal Microbiota, Live-jslm (REBYOTA) in Adults With Recurrent Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {80}, number = {1}, pages = {43-51}, pmid = {39180326}, issn = {1537-6591}, support = {//Ferring Pharmaceuticals/ ; }, mesh = {Humans ; *Clostridium Infections/drug therapy ; Male ; Female ; Middle Aged ; Prospective Studies ; *Fecal Microbiota Transplantation ; Adult ; Aged ; *Clostridioides difficile ; *Anti-Bacterial Agents/therapeutic use/administration & dosage ; Feces/microbiology ; Canada ; Recurrence ; Treatment Outcome ; Gastrointestinal Microbiome ; United States ; Young Adult ; }, abstract = {BACKGROUND: The aim of this study was to evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA)-the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the US Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment.

METHODS: PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24-72 hours of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively.

RESULTS: Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups.

CONCLUSIONS: RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date, and findings support use of RBL to prevent rCDI in a broad patient population.

CLINICAL TRIALS REGISTRATION: NCT03931941.}, } @article {pmid39892949, year = {2025}, author = {McGann, C and Phyu, R and Bittinger, K and Mukhopadhyay, S}, title = {Role of the Microbiome in Neonatal Infection: Pathogenesis and Implications for Management.}, journal = {Clinics in perinatology}, volume = {52}, number = {1}, pages = {147-166}, doi = {10.1016/j.clp.2024.10.010}, pmid = {39892949}, issn = {1557-9840}, mesh = {Humans ; Infant, Newborn ; *Probiotics/therapeutic use ; *Gastrointestinal Microbiome ; *Anti-Bacterial Agents/therapeutic use ; *Fecal Microbiota Transplantation/methods ; Neonatal Sepsis/microbiology/therapy ; Microbiota ; }, abstract = {The human microbiome refers to the collective genome of microorganisms, including bacteria, fungi, and viruses residing on human body surfaces that are in contact with the environment. Together these communities protect against invasive infections. Conversely, when disrupted, the microbiome can be the source of pathogens causing invasive infection. Interventions to manipulate it via probiotics, antibiotics, and fecal transplantation are available. The risk benefit of these interventions remains unclear. In this review, the authors discuss evidence linking the gut microbiome to neonatal sepsis and also discuss the challenges for translating this knowledge into better clinical care.}, } @article {pmid39890521, year = {2025}, author = {Rafie, E and Zugman, M and Pal, SK and Routy, B and Elkrief, A}, title = {What Is the Role of Fecal Microbiota Transplantation in Immunotherapy Trials? Current Perspectives and Future Directions.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2024.12.009}, pmid = {39890521}, issn = {2405-4569}, abstract = {Immune checkpoint inhibitors (ICIs) are rapidly transforming the treatment landscape of genitourinary and other immunogenic malignancies. Despite these advances, biomarkers for the prediction of ICI response remain to be established. The gut microbiome has been identified as a modulator of immune regulation and a potential regulator of response to ICIs. Fecal microbiota transplantation (FMT) has emerged as a potential novel therapeutic tool to enhance ICI response, as demonstrated in several trials, spanning across genitourinary malignancies as well as others. While safety and clinical potential of FMT have been demonstrated, FMT parameters including optimal treatment regimens, bowel preparation protocols, patient selection, and donor-host compatibility need to be defined. Furthermore, targeted interventions including probiotic supplementation represent promising therapeutic avenues meriting further study.}, } @article {pmid39889629, year = {2025}, author = {Zhu, W and Hu, Y and Shi, Y and Bao, H and Cheng, X and Jiang, M and Peng, Z and Song, J and Fang, F and Jian, C and Yuan, W and Chen, J and Shu, X}, title = {Sleep deprivation accelerates Parkinson's disease via modulating gut microbiota associated microglial activation and oxidative stress.}, journal = {Microbiological research}, volume = {293}, number = {}, pages = {128077}, doi = {10.1016/j.micres.2025.128077}, pmid = {39889629}, issn = {1618-0623}, abstract = {The interplay between Parkinson's disease (PD) and sleep disturbances suggests that sleep problems constitute a risk factor for PD progression, but the underlying mechanisms remain unclear. Microglial activation and oxidative stress are considered to play an important role in the pathogenesis of aging and neurodegenerative diseases. We hypothesized that sleep deprivation (SD) could exacerbate PD progression via modulating microglial activation and oxidative stress. To test this hypothesis, we established a PD mouse model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), then subjected the mice to SD. A battery of behavioral tests, including rotarod, pole, adhesive removal, and open field tests, were used to assess motor function. Our study showed that SD exacerbated motor deficits, loss of tyrosine hydroxylase (TH), microglial activation and oxidative stress damage in PD model mice. Fecal microbiota transplantation experiments revealed that SD mediated PD progression, microglial activation and oxidative stress via the gut microbiota. 16S rRNA sequencing analysis indicated that SD increased the abundances of bacteria such as Bacteroidaceae, while decreasing the abundances of bacteria including Lactobacillus. Non-targeted metabolomic analysis of gut microbiota-derived metabolites revealed that SD significantly increased the production of adenosine (ADO), a purine metabolite. Probiotic supplementation reversed the effects of SD on motor deficits, dopaminergic neuron loss, microglial activation and oxidative stress damage in PD mice; it also decreased SD-induced ADO production. Administration of Adenosine A2A receptor (A2AR) inhibitors, Istradefylline (Ist), attenuated the roles of SD and ADO in promoting microglial activation, oxidative stress and PD progression. Taken together, our findings indicate that SD accelerates PD progression via regulating microbiota associated microglial activation and oxidative stress, suggesting that efforts to improve sleep quality can be used to prevent and treat PD.}, } @article {pmid39887665, year = {2025}, author = {Zeng, X and Sun, L and Xie, H and Gong, S and Lu, C and Xu, Z and Guan, H and Han, B and Wang, W and Zhang, Z and Zhou, J and Wang, S and Chen, Y and Xiao, W}, title = {Lactobacillus johnsonii Generates Cyclo(pro-trp) and Promotes Intestinal Ca[2+] Absorption to Alleviate CKD-SHPT.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2414678}, doi = {10.1002/advs.202414678}, pmid = {39887665}, issn = {2198-3844}, support = {82270585//National Natural Science Foundation of China/ ; }, abstract = {Patients with chronic kidney disease (CKD) are at a high risk of developing secondary hyperparathyroidism (SHPT), which may cause organ dysfunction and increase patient mortality. The main clinical interventions for CKD-SHPT involve calcium supplements to boost absorption, but ineffective for some patients, and the reasons remain unclear. Here, CKD mice are divided into high and low groups based on intact parathyroid hormone (iPTH) levels. The high group exhibits significant changes in gut microbes, including a decrease in Lactobacillus, an increase in parathyroid hyperplasia, and a decrease in intestinal calcium. Fecal microbiota transplantation and L. johnsonii colonization indicate a link between gut microbes and CKD-SHPT. Clinically, higher L. johnsonii levels are correlated with milder hyperparathyroidism CKD-SHPT. The receiver operating characteristic (ROC) curve for L. johnsonii abundance and surgical risk is 0.81, with the calibration curve confirming predictive accuracy, and decision curve analysis revealing good clinical applicability. In vivo and in vitro experiments show that cyclo(pro-trp) enhance calcium inflow and lower iPTH levels in intestinal epithelial cells via a calcium-sensing receptor and transient receptor potential vanilloid 4 pathways. This study identified the crucial role of L. johnsonii in CKD-SHPT, unveiling a new mechanism for calcium imbalance and offering novel strategies for SHPT treatment and drug development.}, } @article {pmid39887373, year = {2025}, author = {Byrd, DA and Damerell, V and Gomez Morales, MF and Hogue, SR and Lin, T and Ose, J and Himbert, C and Ilozumba, MN and Kahlert, C and Shibata, D and Toriola, AT and Li, CI and Figueiredo, J and Stephens, WZ and Warby, CA and Hardikar, S and Siegel, EM and Round, J and Ulrich, CM and Gigic, B}, title = {The gut microbiome is associated with disease-free survival in stage I-III colorectal cancer patients.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.35342}, pmid = {39887373}, issn = {1097-0215}, support = {//ERA-NET on Translational Cancer Research (TRANSCAN)/ ; //Heidelberger Stiftung Chirurgie, Heidelberg University Hospital/ ; //Medizinische Fakultät Heidelberg, Universität Heidelberg/ ; //Matthias-Lackas Foundations/ ; //Stiftung LebensBlicke/ ; R01 CA189184/NH/NIH HHS/United States ; U01 CA206110/NH/NIH HHS/United States ; //Rahel Goitein-Straus-Program/ ; 01KD2101D//German Federal Ministry of Education and Research/ ; 01KT1503//German Federal Ministry of Education and Research/ ; }, abstract = {Colorectal cancer (CRC) is the second overall leading cause of cancer death in the United States, with recurrence being a frequent cause of mortality. Approaches to improve disease-free survival (DFS) are urgently needed. The gut microbiome, reflected in fecal samples, is likely mechanistically linked to CRC progression and may serve as a non-invasive biomarker. Accordingly, we leveraged baseline fecal samples from N = 166 stage I-III CRC patients in the ColoCare Study, a prospective cohort of newly diagnosed CRC patients. We sequenced the V3 and V4 regions of the 16S rRNA gene to characterize fecal bacteria. We calculated estimates of alpha diversity, beta diversity, and a priori- and exploratory-selected bacterial presence/absence and relative abundance. Associations of microbial metrics with DFS were estimated using multivariable Cox proportional hazards models. We found that alpha diversity was strongly associated with improved DFS, most strongly among rectal cancer patients (Shannon HRrectum = 0.40 95% CI = 0.19, 0.87; p = .02). Overall microbiome composition differences (beta diversity), as characterized by principal coordinate axes, were statistically significantly associated with DFS. Peptostreptococcus was statistically significantly associated with worse DFS (HR = 1.62, 95% CI = 1.13, 2.31; p = .01 per 1-SD) and Order Clostridiales was associated with improved DFS (HR = 0.62, 95% CI = 0.43-0.88; p = .01 per 1-SD). In exploratory analyses, Coprococcus and Roseburia were strongly associated with improved DFS. Overall, higher bacterial diversity and multiple bacteria were strongly associated with DFS. Metagenomic sequencing to elucidate species, gene, and functional level details among larger, diverse patient populations are critically needed to support the microbiome as a biomarker of CRC outcomes.}, } @article {pmid39887250, year = {2025}, author = {Tang, X and Zeng, T and Deng, W and Zhao, W and Liu, Y and Huang, Q and Deng, Y and Xie, W and Huang, W}, title = {Gut microbe-derived betulinic acid alleviates sepsis-induced acute liver injury by inhibiting macrophage NLRP3 inflammasome in mice.}, journal = {mBio}, volume = {}, number = {}, pages = {e0302024}, doi = {10.1128/mbio.03020-24}, pmid = {39887250}, issn = {2150-7511}, abstract = {UNLABELLED: Sepsis-induced acute liver injury (SALI) is a prevalent and life-threatening complication associated with sepsis. The gut microbiota plays a crucial role in the maintenance of health and the development of diseases. The impact of physical exercise on gut microbiota modulation has been well-documented. However, the potential impact of gut microbiome on exercise training-induced protection against SALI remains uncertain. Here, we discovered exercise training ameliorated SALI and systemic inflammation in septic mice. Notably, gut microbiota pre-depletion abolished the protective effects of exercise training in SALI mice. Fecal microbiota transplantation treatment revealed that exercise training-associated gut microbiota contributed to the beneficial effect of exercise training on SALI. Exercise training modulated the metabolism of Ligilactobacillus and enriched betulinic acid (BA) levels in mice. Functionally, BA treatment conferred protection against SALI by inhibiting the hepatic inflammatory response in mice. BA bound and inactivated hnRNPA2B1, thus suppressing NLRP3 inflammasome activation in macrophages. Collectively, this study reveals gut microbiota is involved in the protective effects of exercise training against SALI, and gut microbiota-derived BA inhibits the hepatic inflammatory response via the hnRNPA2B1-NLRP3 axis, providing a potential therapeutic strategy for SALI.

IMPORTANCE: Sepsis is characterized by a dysregulated immune response to an infection that leads to multiple organ dysfunction. The occurrence of acute liver injury is frequently observed during the initial stage of sepsis and is directly linked to mortality in the intensive care unit. The preventive effect of physical exercise on SALI is well recognized, yet the underlying mechanism remains poorly elucidated. Exercise training alters the gut microbiome in mice, increasing the abundance of Ligilactobacillus and promoting the generation of BA. Additionally, BA supplementation can suppress the NLRP3 inflammasome activation in macrophages by directly binding to hnRNPA2B1, thereby mitigating SALI. These results highlight the beneficial role of gut microbiota-derived BA in inhibiting the hepatic inflammatory response, which represents a crucial stride toward implementing microbiome-based therapeutic strategies for the clinical management of sepsis.}, } @article {pmid39885417, year = {2025}, author = {Abdel-Raoof Fouda, M and Abdel-Wahhab, M and Abdelkader, AE and Ibrahim, ME and Elsheikh, TA and Aldeweik, HM and Elfeky, N}, title = {Effect of gut microbiota changes on cytokines IL-10 and IL-17 levels in liver transplantation patients.}, journal = {BMC infectious diseases}, volume = {25}, number = {1}, pages = {140}, pmid = {39885417}, issn = {1471-2334}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Liver Transplantation ; Male ; Female ; *Interleukin-17/blood ; *Interleukin-10/blood ; Middle Aged ; Adult ; Feces/microbiology ; Bacteria/classification/isolation & purification ; Dysbiosis/microbiology ; Aged ; }, abstract = {BACKGROUND: Liver transplantation (LT) is a critical intervention for individuals with end-stage liver disease; yet, post-transplant problems, especially infections, graft rejection, and chronic liver disease, are often linked to systemic inflammation. Cytokines, small signaling molecules, significantly influence immune responses during and post-liver transplantation. Nonetheless, the intricate relationships among cytokines, immune responses, and the gut microbiota, especially gut dysbiosis, are still inadequately comprehended. Thus, this study aims to identify the gut microbiota (GM) and determine their relationship to cytokines (IL-17 and IL-10) in LT patients, due to their importance in enhancing the recovery rate.

RESULT: The research included 31 liver transplant (LT) patients from the Gastroenterology Surgical Center at Mansoura University, resulting in the collection of 174 stool and blood samples from all participants. Fourteen bacterial species have been identified in samples collected at three intervals: one week before, one week post, and two weeks post LT. A change in gut microbiota composition was noted, characterized by a rise in potentially pathogenic bacteria such as Enterococci and Enterobacteriaceae (including Escherichia coli and Klebsiella) and a reduction in beneficial bacteria such as Bacteroidetes and Firmicutes. The examination of patient demographic and clinical data revealed no significant correlations between sex, age, or diagnostic categories and gut microbiota composition. The findings of the Multivariate Analysis of Variance (MANOVA) indicated a substantial effect of gut microbiota composition on cytokine levels (IL-10 and IL-17), with all tests producing p-values of 0.001. The assessment of cytokine levels indicated fluctuating variations at several time points following surgery. IL-10 levels in the GM groups exhibited a statistically significant elevation during the second week post-surgery (p = 0.036), suggesting a potential recovery-related anti-inflammatory response. In contrast, IL-17 levels rose in the NI group over time, indicating a transition to a pro-inflammatory condition.

CONCLUSION: This study emphasizes the pivotal role of the gut microbiota in regulating immune responses following transplantation.}, } @article {pmid39881980, year = {2024}, author = {Renk, H and Schoppmeier, U and Müller, J and Kuger, V and Neunhoeffer, F and Gille, C and Peter, S}, title = {Oxygenation and intestinal perfusion and its association with perturbations of the early life gut microbiota composition of children with congenital heart disease.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1468842}, pmid = {39881980}, issn = {1664-302X}, abstract = {BACKGROUND: Early life gut microbiota is known to shape the immune system and has a crucial role in immune homeostasis. Only little is known about composition and dynamics of the intestinal microbiota in infants with congenital heart disease (CHD) and potential influencing factors.

METHODS: We evaluated the intestinal microbial composition of neonates with CHD (n = 13) compared to healthy controls (HC, n = 30). Fecal samples were analyzed by shotgun metagenomics. Different approaches of statistical modeling were applied to assess the impact of influencing factors on variation in species composition. Unsupervised hierarchical clustering of the microbial composition of neonates with CHD was used to detect associations of distinct clusters with intestinal tissue oxygenation and perfusion parameters, obtained by the "oxygen to see" (O2C) method.

RESULTS: Overall, neonates with CHD showed an intestinal core microbiota dominated by the genera Enterococcus (27%) and Staphylococcus (20%). Furthermore, a lower abundance of the genera Bacteroides (8% vs. 14%), Parabacteroides (1% vs. 3%), Bifidobacterium (4% vs. 12%), and Escherichia (8% vs. 23%) was observed in CHD compared to HCs. CHD patients that were born by vaginal delivery showed a lower fraction of the genera Bacteroides (15% vs. 21%) and Bifidobacterium (7% vs. 22%) compared to HCs and in those born by cesarean section, these genera were not found at all. In infants with CHD, we found a significant impact of oxygen saturation (SpO2) on relative abundances of the intestinal core microbiota by multivariate analysis of variance (F[8,2] = 24.9, p = 0.04). Statistical modeling suggested a large proportional shift from a microbiota dominated by the genus Streptococcus (50%) in conditions with low SpO2 towards the genus Enterococcus (61%) in conditions with high SpO2. We identified three distinct compositional microbial clusters, corresponding neonates differed significantly in intestinal blood flow and global gut perfusion.

CONCLUSION: Early life differences in gut microbiota of CHD neonates versus HCs are possibly linked to oxygen levels. Delivery method may affect microbiota stability. However, further studies are needed to assess the effect of potential interventions including probiotics or fecal transplants on early life microbiota perturbations in neonates with CHD.}, } @article {pmid39880356, year = {2025}, author = {Wang, S and Yan, K and Dong, Y and Chen, Y and Song, J and Chen, Y and Liu, X and Qi, R and Zhou, X and Zhong, J and Li, J}, title = {The influence of microplastics on hypertension-associated cardiovascular injury via the modulation of gut microbiota.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {}, number = {}, pages = {125760}, doi = {10.1016/j.envpol.2025.125760}, pmid = {39880356}, issn = {1873-6424}, abstract = {Microplastics (MPs) have been found to interfere with the gut microbiota and compromise the integrity of the gut barrier. Excessive exposure to MPs markedly elevates the risk of cardiovascular disease, yet their influence on hypertension remains elusive, calling for investigation into their potential impacts on blood pressure (BP) regulation. In the present study, an increase in the concentration of MPs was observed in the fecal samples of individuals suffering from hypertension, as compared to the controls. Oral administration of MPs led to obvious increases in systolic, diastolic and mean BP levels in mice. MPs were associated with promoting myocardial hypertrophy, fibrosis, and cardiac remodeling through alterations in gut microbial composition, such as Prevotella and Coprobacillus, or fecal metabolites Betaine and Glycyrrhetinic acid. The hypertensive damage mediated by MPs was significantly mitigated by the high-fiber diet or antibiotics that targeted the gut microbiota. Notablely, fecal microbiota transplantation from mice treated with MPs led to an increase in systolic BP levels and the development of cardiac dysfunction. Our findings offer valuable insights into the complex interplay between MPs and the gut microbiome in the context of hypertension, and suggest potential strategies for reducing the vascular and cardiac injury caused by MPs.}, } @article {pmid39879970, year = {2025}, author = {Stallmach, A}, title = {[The gastrointestinal microbiome - vision and mission].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {150}, number = {4}, pages = {157-162}, doi = {10.1055/a-2303-3368}, pmid = {39879970}, issn = {1439-4413}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Germany ; Dysbiosis ; Clostridium Infections/therapy ; }, abstract = {The gastrointestinal microbiome influences physiological functions and is altered in a variety of diseases. The causality of "dysbiosis" in the pathogenesis is not always proven; association studies are often involved. Patients with IBD, bacteria, fungi, bacteriophages, and archaea show disease-typical patterns associated with metabolome disturbances. Fecal microbiome transfer (FMT) for treating various diseases is the subject of numerous clinical studies. Currently, recurrent Clostridioides difficile infection (rCDI) is the only confirmed indication recommended in medical guidelines. In Germany, the FMT is subject to the Medicines Act and may only be carried out as part of individual healing attempts or clinical studies. For patient safety, repeated donor screening, ideally with the construction of a chair bench, is necessary. This significantly limits the nationwide availability of the FMT in Germany. Microbiota-based therapeutics prepared from the stool of tested donors have recently been approved by the US Food and Drug Administration (FDA) for the prevention of rCDI. More microbiome-based medicines can be expected in the future.}, } @article {pmid39879969, year = {2025}, author = {Weirauch, T and Vehreschild, MJGT}, title = {[Nosocomial gastrointestinal infections and Clostridioides difficile].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {150}, number = {4}, pages = {149-156}, doi = {10.1055/a-2303-3321}, pmid = {39879969}, issn = {1439-4413}, mesh = {Humans ; *Cross Infection/epidemiology ; *Clostridium Infections/therapy/epidemiology ; *Anti-Bacterial Agents/therapeutic use ; *Fecal Microbiota Transplantation ; Clostridioides difficile ; Germany ; Diarrhea/microbiology ; Fidaxomicin/therapeutic use ; Vancomycin/therapeutic use ; }, abstract = {German surveillance data from 2022 reported a prevalence of nosocomial infections among hospitalized patients of 5,2%. Clostridioides-difficile-infections (CDI) are the most frequent cause of nosocomial diarrhea. They are usually caused by antibiotic exposure and the subsequent changes in the gut microbiota. Clinical manifestation ranges from asymptomatic colonization over moderate diarrhea to severe pseudomembranous colitis. According to the current German Gastrointestinal Infection Guidelines, fidaxomicin is the preferred treatment option for CDI, especially in patients at high risk of recurrence or those already suffering from recurrence. Vancomycin can also be used as an alternative for initial CDI treatment. Fecal microbiota transplantation is considered a treatment approach for patients with multiple recurrences.}, } @article {pmid39879083, year = {2025}, author = {Carroll, A and Bell, MJ and Bleach, ECL and Turner, D and Williams, LK}, title = {Impact of dairy calf management practices on the intestinal tract microbiome pre-weaning.}, journal = {Journal of medical microbiology}, volume = {74}, number = {1}, pages = {}, doi = {10.1099/jmm.0.001957}, pmid = {39879083}, issn = {1473-5644}, mesh = {Animals ; Cattle ; *Gastrointestinal Microbiome/physiology ; *Weaning ; *Animal Husbandry/methods ; Dairying ; }, abstract = {Introduction. Microbiota in the gastrointestinal tract (GIT) consisting of the rumen and hindgut (the small intestine, cecum and colon) in dairy calves play a vital role in their growth and development. This review discusses the development of dairy calf intestinal microbiomes with an emphasis on the impact that husbandry and rearing management have on microbiome development, health and growth of pre-weaned dairy calves.Discussion. The diversity and composition of the microbes that colonize the lower GIT (small and large intestine) can have a significant impact on the growth and development of the calf, through influence on nutrient metabolism, immune modulation, resistance or susceptibility to infection, production outputs and behaviour modification in adult life. The colonization of the calf intestinal microbiome dynamically changes from birth, increasing microbial richness and diversity until weaning, where further dynamic and drastic microbiome change occurs. In dairy calves, neonatal microbiome development prior to weaning is influenced by direct and indirect factors, some of which could be considered stressors, such as maternal interaction, environment, diet, husbandry and weaning practices. The specific impact of these can dictate intestinal microbial colonization, with potential lifelong consequences.Conclusion. Evidence suggests the potential detrimental effect that sudden changes and stress may have on calf health and growth due to management and husbandry practices, and the importance of establishing a stable yet diverse intestinal microbiome population at an early age is essential for calf success. The possibility of improving the health of calves through intestinal microbiome modulation and using alternative strategies including probiotic use, faecal microbiota transplantation and novel approaches of microbiome tracking should be considered to support animal health and sustainability of dairy production systems.}, } @article {pmid39878866, year = {2025}, author = {Zheng, Y and Yu, Y and Chen, M and Zhang, H and Wang, W and Fan, X and Sun, L and Tang, L and Ta, D}, title = {Abdominal LIPUS Stimulation Prevents Cognitive Decline in Hind Limb Unloaded Mice by Regulating Gut Microbiota.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39878866}, issn = {1559-1182}, abstract = {Weightlessness usually causes disruption of the gut microbiota and impairs cognitive function. There is a close connection between gut microbiota and neurological diseases. Low-intensity pulsed ultrasound (LIPUS) has a beneficial effect on reducing intestinal inflammation. So we wondered if abdominal LIPUS stimulation can have a positive impact on weightlessness induced cognitive decline by reducing intestinal dysfunction. The findings revealed that the hind limb unloaded mice exhibited evident disruption in intestinal structure and gut microbial homeostasis, along with impairment in their learning and memory capabilities. However, 4-week abdominal LIPUS treatment improved intestinal function in hind limb unloaded mice, characterized by upregulation of tight junction proteins ZO-1 and Occludin expression in the colon, increased diversity and abundance of intestinal microbiota, decreased serum lipopolysaccharide (LPS), and increased short chain fatty acids in colon contents. The hind limb unloaded mice treated with LIPUS exhibited heightened activity levels, improved exploratory tendencies, and significantly enhanced learning and memory faculties, and elevated expression of neuroadaptation-related proteins such as PSD95, GAP43, P-CREB, BDNF, and its receptor TRKB in the hippocampus. Furthermore, the hind limb unloaded mice receiving fecal transplants from the mice whose abdomens were irradiated with LIPUS displayed enhanced cognitive abilities and improved intestinal structure, akin to the outcomes observed in hind limb unloaded mice who received LIPUS abdominal treatment directly. The above results indicate that LIPUS enhances intestinal structure and microbiota, which helps alleviate cognitive impairment caused by weightlessness. LIPUS could be a potential strategy to simultaneously improve gut dysfunction and cognitive decline in astronauts or bedridden patients.}, } @article {pmid39779879, year = {2025}, author = {Pribyl, AL and Hugenholtz, P and Cooper, MA}, title = {A decade of advances in human gut microbiome-derived biotherapeutics.}, journal = {Nature microbiology}, volume = {10}, number = {2}, pages = {301-312}, pmid = {39779879}, issn = {2058-5276}, mesh = {Humans ; *Gastrointestinal Microbiome ; Biological Therapy/methods ; Bacteria/genetics/classification ; Fecal Microbiota Transplantation ; Feces/microbiology ; Probiotics/therapeutic use ; }, abstract = {Microbiome science has evolved rapidly in the past decade, with high-profile publications suggesting that the gut microbiome is a causal determinant of human health. This has led to the emergence of microbiome-focused biotechnology companies and pharmaceutical company investment in the research and development of gut-derived therapeutics. Despite the early promise of this field, the first generation of microbiome-derived therapeutics (faecal microbiota products) have only recently been approved for clinical use. Next-generation therapies based on readily culturable and as-yet-unculturable colonic bacterial species (with the latter estimated to comprise 63% of all detected species) have not yet progressed to pivotal phase 3 trials. This reflects the many challenges involved in developing a new class of drugs in an evolving field. Here we discuss the evolution of the live biotherapeutics field over the past decade, from the development of first-generation products to the emergence of rationally designed second- and third-generation live biotherapeutics. Finally, we present our outlook for the future of this field.}, } @article {pmid39877812, year = {2021}, author = {Zhu, W and Dykstra, K and Zhang, L and Xia, Z}, title = {Gut Microbiome as Potential Therapeutics in Multiple Sclerosis.}, journal = {Current treatment options in neurology}, volume = {23}, number = {11}, pages = {}, pmid = {39877812}, issn = {1092-8480}, support = {R01 NS098023/NS/NINDS NIH HHS/United States ; R01 NS124882/NS/NINDS NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: The gut microbiome is an emerging arena to investigate multiple sclerosis (MS) pathogenesis and potential therapeutics. In this review, we summarize the available data and postulate the feasibilities of potential MS therapeutic approaches that modulate the gut microbiome.

RECENT FINDINGS: Growing evidence indicates dysbiosis in the gut bacterial ecosystem in MS. Diet and other interventions produce biologically significant changes in the gut bacterial communities and functions, can potentially regulate the immune system, and benefit people with MS. While well-conducted investigations of the therapeutic mechanisms for targeting gut microbiome in animal models and humans remain limited, promising connections between various mechanisms of gut microbiome regulation and beneficial effects on MS outcomes are emerging.

SUMMARY: To date, studies examining the microbiome-based therapies in MS remain limited in number and follow-up duration. There is a clear need to determine the long-term efficacy and safety of these approaches, and to identify their underlying mechanisms of actions.}, } @article {pmid39875017, year = {2025}, author = {Qin, L and Fan, B and Zhou, Y and Zheng, J and Diao, R and Wang, F and Liu, J}, title = {Targeted Gut Microbiome Therapy: Applications and Prospects of Probiotics, Fecal Microbiota Transplantation and Natural Products in the Management of Type 2 Diabetes.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107625}, doi = {10.1016/j.phrs.2025.107625}, pmid = {39875017}, issn = {1096-1186}, abstract = {Type 2 diabetes mellitus (T2DM) is considered as one of the most pressing public health challenges worldwide. Studies have shown significant differences in the gut microbiota between healthy individuals and T2DM patients, suggesting that gut microorganisms may play a key role in the onset and progression of T2DM. This review systematically summarizes the relationship between gut microbiota and T2DM, and explores the mechanisms through which gut microorganisms may alleviate T2DM. Additionally, it evaluates the potential of probiotics, fecal microbiota transplantation (FMT)/virome transplantation (FVT), and natural products in modulating gut microbiota to treat T2DM. Although existing studies have suggested that these interventions may delay or even halt the progression of T2DM, most research remained limited to animal models and observational clinical studies, with a lack of high-quality clinical data. This has led to an imbalance between theoretical research and clinical application. Although some studies have explored the regulatory role of the gut virome on the gut microbiota, research in this area remains in its early stages. Based on these current studies, future research should be focused on large-scale, long-term clinical studies and further investigation on the potential role of the gut virome in T2DM. In conclusion, this review aims to summarize the current evidence and explore the applications of gut microbiota in T2DM treatment, as well as providing recommendations for further investigation in this field.}, } @article {pmid39874238, year = {2025}, author = {Scher, JU and Nayak, R and Clemente, JC}, title = {Microbiome research in autoimmune and immune-mediated inflammatory diseases: lessons, advances and unmet needs.}, journal = {Annals of the rheumatic diseases}, volume = {84}, number = {1}, pages = {9-13}, doi = {10.1136/ard-2024-225735}, pmid = {39874238}, issn = {1468-2060}, mesh = {Humans ; *Autoimmune Diseases/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology/physiology ; *Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Microbiota/immunology ; Arthritis, Rheumatoid/immunology/microbiology ; Lupus Erythematosus, Systemic/immunology/microbiology ; Immune System Diseases/immunology/microbiology ; }, abstract = {The increasing prevalence of autoimmune and immune-mediated diseases (AIMDs) underscores the need to understand environmental factors that contribute to their pathogenesis, with the microbiome emerging as a key player. Despite significant advancements in understanding how the microbiome influences physiological and inflammatory responses, translating these findings into clinical practice remains challenging. This viewpoint reviews the progress and obstacles in microbiome research related to AIMDs, examining molecular techniques that enhance our understanding of microbial contributions to disease. We discuss significant discoveries linking specific taxa and metabolites to diseases such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis, highlighting the role of gut dysbiosis and host-microbiome interactions. Furthermore, we explore the potential of microbiome-based therapeutics, including faecal microbiota transplantation and pharmacomicrobiomics, while addressing the challenges of identifying robust microbial targets. We advocate for integrative, transdisease studies and emphasise the need for diverse cohort research to generalise findings across populations. Understanding the microbiome's role in AIMDs will pave the way for personalised medicine and innovative therapeutic strategies.}, } @article {pmid39873952, year = {2025}, author = {Pezeshki, B and Abdulabbas, HT and Alturki, AD and Mansouri, P and Zarenezhad, E and Nasiri-Ghiri, M and Ghasemian, A}, title = {Synergistic Interactions Between Probiotics and Anticancer Drugs: Mechanisms, Benefits, and Challenges.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39873952}, issn = {1867-1314}, abstract = {Research into the role of probiotics-often referred to as "living supplements"-in cancer therapy is still in its early stages, and uncertainties regarding their effectiveness remain. Relevantly, chemopreventive and therapeutic effects of probiotics have been determined. There is also substantial evidence supporting their potential in cancer treatment such as immunotherapy. Probiotics employ various mechanisms to inhibit cancer initiation and progression. These include colonizing and protecting the gastrointestinal tract (GIT), producing metabolites, inducing apoptosis and autophagy, exerting anti-inflammatory properties, preventing metastasis, enhancing the effectiveness of immune checkpoint inhibitors (ICIs), promoting cancer-specific T cell infiltration, arresting the cell cycle, and exhibiting direct or indirect synergistic effects with anticancer drugs. Additionally, probiotics have been shown to activate tumor suppressor genes and inhibit pro-inflammatory transcription factors. They also increase reactive oxygen species production within cancer cells. Synergistic interactions between probiotics and various anticancer drugs, such as cisplatin, cyclophosphamide, 5-fluorouracil, trastuzumab, nivolumab, ipilimumab, apatinib, gemcitabine, tamoxifen, sorafenib, celecoxib and irinotecan have been observed. The combination of probiotics with anticancer drugs holds promise in overcoming drug resistance, reducing recurrence, minimizing side effects, and lowering treatment costs. In addition, fecal microbiota transplantation (FMT) and prebiotics supplementation has increased cytotoxic T cells within tumors. However, probiotics may leave some adverse effects such as risk of infection and gastrointestinal effects, antagonistic effects with drugs, and different responses among patients. These findings highlight insights for considering specific strains and engineered probiotic applications, preferred doses and timing of treatment, and personalized therapies to enhance the efficacy of cancer therapy. Accordingly, targeted interventions and guidelines establishment needs extensive randomized controlled trials as probiotic-based cancer therapy has not been approved by Food and Drug Administration (FDA).}, } @article {pmid39873191, year = {2025}, author = {An, L and Li, S and Chang, Z and Lei, M and He, Z and Xu, P and Zhang, S and Jiang, Z and Iqbal, MS and Sun, X and Liu, H and Duan, X and Wu, W}, title = {Gut microbiota modulation via fecal microbiota transplantation mitigates hyperoxaluria and calcium oxalate crystal depositions induced by high oxalate diet.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2457490}, pmid = {39873191}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome ; *Hyperoxaluria/therapy/metabolism ; *Fecal Microbiota Transplantation ; *Calcium Oxalate/metabolism/chemistry ; Rats ; Male ; *Oxalates/metabolism/urine ; Diet ; Rats, Sprague-Dawley ; Kidney/metabolism/microbiology/pathology ; Bacteria/classification/metabolism/genetics/isolation & purification ; Disease Models, Animal ; Kidney Calculi/therapy/prevention & control/microbiology/metabolism/diet therapy ; Feces/microbiology/chemistry ; }, abstract = {Hyperoxaluria, including primary and secondary hyperoxaluria, is a disorder characterized by increased urinary oxalate excretion and could lead to recurrent calcium oxalate kidney stones, nephrocalcinosis and eventually end stage renal disease. For secondary hyperoxaluria, high dietary oxalate (HDOx) or its precursors intake is a key reason. Recently, accumulated studies highlight the important role of gut microbiota in the regulation of oxalate homeostasis. However, the underlying mechanisms involving gut microbiota and metabolite disruptions in secondary hyperoxaluria remain poorly understood. Here, we investigated the therapeutic efficacy of fecal microbiota transplantation (FMT) sourced from healthy rats fed with standard pellet diet against urinary oxalate excretion, renal damage and calcium oxalate (CaOx) crystal depositions via using hyperoxaluria rat models. We observed dose-dependent increases in urinary oxalate excretion and CaOx crystal depositions due to hyperoxaluria, accompanied by significant reductions in gut microbiota diversity characterized by shifts in Ruminococcaceae_UCG-014 and Parasutterella composition. Metabolomic analysis validated these findings, revealing substantial decreases in key metabolites associated with these microbial groups. Transplanting microbes from healthy rats effectively reduced HDOx-induced urinary oxalate excretion and CaOx crystal depositions meanwhile restoring Ruminococcaceae_UCG-014 and Parasutterella populations and their associated metabolites. Furthermore, FMT treatment could significantly decrease the urinary oxalate excretion and CaOx crystal depositions in rat kidneys via, at least in part, upregulating the expressions of intestinal barrier proteins and oxalate transporters in the intestine. In conclusion, our study emphasizes the effectiveness of FMT in countering HDOx-induced hyperoxaluria by restoring gut microbiota and related metabolites. These findings provide insights on the complex connection between secondary hyperoxaluria caused by high dietary oxalate and disruptions in gut microbiota, offering promising avenues for targeted therapeutic strategies.}, } @article {pmid39870907, year = {2025}, author = {Misselwitz, B and Haller, D}, title = {[The intestinal microbiota in inflammatory bowel diseases].}, journal = {Innere Medizin (Heidelberg, Germany)}, volume = {}, number = {}, pages = {}, pmid = {39870907}, issn = {2731-7099}, abstract = {BACKGROUND: The intestinal microbiota comprises all living microorganisms in the gastrointestinal tract and is crucial for its function. Clinical observations and laboratory findings confirm a central role of the microbiota in chronic inflammatory bowel diseases (IBD). However, many mechanistic details remain unclear.

OBJECTIVES: Changes in the microbiota and the causal relationship with the pathogenesis of IBD are described and current and future diagnostic and therapeutic options are discussed.

MATERIALS AND METHODS: Narrative review.

RESULTS: The intestinal microbiota is altered in composition, diversity, and function in IBD patients, but specific (universal) IBD-defining bacteria have not been identified. The healthy microbiota has numerous anti-inflammatory functions such as the production of short-chain fatty acids or competition with pathogens. In contrast, the IBD microbiota promotes inflammation through the destruction of the intestinal barrier and direct interaction with the immune system. The balance between pro- and anti-inflammatory effects of the microbiota appears to be crucial for the development of intestinal inflammation. Microbiota-based IBD diagnostics show promise but are not yet ready for clinical use. Probiotics and fecal microbiota transplantation have clinical effects, especially in ulcerative colitis, but the potential of microbiota-based therapies is far from being fully realized.

CONCLUSION: IBD dysbiosis remains undefined so far. It is unclear how the many parallel pro- and anti-inflammatory mechanisms contribute to IBD pathogenesis. An inadequate mechanistic understanding hinders the development of microbiota-based diagnostics and therapies.}, } @article {pmid39870349, year = {2025}, author = {Vázquez-Cuesta, S and Olmedo, M and Kestler, M and Álvarez-Uría, A and De la Villa, S and Alcalá, L and Marín, M and Rodríguez-Fernández, S and Sánchez-Martínez, C and Muñoz, P and Bouza, E and Reigadas, E}, title = {Prospective analysis of biomarkers associated with successful faecal microbiota transplantation in recurrent Clostridioides difficile Infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2025.01.026}, pmid = {39870349}, issn = {1469-0691}, abstract = {OBJECTIVES: Faecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection (R-CDI). This study aimed to identify calprotectin and microbiome characteristics as potential biomarkers of FMT success.

METHODS: We conducted a prospective study of patients who underwent oral FMT (single dose of 4-5 capsules) for R-CDI (January 2018 to December 2022). Samples were collected at three time points: at CDI diagnosis, within 24 hours prior to FMT administration, and 30 days post-FMT. Calprotectin levels were assessed and the V4 region of the 16S rRNA gene was sequenced to analyse the microbiota composition. Sequencing data analysis and statistical analysis were performed using MOTHUR and R.

RESULTS: Ninety-seven patients underwent FMT (totalling 105 procedures). A total of 221 samples were processed, including 21 donor samples, 24 capsule contents, and 176 patient faecal samples (39 at diagnosis, 63 pre-FMT, and 74 post-FMT). FMT achieved an overall success rate of 85.1% (86/101 cases). The abundance of Bacteroides, Ruminococcus, Megamonas, and certain Prevotella operational taxonomic units (OTUs) was significantly higher in capsules associated with 100% success compared to less effective capsules. FMT engraftment was observed in 95% of patients with favourable outcomes versus 62% of those with recurrences (p = 0.006). Additionally, a negative correlation was found between calprotectin levels and specific microbial genera, suggesting an association with successful outcomes.

CONCLUSIONS: This study highlights differences in the evolution of faecal microbiota, bacterial engraftment, and inflammation markers (e.g., calprotectin) between patients with varying FMT outcomes. Potential biomarkers for successful FMT were identified, providing valuable insights for optimizing FMT strategies.}, } @article {pmid39870263, year = {2025}, author = {Ren, P and Liu, M and Wei, B and Tang, Q and Wang, Y and Xue, C}, title = {Fucoidan exerts antitumor effects by regulating gut microbiota and tryptophan metabolism.}, journal = {International journal of biological macromolecules}, volume = {300}, number = {}, pages = {140334}, doi = {10.1016/j.ijbiomac.2025.140334}, pmid = {39870263}, issn = {1879-0003}, abstract = {Fucoidan, a water-soluble polysaccharide derived from marine organisms, has garnered significant attention for its ability to regulate gut microbiota and its anti-tumor properties. However, the existence of a correlation between the anti-tumor effect of fucoidan and its regulation of the gut microbiota remains unknown. In pursuit of this objective, we culled the gut microbiota of mice with broad-spectrum antibiotics to generate pseudo-sterile tumor-bearing mice. Subsequently, fecal microbial transplants were introduced into the pseudo-sterile tumor-bearing mice. The antitumor effects of fucoidan were found to be dependent on the gut microbiota. Fucoidan promoted the proliferation of Akkermansia, Bifidobacterium and Lactobacillus, which have immunomodulatory effects. Furthermore, through regulation of gut microbiota, fucoidan influenced the metabolic process of tryptophan and facilitated its conversion to indole-3-acetic acid. In addition, fucoidan decreased the kynurenine/tryptophan ratio in serum, increased the proportion of CD8+ T cells, and suppressed the expression level of IDO1 in tumor tissues. Our results confirm that fucoidan enhances anti-tumor immune responses and subsequently exhibits anti-tumor effects by modulating the gut microbiota. Our research contributes to the comprehension of the mechanism of anti-tumor effects of fucoidan and facilitates the development of fucoidan as a dietary supplement for cancer patients.}, } @article {pmid39230037, year = {2025}, author = {Vaughn, BP and Khoruts, A and Fischer, M}, title = {Diagnosis and Management of Clostridioides difficile in Inflammatory Bowel Disease.}, journal = {The American journal of gastroenterology}, volume = {120}, number = {2}, pages = {313-319}, doi = {10.14309/ajg.0000000000003076}, pmid = {39230037}, issn = {1572-0241}, mesh = {Humans ; *Clostridium Infections/diagnosis/therapy ; *Inflammatory Bowel Diseases/complications/diagnosis/microbiology/therapy ; *Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; Risk Factors ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Recurrence ; Broadly Neutralizing Antibodies ; Antibodies, Monoclonal ; }, abstract = {Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI), which can lead to worse IBD outcomes. The diagnosis of CDI in patients with IBD is complicated by higher C. difficile colonization rates and shared clinical symptoms of intestinal inflammation. Traditional risk factors for CDI, such as antibiotic exposure, may be lacking in patients with IBD because of underlying intestinal microbiota dysbiosis. Although CDI disproportionately affects people with IBD, patients with IBD are typically excluded from CDI clinical trials creating a knowledge gap in the diagnosis and management of these 2 diseases. This narrative review aims to provide a comprehensive overview of the diagnosis, treatment, and prevention of CDI in patients with IBD. Distinguishing CDI from C. difficile colonization in the setting of an IBD exacerbation is important to avoid treatment delays. When CDI is diagnosed, extended courses of anti- C. difficile antibiotics may lead to better CDI outcomes. Regardless of a diagnosis of CDI, the presence of C. difficile in a patient with IBD should prompt a disease assessment of the underlying IBD. Microbiota-based therapies and bezlotoxumab seem to be effective in preventing CDI recurrence in patients with IBD. Patients with IBD should be considered at high risk of CDI recurrence and evaluated for a preventative strategy when diagnosed with CDI. Ultimately, the comanagement of CDI in a patient with IBD requires a nuanced, patient-specific approach to distinguish CDI from C. difficile colonization, prevent CDI recurrence, and manage the underlying IBD.}, } @article {pmid39869428, year = {2025}, author = {Kayal, M and Boland, B}, title = {Approach to Therapy for Chronic Pouchitis.}, journal = {Annual review of medicine}, volume = {76}, number = {1}, pages = {167-173}, doi = {10.1146/annurev-med-032224-120544}, pmid = {39869428}, issn = {1545-326X}, mesh = {*Pouchitis/etiology/therapy ; Humans ; Chronic Disease ; *Proctocolectomy, Restorative/adverse effects/methods ; *Anti-Bacterial Agents/therapeutic use ; *Colitis, Ulcerative/surgery ; Colonic Pouches/adverse effects ; Probiotics/therapeutic use ; Fecal Microbiota Transplantation/methods ; }, abstract = {Chronic pouchitis (CP) occurs in approximately 20% of patients with ulcerative colitis after total proctocolectomy with ileal pouch anal anastomosis and is categorized as antibiotic dependent, antibiotic refractory, or Crohn's disease-like. The management of CP is challenging because of limited evidence and few randomized controlled trials. In this review, we discuss the medical management of CP and its supporting data delineated by type of therapy.}, } @article {pmid39869016, year = {2025}, author = {Martin Fuentes, A}, title = {The role of the microbiome in skin cancer development and treatment.}, journal = {Current opinion in oncology}, volume = {}, number = {}, pages = {}, doi = {10.1097/CCO.0000000000001120}, pmid = {39869016}, issn = {1531-703X}, abstract = {PURPOSE OF REVIEW: Recent research underscores the significant influence of the skin and gut microbiota on melanoma and nonmelanoma skin cancer (NMSC) development and treatment outcomes. This review aims to synthesize current findings on how microbiota modulates immune responses, particularly enhancing the efficacy of immunotherapies such as immune checkpoint inhibitors (ICIs).

RECENT FINDINGS: The microbiota's impact on skin cancer is multifaceted, involving immune modulation, inflammation, and metabolic interactions. Beneficial strains like Bifidobacterium and Lactobacillus have shown potential in supporting anti-PD-1 and anti-CTLA-4 therapies by promoting T-cell activation and immune surveillance. Evidence from preclinical and clinical studies, including fecal microbiota transplantation (FMT), highlights improved response rates in patients with microbiota-rich profiles. Notably, certain bacterial metabolites, such as inosine, contribute to enhanced antitumor activity by stimulating IFN-γ in CD8+ T cells.

SUMMARY: Understanding the interplay between microbiota and skin cancer treatment opens promising avenues for adjunctive therapies. Probiotic and prebiotic interventions, FMT, and microbiota modulation are emerging as complementary strategies to improve immunotherapy outcomes and address treatment resistance in melanoma and NMSC.}, } @article {pmid39868555, year = {2025}, author = {Chatterjee, J and Qi, X and Mu, R and Li, X and Eligator, T and Ouyang, M and Bozeman, SL and Rodgers, R and Aggarwal, S and Campbell, DE and Schriefer, LA and Baldridge, MT and Gutmann, DH}, title = {Intestinal Bacteroides drives glioma progression by regulating CD8+ T cell tumor infiltration.}, journal = {Neuro-oncology}, volume = {}, number = {}, pages = {}, doi = {10.1093/neuonc/noaf024}, pmid = {39868555}, issn = {1523-5866}, abstract = {BACKGROUND: The intestinal microbiota regulates normal brain physiology and the pathogenesis of several neurological disorders. While prior studies suggested that this regulation operates through immune cells, the underlying mechanisms remain unclear. Leveraging two well characterized murine models of low-grade glioma (LGG) occurring in the setting of the neurofibromatosis type 1 (NF1) cancer predisposition syndrome, we sought to determine the impact of the gut microbiome on optic glioma progression.

METHODS: Nf1-mutant mice genetically engineered to develop optic pathway gliomas (Nf1OPG mice) by 3 months of age were reared under germ-free (GF) conditions, treated with specific cocktails of antibiotics, or given fecal matter transplants (FMTs). Intestinal microbial species were identified by 16S genotyping. Neutralizing TGFβ antibodies were delivered systemically, while in vitro experiments used isolated murine microglia and T cells. Single cell RNA sequencing analysis was performed using established methods.

RESULTS: Nf1 OPG mice raised in a GF environment or postnatally treated with vancomycin did not harbor optic gliomas or exhibit OPG-induced retinal nerve fiber layer thinning, which was reversed following conventionally raised mouse FMT or colonization with Bacteroides species. Moreover, this intestinal microbiota-regulated gliomagenesis was mediated by circulating TGFβ, such that systemic TGFβ neutralization reduced Nf1-OPG growth. TGFβ was shown to act on tumor-associated monocytes to induce Ccl3 expression and recruit CD8+ T cells necessary for glioma growth.

CONCLUSIONS: Taken together, these findings establish, for the first time, a mechanistic relationship between Bacteroides in the intestinal microbiome and NF1-LGG pathobiology, suggesting both future predictive risk assessment strategies and therapeutic opportunities.}, } @article {pmid39868290, year = {2025}, author = {Weagley, J and Makimaa, H and Cárdenas, LAC and Romani, A and Sullender, M and Aggarwal, S and Hogarty, M and Rodgers, R and Kennedy, E and Foster, L and Schriefer, LA and Baldridge, MT}, title = {Dynamics of Bacterial and Viral Transmission in Experimental Microbiota Transplantation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2025.01.15.633206}, pmid = {39868290}, issn = {2692-8205}, abstract = {Mouse models are vital tools for discerning the relative contributions of host and microbial genetics to disease, often requiring the transplantation of microbiota between different mouse strains. Transfer methods include antibiotic treatment of recipients and colonization using either co-housing with donors or the transplantation of fecal or cecal donor material. However, the efficiency and dynamics of these methods in reconstituting recipients with donor microbes is not well understood. We thus directly compared co-housing, fecal transplantation, and cecal transplantation methods. Donor mice from Taconic Biosciences, possessing distinct microbial communities, served as the microbial source for recipient mice from Jackson Laboratories, which were treated with antibiotics to disrupt their native microbiota. We monitored microbial populations longitudinally over the course of antibiotics treatment and reconstitution using 16S rRNA gene sequencing, quantitative PCR, and shotgun sequencing of viral-like particles. As expected, antibiotic treatment rapidly depleted microbial biomass and diversity, with slow and incomplete natural recovery of the microbiota in non-transplanted control mice. While all transfer methods reconstituted recipient mice with donor microbiota, co-housing achieved this more rapidly for both bacterial and viral communities. This study provides valuable insights into microbial transfer methods, enhancing reproducibility and informing best practices for microbiota transplantation in mouse models.}, } @article {pmid39864578, year = {2025}, author = {Attiq, A}, title = {Early-Life Antibiotic Exposures: Paving the Pathway for Dysbiosis-Induced Disorders.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {177298}, doi = {10.1016/j.ejphar.2025.177298}, pmid = {39864578}, issn = {1879-0712}, abstract = {Microbiota encompasses a diverse array of microorganisms inhabiting specific ecological niches. Gut microbiota significantly influences physiological processes, including gastrointestinal motor function, neuroendocrine signalling, and immune regulation. They play a crucial role in modulating the central nervous system and bolstering body defence mechanisms by influencing the proliferation and differentiation of innate and adaptive immune cells. Given the potential consequences of antibiotic therapy on gut microbiota equilibrium, there is a need for prudent antibiotic use to mitigate associated risks. Observational studies have linked increased antibiotic usage to various pathogenic conditions, including obesity, inflammatory bowel disease, anxiety-like effects, asthma, and pulmonary carcinogenesis. Addressing dysbiosis incidence requires proactive measures, including prophylactic use of β-lactamase drugs (SYN-004, SYN-006, and SYN-007), hydrolysing the β-lactam in the proximal GIT for maintaining intestinal flora homeostasis. Prebiotic and probiotic supplementations are crucial in restoring intestinal flora equilibrium by competing with pathogenic bacteria for nutritional resources and adhesion sites, reducing luminal pH, neutralising toxins, and producing antimicrobial agents. Faecal microbiota transplantation (FMT) shows promise in restoring gut microbiota composition. Rational antibiotic use is essential to preserve microflora and improve patient compliance with antibiotic regimens by mitigating associated side effects. Given the significant implications on gut microbiota composition, concerted intervention strategies must be pursued to rectify and reverse the occurrence of antibiotic-induced dysbiosis. Here, antibiotics-induced microbiota dysbiosis mechanisms and their systemic implications are reviewed. Moreover, proposed interventions to mitigate the impact on gut microflora are also discussed herein.}, } @article {pmid39863610, year = {2025}, author = {Reddi, S and Senyshyn, L and Ebadi, M and Podlesny, D and Minot, SS and Gooley, T and Kabage, AJ and Hill, GR and Lee, SJ and Khoruts, A and Rashidi, A}, title = {Fecal microbiota transplantation to prevent acute graft-versus-host disease: pre-planned interim analysis of donor effect.}, journal = {Nature communications}, volume = {16}, number = {1}, pages = {1034}, pmid = {39863610}, issn = {2041-1723}, support = {P30 CA015704/CA/NCI NIH HHS/United States ; ACT9016-24//Leukemia and Lymphoma Society (Leukemia & Lymphoma Society)/ ; }, mesh = {Humans ; *Graft vs Host Disease/prevention & control/microbiology ; *Fecal Microbiota Transplantation/methods ; Male ; Female ; Middle Aged ; Adult ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Double-Blind Method ; *Tissue Donors ; *Transplantation, Homologous/adverse effects ; Feces/microbiology ; Acute Disease ; Aged ; Young Adult ; }, abstract = {Gut microbiota disruptions after allogeneic hematopoietic cell transplantation (alloHCT) are associated with increased risk of acute graft-versus-host disease (aGVHD). We designed a randomized, double-blind placebo-controlled trial to test whether healthy-donor fecal microbiota transplantation (FMT) early after alloHCT reduces the incidence of severe aGVHD. Here, we report the results from the single-arm run-in phase which identified the best of 3 stool donors for the randomized phase. The primary and key secondary endpoints were microbiota engraftment and severe aGVHD, respectively. Three cohorts of patients (20 total) received FMT, each from a different donor. FMT was safe and effective in restoring microbiota diversity and commensal species. Microbiota engraftment, determined from shotgun sequencing data, correlated with larger microbiota compositional shifts toward donor and better clinical outcomes. Donor 3 yielded a median engraftment rate of 66%, higher than donors 1 (P = 0.02) and 2 (P = 0.03) in multivariable analysis. Three patients developed severe aGVHD; all 3 had received FMT from donor 1. Donor 3 was selected as the sole donor for the randomized phase. Our findings suggest a clinically relevant donor effect and demonstrate feasibility of evidence-based donor selection. FMT is a holistic microbiota restoration approach that can be performed as a precision therapeutic. ClinicalTrials.gov identifier NCT06026371.}, } @article {pmid39863438, year = {2025}, author = {Jin, J and Cai, X and Rao, P and Xu, J and Li, J}, title = {Microbiota and immune dynamics in rheumatoid arthritis: Mechanisms and therapeutic potential.}, journal = {Best practice & research. Clinical rheumatology}, volume = {}, number = {}, pages = {102035}, doi = {10.1016/j.berh.2025.102035}, pmid = {39863438}, issn = {1532-1770}, abstract = {Rheumatoid arthritis (RA) is a complex autoimmune disease with growing evidence implicating the microbiota as a critical contributor to its pathogenesis. This review explores the multifaceted roles of microbial dysbiosis in RA, emphasizing its impact on immune cell modulation, autoantibody production, gut barrier integrity, and joint inflammation. Animal models reveal how genetic predisposition and environmental factors interact with specific microbial taxa to influence disease susceptibility. Dysbiosis-driven metabolic disruptions, including alterations in short-chain fatty acids and bile acids, further exacerbate immune dysregulation and systemic inflammation. Emerging therapeutic strategies-probiotics, microbial metabolites, fecal microbiota transplantation, and antibiotics-offer innovative avenues for restoring microbial balance and mitigating disease progression. By integrating microbiota-targeted approaches with existing treatments, this review highlights the potential to revolutionize RA management through precision medicine and underscores the need for further research to harness the microbiota's therapeutic potential.}, } @article {pmid39863236, year = {2025}, author = {Qin, N and Liu, H and Wang, X and Liu, Y and Chang, H and Xia, X}, title = {Sargassum fusiforme polysaccharides protect mice against Citrobacter rodentium infection via intestinal microbiota-driven microRNA-92a-3p-induced Muc2 production.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {140271}, doi = {10.1016/j.ijbiomac.2025.140271}, pmid = {39863236}, issn = {1879-0003}, abstract = {Sargassum fusiforme, widely consumed in Asian countries, has been proven to have various biological activities. However, the impacts and mechanisms of Sargassum fusiforme polysaccharides (SFPs) on intestinal bacterial infection are not yet fully understood. Our findings indicate that SFPs pretreatment ameliorates intestinal inflammation by reducing C. rodentium colonization, increasing colon length and levels of IL-10 and IL-22, decreasing IL-1β, IL-6, TNF-α, and IL-17 levels, inhibiting colonic crypt elongation and hyperplasia, and enhancing the intestinal mucosal barrier. The protective effects against intestinal bacterial infection are linked to enhanced clearance of C. rodentium and improvements in the intestinal mucosal barrier and C. rodentium-induced intestinal microbiota dysbiosis. Fecal microbiota transplantation experiments were conducted to evaluate the functional impact of microbiota induced by SFPs. The results suggest that intestinal microbiota modified by SFPs effectively countered C. rodentium infection. In addition, our study identified that miRNA-92a-3p is partially complementary to the 3'-UTR of the Notch1 gene, thereby repressing the Notch1-Hes1 signaling pathway and enhancing Muc2 secretion. Taken together, these findings reveal that SFPs protect mice from C. rodentium infection by activating the miR-92a-3p/Notch1-Hes1 regulatory axis driven by the intestinal microbiota, which stimulates Muc2 production to maintain intestinal barrier homeostasis.}, } @article {pmid39862968, year = {2025}, author = {Huang, P and Di, L and Cui, S and Wang, X and Cao, T and Jiang, S and Huang, L}, title = {Postoperative delirium after cardiac surgery associated with perioperative gut microbiota dysbiosis: Evidence from human and antibiotic-treated mouse model.}, journal = {Anaesthesia, critical care & pain medicine}, volume = {}, number = {}, pages = {101484}, doi = {10.1016/j.accpm.2025.101484}, pmid = {39862968}, issn = {2352-5568}, abstract = {BACKGROUND: Research links gut microbiota to postoperative delirium (POD) through the gut-brain axis. However, changes in gut microbiota and fecal short-chain fatty acids (SCFAs) in POD patients during the perioperative period and their association with POD are unclear.

METHODS: We conducted a nested case-control study among patients undergoing off-pump coronary artery bypass grafting, focusing on POD as the main outcome. POD patients were matched 1:1 with non-POD patients based on sociodemographic characteristics, health, and diet. Fecal samples were collected pre- and post-surgery to assess gut microbiota and SCFA changes. Postoperative fecal samples were transplanted into antibiotic-treated mice to evaluate delirium-like behavior and neuroinflammation.

RESULTS: Out of 120 patients, 60 were matched. Before surgery, gut microbiota in both groups was similar. After surgery, POD patients had lower alpha diversity and distinct microbiota compared to non-POD patients. LEfSe analysis showed POD was linked to increased opportunistic pathogens (Enterococcus) and decreased SCFA producers (Bacteroides, Ruminococcus, etc.). SCFAs were significantly reduced in POD patients and negatively correlated with delirium severity and plasma inflammation. Mice receiving fecal transplants from POD patients exhibited delirium-like behavior and neuroinflammation.

CONCLUSIONS: Postoperative delirium is associated with gut microbiota dysbiosis, marked by an increase in opportunistic pathogens and a decrease in SCFA-producing genera.

REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300070477.}, } @article {pmid39862808, year = {2025}, author = {Xiao, Y and He, X and Zhang, H and Wu, X and Ai, R and Xu, J and Wen, Q and Zhang, F and Cui, B}, title = {Washed microbiota transplantation effectively improves nutritional status in gastrointestinal disease-related malnourished children.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {132}, number = {}, pages = {112679}, doi = {10.1016/j.nut.2024.112679}, pmid = {39862808}, issn = {1873-1244}, abstract = {BACKGROUND AND AIM: Gut microbiota dysbiosis plays a critical role in malnutrition caused by food intolerance and intestinal inflammation in children, which needs to be addressed. We assessed the efficacy and safety of washed microbiota transplantation (WMT) for gastrointestinal disease-related malnourished children.

METHODS: This was a prospective observational study involving gastrointestinal disease-related malnourished pediatric patients who underwent WMT. The primary outcome was the clinical response rate at 3 mo post-WMT. Clinical response was defined as an improvement in the children's nutritional status of one level or more. The secondary outcomes were changes in gastrointestinal symptoms, laboratory nutritional indicators, and adverse events during the WMT procedure.

RESULTS: 29 patients undergoing 74 WMTs were included for analysis. In total, 48.3% (14/29) of patients achieved clinical response post-WMT. Gastrointestinal symptoms, including diarrhea, mucous stool, abdominal pain, abdominal distention, and hematochezia, were significantly relieved post-WMT (all P < 0.05). Serum albumin and prealbumin levels were increased significantly post-WMT (P = 0.028 and 0.028, respectively). Eight self-limiting and transient adverse events, including diarrhea, abdominal pain, and abdominal distension, occurred after WMT.

CONCLUSION: This study indicated that WMT might be effective and safe for improving nutritional status and gastrointestinal symptoms in gastrointestinal disease-related malnourished children at 3-mo follow-up. WMT was expected to be a new therapeutic option for these patients.}, } @article {pmid39861773, year = {2025}, author = {Ortiz-Islas, E and Montes, P and Rodríguez-Pérez, CE and Ruiz-Sánchez, E and Sánchez-Barbosa, T and Pichardo-Rojas, D and Zavala-Tecuapetla, C and Carvajal-Aguilera, K and Campos-Peña, V}, title = {Evolution of Alzheimer's Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy.}, journal = {Pharmaceutics}, volume = {17}, number = {1}, pages = {}, pmid = {39861773}, issn = {1999-4923}, support = {CF-2023-G-971 and CBF-2023-2024-1982//Ciencia de Frontera/ ; }, abstract = {Alzheimer's disease (AD) represents an escalating global health crisis, constituting the leading cause of dementia among the elderly and profoundly impairing their quality of life. Current FDA-approved drugs, such as rivastigmine, donepezil, galantamine, and memantine, offer only modest symptomatic relief and are frequently associated with significant adverse effects. Faced with this challenge and in line with advances in the understanding of the pathophysiology of this neurodegenerative condition, various innovative therapeutic strategies have been explored. Here, we review novel approaches inspired by advanced knowledge of the underlying pathophysiological mechanisms of the disease. Among the therapeutic alternatives, immunotherapy stands out, employing monoclonal antibodies to specifically target and eliminate toxic proteins implicated in AD. Additionally, the use of medicinal plants is examined, as their synergistic effects among components may confer neuroprotective properties. The modulation of the gut microbiota is also addressed as a peripheral strategy that could influence neuroinflammatory and degenerative processes in the brain. Furthermore, the therapeutic potential of emerging approaches, such as the use of microRNAs to regulate key cellular processes and nanotherapy, which enables precise drug delivery to the central nervous system, is analyzed. Despite promising advances in these strategies, the incidence of Alzheimer's disease continues to rise. Therefore, it is proposed that achieving effective treatment in the future may require the integration of combined approaches, maximizing the synergistic effects of different therapeutic interventions.}, } @article {pmid39859091, year = {2025}, author = {Almonajjed, MB and Wardeh, M and Atlagh, A and Ismaiel, A and Popa, SL and Rusu, F and Dumitrascu, DL}, title = {Impact of Microbiota on Irritable Bowel Syndrome Pathogenesis and Management: A Narrative Review.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {61}, number = {1}, pages = {}, pmid = {39859091}, issn = {1648-9144}, mesh = {Humans ; *Irritable Bowel Syndrome/therapy/microbiology/physiopathology ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation/methods ; *Probiotics/therapeutic use ; Brain-Gut Axis/physiology ; Dysbiosis/therapy/complications ; Quality of Life ; Synbiotics/administration & dosage ; Prebiotics/administration & dosage ; }, abstract = {Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder, affecting 3-5% of the global population and significantly impacting patients' quality of life and healthcare resources. Alongside physical symptoms such as abdominal pain and altered bowel habits, many individuals experience psychological comorbidities, including anxiety and depression. Recent research has highlighted the critical role of the gut microbiota in IBS, with dysbiosis, characterized by an imbalance in microbial diversity, frequently observed in patients. The gut-brain axis, a bidirectional communication network between the gut and central nervous system, plays a central role in the development of IBS symptoms. Although interventions such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) have demonstrated potential in modulating the gut microbiota and alleviating symptoms, their efficacy remains an area of ongoing investigation. This review examines the interactions between the gut microbiota, immune system, and brain, emphasizing the need for personalized therapeutic strategies. Future research should aim to identify reliable microbiota-based biomarkers for IBS and refine microbiome-targeted therapies to enhance patient outcomes.}, } @article {pmid39858858, year = {2025}, author = {Onisiforou, A and Charalambous, EG and Zanos, P}, title = {Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer's Disease Pathogenesis-From Gut Microbiota and Viruses to Brain Biofilms.}, journal = {Microorganisms}, volume = {13}, number = {1}, pages = {}, pmid = {39858858}, issn = {2076-2607}, support = {#101031962//European Commission Marie Skłodowska-Curie fellowship/ ; EXCELLENCE/0421/0543//Research & Innovation Foundation of Cyprus - Excellence Hubs 2021/ ; NA//IDSA Foundation/ ; }, abstract = {For decades, Alzheimer's Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as the primary driver of the disease. However, the consistent failure of Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores the need to rethink our approach to AD treatment. Emerging evidence points to microbial infections as environmental factors in AD pathoetiology. Although a definitive causal link remains unestablished, the collective evidence is compelling. This review explores unconventional perspectives and emerging paradigms regarding microbial involvement in AD pathogenesis, emphasizing the gut-brain axis, brain biofilms, the oral microbiome, and viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes brain Aβ accumulation, emphasizing gut-brain signaling pathways. Viral infections like Herpes Simplex Virus Type 1 (HSV-1) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead to AD by modulating host processes like the immune system. Aβ peptide's antimicrobial function as a response to microbial infection might inadvertently promote AD. We discuss potential microbiome-based therapies as promising strategies for managing and potentially preventing AD progression. Fecal microbiota transplantation (FMT) restores gut microbial balance, reduces Aβ accumulation, and improves cognition in preclinical models. Probiotics and prebiotics reduce neuroinflammation and Aβ plaques, while antiviral therapies targeting HSV-1 and vaccines like the shingles vaccine show potential to mitigate AD pathology. Developing effective treatments requires standardized methods to identify and measure microbial infections in AD patients, enabling personalized therapies that address individual microbial contributions to AD pathogenesis. Further research is needed to clarify the interactions between microbes and Aβ, explore bacterial and viral interplay, and understand their broader effects on host processes to translate these insights into clinical interventions.}, } @article {pmid39858421, year = {2024}, author = {Gabrielli, M and Zileri Dal Verme, L and Zocco, MA and Nista, EC and Ojetti, V and Gasbarrini, A}, title = {The Role of the Gastrointestinal Microbiota in Parkinson's Disease.}, journal = {Biomolecules}, volume = {15}, number = {1}, pages = {}, pmid = {39858421}, issn = {2218-273X}, mesh = {*Parkinson Disease/microbiology/metabolism ; Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/microbiology ; *Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; Helicobacter Infections/microbiology ; Prebiotics ; Brain-Gut Axis/physiology ; Helicobacter pylori ; }, abstract = {BACKGROUND/OBJECTIVES: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons leading to debilitating motor and non-motor symptoms. Beyond its well-known neurological features, emerging evidence underscores the pivotal role of the gut-brain axis and gastrointestinal microbiota in PD pathogenesis. Dysbiosis has been strongly linked to PD and is associated with increased intestinal permeability, chronic inflammation, and the production of neurotoxic metabolites that may exacerbate neuronal damage.

METHODS: This review delves into the complex interplay between PD and dysbiosis, shedding light on two peculiar subsets of dysbiosis, Helicobacter pylori infection and small-intestinal bacterial overgrowth. These conditions may not only contribute to PD progression but also influence therapeutic responses such as L-dopa efficacy.

CONCLUSIONS: The potential to modulate gut microbiota through probiotics, prebiotics, and synbiotics; fecal microbiota transplantation; and antibiotics represents a promising frontier for innovative PD treatments. Despite this potential, the current evidence is limited by small sample sizes and methodological variability across studies. Rigorous, large-scale, randomized placebo-controlled trials with standardized treatments in terms of composition, dosage, and duration are urgently needed to validate these findings and pave the way for microbiota-based therapeutic strategies in PD management.}, } @article {pmid39858303, year = {2024}, author = {Morado, F and Nanda, N}, title = {A Review of Therapies for Clostridioides difficile Infection.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39858303}, issn = {2079-6382}, abstract = {Clostridioides difficile is an urgent public health threat that affects approximately half a million patients annually in the United States. Despite concerted efforts aimed at the prevention of Clostridioides difficile infection (CDI), it remains a leading cause of healthcare-associated infections. CDI is associated with significant clinical, social, and economic burdens. Therefore, it is imperative to provide optimal and timely therapy for CDI. We conducted a systematic literature review and offer treatment recommendations based on available evidence for the treatment and prevention of CDI.}, } @article {pmid39857680, year = {2025}, author = {Radoš, L and Golčić, M and Mikolašević, I}, title = {The Relationship Between the Modulation of Intestinal Microbiota and the Response to Immunotherapy in Patients with Cancer.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857680}, issn = {2227-9059}, abstract = {The intestinal microbiota is an important part of the human body, and its composition can affect the effectiveness of immunotherapy. In the last few years, the modulation of intestinal microbiota in order to improve the effectiveness of immunotherapy has become a current topic in the scientific community, but there is a lack of research in this area. In this review, the goal was to analyze the current relevant literature related to the modulation of intestinal microbiota and the effectiveness of immunotherapy in the treatment of cancer. The effects of antibiotics, probiotics, diet, and fecal microbial transplantation were analyzed separately. It was concluded that the use of antibiotics, especially broad-spectrum types or larger quantities, causes dysbiosis of the intestinal microbiota, which can reduce the effectiveness of immunotherapy. While dysbiosis could be repaired by probiotics and thus improve the effectiveness of immunotherapy, the use of commercial probiotics without evidence of intestinal dysbiosis has not yet been sufficiently tested to confirm its safety for cancer for immunotherapy-treated cancer patients. A diet consisting of sufficient amounts of fiber, as well as a diet with higher salt content positively correlates with the success of immunotherapy. Fecal transplantation is a safe and realistic adjuvant option for the treatment of cancer patients with immunotherapy, but more clinical trials are necessary. Modulating the microbiota composition indeed changes the effectiveness of immunotherapy, but in the future, more human studies should be organized to precisely determine the types and procedures of microbiota modulation.}, } @article {pmid39857657, year = {2024}, author = {Li, W and Gao, W and Yan, S and Yang, L and Zhu, Q and Chu, H}, title = {Gut Microbiota as Emerging Players in the Development of Alcohol-Related Liver Disease.}, journal = {Biomedicines}, volume = {13}, number = {1}, pages = {}, pmid = {39857657}, issn = {2227-9059}, support = {National Nature Science Foundation of China (No.81974078, No.81570530, and No.81370550)//Ling Yang/ ; National Key R&D Program of China (No.2022YFA1305600)//Huikuan Chu/ ; Ministry of Science and Technology of China (No.2023YFC2413804)//Ling Yang/ ; Natural Science Foundation of Hubei Province (No.2019ACA1333)//Ling Yang/ ; }, abstract = {The global incidence and mortality rates of alcohol-related liver disease are on the rise, reflecting a growing health concern worldwide. Alcohol-related liver disease develops due to a complex interplay of multiple reasons, including oxidative stress generated during the metabolism of ethanol, immune response activated by immunogenic substances, and subsequent inflammatory processes. Recent research highlights the gut microbiota's significant role in the progression of alcohol-related liver disease. In patients with alcohol-related liver disease, the relative abundance of pathogenic bacteria, including Enterococcus faecalis, increases and is positively correlated with the level of severity exhibited by alcohol-related liver disease. Supplement probiotics like Lactobacillus, as well as Bifidobacterium, have been found to alleviate alcohol-related liver disease. The gut microbiota is speculated to trigger specific signaling pathways, influence metabolite profiles, and modulate immune responses in the gut and liver. This research aimed to investigate the role of gut microorganisms in the onset and advancement of alcohol-related liver disease, as well as to uncover the underlying mechanisms by which the gut microbiota may contribute to its development. This review outlines current treatments for reversing gut dysbiosis, including probiotics, fecal microbiota transplantation, and targeted phage therapy. Particularly, targeted therapy will be a vital aspect of future alcohol-related liver disease treatment. It is to be hoped that this article will prove beneficial for the treatment of alcohol-related liver disease.}, } @article {pmid39855927, year = {2025}, author = {Wang, X and Zhao, D and Bi, D and Li, L and Tian, H and Yin, F and Zuo, T and Ianiro, G and Han, YW and Li, N and Chen, Q and Qin, H}, title = {Fecal microbiota transplantation: transitioning from chaos and controversial realm to scientific precision era.}, journal = {Science bulletin}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.scib.2025.01.029}, pmid = {39855927}, issn = {2095-9281}, abstract = {With the popularization of modern lifestyles, the spectrum of intestinal diseases has become increasingly diverse, presenting significant challenges in its management. Traditional pharmaceutical interventions have struggled to keep pace with these changes, leaving many patients refractory to conventional pharmaceutical treatments. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic approach for enterogenic diseases. Still, controversies persist regarding its active constituents, mechanism of action, scheme of treatment evaluation, indications, and contraindications. In this review, we investigated the efficacy of FMT in addressing gastrointestinal and extraintestinal conditions, drawing from follow-up data on over 8000 patients. We systematically addressed the controversies surrounding FMT's clinical application. We delved into key issues such as its technical nature, evaluation methods, microbial restoration mechanisms, and impact on the host-microbiota interactions. Additionally, we explored the potential colonization patterns of FMT-engrafted new microbiota throughout the entire intestine and elucidated the specific pathways through which the new microbiota modulates host immunity, metabolism, and genome.}, } @article {pmid39855612, year = {2025}, author = {Sutanto, H and Elisa, E and Rachma, B and Fetarayani, D}, title = {Gut Microbiome Modulation in Allergy Treatment: The Role of Fecal Microbiota Transplantation.}, journal = {The American journal of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.amjmed.2025.01.005}, pmid = {39855612}, issn = {1555-7162}, abstract = {The prevalence of allergic diseases has been rising, paralleling lifestyle changes and environmental exposures that have altered human microbiome composition. This review article examines the intricate relationship between the gut microbiome and allergic diseases, emphasizing the potential of fecal microbiota transplantation as a promising novel treatment approach. It explains how reduced microbial exposure in modern societies contributes to immune dysregulation and the increasing incidence of allergies. The discussion also addresses immune homeostasis and its modulation by the gut microbiome, highlighting the shift from eubiosis to dysbiosis in allergic conditions. Furthermore, this article reviews existing studies and emerging research on the role of fecal microbiota transplantation in restoring microbial balance, providing insights into its mechanisms, efficacy, and safety.}, } @article {pmid39854760, year = {2025}, author = {Chen, S and Zhang, D and Li, D and Zeng, F and Chen, C and Bai, F}, title = {Microbiome characterization of patients with Crohn disease and the use of fecal microbiota transplantation: A review.}, journal = {Medicine}, volume = {104}, number = {4}, pages = {e41262}, doi = {10.1097/MD.0000000000041262}, pmid = {39854760}, issn = {1536-5964}, support = {2021818//Hainan Province Clinical Medical Center/ ; YSPTZX202313//The specific research fund of The Innovation Platform for Academicians of Hainan Province/ ; 22A200078//Hainan Provincial Health Industry Research Project/ ; Qhyb2022-133//Hainan Provincial Postgraduate Innovation Research Project/ ; }, mesh = {Humans ; *Crohn Disease/therapy/microbiology ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; }, abstract = {Inflammatory bowel disease is a chronic inflammatory condition predominantly affecting the intestines, encompassing both ulcerative colitis and Crohn disease (CD). As one of the most common gastrointestinal disorders, CD's pathogenesis is closely linked with the intestinal microbiota. Recently, fecal microbiota transplantation (FMT) has gained attention as a potential treatment for CD, with the effective reestablishment of intestinal microecology considered a crucial mechanism of FMT therapy. This article synthesizes the findings of population-based cohort studies to enhance our understanding of gut microbial characteristics in patients with CD. It delves into the roles of "beneficial" and "pathogenic" bacteria in CD's development. This article systematically reviews and compares data on clinical response rates, remission rates, adverse events, and shifts in bacterial microbiota. Among these studies, gut microbiome analysis was conducted in only 7, and a single study examined the metabolome. Overall, FMT has demonstrated a partial restoration of typical CD-associated microbiological alterations, leading to increased α-diversity in responders and a moderate shift in patient microbiota toward the donor profile. Several factors, including donor selection, delivery route, microbial state (fresh or frozen), and recipient condition, are identified as pivotal in influencing FMT's effectiveness. Future prospective clinical studies with larger patient cohorts and improved methodologies are imperative. In addition, standardization of FMT procedures, coupled with advanced genomic techniques such as macroproteomics and culture genomics, is necessary. These advancements will further clarify the bacterial microbiota alterations that significantly contribute to FMT's therapeutic effects in CD treatment, as well as elucidate the underlying mechanisms of action.}, } @article {pmid39854205, year = {2025}, author = {Yang, CJ and Peng, YS and Sung, PC and Hsieh, SY}, title = {Protocol for oral fecal gavage to reshape the gut microbiota in mice.}, journal = {STAR protocols}, volume = {6}, number = {1}, pages = {103585}, doi = {10.1016/j.xpro.2024.103585}, pmid = {39854205}, issn = {2666-1667}, abstract = {Fecal microbiota transplantation (FMT) is clinically applied, while oral FMT (oral fecal gavage [OFG]) is preferred for experimental mice. Here, we present a protocol for OFG in antibiotic-pretreated mice, demonstrating the progressive, time-dependent evolution of the gut microbiota in the recipients. We describe steps for fecal sample collection and preparation procedures, oral gavage, and monitoring gut microbiota changes. This protocol serves as a general guide for reshaping the gut microbiota in recipient mice for various experimental applications. For complete details on the use and execution of this protocol, please refer to Yang et al.[1].}, } @article {pmid39854158, year = {2025}, author = {Lau, RI and Su, Q and Ng, SC}, title = {Long COVID and gut microbiome: insights into pathogenesis and therapeutics.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2457495}, doi = {10.1080/19490976.2025.2457495}, pmid = {39854158}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Fecal Microbiota Transplantation ; *COVID-19/therapy/microbiology ; *Probiotics/therapeutic use ; *Dysbiosis/therapy/microbiology ; *SARS-CoV-2 ; *Post-Acute COVID-19 Syndrome ; Prebiotics/administration & dosage ; }, abstract = {Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.}, } @article {pmid39851261, year = {2025}, author = {Zhao, X and Qiu, Y and Liang, L and Fu, X}, title = {Interkingdom signaling between gastrointestinal hormones and the gut microbiome.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2456592}, doi = {10.1080/19490976.2025.2456592}, pmid = {39851261}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; Animals ; *Dysbiosis/microbiology ; *Gastrointestinal Hormones/metabolism ; *Bacteria/metabolism/classification/genetics ; Fecal Microbiota Transplantation ; Signal Transduction ; Homeostasis ; Inflammatory Bowel Diseases/microbiology/metabolism ; Gastrointestinal Tract/microbiology/metabolism ; }, abstract = {The interplay between the gut microbiota and gastrointestinal hormones plays a pivotal role in the health of the host and the development of diseases. As a vital component of the intestinal microecosystem, the gut microbiota influences the synthesis and release of many gastrointestinal hormones through mechanisms such as modulating the intestinal environment, producing metabolites, impacting mucosal barriers, generating immune and inflammatory responses, and releasing neurotransmitters. Conversely, gastrointestinal hormones exert feedback regulation on the gut microbiota by modulating the intestinal environment, nutrient absorption and utilization, and the bacterial biological behavior and composition. The distributions of the gut microbiota and gastrointestinal hormones are anatomically intertwined, and close interactions between the gut microbiota and gastrointestinal hormones are crucial for maintaining gastrointestinal homeostasis. Interventions leveraging the interplay between the gut microbiota and gastrointestinal hormones have been employed in the clinical management of metabolic diseases and inflammatory bowel diseases, such as bariatric surgery and fecal microbiota transplantation, offering promising targets for the treatment of dysbiosis-related diseases.}, } @article {pmid39850178, year = {2024}, author = {Gandhi, DN and Pande, DN and Harikrishna, A and Advilkar, A and Basavan, I and Ansari, R}, title = {Beyond the Brain: Attention Deficit/Hyperactivity Disorder and the Gut-Brain Axis.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e76291}, pmid = {39850178}, issn = {2168-8184}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a complex neurodevelopmental condition, predominantly affecting children, characterized by inattention, hyperactivity, and impulsivity. A growing body of evidence has highlighted the potential influence of the gut microbiota on the onset and presentation of ADHD symptoms. The gut microbiota, a diverse microbial ecosystem residing within the gastrointestinal tract, exerts multiple effects on systemic physiology, including immune modulation, metabolic regulation, and neuronal signalling. The bidirectional gut-brain axis serves as a conduit for communication between gut microbes and the central nervous system, implicating its disruption in neurodevelopmental disorders such as ADHD. This comprehensive literature review aims to shed light on how alterations in the gut microbiota influence the development and manifestation of ADHD symptoms. Examining potential mechanisms involving gut microbial metabolites and their impact on neurotransmitter modulation, neuro-endocrine signalling and neuroinflammation, we dissect the intricate interplay shaping ADHD pathology. Insights into these complex interactions hold promise for personalized therapeutic interventions aimed at modulating the gut microbiota to ameliorate ADHD symptoms. Discussions encompass dietary interventions, faecal microbiota-targeted therapies, and emerging probiotic approaches, underscoring their potential as adjunctive or alternative strategies in managing ADHD. Further research elucidating the precise mechanisms driving these interactions may pave the way for targeted and personalized interventions for individuals grappling with ADHD.}, } @article {pmid39848238, year = {2025}, author = {Szajewska, H}, title = {An Overview of Early-Life Gut Microbiota Modulation Strategies.}, journal = {Annals of nutrition & metabolism}, volume = {}, number = {}, pages = {1-6}, doi = {10.1159/000541492}, pmid = {39848238}, issn = {1421-9697}, abstract = {BACKGROUND: The gut microbiota, or microbiome, is essential for human health. Early-life factors such as delivery mode, diet, and antibiotic use shape its composition, impacting both short- and long-term health outcomes. Dysbiosis, or alterations in the gut microbiota, is linked to conditions such as allergies, asthma, obesity, diabetes, inflammatory bowel disease, and necrotizing enterocolitis in preterm infants.

SUMMARY: This article reviews current strategies to influence the early-life gut microbiome and their potential health impacts. It also briefly summarizes guidelines on using biotics for gastrointestinal and allergic diseases in children. Key strategies include vaginal or fecal microbiota transplantation for cesarean-born infants, breastfeeding, and biotic-supplemented formulas. While vaginal microbial transfer and maternal fecal microbiota transplantation show short-term benefits, further research is needed to determine long-term safety and efficacy. Breast milk, rich in human milk oligosaccharides, promotes a healthy microbiota and offers protection against infections. Biotic-supplemented formulas can improve the gut microbiota in formula-fed infants and show clinical effects, though each biotic must be evaluated separately. Probiotics given as dietary supplements outside of infant formulas show promise for treating gastrointestinal disorders but require further investigation.}, } @article {pmid39845805, year = {2024}, author = {Shen, Y and Gao, Y and Yang, G and Zhao, Z and Zhao, Y and Gao, L and Li, S}, title = {Anti-colorectal cancer effect of total minor ginsenosides produced by lactobacilli transformation of major ginsenosides by inducing apoptosis and regulating gut microbiota.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1496346}, pmid = {39845805}, issn = {1663-9812}, abstract = {OBJECTIVE: Minor ginsenosides have demonstrated promising anticancer effects in previous reports. Total minor ginsenosides (TMG) were obtained through the fermentation of major ginsenosides with Lactiplantibacillus plantarum, and potential anticancer effects of TMGs on the mouse colon cancer cell line CT26.WT, in vitro and in vivo, were investigated.

MATERIALS AND METHODS: We employed the Cell Counting Kit-8 (CCK-8), TdT-mediated dUTP nick end labeling (TUNEL), and Western blot analysis in vitro to explore the anti-proliferative and pro-apoptotic functions of TMG in CT26.WT cells. In vivo, a xenograft model was established by subcutaneously injecting mice with CT26.WT cells and administering a dose of 100 mg/kg/day TMG to the tumor-bearing mice. The level of apoptosis and expression of various proteins in the tumor tissues were detected by immunohistochemistry and Western blot. High-throughput 16S rRNA sequencing was used to determine the alterations in the gut microbiota.

RESULTS: In vitro studies demonstrated that TMG significantly inhibited proliferation and promoted apoptosis in CT26.WT cells. Interestingly, TMG induced apoptosis in CT26.WT cells by affecting the Bax/Bcl-2/caspase-3 pathway. Furthermore, the result of the transplanted tumor model indicated that TMG substantially enhanced the activities of Bax and caspase-3, reduced the activity of Bcl-2, and suppressed the expression of Raf/MEK/ERK protein levels. Fecal analysis revealed that TMG reconstructed the gut microbiota in colorectal cancer-affected mice by augmenting the abundance of the advantageous bacterium Lactobacillus and decreasing the abundance of the harmful bacterium Proteus.

CONCLUSION: TMG can exhibit potent anti-colorectal cancer effects through diverse apoptotic mechanisms, with their mode of action closely related to the regulation of gut microbiota.}, } @article {pmid39845049, year = {2024}, author = {Wu, R and Mai, Z and Song, X and Zhao, W}, title = {Hotspots and research trends of gut microbiome in polycystic ovary syndrome: a bibliometric analysis (2012-2023).}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1524521}, pmid = {39845049}, issn = {1664-302X}, abstract = {INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common gynecological condition affecting individuals of reproductive age and is linked to the gut microbiome. This study aimed to identify the hotspots and research trends within the domain of the gut microbiome in PCOS through bibliometric analysis.

METHODS: Utilizing bibliometric techniques, we examined the literature on the gut microbiome in PCOS from the Web of Science Core Collection spanning the period from 2012 to 2023. Analytical tools such as CiteSpace, VOSviewer, and Bibliometric R packages were employed to evaluate various metrics, including countries/regions, institutions, authors, co-cited authors, authors' H-index, journals, co-references, and keywords.

RESULTS: A total of 191 publications were identified in the field of gut microbiome in PCOS, with an increase in annual publications from 2018 to 2023. People's Republic of China was the most productive country, followed by the United States of America (USA), India. Shanghai Jiao Tong University, Fudan University, and Beijing University of Chinese Medicine were the top three most publications institutions. Thackray VG was identified as the most prolific author, holding the highest H-index, while Liu R received the highest total number of citations. The journal "Frontiers in Endocrinology" published the most articles in this domain. The most frequently co-cited reference was authored by Qi XY. The analysis of keyword burst detection identified "bile acids" (2021-2023) as the leading frontier keyword. Additionally, "gut dysbiosis," "phenotypes," "adolescents," "metabolomics," "metabolites," "fecal microbiota transplantation," and "IL-22" have emerged as the primary keywords reflecting recent research trends.

CONCLUSION: This bibliometric analysis explores how the gut microbiome influences endocrine and metabolic disorders related to PCOS, emphasizing its role in the development of PCOS and treatments targeting the gut microbiome. The findings serve as a valuable resource for researchers, enabling them to identify critical hotspots and emerging areas of investigation in this field.}, } @article {pmid39844078, year = {2025}, author = {Fan, X and Li, J and Gao, Y and Li, L and Zhang, H and Bi, Z}, title = {The mechanism of enterogenous toxin methylmalonic acid aggravating calcium-phosphorus metabolic disorder in uremic rats by regulating the Wnt/β-catenin pathway.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {19}, pmid = {39844078}, issn = {1528-3658}, mesh = {Animals ; Rats ; *Wnt Signaling Pathway ; *Calcium/metabolism ; Male ; *Phosphorus/metabolism ; *Uremia/metabolism/etiology ; *Methylmalonic Acid/metabolism ; Podocytes/metabolism/pathology ; Gastrointestinal Microbiome/drug effects ; Disease Models, Animal ; Rats, Sprague-Dawley ; Apoptosis/drug effects ; beta Catenin/metabolism ; Kidney/pathology/metabolism ; }, abstract = {BACKGROUND: Uremia (UR) is caused by increased UR-related toxins in the bloodstream. We explored the mechanism of enterogenous toxin methylmalonic acid (MMA) in calcium-phosphorus metabolic disorder in UR rats via the Wnt/β-catenin pathway.

METHODS: The UR rat model was established by 5/6 nephrectomy. The fecal bacteria of UR rats were transplanted into Sham rats. Sham rats were injected with exogenous MMA or Salinomycin (SAL). Pathological changes in renal/colon tissues were analyzed. MMA concentration, levels of renal function indicators, serum inflammatory factors, Ca[2+]/P[3+], and parathyroid hormone, intestinal flora structure, fecal metabolic profile, intestinal permeability, and glomerular filtration rate (GFR) were assessed. Additionally, rat glomerular podocytes were cultured, with cell viability and apoptosis measured.

RESULTS: Intestinal flora richness and diversity in UR rats were decreased, along with unbalanced flora structure. Among the screened 133 secondary differential metabolites, the MMA concentration rose, showing the most significant difference. UR rat fecal transplantation caused elevated MMA concentration in the serum and renal tissues of Sham rats. The intestinal flora metabolite MMA or exogenous MMA promoted intestinal barrier impairment, increased intestinal permeability, induced glomerular podocyte loss, and reduced GFR, causing calcium-phosphorus metabolic disorder. The intestinal flora metabolite MMA or exogenous MMA induced inflammatory responses and facilitated glomerular podocyte apoptosis by activating the Wnt/β-catenin pathway, which could be counteracted by repressing the Wnt/β-catenin pathway.

CONCLUSIONS: Enterogenous toxin MMA impelled intestinal barrier impairment in UR rats, enhanced intestinal permeability, and activated the Wnt/β-catenin pathway to induce glomerular podocyte loss and reduce GFR, thus aggravating calcium-phosphorus metabolic disorder.}, } @article {pmid39840995, year = {2025}, author = {Hua, D and Yang, Q and Li, X and Zhou, X and Kang, Y and Zhao, Y and Wu, D and Zhang, Z and Li, B and Wang, X and Qi, X and Chen, Z and Cui, G and Hong, W}, title = {The combination of Clostridium butyricum and Akkermansia muciniphila mitigates DSS-induced colitis and attenuates colitis-associated tumorigenesis by modulating gut microbiota and reducing CD8[+] T cells in mice.}, journal = {mSystems}, volume = {}, number = {}, pages = {e0156724}, doi = {10.1128/msystems.01567-24}, pmid = {39840995}, issn = {2379-5077}, abstract = {UNLABELLED: The gut microbiota is closely associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC). Probiotics such as Clostridium butyricum (CB) or Akkermansia muciniphila (AKK) have the potential to treat inflammatory bowel disease (IBD) or colorectal cancer (CRC). However, research on the combined therapeutic effects and immunomodulatory mechanisms of CB and AKK in treating IBD or CRC has never been studied. This study evaluates the potential of co-administration of CB and AKK in treating DSS/AOM-induced IBD and colitis-associated CRC. Our results indicate that compared to mono-administration, the co-administration of CB and AKK not only significantly alleviates symptoms such as weight loss, colon shortening, and increased Disease Activity Index in IBD mice but also regulates the gut microbiota composition and effectively suppresses colonic inflammatory responses. In the colitis-associated CRC mice model, a combination of CB and AKK significantly alleviates weight loss and markedly reduces inflammatory infiltration of macrophages and cytotoxic T lymphocytes (CTLs) in the colon, thereby regulating anti-tumor immunity and inhibiting the occurrence of inflammation-induced CRC. In addition, we found that the combined probiotic therapy of CB and AKK can enhance the sensitivity of colitis-associated CRC mice to the immune checkpoint inhibitor anti-mouse PD-L1 (aPD-L1), significantly improving the anti-tumor efficacy of immunotherapy and the survival rate of colitis-associated CRC mice. Furthermore, fecal microbiota transplantation therapy showed that transplanting feces from CRC mice treated with the co-administration of CB and AKK into other CRC mice alleviated the tumor loads in the colon and significantly extended their survival rate. Our study suggests that the combined use of two probiotics, CB and AKK, can not only alleviate chronic intestinal inflammation but also inhibit the progression to CRC. This may be a natural and relatively safe method to support the gut microbiota and enhance the host's immunity against cancer.

IMPORTANCE: Our study suggests that the combined administration of CB and AKK probiotics, as opposed to a single probiotic strain, holds considerable promise in preventing the advancement of IBD to CRC. This synergistic effect is attributed to the ability of this probiotic combination to more effectively modulate the gut microbiota, curb inflammatory reactions, bolster the efficacy of immunotherapeutic approaches, and optimize treatment results via fecal microbiota transplantation.}, } @article {pmid39840614, year = {2025}, author = {Liu, W and Wang, J and Yang, H and Li, C and Lan, W and Chen, T and Tang, Y}, title = {The Metabolite Indole-3-Acetic Acid of Bacteroides Ovatus Improves Atherosclerosis by Restoring the Polarisation Balance of M1/M2 Macrophages and Inhibiting Inflammation.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2413010}, doi = {10.1002/advs.202413010}, pmid = {39840614}, issn = {2198-3844}, support = {82360105//Innovative Research Group Project of the National Natural Science Foundation of China/ ; 20232ACB206001//Natural Science Foundation of Jiangxi Province/ ; 20223BBG71010//Key Research and Development Program of Jiangxi Province/ ; 2024SSY07061//Jiangxi Province Key Laboratory of bioengineering drugs/ ; }, abstract = {Emerging research has highlighted the significant role of the gut microbiota in atherosclerosis (AS), with microbiota-targeted interventions offering promising therapeutic potential. A central component of this process is gut-derived metabolites, which play a crucial role in mediating the distal functioning of the microbiota. In this study, a comprehensive microbiome-metabolite analysis using fecal and serum samples from patients with atherosclerotic cardiovascular disease and volunteers with risk factors for coronary heart disease and culture histology is performed, and identified the core strain Bacteroides ovatus (B. ovatus). Fecal microbiota transplantation experiments further demonstrated that the gut microbiota significantly influences AS progression, with B. ovatus alone exerting effects comparable to volunteer feces from volunteers. Notably, B. ovatus alleviated AS primarily by restoring the intestinal barrier and enhancing bile acid metabolism, particularly through the production of indole-3-acetic acid (IAA), a tryptophan-derived metabolite. IAA inhibited the TLR4/MyD88/NF-κB pathway in M1 macrophages, promoted M2 macrophage polarisation, and restored the M1/M2 polarisation balance, ultimately reducing aortic inflammation. These findings clarify the mechanistic interplay between the gut microbiota and AS, providing the first evidence that B. ovatus, a second-generation probiotic, can improve bile acid metabolism and reduce inflammation, offering a theoretical foundation for future AS therapeutic applications involving this strain.}, } @article {pmid39840031, year = {2024}, author = {Lim, MY and Hong, S and Nam, YD}, title = {Understanding the role of the gut microbiome in solid tumor responses to immune checkpoint inhibitors for personalized therapeutic strategies: a review.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1512683}, pmid = {39840031}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/immunology ; *Immune Checkpoint Inhibitors/therapeutic use ; *Neoplasms/immunology/therapy/drug therapy/microbiology ; *Precision Medicine ; Animals ; Immunotherapy/methods ; Treatment Outcome ; }, abstract = {Immunotherapy, especially immune checkpoint inhibitor (ICI) therapy, has yielded remarkable outcomes for some patients with solid cancers, but others do not respond to these treatments. Recent research has identified the gut microbiota as a key modulator of immune responses, suggesting that its composition is closely linked to responses to ICI therapy in cancer treatment. As a result, the gut microbiome is gaining attention as a potential biomarker for predicting individual responses to ICI therapy and as a target for enhancing treatment efficacy. In this review, we discuss key findings from human observational studies assessing the effect of antibiotic use prior to ICI therapy on outcomes and identifying specific gut bacteria associated with favorable and unfavorable responses. Moreover, we review studies investigating the possibility of patient outcome prediction using machine learning models based on gut microbiome data before starting ICI therapy and clinical trials exploring whether gut microbiota modulation, for example via fecal microbiota transplantation or live biotherapeutic products, can improve results of ICI therapy in patients with cancer. We also briefly discuss the mechanisms through which the gut microbial-derived products influence immunotherapy effectiveness. Further research is necessary to fully understand the complex interactions between the host, gut microbiota, and immunotherapy and to develop personalized strategies that optimize responses to ICI therapy.}, } @article {pmid39839105, year = {2024}, author = {Correa Lopes, B and Turck, J and Tolbert, MK and Giaretta, PR and Suchodolski, JS and Pilla, R}, title = {Prolonged storage reduces viability of Peptacetobacter (Clostridium) hiranonis and core intestinal bacteria in fecal microbiota transplantation preparations for dogs.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1502452}, pmid = {39839105}, issn = {1664-302X}, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has been described useful as an adjunct treatment for chronic enteropathy in dogs. Different protocols can be used to prepare and store FMT preparations, however, the effect of these methods on microbial viability is unknown. We aimed (1) to assess the viability of several core intestinal bacterial species by qPCR and (2) to assess Peptacetobacter (Clostridium) hiranonis viability through culture to further characterize bacterial viability in different protocols for FMT preparations.

METHODS: Bacterial abundances were assessed in feces from six healthy dogs by qPCR after propidium monoazide (PMA-qPCR) treatment for selective quantitation of viable bacteria. Conservation methods tested included lyophilization (stored at 4°C and at -20°C) and freezing with glycerol-saline solution (12.5%) and without any cryoprotectant (stored at -20°C). Additionally, the abundance of P. hiranonis was quantified using bacterial culture.

RESULTS: Using PMA-qPCR, the viability of Faecalibacterium, Escherichia coli, Streptococcus, Blautia, Fusobacterium, and P. hiranonis was reduced in lyophilized fecal samples kept at 4°C and -20°C up to 6 months (p < 0.05). In frozen feces without cryoprotectant, only Streptococcus and E. coli were not significantly reduced for up to 3 months (p > 0.05). Lastly, no differences were observed in the viability of those species in glycerol-preserved samples up to 6 months (p > 0.05). When using culture to evaluate the viability of P. hiranonis, we observed that P. hiranonis abundance was lower in lyophilized samples kept at 4°C than -20°C; and P. hiranonis abundance was higher in glycerol-preserved samples for up to 6 months than in samples preserved without glycerol for up to 3 months. Moreover, the highest abundance of P. hiranonis was observed in glycerol-preserved feces. After 3 months, P. hiranonis was undetectable by culture in 83% (5/6) of the frozen samples without glycerol.

DISCUSSION: While the lyophilization procedure initially reduced P. hiranonis abundance, P. hiranonis viability was stable thereafter for up to 6 months at -20°C. The higher bacterial viability detected in fecal samples preserved with glycerol confirms the use of this cryoprotectant as a reliable method to keep bacteria alive in the presence of fecal matrix for FMT purposes.}, } @article {pmid39838262, year = {2025}, author = {Ye, J and Shi, R and Wu, X and Fan, H and Zhao, Y and Hu, X and Wang, L and Bo, X and Li, D and Ge, Y and Wang, D and Xia, B and Zhao, Z and Xiao, C and Zhao, B and Wang, Y and Liu, X}, title = {Stevioside mitigates metabolic dysregulation in offspring induced by maternal high-fat diet: the role of gut microbiota-driven thermogenesis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2452241}, doi = {10.1080/19490976.2025.2452241}, pmid = {39838262}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Female ; *Diet, High-Fat/adverse effects ; Pregnancy ; Mice ; *Diterpenes, Kaurane/pharmacology/metabolism ; *Glucosides/pharmacology/metabolism ; *Thermogenesis/drug effects ; *Mice, Inbred C57BL ; Pregnancy in Obesity/metabolism ; Male ; Prenatal Exposure Delayed Effects/microbiology ; Bacteria/classification/metabolism/isolation & purification/genetics/drug effects ; Lactobacillus/metabolism ; Lipid Metabolism/drug effects ; Obesity/metabolism/microbiology ; Dietary Supplements ; }, abstract = {Maternal obesity poses a significant threat to the metabolic profiles of offspring. Microorganisms acquired from the mother early in life critically affect the host's metabolic functions. Natural non-nutritive sweeteners, particularly stevioside (STV), play a crucial role in reducing obesity and affecting gut microbiota composition. Based on this, we hypothesized that maternal STV supplementation could improve the health of mothers and offspring by altering their gut microbiota. Our study found that maternal STV supplementation reduced obesity during pregnancy, decreased abnormal lipid accumulation in offspring mice caused by maternal obesity, and modified the gut microbiota of both dams and offspring, notably increasing the abundance of Lactobacillus apodemi (L. apodemi). Co-housing and fecal microbiota transplant experiments confirmed that gut microbiota mediated the effects of STV on metabolic disorders. Furthermore, treatment with L. apodemi alone replicated the beneficial effects of STV, which were associated with increased thermogenesis. In summary, maternal STV supplementation could alleviate lipid metabolic disorders in offspring by enhancing L. apodemi levels and promoting thermogenic activity, potentially involving changes in bile acid metabolism pathways.}, } @article {pmid39837364, year = {2025}, author = {Liu, H and Yang, S and Zhang, Q and Wang, S and Zhang, B and Xu, Y and Fu, X and Zhou, S and Zhang, P and Wang, H and Di, L and Xu, X and Xu, X and Liu, C and Yang, C and Wang, Y and Jiang, R}, title = {S-ketamine alleviates morphine-induced hyperalgesia via decreasing the gut Enterobacteriaceae levels: Comparison with R-ketamine.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2025.01.022}, pmid = {39837364}, issn = {1873-7544}, abstract = {BACKGROUND: Opioid-induced hyperalgesia (OIH) is a serious complication during the pain treatment. Ketamine has been commonly reported to treat OIH, but the mechanisms remain unclear. Gut microbiota is recently recognized as one of the important mechanisms underlying the occurrence and treatment of OIH. However, whether ketamine enantiomers could alleviate OIH through gut microbiota that still needs to be clarified.

METHODS: The OIH model was established by morphine injection for 3 consecutive days, followed by hierarchical clustering analysis of behavioral results into susceptible or resilient group. Broad-spectrum antibiotic cocktail (ABx) was used to eradicated the gut microbiota of mice. Subsequently, fecal microbiota transplantation (FMT) was performed. S- or R-ketamine was administered as pretreatment 30 min before morphine injection. Fecal samples were collected for 16S rRNA gene sequencing after completion of all behavioral tests.

RESULTS: Approximately 60% of the mice developed OIH after morphine exposure with abnormal locomotion and anxiety-like behaviors. Pseudo germ-free mice treated with ABx did not develop hyperalgesia, whereas pseudo germ-free mice that received fecal microbiota transplantation from OIH mice developed hyperalgesia. Interestingly, S-ketamine but not R-ketamine rescued mice from OIH. The principal co-ordinates analysis (PCoA) suggested that the distribution of gut microbiota differed among the groups. Importantly, levels of Enterobacteriaceae were increased in OIH susceptible group, while decreased after S-ketamine treatment.

CONCLUSION: S-ketamine but not R-ketamine was able to alleviate morphine-induced OIH, and this mechanism is probably related to decreasing the levels of gut Enterobacteriaceae.}, } @article {pmid39836853, year = {2024}, author = {Aristizábal, AM and Montaña, LP and Gutiérrez, J and Medina, D and Franco, AA and Manzi, E and Zapata, ÁD and Mosquera, W}, title = {Intra-mesenteric steroids for steroid-refractory graft-versus-host disease in pediatric patients: A safe option.}, journal = {Biomedica : revista del Instituto Nacional de Salud}, volume = {44}, number = {Sp. 2}, pages = {63-71}, doi = {10.7705/biomedica.7394}, pmid = {39836853}, issn = {2590-7379}, mesh = {Humans ; *Graft vs Host Disease/drug therapy/etiology ; Child ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Adolescent ; Male ; Female ; Child, Preschool ; *Methylprednisolone/therapeutic use/administration & dosage ; Retrospective Studies ; Drug Resistance ; Infant ; Glucocorticoids/therapeutic use ; }, abstract = {INTRODUCTION: Graft-versus-host disease is a serious complication after hematopoietic stem cell transplantation and is a major cause of death post-transplantation. Approximately 50% of acute graft-versus-host disease patients do not respond to systemic steroids and their prognosis is poor regardless of the treatment. This study describes our experience with pediatric patients diagnosed with steroid-refractory graft-versus-host disease who received intra-mesenteric steroid treatment.

OBJECTIVE: To determine the outcomes of intra-mesenteric steroid use in the management of pediatric patients diagnosed with refractory graft-versus-host disease.

MATERIALS AND METHODS: The study included patients under 18 years old with allogeneic hematopoietic stem cell transplantation who underwent intra-mesenteric steroid injection for resistant gastrointestinal graft-versus-host disease between January, 2016, and December, 2021. Methylprednisolone was administered via intra-arterial injection through the celiac trunk and the superior and inferior mesenteric arteries.

RESULTS: We collected data on 21 patients: nine (90%) responded with a subjective decrease in fecal output and a reduction in bilirubin and transaminases. Seven patients required a second intra-mesenteric injection and presented a complete response in 85% of the cases. Only one patient experienced local complications after the procedure. Twelve patients (57%) died with one death due to acute graft-versus-host disease.

CONCLUSION: Reports in the adult population have shown an approximately 50% response rate with few complications, making it a second-line management standard. As far as we know, this is the largest pediatric cohort reported in Latin America. Our findings suggest that intra-mesenteric steroid administration for managing hepatic and gastrointestinal graftversus-host disease may be considered an early adjuvant treatment in patients with steroidrefractory graft-versus-host disease.}, } @article {pmid39836604, year = {2025}, author = {Wu, X and Wei, J and Ran, W and Liu, D and Yi, Y and Gong, M and Liu, X and Gong, Q and Li, H and Gao, J}, title = {The Gut Microbiota-Xanthurenic Acid-Aromatic Hydrocarbon Receptor Axis Mediates the Anticolitic Effects of Trilobatin.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2412234}, doi = {10.1002/advs.202412234}, pmid = {39836604}, issn = {2198-3844}, support = {GCC[2023]042//Guizhou Province/ ; HZ(2024)302//Science and technology project of Zunyi/ ; ZYSE-2022-02//Zunyi Medical University/ ; [2021]1350-037//Talent project of Guizhou platform/ ; 2022(2022JH2/101300058)//Liaoning Province/ ; }, abstract = {Current treatments for ulcerative colitis (UC) remain limited, highlighting the need for novel therapeutic strategies. Trilobatin (TLB), a naturally derived food additive, exhibits potential anti-inflammatory properties. In this study, a dextran sulfate sodium (DSS)-induced animal model is used to investigate the effects of TLB on UC. It is found TLB significantly alleviates DSS-induced UC in mice, as evidenced by a reduction in the disease activity index, an increase in colon length, improvement in histopathological lesions. Furthermore, TLB treatment results in a decrease in proinflammatory cytokines and an increase in anti-inflammatory cytokines. TLB mitigates UC by modulating the intestinal microbiota, particularly Akkermansia, which enhances tryptophan metabolism and upregulates the production of xanthurenic acid (XANA). To confirm the role of TLB-induced microbiota changes, experiments are performed with pseudogerm-free mice and fecal transplantation. It is also identified XANA as a key metabolite that mediates TLB's protective effects. Both TLB and XANA markedly activate the aromatic hydrocarbon receptor (AhR). Administration of an AhR antagonist abrogates their protective effects, thereby confirming the involvement of AhR in the underlying mechanism. In conclusion, the study reveals a novel mechanism through which TLB alleviates UC by correcting microbiota imbalances, regulating tryptophan metabolism, enhancing XANA production, and activating AhR.}, } @article {pmid39834471, year = {2024}, author = {Song, Y and Liu, S and Zhang, L and Zhao, W and Qin, Y and Liu, M}, title = {The effect of gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review and network meta-analysis.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1470185}, pmid = {39834471}, issn = {2296-861X}, abstract = {BACKGROUND: The incidence of NAFLD is increasing. Preclinical evidences indicate that modulation of the gut microbiome could be a promising target in nonalcoholic fatty liver disease.

METHOD: A systematic review and network meta-analysis was conducted to compare the effect of probiotics, synbiotics, prebiotics, fecal microbiota transplant, and antibiotics on the liver-enzyme, metabolic effects and liver-specific in patients with NAFLD. The randomized controlled trails (RCTs), limited to English language were searched from database such as Pubmed, Embase, Web of science and Cochrane Library from inception to November 2024. Review Manager 5.3 was used to to draw a Cochrane bias risk. Inconsistency test and publication-bias were assessed by Stata 14.0. Random effect model was used to assemble direct and indirect evidences. The effects of the intervention were presented as mean differences with 95% confidence interval.

RESULTS: A total of 1921 patients from 37 RCTs were eventually included in our study. 23 RCTs evaluated probiotics, 10 RCTs evaluated synbiotics, 4 RCTs evaluated prebiotics, 3 RCTs evaluated FMT and one RCT evaluated antibiotics. Probiotics and synbiotics were associated with a significantly reduction in alanine aminotransferase [ALT, (MD: -5.09; 95%CI: -9.79, -0.39), (MD: -7.38, 95CI%: -11.94, -2.82)] and liver stiffness measurement by elastograph [LSM, (MD: -0.37;95%CI: -0.49, -0.25), (MD: -1.00;95%CI: -1.59, -0.41)]. In addition to, synbiotics was superior to probiotics in reducing LSM. Synbiotics was associated with a significant reduction of Controlled Attenuation Parameter [CAP, (MD: -39.34; 95%CI: -74.73, -3.95)]. Both probiotics and synbiotics were associated with a significant reduction of aspartate transaminase [AST, (MD: -7.81; 95%CI: -15.49, -0.12), (MD: -13.32; 95%CI: -23, -3.64)]. Probiotics and Allogenic FMT was associated with a significant reduction of Homeostatic Model Assessment for Insulin Resistance [HOMA-IR, (MD: -0.7, 95%CI: -1.26, -0.15), (MD: -1.8, 95%CI: -3.53, - 0.07)]. Probiotics was associated with a significant reduction of body mass index [BMI, MD: -1.84, 95%CI: -3.35, -0.33].

CONCLUSION: The supplement of synbiotics and probiotics maybe a promising way to improve liver-enzyme, LSM, and steatosis in patients with NAFLD. More randomized controlled trials are needed to determine the efficacy of FMT and antibiotics on NAFLD. And the incidence of adverse events of MTTs should be further explored.

https://www.crd.york.ac.uk/prospero/, CRD42023450093.}, } @article {pmid39829898, year = {2025}, author = {Ni, M and Fan, Y and Liu, Y and Li, Y and Qiao, W and Davey, LE and Zhang, XS and Ksiezarek, M and Mead, E and Touracheau, A and Jiang, W and Blaser, MJ and Valdivia, RH and Fang, G}, title = {Epigenetic phase variation in the gut microbiome enhances bacterial adaptation.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, pmid = {39829898}, issn = {2692-8205}, abstract = {The human gut microbiome within the gastrointestinal tract continuously adapts to variations in diet, medications, and host physiology. A central strategy for genetic adaptation is epigenetic phase variation (ePV) mediated by bacterial DNA methylation, which can regulate gene expression, enhance clonal heterogeneity, and enable a single bacterial strain to exhibit variable phenotypic states. Genome-wide and site-specific ePV have been well characterized in human pathogens' antigenic variation and virulence factor production. However, the role of ePV in facilitating adaptation within the human microbiome remains poorly understood. Here, we comprehensively cataloged genome-wide and site-specific ePV in human infant and adult gut microbiomes. First, using long-read metagenomic sequencing, we detected genome-wide ePV mediated by complex structural variations of DNA methyltransferases, highlighting the ones associated with antibiotics or fecal microbiota transplantation. Second, we analyzed an extensive collection of public short-read metagenomic sequencing datasets, uncovering a greater prevalence of genome-wide ePV in the human gut microbiome. Third, we quantitatively detected site-specific ePVs using single-molecule methylation analysis to identify dynamic variations associated with antibiotic treatment or probiotic engraftment. Finally, we performed an in-depth assessment of an Akkermansia muciniphila isolate from an infant, highlighting that ePV can regulate gene expression and enhance the bacterial adaptive capacity by employing a bet-hedging strategy to increase tolerance to differing antibiotics. Our findings indicate that epigenetic modifications are a common and broad strategy used by bacteria in the human gut to adapt to their environment.}, } @article {pmid39829204, year = {2025}, author = {Liu, C and Wong, PY and Barua, N and Li, B and Wong, HY and Zhang, N and Chow, SKH and Wong, SH and Yu, J and Ip, M and Cheung, WH and Duque, G and Brochhausen, C and Sung, JJY and Wong, RMY}, title = {From Clinical to Benchside: Lacticaseibacillus and Faecalibacterium Are Positively Associated With Muscle Health and Alleviate Age-Related Muscle Disorder.}, journal = {Aging cell}, volume = {}, number = {}, pages = {e14485}, doi = {10.1111/acel.14485}, pmid = {39829204}, issn = {1474-9726}, support = {C4032-21GF//Collaborative Research Fund, HKSAR Research Grants Council/ ; 14116223//General Research Fund, HKSAR Research Grants Council/ ; }, abstract = {Sarcopenia is an age-related muscle disorder that increases risks of adverse clinical outcomes, but its treatments are still limited. Gut microbiota is potentially associated with sarcopenia, and its role is still unclear. To investigate the role of gut microbiota in sarcopenia, we first compared gut microbiota and metabolites composition in old participants with or without sarcopenia. Fecal microbiota transplantation (FMT) from human donors to antibiotic-treated recipient mice was then performed. Specific probiotics and their mechanisms to treat aged mice were identified. Old people with sarcopenia had different microbial composition and metabolites, including Paraprevotella, Lachnospira, short-chain fatty acids, and purine. After FMT, mice receiving microbes from people with sarcopenia displayed lower muscle mass and strength compared with those receiving microbes from non-sarcopenic donors. Lacticaseibacillus rhamnosus (LR) and Faecalibacterium prausnitzii (FP) were positively related to muscle health of old people, and enhanced muscle mass and function of aged mice. Transcriptomics showed that genes related to tricarboxylic acid cycle (TCA) were enriched after treatments. Metabolic analysis showed increased substrates of TCA cycle in both LR and FP supernatants. Muscle mitochondria density, ATP content, NAD[+]/NADH, mitochondrial dynamics and biogenesis proteins, as well as colon tight junction proteins of aged mice were improved by both probiotics. LR and the combination of two probiotics also benefit intestinal immune health by reducing CD8[+] IFNγ[+] T cells. Gut microbiota dysbiosis is a pathogenesis of sarcopenia, and muscle-related probiotics could alleviate age-related muscle disorders mainly through mitochondria improvement. Further clinical translation is warranted.}, } @article {pmid39827989, year = {2025}, author = {Cheng, CK and Ye, L and Wang, Y and Wang, YL and Xia, Y and Wong, SH and Chen, S and Huang, Y}, title = {Exercised gut microbiota improves vascular and metabolic abnormalities in sedentary diabetic mice through gut‒vascular connection.}, journal = {Journal of sport and health science}, volume = {}, number = {}, pages = {101026}, doi = {10.1016/j.jshs.2025.101026}, pmid = {39827989}, issn = {2213-2961}, abstract = {BACKGROUND: Exercise elicits cardiometabolic benefits, reducing the risks of cardiovascular diseases and type 2 diabetes. This study aimed to investigate the vascular and metabolic effects of gut microbiota from exercise-trained donors on sedentary mice with type 2 diabetes and the potential mechanism.

METHODS: Leptin receptor-deficient diabetic (db/db) and nondiabetic (db/m[+]) mice underwent running treadmill exercise for 8 weeks, during which fecal microbiota transplantation (FMT) was parallelly performed from exercise-trained to sedentary diabetic (db/db) mice. Endothelial function, glucose homeostasis, physical performance, and vascular signaling of recipient mice were assessed. Vascular and intestinal stresses, including inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, were investigated. RNA sequencing analysis on mouse aortic and intestinal tissues was performed. Gut microbiota profiles of recipient mice were evaluated by metagenomic sequencing.

RESULTS: Chronic exercise improved vascular and metabolic abnormalities in donor mice. Likewise, FMT from exercised donors retarded body weight gain and slightly improved grip strength and rotarod performance in recipient mice. Exercise-associated FMT enhanced endothelial function in different arteries, suppressed vascular and intestinal stresses, and improved glucose homeostasis in recipient mice, with noted microRNA-181b upregulation in aortas and intestines. Altered gut microbiota profiles and gut-derived factors (e.g., short-chain fatty acids and glucagon-like peptide-1) as well as improved intestinal integrity shall contribute to the cardiometabolic benefits, implying a gut‒vascular connection.

CONCLUSION: This proof-of-concept study indicates that exercised microbiota confers cardiometabolic benefits on sedentary db/db mice, extending the beneficial mechanism of exercise through gut‒vascular communication. The findings open up new therapeutic opportunities for cardiometabolic diseases and shed light on the development of exercise mimetics by targeting the gut microbiota.}, } @article {pmid39827465, year = {2025}, author = {Zhang, Y and Hao, R and Chen, J and Huang, K and Li, S and Cao, H and Guan, X}, title = {Gut-Derived Ursodeoxycholic Acid from Saponins of Quinoa Regulated Colitis via Inhibiting the TLR4/NF-κB Pathway.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c09151}, pmid = {39827465}, issn = {1520-5118}, abstract = {Alteration of the gut microbiota and its metabolites plays a key role in the development of inflammatory bowel disease (IBD). Here, we investigated the mechanism of saponins, a byproduct from quinoa (SQ) processing, in regulating IBD. SQ ameliorated gut microbiota dysbiosis revealed by 16S rRNA sequencing and improved colonic antioxidant activities and barrier integrity in dextran sulfate sodium (DSS)-treated mice. Broad-spectrum antibiotics further proved that the gut-protective effects of SQ were mediated by gut microbiota. Next, fecal microbiota transplantation (FMT) of SQ-induced gut microbiota/metabolites to inoculate DSS-treated mice alleviated colitis significantly. Untargeted metabolomics and lipidomics revealed that ursodeoxycholic acid (UDCA) was enriched as a microbial metabolite after SQ supplementation. UDCA was then found to attenuate DSS-induced colitis in vivo by targeting the TLR4/NF-κB pathway, which was also verified in a Caco-2 cell model treated with a TLR4 agonist/antagonist. Overall, our findings established that gut microbiota-UDCA-TLR4/NF-κB signaling plays a key role in mediating the protective effects of SQ.}, } @article {pmid39826789, year = {2025}, author = {Du, X and Liu, L and Yang, L and Zhang, Y and Dong, K and Li, Y and Chen, Y and Yang, Q and Zhu, X and Li, Q}, title = {Cumulative experience meets modern science: Remarkable effects of TongXieYaoFang formula on facilitating intestinal mucosal healing and secretory function.}, journal = {Journal of ethnopharmacology}, volume = {341}, number = {}, pages = {119370}, doi = {10.1016/j.jep.2025.119370}, pmid = {39826789}, issn = {1872-7573}, abstract = {TongXieYaoFang (TXYF), a classical formula used in Traditional Chinese Medicine, is renowned for its efficacy in treating chronic abdominal pain and diarrhoea. Modern research suggests that fundamental relief from these symptoms depends on complete intestinal mucosal healing, which normalises gut secretory functions. Consensus between traditional and modern medical theories indicates that TXYF is particularly suitable for treating the remission phase of ulcerative colitis (UC). Unfortunately, its potential in the remission phase has not received sufficient attention, and its use has been largely limited to a supportive role during the acute phase.

AIM OF THE STUDY: This study aimed to elucidate the efficacy of TXYF in promoting intestinal mucosal healing and enhancing gut secretory function during the non-acute damage phase, as well as to identify the underlying mechanisms contributing to its effects.

METHODS: A mouse model of dextran sulphate sodium salt (DSS)-induced colitis was optimised to specifically evaluate the effects of TXYF on mucosal healing during the repair phase. The effects of TXYF on murine colon function were assessed by measuring faecal pellet count and water content, and further evaluated through immunohistochemical analyses. The underlying mechanisms of action of TXYF were elucidated using mouse intestinal organoid cultures, intestinal stem cell (ISCs) transplantation, immunofluorescence, and western blotting. Active components of TXYF were identified via LC-MS/MS analysis and integrated with network pharmacology for bioinformatics assessment.

RESULTS: TXYF significantly promoted mucosal healing, as reflected by reduced disease activity scores, increased colon length, enhanced epithelial proliferation, and decreased histological damage. Furthermore, TXYF enhanced the recovery of critical intestinal functions, including barrier integrity, absorption, secretion, and motility. Notably, the improvement in the secretory function was particularly pronounced. Mechanistically, these therapeutic effects were mediated by the upregulation of the Atonal homolog 1/SAM pointed domain containing ETS transcription factor/Mucin 2 pathway, which facilitates the differentiation and maturation of ISCs into goblet cells, thereby contributing to both mucosal repair and enhanced secretory function.

CONCLUSIONS: Our study demonstrated that TXYF significantly promotes intestinal mucosal healing and enhances secretory function. These findings offer a solid basis for exploring the potential applications of TXYF in UC management during the remission phase.}, } @article {pmid39809266, year = {2025}, author = {Wang, D and Jiang, Y and Jiang, J and Pan, Y and Yang, Y and Fang, X and Liang, L and Li, H and Dong, Z and Fan, S and Ma, D and Zhang, XS and Li, H and He, Y and Li, N}, title = {Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia.}, journal = {Cell reports. Medicine}, volume = {6}, number = {1}, pages = {101919}, doi = {10.1016/j.xcrm.2024.101919}, pmid = {39809266}, issn = {2666-3791}, mesh = {*Gastrointestinal Microbiome/genetics ; *Autism Spectrum Disorder/metabolism/microbiology/genetics ; *gamma-Aminobutyric Acid/metabolism ; Humans ; Animals ; Female ; Male ; Mice ; Child ; Child, Preschool ; Metabolomics/methods ; RNA, Ribosomal, 16S/genetics ; Escherichia/metabolism/genetics ; Feces/microbiology ; Glutamic Acid/metabolism ; Mice, Inbred C57BL ; Escherichia coli/genetics/metabolism ; Metabolome ; }, abstract = {Gut microbiota (GM) alterations have been implicated in autism spectrum disorder (ASD), yet the specific functional architecture remains elusive. Here, employing multi-omics approaches, we investigate stool samples from two distinct cohorts comprising 203 children with mild ASD or typical development. In our screening cohort, regression-based analysis for metabolomic profiling identifies an elevated γ-aminobutyric acid (GABA) to glutamate (Glu) ratio as a metabolic signature of ASD, independent of age and gender. In the validating cohort, we affirm the GABA/Glu ratio as an ASD diagnostic indicator after adjusting for geography, age, gender, and specific food-consuming frequency. Integrated analysis of metabolomics, 16S rRNA sequencing, and metagenomics reveals a correlation between overrepresented Escherichia and disrupted GABA metabolism. Furthermore, we observe social behavioral impairments in weaning mice transplanted with E. coli, suggesting a potential link to ASD symptomatology. Collectively, these findings provide insights into potential diagnostic and therapeutic strategies aimed at evaluating and restoring gut microbial neurotransmitter homeostasis.}, } @article {pmid39826698, year = {2025}, author = {Song, Y and Cui, Y and Zhong, Y and Wang, Y and Zheng, X}, title = {Fecal microbiota transplantation combined with inulin promotes the development and function of early immune organs in chicks.}, journal = {Journal of biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jbiotec.2025.01.012}, pmid = {39826698}, issn = {1873-4863}, abstract = {Modern management of chicks hinders the vertical transmission of intestinal microbiota, which is closely related to immunity. Inulin is a substrate that can be utilized by the microbiota. This study aimed to determine whether fecal microbiota transplantation (FMT) combined with inulin played a "1+1>2" role in enhancing the development and function of immune organs. Chicks were treated with 1% inulin and/or fecal microbiota suspension on days 1-6. The growth performance, immune organ development, and immune indicators were evaluated on days 7, 14, and 21. Results showed that the combination of FMT and inulin significantly increased the immune organ index on day 7 and promoted the morphological structure and the expression of proliferating cell nuclear antigen (PCNA) in immune organs on days 7, 14, and 21. Each treatment increased the gene expression of interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-2 (IL-2), B cell-activating factor receptor (BAFFR), B cell linker (BLNK), C-X-C Motif Chemokine Ligand 12 (CXCL12), C-X-C Motif Chemokine Receptor 4 (CXCR4), and Biotin (Bu-1) to varying degrees. FMT combined with inulin significantly increased the expression of IgA-positive cells on days 7 and 14. In conclusion, the synergistic effect of FMT and inulin had beneficial impacts on the development and function of immune organs.}, } @article {pmid39826450, year = {2025}, author = {Zhu, Z and Zuo, S and Zhu, Z and Wang, C and Du, Y and Chen, F}, title = {THSWD upregulates the LTF/AMPK/mTOR/Becn1 axis and promotes lysosomal autophagy in hepatocellular carcinoma cells by regulating gut flora and metabolic reprogramming.}, journal = {International immunopharmacology}, volume = {148}, number = {}, pages = {114091}, doi = {10.1016/j.intimp.2025.114091}, pmid = {39826450}, issn = {1878-1705}, abstract = {THSWD has the effect of reducing inflammation, improving microcirculation, and regulating immune status in patients with hepatocellular carcinoma. Regardless of its clear therapeutic effect, the underlying mechanism of action against hepatocellular carcinoma is not clear. To identify critical gut microbiota and its associated metabolites related to THSWD inhibition against hepatocellular carcinoma progression, we assessed the microbe-dependent anti-hepatocellular carcinoma effects of THSWD through 16 s rRNA gene sequencing, fecal microbial transplantation and antibiotic treatment. Metabolic analyses, transcriptomic analyses, and molecular experiments were performed to explore how THSWD modulates the gut microbiota against hepatocellular carcinoma progression. As confirmed by in vivo and in vitro assays, THSWD reduced tumour growth rate and promoted apoptosis in hepatocellular carcinoma cells in hepatocellular carcinoma model mice, and liver and kidney indexes were detected and confirmed the safety of THSWD. Transcriptomic analysis revealed that the targets of THSWD were significantly enriched in multiple lysosomal autophagy signalling pathways, suggesting that lysosomal autophagy is probably associated with THSWD's therapeutic effect. Based on the integrated data analysis, THSWD delays hepatocellular carcinoma progression by increasing the intestinal microbiota Duncaniella and augmenting the metabolite glabrol, and the joint analysis of metabolic and genomic data suggests that this metabolite is associated with lysosomal autophagy, and cellular experiments confirmed that the The differential metabolite glabrol induces apoptosis in hepatocellular carcinoma cells by triggering the lysosomal autophagy-mediated apoptosis signalling pathway. Supplementation with glabrol metabolites up regulates the LTF/AMPK/mTOR/Beclin1 axis and promotes hepatocellular carcinoma cells with lysosomal autophagy and induced apoptosis in hepatocellular carcinoma cells.}, } @article {pmid39826104, year = {2025}, author = {Lin, A and Jiang, A and Huang, L and Li, Y and Zhang, C and Zhu, L and Mou, W and Liu, Z and Zhang, J and Cheng, Q and Wei, T and Luo, P}, title = {From chaos to order: optimizing fecal microbiota transplantation for enhanced immune checkpoint inhibitors efficacy.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2452277}, doi = {10.1080/19490976.2025.2452277}, pmid = {39826104}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Immune Checkpoint Inhibitors/therapeutic use ; *Gastrointestinal Microbiome ; *Neoplasms/therapy/microbiology ; Animals ; Immunotherapy/methods ; Tumor Microenvironment/drug effects ; Treatment Outcome ; Combined Modality Therapy ; }, abstract = {The integration of fecal microbiota transplantation (FMT) with immune checkpoint inhibitors (ICIs) presents a promising approach for enhancing cancer treatment efficacy and overcoming therapeutic resistance. This review critically examines the controversial effects of FMT on ICIs outcomes and elucidates the underlying mechanisms. We investigate how FMT modulates gut microbiota composition, microbial metabolite profiles, and the tumor microenvironment, thereby influencing ICIs effectiveness. Key factors influencing FMT efficacy, including donor selection criteria, recipient characteristics, and administration protocols, are comprehensively discussed. The review delineates strategies for optimizing FMT formulations and systematically monitoring post-transplant microbiome dynamics. Through a comprehensive synthesis of evidence from clinical trials and preclinical studies, we elucidate the potential benefits and challenges of combining FMT with ICIs across diverse cancer types. While some studies report improved outcomes, others indicate no benefit or potential adverse effects, emphasizing the complexity of host-microbiome interactions in cancer immunotherapy. We outline critical research directions, encompassing the need for large-scale, multi-center randomized controlled trials, in-depth microbial ecology studies, and the integration of multi-omics approaches with artificial intelligence. Regulatory and ethical challenges are critically addressed, underscoring the imperative for standardized protocols and rigorous long-term safety assessments. This comprehensive review seeks to guide future research endeavors and clinical applications of FMT-ICIs combination therapy, with the potential to improve cancer patient outcomes while ensuring both safety and efficacy. As this rapidly evolving field advances, maintaining a judicious balance between openness to innovation and cautious scrutiny is crucial for realizing the full potential of microbiome modulation in cancer immunotherapy.}, } @article {pmid39825784, year = {2025}, author = {Zhang, R and Sun, X and Lu, H and Zhang, X and Zhang, M and Ji, X and Yu, X and Tang, C and Wu, Z and Mao, Y and Zhu, J and Ji, M and Yang, Z}, title = {Akkermansia muciniphila Mediated the Preventive Effect of Disulfiram on Acute Liver Injury via PI3K/Akt Pathway.}, journal = {Microbial biotechnology}, volume = {18}, number = {1}, pages = {e70083}, pmid = {39825784}, issn = {1751-7915}, support = {2024YQFH05//"YiQi''funding project/ ; }, mesh = {*Akkermansia ; *Phosphatidylinositol 3-Kinases/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Proto-Oncogene Proteins c-akt/metabolism ; Animals ; *Disulfiram/pharmacology ; *RNA, Ribosomal, 16S/genetics ; *Chemical and Drug Induced Liver Injury/prevention & control ; Male ; Apoptosis/drug effects ; Signal Transduction/drug effects ; Disease Models, Animal ; Hepatocytes/drug effects ; Mice ; DNA, Ribosomal/genetics/chemistry ; }, abstract = {Acetaminophen induced acute liver injury (ALI) has a high incidence and is a serious medical problem, but there is a lack of effective treatment. The enterohepatic axis is one of the targets of recent attention due to its important role in liver diseases. Disulfiram (DSF) is a multitarget drug that has been proven to play a role in a variety of liver diseases and can affect intestinal flora, but whether it can alleviate ALI is not clear. We utilised bacterial 16S rRNA gene profiling, antimicrobial treatments, and faecal microbiota transplantation tests to explore whether DSF therapy for ALI is dependent on gut microbiota. Our findings indicate that DSF primarily restores intestinal microbiome balance by modulating the abundance of Akkermansia muciniphila (A. muciniphila), leading to significant alleviation of ALI symptoms in a gut microbiota dependent manner. We also found that A. muciniphila can promote the activation of PI3K/Akt pathway, correct the Bcl-2/Bax ratio, and further inhibit hepatocyte apoptosis. In conclusion, DSF ameliorates ALI by modulating the intestinal microbiome and activating the PI3K/AKT pathway through A. muciniphila.}, } @article {pmid39824679, year = {2025}, author = {Elyas, S and Barata, P and Vaishampayan, U}, title = {Clinical Applications of Microbiome in Renal Cell Carcinoma.}, journal = {European urology focus}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.euf.2024.12.006}, pmid = {39824679}, issn = {2405-4569}, abstract = {Advancements in microbiome research reveal its impact on cancer treatment outcomes, particularly in renal cell carcinoma (RCC). While immune checkpoint inhibitors (ICIs) have improved survival in metastatic RCC, composition of the gut microbiome has the potential to influence their efficacy. Antibiotic-induced microbiome disruptions correlate with diminished outcomes, while strains such as Akkermansia muciniphila, Clostridium butyricum, and others enhance immune responses and progression-free survival. Some prebiotics such as inulin gel can alter the gut flora to overcome the resistant strains occurring in response to immune therapy. This mini-review explores microbiome-targeted interventions, such as pre/probiotics and fecal microbiota transplantation, for overcoming ICI resistance. Although promising, prospective randomized trials are needed to standardize clinical applications and optimize microbiome-targeted treatments. The standard use of gut-modulating therapy cannot be recommended at present outside of clinical trials. A double-blind placebo-controlled randomized trial of ICI ± gut modulating therapy is being planned in frontline therapy of advanced RCC (BIOFRONT trial by the Southwest Oncology Group).}, } @article {pmid39821840, year = {2025}, author = {Vinterberg, JE and Oddsdottir, J and Nye, M and Pinton, P}, title = {Management of Recurrent Clostridioides difficile Infection (rCDI): A Systematic Literature Review to Assess the Feasibility of Indirect Treatment Comparison (ITC).}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, pmid = {39821840}, issn = {2193-8229}, abstract = {Recurrent Clostridioides difficile infection (rCDI) is a major cause of increased morbidity, mortality, and healthcare costs. Fecal-microbiota-based therapies are recommended for rCDI on completion of standard-of-care (SoC) antibiotics to prevent further recurrence: these therapies include conventional fecal-microbiota transplantation and the US Food and Drug Administration-approved therapies REBYOTA® (RBL) and VOWST Oral Spores™ (VOS). As an alternative to microbiota-based therapies, bezlotoxumab, a monoclonal antibody, is used as adjuvant to SoC antibiotics to prevent rCDI. There are no head-to-head clinical trials comparing different microbiota-based therapies or bezlotoxumab for rCDI. To address this gap, we conducted a systematic literature review to identify clinical trials on rCDI treatments and assess the feasibility of using them to conduct an indirect treatment comparison (ITC). The feasibility analysis determined that trial heterogeneity, particularly relating to inclusion criteria, may significantly compromise ITC and prevent cross-trial comparisons. Our analysis underlines the need to adopt standardized protocols to ensure comparability across trials.}, } @article {pmid39821715, year = {2025}, author = {Berry, P and Khanna, S}, title = {The evolving landscape of live biotherapeutics in the treatment of Clostridioides difficile infection.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, pmid = {39821715}, issn = {0975-0711}, abstract = {Clostridioides difficile (C. difficile) infection (CDI) is common after antibiotic exposure and presents significant morbidity, mortality and healthcare costs worldwide. The rising incidence of recurrent CDI, driven by hypervirulent strains, widespread antibiotic use and increased community transmission, has led to an urgent need for novel therapeutic strategies. Conventional antibiotic treatments, although effective, face limitations due to rising antibiotic resistance and high recurrence rates, which can reach up to 60% after multiple infections. This has prompted exploration of alternative therapies such as fecal microbiota-based therapies, including fecal microbiota transplantation (FMT) and live biotherapeutics (LBPs), which demonstrate superior efficacy in preventing recurrence. They are aimed at restoring the gut microbiota. Fecal microbiota, live-jslm and fecal microbiota spores, live-brpk have been approved by the U.S. Food and Drug Administration in individuals aged 18 years or older for recurrent CDI after standard antimicrobial treatment. They have demonstrated high efficacy and a favorable safety profile in clinical trials. Another LBP under study includes VE-303, which is not derived from human donor stool. This review provides a comprehensive overview of the current therapeutic landscape for CDI, including its epidemiology, pathophysiology, risk factors, diagnostic modalities and treatment strategies. The review delves into the emerging role of live biotherapeutics, with a particular focus on fecal microbiota-based therapies. We explore their development, mechanisms of action, clinical applications and potential to revolutionize CDI management.}, } @article {pmid39821305, year = {2025}, author = {Shi, L and Duan, Y and Fang, N and Zhang, N and Yan, S and Wang, K and Hou, T and Wang, Z and Jiang, X and Gao, Q and Zhang, S and Li, Y and Zhang, Y and Gong, Y}, title = {Lactobacillus gasseri prevents ibrutinib-associated atrial fibrillation through butyrate.}, journal = {Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology}, volume = {}, number = {}, pages = {}, doi = {10.1093/europace/euaf018}, pmid = {39821305}, issn = {1532-2092}, abstract = {Ibrutinib, a widely used anti-cancer drug, is known to significantly increase the susceptibility to atrial fibrillation (AF). While it is recognized that drugs can reshape the gut microbiota, influencing both therapeutic effectiveness and adverse events, the role of gut microbiota in ibrutinib-induced AF remains largely unexplored. Utilizing 16S rRNA gene sequencing, fecal microbiota transplantation, metabonomics, electrophysiological examination, and molecular biology methodologies, we sought to validate the hypothesis that gut microbiota dysbiosis promotes ibrutinib-associated AF and to elucidate the underlying mechanisms. We found that ibrutinib administration predisposes rats to AF. Interestingly, ibrutinib-associated microbial transplantation conferred increased susceptibility to AF in rats. Notably, ibrutinib induced a significantly decrease in the abundance of Lactobacillus gasseri (L. gasseri), and oral supplementation of L. gasseri or its metabolite, butyrate, effectively prevented rats from ibrutinib-induced AF. Mechanistically, butyrate inhibits the generation of reactive oxygen species (ROS), thereby ameliorating atrial structural remodeling. Furthermore, we demonstrated that ibrutinib inhibited the growth of L. gasseri by disrupting the intestinal barrier integrity. Collectively, our findings provide compelling experimental evidence supporting the potential efficacy of targeting gut microbes in preventing ibrutinib-associated AF, opening new avenues for therapeutic interventions.}, } @article {pmid39747680, year = {2025}, author = {Menon, R and Bhattarai, SK and Crossette, E and Prince, AL and Olle, B and Silber, JL and Bucci, V and Faith, J and Norman, JM}, title = {Multi-omic profiling a defined bacterial consortium for treatment of recurrent Clostridioides difficile infection.}, journal = {Nature medicine}, volume = {31}, number = {1}, pages = {223-234}, pmid = {39747680}, issn = {1546-170X}, mesh = {*Clostridium Infections/therapy/microbiology ; Humans ; *Clostridioides difficile ; *Recurrence ; *Gastrointestinal Microbiome ; *Anti-Bacterial Agents/therapeutic use ; Feces/microbiology ; Male ; Female ; Fecal Microbiota Transplantation ; Middle Aged ; Bile Acids and Salts/metabolism ; Adult ; Aged ; Multiomics ; }, abstract = {Donor-derived fecal microbiota treatments are efficacious in preventing recurrent Clostridioides difficile infection (rCDI), but they have inherently variable quality attributes, are difficult to scale and harbor the risk of pathogen transfer. In contrast, VE303 is a defined consortium of eight purified, clonal bacterial strains developed for prevention of rCDI. In the phase 2 CONSORTIUM study, high-dose VE303 was well tolerated and reduced the odds of rCDI by more than 80% compared to placebo. VE303 organisms robustly colonized the gut in the high-dose group and were among the top taxa associated with non-recurrence. Multi-omic modeling identified antibiotic history, baseline stool metabolites and serum cytokines as predictors of both on-study CDI recurrence and VE303 colonization. VE303 potentiated early recovery of the host microbiome and metabolites with increases in short-chain fatty acids, secondary bile acids and bile salt hydrolase genes after antibiotic treatment for CDI, which is considered important to prevent CDI recurrences. These results support the idea that VE303 promotes efficacy in rCDI through multiple mechanisms.}, } @article {pmid39816955, year = {2025}, author = {Wang, Q and Ji, J and Xiao, S and Wang, J and Yan, X and Fang, L}, title = {Explore Alteration of Lung and Gut Microbiota in a Murine Model of OVA-Induced Asthma Treated by CpG Oligodeoxynucleotides.}, journal = {Journal of inflammation research}, volume = {18}, number = {}, pages = {445-461}, pmid = {39816955}, issn = {1178-7031}, abstract = {AIM: We sought to investigate the impact of CpG oligodeoxynucleotides (CpG-ODN) administration on the lung and gut microbiota in asthmatic mice, specifically focusing on changes in composition, diversity, and abundance, and to elucidate the microbial mechanisms underlying the therapeutic effects of CpG-ODN and identify potential beneficial bacteria indicative of its efficacy.

METHODS: HE staining were used to analyze inflammation in lung, colon and small intestine tissues. High-throughput sequencing technology targeting 16S rRNA was employed to analyze the composition, diversity, and correlation of microbiome in the lung, colon and small intestine of control, model and CpG-ODN administration groups.

RESULTS: (1) Histopathologically, both lung and intestinal tissue in asthmatic mice exhibited significant structural damage and inflammatory response, whereas the structure of both lung and intestinal tissue approached normal levels, accompanied by a notable improvement in the inflammatory response after CpG-ODN treatment. (2) In the specific microbiota composition analysis, bacterial dysbiosis observed in the asthmatic mice, accompanied by enrichment of Proteobacteria found to cause lung and intestinal epithelial damage and inflammatory reaction. After CpG-ODN administration, bacterial dysbiosis was improved, and a notable enrichment of beneficial bacteria, indicating a novel microecology. Meanwhile Oscillospira and Clostridium were identified as two biomarkers of the CpG-ODN treatment. (3) Heatmap analysis revealed significant correlations among lung, small intestine, and colon microbiota.

CONCLUSION: CpG-ODN treatment can ameliorate OVA-induced asthma in mice. One side, preserving the structural integrity of the lung and intestine, safeguarding the mucosal physical barrier, the other side, improving the dysbiosis of lung and gut microbiota in asthmatic mice. Beneficial bacteria and metabolites take up microecological advantages, regulate immune cells and participate in the mucosal immune response to protect the immune barrier. Meanwhile, Oscillospira and Clostridium as biomarkers for CpG-ODN treatment, has reference significance for exploring precise Fecal microbiota transplantation treatment for asthma.}, } @article {pmid39814666, year = {2025}, author = {Shekhar, S and Schwarzer, M and Dhariwal, A and Petersen, FC}, title = {Nasal microbiota transplantation: a gateway to novel treatments.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2024.12.010}, pmid = {39814666}, issn = {1878-4380}, abstract = {Two recent studies have highlighted the potential of nasal microbiota transplantation (NMT) to treat chronic rhinosinusitis (CRS). Here we evaluate these findings and propose that lessons from fecal microbiota transplantation (FMT) could guide NMT development, with possible implications for combating antimicrobial resistance in respiratory infections.}, } @article {pmid39813598, year = {2025}, author = {Ren, M and Xia, Y and Pan, H and Zhou, X and Yu, M and Ji, F}, title = {Duodenal-jejunal bypass ameliorates MASLD in rats by regulating gut microbiota and bile acid metabolism through FXR pathways.}, journal = {Hepatology communications}, volume = {9}, number = {2}, pages = {}, pmid = {39813598}, issn = {2471-254X}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Receptors, Cytoplasmic and Nuclear/metabolism ; Rats ; *Bile Acids and Salts/metabolism ; *Duodenum/surgery/metabolism/microbiology ; Male ; *Fecal Microbiota Transplantation ; Jejunum/surgery/metabolism ; Rats, Sprague-Dawley ; Disease Models, Animal ; Fatty Liver/metabolism ; Anti-Bacterial Agents/pharmacology ; Diet, High-Fat ; Gastric Bypass ; Insulin Resistance ; }, abstract = {BACKGROUND: Although bariatric and metabolic surgical methods, including duodenal-jejunal bypass (DJB), were shown to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in clinical trials and experimental rodent models, their underlying mechanisms remain unclear. The present study therefore evaluated the therapeutic effects and mechanisms of action of DJB in rats with MASLD.

METHODS: Rats with MASLD were randomly assigned to undergo DJB or sham surgery. Rats were orally administered a broad-spectrum antibiotic cocktail (Abx) or underwent fecal microbiota transplantation to assess the role of gut microbiota in DJB-induced improvement of MASLD. Gut microbiota were profiled by 16S rRNA gene sequencing and metagenomic sequencing, and bile acids (BAs) were analyzed by BA-targeted metabolomics.

RESULTS: DJB alleviated hepatic steatosis and insulin resistance in rats with diet-induced MASLD. Abx depletion of bacteria abrogated the ameliorating effects of DJB on MASLD. Fecal microbiota transplantation from rats that underwent DJB improved MASLD in high-fat diet-fed recipients by reshaping the gut microbiota, especially by significantly reducing the abundance of Clostridium. This, in turn, suppressed secondary BA biosynthesis and activated the hepatic BA receptor, farnesoid X receptor. Inhibition of farnesoid X receptor attenuated the ameliorative effects of post-DJB microbiota on MASLD.

CONCLUSIONS: DJB ameliorates MASLD by regulating gut microbiota and BA metabolism through hepatic farnesoid X receptor pathways.}, } @article {pmid39812804, year = {2025}, author = {Sobral, J and Empadinhas, N and Esteves, AR and Cardoso, SM}, title = {Impact of Nutrition on the Gut Microbiota: Implications for Parkinson's Disease.}, journal = {Nutrition reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/nutrit/nuae208}, pmid = {39812804}, issn = {1753-4887}, support = {//Portuguese national funds/ ; //FCT/ ; }, abstract = {Parkinson's disease (PD) is a multifactorial neurodegenerative disease that is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta and by the anomalous accumulation of α-synuclein aggregates into Lewy bodies and Lewy neurites. Research suggests 2 distinct subtypes of PD: the brain-first subtype if the pathology arises from the brain and then spreads to the peripheral nervous system (PNS) and the body-first subtype, where the pathological process begins in the PNS and then spreads to the central nervous system. This review primarily focuses on the body-first subtype. The influence of the gut microbiota on the development of PD has been the subject of growing interest among researchers. It has been suggested that gut inflammation may be closely associated with pathogenesis in PD, therefore leading to the hypothesis that gut microbiota modulation could play a significant role in this process. Nutrition can influence gut health and alter the risk and progression of PD by altering inflammatory markers. This review provides an overview of recent research that correlates variations in gut microbiota composition between patients with PD and healthy individuals with the impact of certain nutrients and dietary patterns, including the Mediterranean diet, the Western diet, and the ketogenic diet. It explores how these diets influence gut microbiota composition and, consequently, the risk of PD. Last, it examines fecal transplantation and the use of prebiotics, probiotics, or synbiotics as potential therapeutic strategies to balance the gut microbiome, aiming to reduce the risk or delay the progression of PD.}, } @article {pmid39812540, year = {2025}, author = {Cerna, C and Vidal-Herrera, N and Silva-Olivares, F and Álvarez, D and González-Arancibia, C and Hidalgo, M and Aguirre, P and González-Urra, J and Astudillo-Guerrero, C and Jara, M and Porras, O and Cruz, G and Hodar, C and Llanos, P and Urrutia, P and Ibacache-Quiroga, C and Nevzorova, Y and Cubero, FJ and Fuenzalida, M and Thomas-Valdés, S and Jorquera, G}, title = {Fecal Microbiota Transplantation from Young-Trained Donors Improves Cognitive Function in Old Mice Through Modulation of the Gut-Brain Axis.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1089}, pmid = {39812540}, issn = {2152-5250}, abstract = {The gut-brain axis is a bidirectional communication pathway that modulates cognitive function. A dysfunctional gut-brain axis has been associated with cognitive impairments during aging. Therefore, we propose evaluating whether modulation of the gut microbiota through fecal microbiota transplantation (FMT) from young-trained donors (YT) to middle-aged or aged mice could enhance brain function and cognition in old age. Twelve-month-old male mice received an initial FMT from YT (YT-Tr) or age-matched donors (Auto-Tr) following antibiotic treatment. Three months later, the mice received a second FMT as reinforcement. Additionally, 18-month-old mice received Auto-Tr, YT-Tr, or FMT from young sedentary donors (YS-Tr). Cognitive function was assessed using novel object recognition and object location memory tests. Long-term potentiation (LTP) in hippocampal brain slices was studied, while neuroinflammation and synaptic plasticity were analyzed in hippocampal samples via qPCR and immunoblot. Gut permeability was evaluated in ileum and colon sections, serum samples were analyzed for cytokine levels, and fecal samples were used to measure short-chain fatty acid (SCFA) levels and perform 16S rRNA gene sequencing. We observed that YT-Tr, whether performed in middle age or old age, improved cognitive function in aged mice. Recognition and spatial memory were significantly enhanced in YT-Tr mice compared to Auto-Tr and YS-Tr groups. Intact LTP was observed in YT-Tr mice at 18 months of age, whereas LTP was impaired in the Auto-Tr group. Neuroinflammation was reduced, and synaptic plasticity modulators such as PSD-95 and FNDC5/Irisin were upregulated in the hippocampus of YT-Tr mice compared to both YS-Tr and Auto-Tr groups. A significant reduction in ileal and colon permeability was detected in YT-Tr animals, along with elevated cecal levels of butyrate and valerate compared to Auto-Tr. Moreover, YT-Tr decreased pro-inflammatory factors and increased anti-inflammatory factors in the serum of aged mice. Beta diversity analysis revealed significant differences in microbial community composition between YT-Tr and Auto-Tr animals, with higher abundances of Akkermansia, Prevotellaceae_UCG-001, and Odoribacter in YT-Tr mice. In conclusion, our study demonstrates that FMT from young-trained donors improves cognitive function and synaptic plasticity by modulating gut permeability, inflammation, SCFA levels, and gut microbiota composition in aged mice.}, } @article {pmid39812347, year = {2025}, author = {Gustafson, KL and Rodriguez, TR and McAdams, ZL and Coghill, LM and Ericsson, AC and Franklin, CL}, title = {Failure of colonization following gut microbiota transfer exacerbates DSS-induced colitis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447815}, pmid = {39812347}, issn = {1949-0984}, support = {T32 GM008396/GM/NIGMS NIH HHS/United States ; T32 OD011126/OD/NIH HHS/United States ; U42 OD010918/OD/NIH HHS/United States ; }, mesh = {Animals ; *Gastrointestinal Microbiome ; *Colitis/microbiology/chemically induced/pathology ; *Dextran Sulfate ; Mice ; *Disease Models, Animal ; *Mice, Inbred C57BL ; *Fecal Microbiota Transplantation ; Bacteria/classification/isolation & purification/genetics/metabolism ; Female ; Specific Pathogen-Free Organisms ; Feces/microbiology ; Inflammatory Bowel Diseases/microbiology ; Male ; }, abstract = {To study the impact of differing specific pathogen-free gut microbiomes (GMs) on a murine model of inflammatory bowel disease, selected GMs were transferred using embryo transfer (ET), cross-fostering (CF), and co-housing (CH). Prior work showed that the GM transfer method and the microbial composition of donor and recipient GMs can influence microbial colonization and disease phenotypes in dextran sodium sulfate-induced colitis. When a low richness GM was transferred to a recipient with a high richness GM via CH, the donor GM failed to successfully colonize, and a more severe disease phenotype resulted when compared to ET or CF, where colonization was successful. By comparing CH and gastric gavage for fecal material transfer, we isolated the microbial component of this effect and determined that differences in disease severity and survival were associated with microbial factors rather than the transfer method itself. Mice receiving a low richness GM via CH and gastric gavage exhibited greater disease severity and higher expression of pro-inflammatory immune mediators compared to those receiving a high richness GM. This study provides valuable insights into the role of GM composition and colonization in disease modulation.}, } @article {pmid39812329, year = {2025}, author = {Zhang, Y and Wang, A and Zhao, W and Qin, J and Zhang, Y and Liu, B and Yao, C and Long, J and Yuan, M and Yan, D}, title = {Microbial succinate promotes the response to metformin by upregulating secretory immunoglobulin a in intestinal immunity.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2450871}, pmid = {39812329}, issn = {1949-0984}, mesh = {*Metformin/pharmacology ; Animals ; *Immunoglobulin A, Secretory/metabolism ; Mice ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Succinic Acid/metabolism ; Up-Regulation/drug effects ; Diabetes Mellitus, Type 2/immunology/drug therapy/metabolism/microbiology ; Bacteroides thetaiotaomicron/drug effects ; Intestines/immunology/microbiology/drug effects ; Male ; Fecal Microbiota Transplantation ; Female ; Hypoglycemic Agents/pharmacology ; Mice, Inbred C57BL ; Mice, Knockout ; }, abstract = {Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus; however, many patients respond poorly to this drug in clinical practice. The potential involvement of microbiota-mediated intestinal immunity and related signals in metformin responsiveness has not been previously investigated. In this study, we successfully constructed a humanized mouse model by fecal transplantation of the gut microbiota from clinical metformin-treated - responders and non-responders, and reproduced the difference in clinical phenotypes of responsiveness to metformin. The abundance of Bacteroides thetaiotaomicron, considered a representative differential bacterium of metformin responsiveness, and the level of secretory immunoglobulin A (SIgA) in intestinal immunity increased significantly in responder recipient mice following metformin treatment. In contrast, no significant alterations in B. thetaiotaomicron and SIgA were observed in non-responder recipient mice. The study of IgA[-/-] mice confirmed that downregulated expression or deficiency of SIgA resulted in non-response to metformin, meaning that metformin was unable to improve dysfunctional glucose metabolism and reduce intestinal and adipose tissue inflammation, ultimately leading to systemic insulin resistance. Furthermore, supplementation with succinate, a microbial product of B. thetaiotaomicron, potentially reversed the non-response to metformin by inducing the production of SIgA. In conclusion, we demonstrated that upregulated SIgA, which could be regulated by succinate, was functionally involved in metformin response through its influence on immune cell-mediated inflammation and insulin resistance. Conversely, an inability to regulate SIgA may result in a lack of response to metformin.}, } @article {pmid39812000, year = {2025}, author = {Zhao, H and Fu, X and Wang, Y and Shang, Z and Li, B and Zhou, L and Liu, Y and Liu, D and Yi, B}, title = {Therapeutic Potential of Vanillic Acid in Ulcerative Colitis Through Microbiota and Macrophage Modulation.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e202400785}, doi = {10.1002/mnfr.202400785}, pmid = {39812000}, issn = {1613-4133}, support = {81760587//National Natural Science Foundation of China/ ; 81760731)//National Natural Science Foundation of China/ ; }, abstract = {This study investigated the protective effects of the dietary polyphenol vanillic acid (VA) on dextran sulfate sodium-induced acute ulcerative colitis (UC) in mice, focusing on its impact on the gut microbiota and inflammatory responses. VA was supplemented following dextran sulfate sodium administration, and key indicators, including body weight, disease activity index, colon length, spleen index, and inflammatory markers, were assessed. VA supplementation significantly alleviated UC symptoms, preserved intestinal barrier integrity, and reduced pro-inflammatory cytokine levels. Additionally, VA positively altered the gut microbiota composition, promoting beneficial bacteria such as Akkermansia muciniphila while suppressing the arachidonic acid metabolism pathway. Fecal microbiota transplantation confirmed that the VA-modified gut microbiota contributed to these protective effects. VA also facilitated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, further mitigating inflammation. These findings highlight the potential of VA as a natural dietary intervention for UC, emphasizing its role in regulating the gut microbiota and inflammatory pathways, which may have significant nutritional relevance in managing inflammatory bowel diseases.}, } @article {pmid39816646, year = {2023}, author = {Karukappadath, RM and Sirbu, D and Zaky, A}, title = {Drug-resistant bacteria in the critically ill: patterns and mechanisms of resistance and potential remedies.}, journal = {Frontiers in antibiotics}, volume = {2}, number = {}, pages = {1145190}, pmid = {39816646}, issn = {2813-2467}, abstract = {Antimicrobial resistance in the intensive care unit is an ongoing global healthcare concern associated with high mortality and morbidity rates and high healthcare costs. Select groups of bacterial pathogens express different mechanisms of antimicrobial resistance. Clinicians face challenges in managing patients with multidrug-resistant bacteria in the form of a limited pool of available antibiotics, slow and potentially inaccurate conventional diagnostic microbial modalities, mimicry of non-infective conditions with infective syndromes, and the confounding of the clinical picture of organ dysfunction associated with sepsis with postoperative surgical complications such as hemorrhage and fluid shifts. Potential remedies for antimicrobial resistance include specific surveillance, adequate and systematic antibiotic stewardship, use of pharmacokinetic and pharmacodynamic techniques of therapy, and antimicrobial monitoring and adequate employment of infection control policies. Novel techniques of combating antimicrobial resistance include the use of aerosolized antibiotics for lung infections, the restoration of gut microflora using fecal transplantation, and orally administered probiotics. Newer antibiotics are urgently needed as part of the armamentarium against multidrug-resistant bacteria. In this review we discuss mechanisms and patterns of microbial resistance in a select group of drug-resistant bacteria, and preventive and remedial measures for combating antibiotic resistance in the critically ill.}, } @article {pmid39811933, year = {2025}, author = {Zhang, L and Wang, K and Huang, L and Deng, B and Chen, C and Zhao, K and Wang, W}, title = {Ganoderic Acid A Alleviates Severe Acute Pancreatitis by Modulating Gut Homeostasis and Inhibiting TLR4-NLRP3 Signaling.}, journal = {Journal of agricultural and food chemistry}, volume = {73}, number = {2}, pages = {1563-1579}, pmid = {39811933}, issn = {1520-5118}, mesh = {Animals ; *Toll-Like Receptor 4/metabolism/genetics ; Mice ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism/genetics ; *Signal Transduction/drug effects ; *Pancreatitis/drug therapy/metabolism/immunology ; Male ; *Mice, Inbred C57BL ; Humans ; *Gastrointestinal Microbiome/drug effects ; *Homeostasis/drug effects ; *Heptanoic Acids/pharmacology ; Mice, Knockout ; Pancreas/immunology/metabolism/drug effects ; Rats ; Lanosterol/analogs & derivatives ; }, abstract = {Background Severe acute pancreatitis (SAP) manifests as a critical state marked by acute abdominal symptoms, often associated with intestinal barrier dysfunction, exacerbating SAP retroactively. Ganoderic acid A (GAA) demonstrates anti-inflammatory properties in various inflammatory disorders. Nonetheless, its potential therapeutic impact on SAP and the underlying mechanisms remain unexplored. Methods In both wild-type and TLR4[-/-] mice, experimental SAP was induced using caerulein plus lipopolysaccharide. Caerulein injections were administered intraperitoneally following 7 days of intragastric GAA administration. Additionally, the potential mechanisms by which GAA ameliorates SAP were further investigated using fecal microbiota transplantation and TLR4-overexpressing IEC-6 cells. Results We observed that GAA treatment significantly ameliorated serum levels of amylase, lipase, and pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in SAP mice. Pretreatment with GAA mitigated pathological injuries and reduced M1 macrophage and neutrophil infiltration in pancreatic or ileal tissues. Additionally, GAA treatment down-regulated TLR4-MAPK/NF-κB signaling and NLRP3 inflammasome activation in the pancreatic and ileal tissues of SAP mice. The results further revealed that the gavage of GAA decreased bacterial translocation (Escherichia coli and EUB338), repaired intestinal barrier dysfunction (ZO-1, occludin, DAO, and FITC), increased lysozyme and MUC2 expression, and raised the levels of short-chain fatty acids. Analysis of the gut microbiome showed that the beneficial effects of GAA treatment were associated with improvements in pancreatitis-associated gut microbiota dysbiosis, characterized by notable increases in α-diversity and the abundance of probiotics such as Akkermansia, GCA-900066575, and Parvibacter. Fecal transplantation experiments further confirmed that GAA exerts protective effects by modulating intestinal flora. The protective role of GAA in intestinal and pancreatic injuries is mediated by the inhibition of TLR4 signaling, as further evidenced in TLR4-deficient mice and TLR4-overexpressed IEC-6 cells. The results of docking indicated that GAA interacts with TLR4 via a hydrophobic interaction. Conclusions The study demonstrates that GAA significantly alleviates SAP through its anti-inflammatory and antioxidant capacities, as well as by restoring intestinal homeostasis, thereby providing insights into novel treatments for SAP.}, } @article {pmid39811913, year = {2025}, author = {Ribeiro, G and Schellekens, H and Cuesta-Marti, C and Maneschy, I and Ismael, S and Cuevas-Sierra, A and Martínez, JA and Silvestre, MP and Marques, C and Moreira-Rosário, A and Faria, A and Moreno, LA and Calhau, C}, title = {A Menu for Microbes: Unraveling Appetite Regulation and Weight Dynamics Through the Microbiota-Brain Connection Across the Lifespan.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00227.2024}, pmid = {39811913}, issn = {1522-1547}, support = {UIDB/4255/2020//Centro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS)/ ; UIDP/4255/2020//Centro de Investigação em Tecnologias e Serviços de Saúde (CINTESIS)/ ; UIDP/04923/2020//Comprehensive Health Research Centre/ ; UIDB/04923/2020//Comprehensive Health Research Centre/ ; SFI/12/RC/2273 _P2//Science Foundation Ireland (SFI)/ ; TC20180025//Food for Health Ireland EI Technology Centre/ ; GOIPG/2023/4836//Irish Research Council (IrishResearch)/ ; CD22/00011//Ministerio de Ciencia e Innovación (MCIN)/ ; MV23/00115//Instituto Carlos III de Salud/ ; Y2020/6600//Comunidad de Madrid (Community of Madrid)/ ; 2020.06333.BD//Fundacao para a Ciencia e a Technologia/ ; }, abstract = {Appetite, as the internal drive for food intake, is often dysregulated in a broad spectrum of conditions associated with over- and under-nutrition across the lifespan. Appetite regulation is a complex, integrative process comprising psychological and behavioral events, peripheral and metabolic inputs, and central neurotransmitter and metabolic interactions. The microbiota-gut-brain axis has emerged as a critical mediator of multiple physiological processes, including energy metabolism, brain function, and behavior. Therefore, the role of the microbiota-gut-brain axis in appetite and obesity is receiving increased attention. Omics approaches such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics in appetite and weight regulation offer new opportunities for featuring obesity phenotypes. Furthermore, gut microbiota-targeted approaches such as pre- pro- post- and synbiotic, personalized nutrition, and fecal microbiota transplantation are novel avenues for precision treatments. The aim of this narrative review is (1) to provide an overview of the role of the microbiota-gut-brain-axis in appetite regulation across the lifespan and (2) to discuss the potential of omics and gut microbiota-targeted approaches to deepen understanding of appetite regulation and obesity.}, } @article {pmid39811513, year = {2025}, author = {Wang, Y and Liu, J}, title = {Interplay between creeping fat and gut microbiota: A brand-new perspective on fecal microbiota transplantation in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {2}, pages = {100024}, pmid = {39811513}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/therapy/immunology ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Animals ; *Dysbiosis ; Mice ; *Disease Models, Animal ; Mesentery ; Adipose Tissue ; Recurrence ; Permeability ; Treatment Outcome ; Intestinal Mucosa/microbiology ; }, abstract = {Inflammatory bowel disease, particularly Crohn's disease (CD), has been linked to modifications in mesenteric adipose tissue (MAT) and the phenomenon known as "creeping fat" (CrF). The presence of CrF is believed to serve as a predictor for early clinical recurrence following surgical intervention in patients with CD. Notably, the incorporation of the mesentery during ileocolic resection for CD has been correlated with a decrease in surgical recurrence, indicating the significant role of MAT in the pathogenesis of CD. While numerous studies have indicated that dysbiosis of the gut microbiota is a critical factor in the development of CD, the functional implications of translocated microbiota within the MAT of CD patients remain ambiguous. This manuscript commentary discusses a recent basic research conducted by Wu et al. In their study, intestinal bacteria from individuals were transplanted into CD model mice, revealing that fecal microbiota transplantation (FMT) from healthy donors alleviated CD symptoms, whereas FMT from CD patients exacerbated these symptoms. Importantly, FMT was found to affect intestinal permeability, barrier function, and the levels of proinflammatory factors and adipokines. Collectively, these findings suggest that targeting MAT and CrF may hold therapeutic potential for patients with CD. However, the study did not evaluate the composition of the intestinal microbiota of the donors or the subsequent alterations in the gut microbiota. Overall, the gut microbiota plays a crucial role in the histopathology of CD, and thus, targeting MAT and CrF may represent a promising avenue for treatment in this patient population.}, } @article {pmid39811502, year = {2025}, author = {Qiao, T and Wen, XH}, title = {Exploring gut microbiota as a novel therapeutic target in Crohn's disease: Insights and emerging strategies.}, journal = {World journal of gastroenterology}, volume = {31}, number = {2}, pages = {100827}, pmid = {39811502}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/therapy/immunology ; Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; *Dysbiosis ; Enteral Nutrition/methods ; Disease Progression ; Animals ; }, abstract = {Extensive research has investigated the etiology of Crohn's disease (CD), encompassing genetic predisposition, lifestyle factors, and environmental triggers. Recently, the gut microbiome, recognized as the human body's second-largest gene pool, has garnered significant attention for its crucial role in the pathogenesis of CD. This paper investigates the mechanisms underlying CD, focusing on the role of 'creeping fat' in disease progression and exploring emerging therapeutic strategies, including fecal microbiota transplantation, enteral nutrition, and therapeutic diets. Creeping fat has been identified as a unique pathological feature of CD and has recently been found to be associated with dysbiosis of the gut microbiome. We characterize this dysbiotic state by identifying key microbiome-bacteria, fungi, viruses, and archaea, and their contributions to CD pathogenesis. Additionally, this paper reviews contemporary therapies, emphasizing the potential of biological therapies like fecal microbiota transplantation and dietary interventions. By elucidating the complex interactions between host-microbiome dynamics and CD pathology, this article aims to advance our understanding of the disease and guide the development of more effective therapeutic strategies for managing CD.}, } @article {pmid39810863, year = {2024}, author = {Uździcki, AW and Wawrzynowicz-Syczewska, M}, title = {Impact of liver transplantation on intestinal and systemic inflammation markers in patients with colitis ulcerosa concomitant with primary sclerosing cholangitis.}, journal = {Przeglad gastroenterologiczny}, volume = {16}, number = {4}, pages = {439-445}, pmid = {39810863}, issn = {1895-5770}, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is an uncommon, chronic liver disease characterised by fibrosis and strictures of a bile ducts, causing cholestasis. In the long term it can lead to complete stenosis leading in turn to liver cirrhosis. In patients with severe form of the disease, the recommended treatment is liver transplantation. Because PSC frequently coexists with ulcerative colitis (UC), it is crucial to determine the effect of liver transplantation on the course of UC.

AIM: The aim was to determine the impact of liver transplantation on intestinal and systemic inflammation markers with UC concomitant with PSC (PSC-UC).

MATERIAL AND METHODS: Sixty-three patients with PSC-UC were enrolled, 25 of whom underwent liver transplantation (OLTx) due to PSC progression. Clinical symptoms, faecal calprotectin levels, C-reactive protein (CRP) serum concentration, erythrocyte sedimentation rate, and white blood cell count (WBC) were obtained.

RESULTS: Faecal calprotectin was significantly higher in the post-OLTx group. Mean calprotectin values were 163% higher - 474 ng/ml and 180 ng/ml (p = 0.024) in the post-OLTx group and in the PSC-UC group without the transplantation, respectively. Calprotectin levels exceeded the upper limit of normal (defined as 200 ng/l) in 66% of liver recipients and in 18% of non-transplanted patients (OR = 9.33, p = 0.011). In the post-OLTx group, also CRP concentration (11.01 mg/l vs. 6.54 mg/l, p = 0.30) and WBC (7.58 K/ml vs. 5.72 K/ml, p = 0.006) were higher than in the PSC-UC group without transplantation.

CONCLUSIONS: We found significantly higher inflammation markers in PSC-UC patients who underwent liver transplantation due to PSC. The effect was strongest in faecal calprotectin levels. In PSC-UC patients after liver transplantation, intensification of UC treatment may be needed, despite the lack of worsening of clinical symptoms.}, } @article {pmid39809955, year = {2025}, author = {Kumar, D and Bishnoi, M and Kondepudi, KK and Sharma, SS}, title = {Gut Microbiota-Based Interventions for Parkinson's Disease: Neuroprotective Mechanisms and Current Perspective.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, pmid = {39809955}, issn = {1867-1314}, abstract = {Recent evidence links gut microbiota alterations to neurodegenerative disorders, including Parkinson's disease (PD). Replenishing the abnormal composition of gut microbiota through gut microbiota-based interventions "prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT)" has shown beneficial effects in PD. These interventions increase gut metabolites like short-chain fatty acids (SCFAs) and glucagon-like peptide-1 (GLP-1), which may protect dopaminergic neurons via the gut-brain axis. Neuroprotective effects of these interventions are mediated by several mechanisms, including the enhancement of neurotrophin and activation of the PI3K/AKT/mTOR signaling pathway, GLP-1-mediated gut-brain axis signaling, Nrf2/ARE pathway, and autophagy. Other pathways, such as free fatty acid receptor activation, synaptic plasticity improvement, and blood-brain and gut barrier integrity maintenance, also contribute to neuroprotection. Furthermore, the inhibition of the TLR4/NF-кB pathway, MAPK pathway, GSK-3β signaling pathway, miR-155-5p-mediated neuroinflammation, and ferroptosis could account for their protective effects. Clinical studies involving gut microbiota-based interventions have shown therapeutic benefits in PD patients, particularly in improving gastrointestinal dysfunction and some neurological symptoms. However, the effectiveness in alleviating motor symptoms remains mild. Large-scale clinical trials are still needed to confirm these findings. This review emphasizes the neuroprotective mechanisms of gut microbiota-based interventions in PD as supported by both preclinical and clinical studies.}, } @article {pmid39806466, year = {2025}, author = {Khemiri, H and Ben Fraj, I and Lorusso, A and Mekki, N and Mangone, I and Gdoura, M and Di Pasqual, A and Cammà, C and Di Lollo, V and Cherni, A and Touzi, H and Sadraoui, A and Meddeb, Z and Hogga, N and Ben Mustapha, I and Barbouche, MR and Ouederni, M and Triki, H and Haddad-Boubaker, S}, title = {SARS-CoV-2 excretion and genetic evolution in nasopharyngeal and stool samples from primary immunodeficiency and immunocompetent pediatric patients.}, journal = {Virology journal}, volume = {22}, number = {1}, pages = {9}, pmid = {39806466}, issn = {1743-422X}, mesh = {Humans ; *SARS-CoV-2/genetics/immunology ; *Feces/virology ; *Nasopharynx/virology ; *COVID-19/virology/immunology ; Child ; Male ; Female ; Child, Preschool ; *RNA, Viral/genetics ; *Virus Shedding ; Infant ; Phylogeny ; Evolution, Molecular ; Primary Immunodeficiency Diseases/genetics ; Adolescent ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Primary Immunodeficiency disorders (PID) can increase the risk of severe COVID-19 and prolonged infection. This study investigates the duration of SARS-CoV-2 excretion and the genetic evolution of the virus in pediatric PID patients as compared to immunocompetent (IC) patients.

MATERIALS AND METHODS: A total of 40 nasopharyngeal and 24 stool samples were obtained from five PID and ten IC children. RNA detection was performed using RT-qPCR, and whole-genome sequencing was conducted with the NexSeq 1000 platform. Data analysis used the nextflow/viralrecon pipeline. Hotspot amino acid frequencies were investigated using GraphPad Prism v10. Phylodynamic analysis was conducted with BEAST software.

RESULTS: In IC children, the viral excretion period lasted up to 14 days in nasopharyngeal swabs, with an average duration of 7 days, and ranged from 7 to 14 days in stool samples. In PID patients, the viral RNA was detected in nasopharyngeal for periods between 7 and 28 days, with an average duration of 15 days, and up to 28 days in stool samples. Two SARS-CoV-2 variants were detected in PID patients: Delta (AY.122) and Omicron (BA.1.1). Patients with antibody and combined deficiencies, exhibited the most prolonged shedding periods in both nasopharyngeal and stool samples and one patient presented complications and fatal outcome. Specific Hotspot amino acid changes were detected in PID: A2821V and R550H (ORF1ab).

CONCLUSION: Our findings underscore the prolonged excretion of SARS-CoV-2 RNA in patients with antibody and combined deficiencies. Thus, specialized care is essential for effectively managing PID patients.}, } @article {pmid39805780, year = {2024}, author = {Ye, LJ and Xu, XF and Chen, SY and Zhang, H and Gan, YX and Meng, T and Ding, R and Li, J and Cao, G and Wang, KL}, title = {[Regulation of Bifidobacterium-short chain fatty acid metabolism and improvement of intestinal toxicity of vinegar-processed Euphorbiae Pekinensis Radix].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {49}, number = {23}, pages = {6331-6341}, doi = {10.19540/j.cnki.cjcmm.20240912.301}, pmid = {39805780}, issn = {1001-5302}, mesh = {Mice ; Animals ; *Fatty Acids, Volatile/metabolism ; *Acetic Acid ; Humans ; Caco-2 Cells ; *Gastrointestinal Microbiome/drug effects ; *Drugs, Chinese Herbal/pharmacology/chemistry ; *Bifidobacterium/drug effects ; RAW 264.7 Cells ; Intestines/drug effects ; Male ; Intestinal Mucosa/metabolism/drug effects ; Feces/microbiology/chemistry ; }, abstract = {To explore the mechanism by which vinegar-processed Euphorbiae Pekinensis Radix regulates gut microbiota and reduces intestinal toxicity, this study aimed to identify key microbial communities related to vinegar-induced detoxification and verify their functions. Using a derivatization method, the study measured the content of short-chain fatty acids(SCFAs) in feces before and after vinegar-processing of Euphorbiae Pekinensis Radix. Combined with the results of previous gut microbiota sequencing, correlation analysis was used to identify key microbial communities related to SCFAs content. Through single-bacterium transplantation experiments, the role of key microbial communities in regulating SCFAs metabolism and alleviating the intestinal toxicity of Euphorbiae Pekinensis Radix was clarified. Fecal extracts were then added to a co-culture system of Caco-2 and RAW264.7 cells, and toxicity differences were evaluated using intestinal tight junction proteins and inflammatory factors as indicators. Additionally, the application of a SCFAs receptor blocker helped confirm the role of SCFAs in reducing intestinal toxicity during vinegar-processing of Euphorbiae Pekinensis Radix. The results of this study indicated that vinegar-processing of Euphorbiae Pekinensis Radix improved the decline in SCFAs content caused by the raw material. Correlation analysis revealed that Bifidobacterium was positively correlated with the levels of acetic acid, propionic acid, isobutyric acid, n-butyric acid, isovaleric acid, and n-valeric acid. RESULTS:: from single-bacterium transplantation experiments demonstrated that Bifidobacterium could mitigate the reduction in SCFAs content induced by raw Euphorbiae Pekinensis Radix, enhance the expression of tight junction proteins, and reduce intestinal inflammation. Similarly, cell experiment results confirmed that fecal extracts from Bifidobacterium-transplanted mice alleviated inflammation and increased the expression of tight junction proteins in intestinal epithelial cells. The use of the free fatty acid receptor-2 inhibitor GLPG0974 verified that this improvement effect was related to the SCFAs pathway. This study demonstrates that Bifidobacterium is the key microbial community responsible for reducing intestinal toxicity in vinegar-processed Euphorbiae Pekinensis Radix. Vinegar-processing increases the abundance of Bifidobacterium, elevates the intestinal SCFAs content, inhibits intestinal inflammation, and enhances the expression of tight junction proteins, thereby improving the intestinal toxicity of Euphorbiae Pekinensis Radix.}, } @article {pmid39804518, year = {2025}, author = {Claytor, JD and Lin, DL and Magnaye, KM and Guerrero, YS and Langelier, CR and Lynch, SV and El-Nachef, N}, title = {Effect of Fecal Microbiota Transplant on Antibiotic Resistance Genes Among Patients with Chronic Pouchitis.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {39804518}, issn = {1573-2568}, abstract = {BACKGROUND: Pouchitis is common among patients with ulcerative colitis (UC) who have had colectomy with ileal pouch-anal anastomosis. Antibiotics are first-line therapy for pouch inflammation, increasing the potential for gut colonization with multi-drug resistant organisms (MDRO). Fecal microbial transplant (FMT) is being studied in the treatment of pouchitis and in the eradication of MDRO. Prior work using aerobic antibiotic culture disks suggests that some patients with chronic pouchitis may regain fluoroquinolone sensitivity after FMT. However, gut MDRO include anaerobic, fastidious organisms that are difficult to culture using traditional methods.

AIM: We aimed to assess whether FMT reduced the abundance of antibiotic resistance genes (ARG) or affected resistome diversity, evenness, or richness in patients with chronic pouchitis.

METHODS: We collected clinical characteristics regarding infections and antibiotic exposures for 18 patients who had previously been enrolled in an observational study investigating FMT as a treatment for pouchitis. Twenty-six pre- and post-FMT stool samples were analyzed using FLASH (Finding Low Abundance Sequences by Hybridization), a CRISPR/Cas9-based shotgun metagenomic sequence enrichment technique that detects acquired and chromosomal bacterial ARGs. Wilcoxon rank sum tests were used to assess differences in clinical characteristics, ARG counts, resistome diversity and ARG richness, pre- and post-FMT.

RESULTS: All 13 of the patients with sufficient stool samples for analysis had recently received antibiotics for pouchitis prior to a single endoscopic FMT. Fecal microbiomes of all patients had evidence of multi-drug resistance genes and ESBL resistance genes at baseline; 62% encoded fluoroquinolone resistance genes. A numerical decrease in overall ARG counts was noted post-FMT, but no statistically significant differences were noted (P = 0.19). Richness and diversity were not significantly altered. Three patients developed infections during the 5-year follow-up period, none of which were associated with MDRO.

CONCLUSION: Antibiotic resistance genes are prevalent among antibiotic-exposed patients with chronic pouchitis. FMT led to a numerical decrease, but no statistically significant change in ARG, nor were there significant changes in the diversity, richness, or evenness of ARGs. Further investigations to improve FMT engraftment and to optimize FMT delivery in patients with inflammatory pouch disorders are warranted.}, } @article {pmid39801363, year = {2025}, author = {Chevalier, C and Tournier, BB and Marizzoni, M and Park, R and Paquis, A and Ceyzériat, K and Badina, AM and Lathuiliere, A and Saleri, S and Cillis, F and Cattaneo, A and Millet, P and Frisoni, GB}, title = {Fecal Microbiota Transplantation (FMT) From a Human at Low Risk for Alzheimer's Disease Improves Short-Term Recognition Memory and Increases Neuroinflammation in a 3xTg AD Mouse Model.}, journal = {Genes, brain, and behavior}, volume = {24}, number = {1}, pages = {e70012}, pmid = {39801363}, issn = {1601-183X}, support = {1216//Velux Stiftung/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; *Alzheimer Disease/therapy/microbiology ; Humans ; Female ; *Gastrointestinal Microbiome ; Memory, Short-Term/physiology ; Neuroinflammatory Diseases/therapy/metabolism ; Disease Models, Animal ; Hippocampus/metabolism ; Aged ; }, abstract = {Human microbiota-associated murine models, using fecal microbiota transplantation (FMT) from human donors, help explore the microbiome's role in diseases like Alzheimer's disease (AD). This study examines how gut bacteria from donors with protective factors against AD influence behavior and brain pathology in an AD mouse model. Female 3xTgAD mice received weekly FMT for 2 months from (i) an 80-year-old AD patient (AD-FMT), (ii) a cognitively healthy 73-year-old with the protective APOEe2 allele (APOEe2-FMT), (iii) a 22-year-old healthy donor (Young-FMT), and (iv) untreated mice (Mice-FMT). Behavioral assessments included novel object recognition (NOR), Y-maze, open-field, and elevated plus maze tests; brain pathology (amyloid and tau), neuroinflammation (in situ autoradiography of the 18 kDa translocator protein in the hippocampus); and gut microbiota were analyzed. APOEe2-FMT improved short-term memory in the NOR test compared to AD-FMT, without significant changes in other behavioral tests. This was associated with increased neuroinflammation in the hippocampus, but no effect was detected on brain amyloidosis and tauopathy. Specific genera, such as Parabacteroides and Prevotellaceae_UGC001, were enriched in the APOEe2-FMT group and associated with neuroinflammation, while genera like Desulfovibrio were reduced and linked to decreased neuroinflammation. Gut microbiota from a donor with a protective factor against AD improved short-term memory and induced neuroinflammation in regions strategic to AD. The association of several genera with neuroinflammation in the APOEe2-FMT group suggests a collegial effect of the transplanted microbiome rather than a single-microbe driver effect. These data support an association between gut bacteria, glial cell activation, and cognitive function in AD.}, } @article {pmid39800714, year = {2025}, author = {Sall, I and Foxall, R and Felth, L and Maret, S and Rosa, Z and Gaur, A and Calawa, J and Pavlik, N and Whistler, JL and Whistler, CA}, title = {Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446423}, pmid = {39800714}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Morphine/administration & dosage ; *Dysbiosis/microbiology ; Mice ; *Butyrates/metabolism ; Male ; *Fecal Microbiota Transplantation ; *Drug Tolerance ; *Analgesics, Opioid/administration & dosage/metabolism ; *Mice, Inbred C57BL ; Bacteria/metabolism/classification/genetics/drug effects ; Probiotics/administration & dosage ; }, abstract = {The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance, which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.}, } @article {pmid39800223, year = {2025}, author = {Lista, S and Munafò, A and Caraci, F and Imbimbo, C and Emanuele, E and Minoretti, P and Pinto-Fraga, J and Merino-País, M and Crespo-Escobar, P and López-Ortiz, S and Monteleone, G and Imbimbo, BP and Santos-Lozano, A}, title = {Gut microbiota in Alzheimer's disease: Understanding molecular pathways and potential therapeutic perspectives.}, journal = {Ageing research reviews}, volume = {104}, number = {}, pages = {102659}, doi = {10.1016/j.arr.2025.102659}, pmid = {39800223}, issn = {1872-9649}, abstract = {Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.}, } @article {pmid39800192, year = {2025}, author = {Bajaj, JS and Fagan, A and Gavis, EA and Sterling, RK and Gallagher, ML and Lee, H and Matherly, SC and Siddiqui, MS and Bartels, A and Mousel, T and Davis, BC and Puri, P and Fuchs, M and Moutsoglou, DM and Thacker, LR and Sikaroodi, M and Gillevet, PM and Khoruts, A}, title = {Microbiota transplant for hepatic encephalopathy in cirrhosis: The THEMATIC trial.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2024.12.047}, pmid = {39800192}, issn = {1600-0641}, abstract = {BACKGROUND: Preventing hepatic encephalopathy (HE) recurrence in cirrhosis, which is associated with an altered gut-liver-brain axis, is an unmet need. Fecal microbiota transplantation (FMT) is beneficial in phase-1 studies, but route and dose-related questions remain.

METHODS: We performed a phase-2 randomized, placebo-controlled, double-blind, clinical trial of capsule and enema FMT in cirrhosis and HE on lactulose and rifaximin. Subjects were randomized into 4 groups receiving 3 active and 0-placebo, 2 active and 1-placebo, 1 active and 2-placebo, or all 3-placebo doses. Each patient received two capsule and one enema FMT and were followed for six months.

PRIMARY OUTCOME: FMT-related serious adverse events/AEs using intention-to-treat analysis. Secondary outcomes were HE recurrence, all-cause hospitalizations, death, donor engraftment, and quality-of-life (QOL). FMT was from a vegan or omnivorous donor.

RESULTS: 60 patients (15/group) with similar baseline characteristics were enrolled.

PRIMARY OUTCOMES: FMT was safe without any FMT-related SAEs/ AEs.

SECONDARY OUTCOMES: Overall SAEs (p=0.96) or death (p=1.0) were similar. There were significant differences in HE recurrence between groups (p=0.035, Cramer's V=0.39). Post-hoc, recurrence was highest in all-placebo vs FMT [40% vs 9%, OR:0.15 (95% CI: 0.04, 0.64)]. Within FMT, HE-recurrence rates were similar regardless of route, doses, or donor type. QOL improved in FMT-recipient groups. Engraftment was highest in those with high pre-FMT Lachnospiraceae and lower in those whose HE recurred.

CONCLUSIONS: In a Phase 2 double-blind, placebo-controlled, randomized clinical trial in cirrhosis with HE on maximal therapy, FMT regardless of dose, route, or donor was safe without any FMT-related adverse events. On post-hoc analysis, groups differed on HE recurrence, which was highest in the placebo-only group and linked with lower baseline Lachnospiraceae and reduced donor engraftment.}, } @article {pmid39798925, year = {2025}, author = {Aleksandrova, RR and Nieuwenhuis, LM and Karmi, N and Zhang, S and Swarte, JC and Björk, JR and Gacesa, R and Blokzijl, H and Connelly, MA and Weersma, RK and Lisman, T and Festen, EAM and de Meijer, VE and , }, title = {Gut microbiome dysbiosis is not associated with portal vein thrombosis in patients with end-stage liver disease: a cross-sectional study.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtha.2024.12.036}, pmid = {39798925}, issn = {1538-7836}, abstract = {BACKGROUND: Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in ESLD patients is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a pro-inflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development.

OBJECTIVES: We investigated whether gut microbiome diversity, bacterial species, metabolic pathways, and TMAO levels are associated with PVT in ESLD patients.

METHODS: Fecal samples, plasma samples and data from ESLD patients and healthy controls were collected through the TransplantLines Biobank and Cohort Study. PVT was defined as a thrombus in the portal vein within a year prior to or after fecal sample collection. Fecal samples were analyzed using Shotgun Metagenomic Sequencing, and TMAO levels were measured in plasma using a Vantera® Clinical Analyzer.

RESULTS: 102 ESLD patients, of which 23 with PVT, and 246 healthy controls were included. No significant difference in gut microbiome diversity was found between patients with PVT and without PVT (P=0.18). Both ESLD groups had significantly lower alpha-diversity compared with controls. Bacteroides fragilis and three Clostridiales species were increased in patients with PVT compared to without PVT. TMAO levels between the three groups were not significantly different.

CONCLUSION: We observed profound differences in gut microbiota between ESLD patients and controls, but minimal differences between ESLD patients with or without PVT. In our cohort, a gut-derived pro-inflammatory state was not associated with presence of PVT in ESLD patients.}, } @article {pmid39797102, year = {2024}, author = {Díez-Madueño, K and de la Cueva Dobao, P and Torres-Rojas, I and Fernández-Gosende, M and Hidalgo-Cantabrana, C and Coto-Segura, P}, title = {Gut Dysbiosis and Adult Atopic Dermatitis: A Systematic Review.}, journal = {Journal of clinical medicine}, volume = {14}, number = {1}, pages = {}, pmid = {39797102}, issn = {2077-0383}, abstract = {Background/Objectives: Research on the relationship between gut microbiota (GM) and atopic dermatitis (AD) has seen a growing interest in recent years. The aim of this systematic review was to determine whether differences exist between the GM of adults with AD and that of healthy adults (gut dysbiosis). Methods: We conducted a systematic review based on the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed using PubMed, EMBASE, and Web of Science. Observational and interventional studies were analyzed. Results: Although the studies showed heterogeneous results, some distinguishing characteristics were found in the intestinal microbial composition of adults with dermatitis. Even though no significant differences in diversity were found between healthy and affected adults, certain microorganisms, such as Bacteroidales, Enterobacteriaceae, and Clostridium (perfringens), were more characteristic of the fecal microbiota in adults with AD. Healthy individuals exhibited lower abundances of aerobic bacteria and higher abundances of short-chain fatty acid-producing species and polyamines. Clinical trials showed that the consumption of probiotics (Bifidobacterium and/or Lactobacillus), fecal microbiota transplants, and balneotherapy modified the fecal microbiota composition of participants and were associated with significant improvements in disease management. Conclusions: In anticipation of forthcoming clinical trials, it is essential to conduct meta-analyses that comprehensively evaluate the effectiveness and safety of interventions designed to modify intestinal flora in the context of AD. Preliminary evidence suggests that certain interventions may enhance adult AD management.}, } @article {pmid39796717, year = {2024}, author = {Kumari, S and Srilatha, M and Nagaraju, GP}, title = {Effect of Gut Dysbiosis on Onset of GI Cancers.}, journal = {Cancers}, volume = {17}, number = {1}, pages = {}, pmid = {39796717}, issn = {2072-6694}, abstract = {Dysbiosis in the gut microbiota plays a significant role in GI cancer development by influencing immune function and disrupting metabolic functions. Dysbiosis can drive carcinogenesis through pathways like immune dysregulation and the release of carcinogenic metabolites, and altered metabolism, genetic instability, and pro-inflammatory signalling, contributing to GI cancer initiation and progression. Helicobacter pylori infection and genotoxins released from dysbiosis, lifestyle and dietary habits are other factors that contribute to GI cancer development. Emerging diagnostic and therapeutic approaches show promise in colorectal cancer treatment, including the multitarget faecal immunochemical test (mtFIT), standard FIT, and faecal microbiota transplantation (FMT) combined with PD-1 inhibitors. We used search engine databases like PubMed, Scopus, and Web of Science. This review discusses the role of dysbiosis in GI cancer onset and explores strategies such as FMT, probiotics, and prebiotics to enhance the immune response and improve cancer therapy outcomes.}, } @article {pmid39796536, year = {2024}, author = {Cuffaro, F and Lamminpää, I and Niccolai, E and Amedei, A}, title = {Nutritional and Microbiota-Based Approaches in Amyotrophic Lateral Sclerosis: From Prevention to Treatment.}, journal = {Nutrients}, volume = {17}, number = {1}, pages = {}, pmid = {39796536}, issn = {2072-6643}, support = {PNRR-MAD-2022-12375798//Ministero della Salute/ ; PE0000006//Ministry of University and Research (MUR)/ ; }, mesh = {*Amyotrophic Lateral Sclerosis/therapy ; Humans ; *Gastrointestinal Microbiome ; *Dysbiosis/therapy ; Probiotics/therapeutic use ; Brain-Gut Axis/physiology ; Fecal Microbiota Transplantation ; Fatty Acids, Omega-3 ; Prebiotics/administration & dosage ; Oxidative Stress ; Nutritional Status ; Diet, Mediterranean ; Antioxidants ; }, abstract = {Metabolic alterations, including hypermetabolism, lipid imbalances, and glucose dysregulation, are pivotal contributors to the onset and progression of Amyotrophic Lateral Sclerosis (ALS). These changes exacerbate systemic energy deficits, heighten oxidative stress, and fuel neuroinflammation. Simultaneously, gastrointestinal dysfunction and gut microbiota (GM) dysbiosis intensify disease pathology by driving immune dysregulation, compromising the intestinal barrier, and altering gut-brain axis (GBA) signaling, and lastly advancing neurodegeneration. Therapeutic and preventive strategies focused on nutrition offer promising opportunities to address these interconnected pathophysiological mechanisms. Diets enriched with antioxidants, omega-3 fatty acids, and anti-inflammatory compounds-such as the Mediterranean diet-have shown potential in reducing oxidative stress and systemic inflammation. Additionally, microbiota-targeted approaches, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation, are emerging as innovative tools to restore microbial balance, strengthen gut integrity, and optimize GBA function. This review highlights the critical need for personalized strategies integrating immunonutrition and microbiota modulation to slow ALS progression, improve quality of life, and develop preventive measures for neurodegenerative and neuroinflammatory diseases. Future research should prioritize comprehensive dietary and microbiota-based interventions to uncover their therapeutic potential and establish evidence-based guidelines for managing ALS and related disorders.}, } @article {pmid39796390, year = {2025}, author = {Yu, R and Zhang, H and Chen, R and Lin, Y and Xu, J and Fang, Z and Ru, Y and Fan, C and Wu, G}, title = {Fecal Microbiota Transplantation from Methionine-Restricted Diet Mouse Donors Improves Alzheimer's Learning and Memory Abilities Through Short-Chain Fatty Acids.}, journal = {Foods (Basel, Switzerland)}, volume = {14}, number = {1}, pages = {}, pmid = {39796390}, issn = {2304-8158}, support = {LQ22H260002//Natural Science Foundation of Zhejiang Province/ ; 82103836//National Natural Science Foundation of China/ ; }, abstract = {Alzheimer's disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer's learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.}, } @article {pmid39795549, year = {2024}, author = {Tsuji, K and Uchida, N and Nakanoh, H and Fukushima, K and Haraguchi, S and Kitamura, S and Wada, J}, title = {The Gut-Kidney Axis in Chronic Kidney Diseases.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {15}, number = {1}, pages = {}, pmid = {39795549}, issn = {2075-4418}, support = {24K11411//the Japanese Society for the Promotion of Science (JSPS)/Grant-in-Aid for Young Scientists/ ; }, abstract = {The gut-kidney axis represents the complex interactions between the gut microbiota and kidney, which significantly impact the progression of chronic kidney disease (CKD) and overall patient health. In CKD patients, imbalances in the gut microbiota promote the production of uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which impair renal function and contribute to systemic inflammation. Mechanisms like endotoxemia, immune activation and oxidative stress worsen renal damage by activating pro-inflammatory and oxidative pathways. Insights into these mechanisms highlight the impact of gut-derived metabolites, bacterial translocation, and immune response changes on kidney health, suggesting new potential approaches for CKD treatment. Clinical applications, such as dietary interventions, prebiotics, probiotics and fecal microbiota transplantation, are promising in adjusting the gut microbiota to alleviate CKD symptoms and slow disease progression. Current research highlights the clinical relevance of the gut-kidney axis, but further study is essential to clarify these mechanisms' diagnostic biomarkers and optimize therapeutic interventions. This review emphasizes the importance of an integrated approach to CKD management, focusing on the gut microbiota as a therapeutic target to limit kidney injury.}, } @article {pmid39736240, year = {2025}, author = {Qiu, M and Geng, H and Zou, C and Zhao, X and Zhao, C and Xie, J and Wang, J and Zhang, N and Hu, Y and Fu, Y and Wang, J and Hu, X}, title = {Intestinal inflammation exacerbates endometritis through succinate production by gut microbiota and SUCNR1-mediated proinflammatory response.}, journal = {International immunopharmacology}, volume = {146}, number = {}, pages = {113919}, doi = {10.1016/j.intimp.2024.113919}, pmid = {39736240}, issn = {1878-1705}, mesh = {Animals ; Female ; *Gastrointestinal Microbiome ; *Endometritis/microbiology/immunology/pathology/metabolism ; *Succinic Acid/metabolism ; Mice ; *Lipopolysaccharides/immunology ; *Mice, Inbred C57BL ; Dysbiosis/immunology ; Receptors, G-Protein-Coupled/metabolism/genetics ; Dextran Sulfate ; Uterus/pathology/immunology/microbiology/metabolism ; Inflammation/immunology ; Disease Models, Animal ; Intestines/immunology/microbiology/pathology ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {Endometritis poses higher health risks to women. Clinical practice has found that gastrointestinal dysfunction is more likely to lead to the occurrence of endometritis. However, the mechanism is unclear. This study explored the influence and mechanism of DSS-induced intestinal inflammation on endometritis. Our findings demonstrate that DSS-induced intestinal inflammation can worsen LPS-induced endometritis in mice, and this effect is dependent on the gut microbiota, as depleting the gut microbiota eliminates this protective effect. Similarly, FMT from DSS-treated mice to recipient mice exacerbates LPS-induced endometritis. In addition, treatment of DSS disrupted an imbalance of succinate-producing and succinate-consuming bacteria and increased the levels of succinate in the gut and uterine tissues. Furthermore, treatment with succinate aggravates LPS-induced endometritis by activating the succinate receptor 1 (SUCNR1), evidenced by inhibition of the activation of SUCNR1 reversed the inflammatory response in uterine tissues induced by succinate during endometritis induced by LPS. Collectively, the results suggested that dysbiosis of the gut microbiota exacerbates LPS-induced endometritis by production and migration of succinate from gut to uterine tissues via the gut-uterus axis, then activates the SUCNR1. This identifies gut-derived succinate as a novel target for treating endometritis, and it indicates that targeting the gut microbiota and its metabolism could be a potential strategy for intervention in endometritis.}, } @article {pmid39792405, year = {2024}, author = {Guo, Z and He, M and Shao, L and Li, Y and Xiang, X and Wang, Q}, title = {The role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease.}, journal = {Journal of cancer research and therapeutics}, volume = {20}, number = {7}, pages = {1964-1973}, doi = {10.4103/jcrt.jcrt_33_24}, pmid = {39792405}, issn = {1998-4138}, mesh = {Humans ; *Graft vs Host Disease/therapy/etiology/microbiology ; *Fecal Microbiota Transplantation/methods ; *Hematopoietic Stem Cell Transplantation/adverse effects/methods ; *Gastrointestinal Microbiome ; Transplantation, Homologous/methods ; Acute Disease ; Treatment Outcome ; }, abstract = {Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most important methods for treating a wide range of hematologic malignancies and bone marrow failure diseases. However, graft-versus-host disease (GVHD), a major complication associated with this method, can seriously affect the survival and quality of life of patients. Acute GVHD (aGVHD) occurs within 100 days after transplantation, and gastrointestinal aGVHD (GI-aGVHD) is one of the leading causes of nonrecurrent death after allo-HSCT. In recent years, fecal microbiota transplantation (FMT) has been attempted as an emerging treatment method for various diseases, including aGVHD after HSCT. Studies have shown encouraging preliminary clinical results after the application of FMT in aGVHD, particularly steroid-resistant aGVHD. Additionally, several studies have demonstrated that the gut microbiota plays an important immunomodulatory role in the pathogenesis of GVHD. Consensus guidelines recommend FMT as a secondary option for the treatment of aGVHD. This article aims to review FMT treatment for GI-aGVHD after allo-HSCT.}, } @article {pmid39791180, year = {2025}, author = {Shakya, R and Sivakumar, PM and Prabhakar, PK}, title = {Gut Microbiota and Diabetes: Pioneering New Treatment Frontiers.}, journal = {Endocrine, metabolic & immune disorders drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/0118715303342579241119155225}, pmid = {39791180}, issn = {2212-3873}, abstract = {Diabetes Mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and poses significant global health challenges. Conventional treatments, such as insulin therapy and lifestyle modifications, have shown limited efficacy in addressing the multifactorial nature of DM. Emerging evidence suggests that gut microbiota, a diverse community of microorganisms critical for metabolism and immune function, plays a pivotal role in metabolic health. Dysbiosis, an imbalance in gut microbiota composition, has been linked to insulin resistance, obesity, and DM. Gut microbiota influences glucose metabolism through mechanisms, including short-chain fatty acid production, gut permeability regulation, and immune system interactions, indicating a bidirectional relationship between microbial health and metabolism. Clinical and experimental studies demonstrate that modulating gut microbiota through dietary interventions (prebiotics, probiotics, synbiotics) improves glycemic control and insulin sensitivity in DM patients. Fecal Microbiota Transplantation (FMT) has also shown promise in restoring healthy gut microbiota and alleviating DM-related metabolic disturbances. However, challenges remain, including the need for personalized treatments due to individual microbiota variability and the unknown long-term effects of these interventions. Future research should focus on elucidating the mechanisms by which gut microbiota influences metabolism and refining personalized approaches to enhance DM management.}, } @article {pmid39791141, year = {2025}, author = {Li, X and Sun, B and Qin, Y and Yue, F and Lü, X}, title = {Amelioration of Obesity-Related Disorders in High-Fat Diet-Fed C57BL/6 Mice Following Fecal Microbiota Transplantation From DL-Norvaline-Dosed Mice.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e202400577}, doi = {10.1002/mnfr.202400577}, pmid = {39791141}, issn = {1613-4133}, support = {2023-ZDLNY-35//Shaanxi Province Science and Technology Plan Project/ ; 2022A02006//Major Scientific and Technological Special Project of Xinjiang Uygur Autonomous Region/ ; }, abstract = {Fecal microbiota transplantation (FMT) could significantly alter the recipient's gut bacteria composition and attenuate obesity and obesity-related metabolic syndromes. DL-norvaline is a nonproteinogenic amino acid and possesses anti-obesity potential. However, the specific mechanisms by which gut microbiota might mediate beneficial effects of DL-norvaline have not been completely elucidated. In this study, DL-norvaline-mediated FMT upregulated the beneficial bacteria (Clostridia_UCG_014, Christensenellales, Bacilli, Ileibacterium, Dubosiella, Lactobacillus, Muribaculaceae, and Bacteroidaceae) and downregulated the harmful bacteria (Tuzzerella and Marinifilaceae), further intestinal inflammation, oxidative stress, and intestinal barrier were alleviated as well as short chain fatty acids levels were increased, thus alleviating glucose and insulin metabolism, improving biochemical indexes and energy metabolism and decreasing body weight gain and tissue weight. However, heat-inactivated FMT did not demonstrate any of those improvements in obese mice. Notably, both DL-norvaline-mediated FMT and heat-inactivated FMT increased Bacteroidaceae and Muribaculaceae, this being a signature of alterations to the gut microbiota marker caused by DL-norvaline. Therefore, the beneficial effects of DL-norvaline were transmissible via FMT. This study highlighted the pivotal involvement of the gut microbiota in the development of obesity and provided a novel insight into the underlying mechanisms of FMT, thereby potentially enhancing the efficacy and refinement of FMT utilization.}, } @article {pmid39791120, year = {2024}, author = {Huang, H and Yang, Y and Wang, X and Wen, B and Yang, X and Zhong, W and Wang, Q and He, F and Li, J}, title = {Gut virome dysbiosis impairs antitumor immunity and reduces 5-fluorouracil treatment efficacy for colorectal cancer.}, journal = {Frontiers in oncology}, volume = {14}, number = {}, pages = {1501981}, pmid = {39791120}, issn = {2234-943X}, abstract = {INTRODUCTION: Despite the established influence of gut bacteria, the role of the gut virome in modulating colorectal cancer (CRC) patient chemotherapy response remains poorly understood. In this study, we investigated the impact of antiviral (AV) drug-induced gut virome dysbiosis on the efficacy of 5-FU in CRC treatment.

METHODS: Using a subcutaneous CRC mouse model, we assessed tumor growth and immune responses following AV treatment, fecal microbiota transplantation (FMT), and 5-FU administration.

RESULTS: AV therapy reduced the abundance of gut DNA and RNA viruses, leading to accelerated tumor growth, shortened survival, and diminished chemotherapy efficacy. FMT restored the gut virome, improving tumor suppression and extending the survival of 5-FU-treated mice. Metagenomic sequencing revealed significant changes in virome composition, AV treatment expanded Kahnovirus, Petivirales, and Enterogokushovirus, whereas FMT enriched Peduovirus STYP1, Mahlunavirus rarus, and Jouyvirus ev207. AV treatment reduced the number of dendritic cells and CD8+ T cells in peripheral blood and tumor tissues, impairing antitumor immunity, FMT reversed these deficiencies. To further investigate the underlying mechanisms, we examined the TLR3-IRF3-IFN-β pathway, essential for recognizing viral RNA and triggering immune responses. AV treatment downregulated this pathway, impairing immune cell recruitment and reducing chemotherapy efficacy, while activation of TLR3 with Poly(I:C) restored pathway function and enhanced the effectiveness of 5-FU.

DISCUSSION: These findings suggest the importance of maintaining gut virome integrity or activating TLR3 as adjunct strategies to enhance chemotherapy outcomes in CRC patients.}, } @article {pmid39791110, year = {2025}, author = {Høyer, KL and Dahl Baunwall, SM and Kornum, DS and Klinge, MW and Drewes, AM and Yderstræde, KB and Thingholm, LB and Mortensen, MS and Mikkelsen, S and Erikstrup, C and Hvas, CL and Krogh, K}, title = {Faecal microbiota transplantation for patients with diabetes type 1 and severe gastrointestinal neuropathy (FADIGAS): a randomised, double-blinded, placebo-controlled trial.}, journal = {EClinicalMedicine}, volume = {79}, number = {}, pages = {103000}, pmid = {39791110}, issn = {2589-5370}, abstract = {BACKGROUND: Diabetic gastroenteropathy is associated with nausea, vomiting, bloating, pain, constipation, and diarrhoea. Current therapies are scarce. We tested faecal microbiota transplantation (FMT) for patients with type 1 diabetes and gastroenteropathy.

METHODS: In a randomised, double-blinded, placebo-controlled pilot trial, adults with type 1 diabetes and moderate-to-severe gastrointestinal symptoms were randomised (1:1) to encapsulated FMT or placebo. Each patient received around 25 capsules containing 50 g of faeces, administered in a single dose. The placebo capsules contained glycerol, saline and food colouring. All patients received FMT as a second intervention. The primary endpoint was number of adverse events of severity grade 2 or more assessed by the Common Terminology Criteria for Adverse Events during the week following the first intervention. Secondary endpoints included gastrointestinal symptoms and quality of life assessed four weeks after treatment. Public trial registration, ClinicalTrials.govNCT04749030.

FINDINGS: We randomised 20 patients to FMT or placebo. Following this intervention, 26 adverse events of grade 2 or more occurred. Four patients in the FMT group reported seven adverse events, and five patients in the placebo group reported 19, with no differences between the groups. The most frequent adverse events were diarrhoea, bloating, and abdominal pain. No serious adverse events were related to the treatment. Patients who received FMT reduced their median Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome score from 58 (IQR 54-65) to 35 (32-48), whereas patients receiving placebo reduced their score from 64 (55-70) to 56 (50-77) (p = 0.01). The Irritable Bowel Syndrome Impact Scale score improved from 108 (101-123) to 140 (124-161) with FMT and 77 (53-129) to 92 (54-142) with placebo (p = 0.02). The Patient Assessment of Gastrointestinal Symptom Severity Index declined from a median of 42 (28-47) to 25 (14-31) after FMT and 47 (31-69) to 41 (36-64) after placebo (p = 0.03).

INTERPRETATION: FMT was safe and improved clinical outcomes for patients with type 1 diabetes suffering from bowel symptoms.

FUNDING: Steno Collaborative Grant.}, } @article {pmid39788762, year = {2025}, author = {Augustijn, QJJ and Grefhorst, A and de Groen, P and Wortelboer, K and Seegers, JFM and Gül, IS and Suenaert, P and Verheij, J and de Vos, WM and Herrema, H and Nieuwdorp, M and Holleboom, AG}, title = {Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e088290}, doi = {10.1136/bmjopen-2024-088290}, pmid = {39788762}, issn = {2044-6055}, mesh = {Humans ; Double-Blind Method ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Adult ; Male ; Randomized Controlled Trials as Topic ; Capsules ; Female ; Middle Aged ; Fatty Liver/therapy ; Feces/microbiology ; Freeze Drying ; }, abstract = {BACKGROUND: The spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, affecting 30% of the world's population, with a significant risk of hepatic and cardiometabolic complications. Different stages of MASLD are accompanied by distinct gut microbial profiles, and several microbial components have been implicated in MASLD pathophysiology. Indeed, earlier studies demonstrated that hepatic necroinflammation was reduced in individuals with MASLD after allogenic faecal microbiota transplantation (FMT) from healthy donors on a vegan diet. Here, we further investigate the therapeutic potential of gut microbiome modulation using a syntrophic combination of next-generation beneficial bacteria with FMT in individuals with advanced MASLD.

METHODS AND ANALYSIS: This trial is a randomised, double-blind, placebo-controlled study investigating the therapeutic potential of lyophilised faecal microbiota capsules (LFMCs) in individuals with metabolic dysfunction-associated steatohepatitis. In this study, 48 participants will be randomised 1:1 to receive either healthy vegan donor LFMCs or placebo for 24 weeks. In addition, all participants will be supplemented with a set of next-generation beneficial bacteria, including Anaerobutyricum soehngenii, pasteurised Akkermansia muciniphila and Bifidobacterium animalis subsp. lactis, as well as fructo-oligosaccharides. A liver biopsy will be performed at baseline and at the end of the trial. In addition, participants will be assessed through MRI, FibroScan, blood tests, faecal samples and continuous glucose monitoring. The first participant was enrolled on 25 April 2023.

ETHICS AND DISSEMINATION: Ethical approval was obtained from the Medical Ethics Committee of the University Medical Centre of Amsterdam. The results of this study will be disseminated through peer-reviewed journals.

TRIAL REGISTRATION NUMBER: The trial is registered on clinicaltrials.gov (NCT05821010).}, } @article {pmid39788096, year = {2025}, author = {Wang, W and Pi, Z and Yu, Y and Zhang, F}, title = {The butterfly effect of the strain richness influences the efficacy of microbiota transplantation.}, journal = {Cell host & microbe}, volume = {33}, number = {1}, pages = {3-5}, doi = {10.1016/j.chom.2024.12.010}, pmid = {39788096}, issn = {1934-6069}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Animals ; Feces/microbiology ; Bacteria/classification ; }, abstract = {Strain-level variation in the gut microbiome modulates its impact on host health. Recently in Nature, Chen-Liaw et al. propose that strain richness is a crucial element in the gut ecosystem, thus influencing efficacy of fecal microbiota transplantation, and provide a theoretical foundation for optimizing microbiota-based treatments and developing microbiota medicine.}, } @article {pmid39787138, year = {2025}, author = {Luo, Y and Zhou, S and Zhang, X and Lin, Y and Liu, J and Cheng, W and Zeng, Y}, title = {The role of the microbiota and metabolites in the treatment of pulmonary fibrosis with UC-MSCs: Integrating fecal metabolomics and 16S rDNA analysis.}, journal = {PloS one}, volume = {20}, number = {1}, pages = {e0313989}, pmid = {39787138}, issn = {1932-6203}, mesh = {Animals ; Mice ; *Pulmonary Fibrosis/therapy/metabolism/pathology/microbiology ; *Metabolomics/methods ; *Feces/microbiology ; *RNA, Ribosomal, 16S/genetics ; Mesenchymal Stem Cell Transplantation/methods ; Mesenchymal Stem Cells/metabolism ; Gastrointestinal Microbiome ; Male ; DNA, Ribosomal/genetics ; Mice, Inbred C57BL ; Disease Models, Animal ; Lung/pathology/metabolism/microbiology ; Bleomycin ; Microbiota ; Cytokines/metabolism ; }, abstract = {INTRODUCTION: Pulmonary fibrosis (PF) is a chronic and irreversible interstitial lung disease characterized by a lack of effective therapies. Mesenchymal stem cells (MSCs) have garnered significant interest in the realm of lung regeneration due to their abundant availability, ease of isolation, and capacity for expansion. The objective of our study was to investigate the potential therapeutic role of umbilical cord-derived MSCs (UC-MSCs) in the management of PF, with a focus on the alterations in the gut microbiota and its metabolites during the use of UC-MSCs for the treatment of pulmonary fibrosis, as well as the possible mechanisms involved.

METHODS: Bleomycin injection was utilized to establish a mouse model of lung fibrosis, followed by the application of 16S rDNA sequencing and LC-MS/MS metabolomics to explore the underlying mechanism of UC-MSC treatment for lung fibrosis. Seventy-five mice were allocated into five groups, namely Control, Model, and low/medium/high dose of UC-MSCs groups, and survival metrics, lung morphology, and the levels of the inflammatory cytokines TNF-α, IL-1β, IL-6, and TGF-β1 were subsequently evaluated. Fecal samples from six mice in each of the Control group, Model group, and UC-MSCs-M groups were collected randomly for 16S rDNA sequencing to analyze the gut microbiota and nontargeted metabolomics.

RESULTS: In comparison to IPF model mice, the three treatment groups exhibited increased survival rates, restored alveolar morphology, and reduced levels of the inflammatory cytokines TNF-α, IL-1β, IL-6, and TGF-β1, confirming the anti-inflammatory properties of UC-MSCs in IPF treatment. The findings from the 16S rDNA assay indicate that UC-MSCs treatment effectively lower α-diversity induced such as Chao 1 and ACE, as well as β-diversity, leading to a decrease in microbiota abundance. The findings from the metabolomics analysis revealed that the metabolites exhibiting notable variances were primarily composed of Lipids and lipid-like molecules, Organoheterocyclic compounds, Organic acids and derivatives, and Benzenoids, indicating the potential of UC-MSCs to exert antifibrotic effects via these metabolic pathways.

CONCLUSION: Umbilical cord-derived mesenchymal stem cells (UC-MSCs) ameliorate bleomycin-induced pulmonary fibrosis symptoms in mice by exerting anti-inflammatory effects and mitigating pulmonary fibrosis through the modulation of gut microbiota disorders and their metabolism. These findings offer novel insights into the potential mechanisms and clinical utility of stem cell therapy for pulmonary fibrosis.}, } @article {pmid39786379, year = {2024}, author = {Yang, Q and Zhu, Y and Jian, X and Qiu, Y and Zhu, Y and Zhao, L and He, Y and An, G and Qiu, L and Guo, J and He, N and Abudumijiti, H and Hu, C and Chen, X and Huang, S and Feng, X and Li, X and Liu, J and Xu, Y and Zhou, W}, title = {Targeting Enterobacter cloacae attenuates osteolysis by reducing ammonium in multiple myeloma.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2024025694}, pmid = {39786379}, issn = {1528-0020}, abstract = {Multiple myeloma (MM)-induced bone disease affects not only patients' quality of life but also their overall survival. Our previous work demonstrated that the gut microbiome plays a crucial role in MM progression and drug resistance. However, the role of altered gut microbiota in MM bone disease remains unclear. In this study, we show that intestinal E. cloacae is significantly enriched in MM patients with osteolysis. Through fecal microbial transplantation and single bacterial colonization experiments in a 5TGM1 MM mouse model, we found that intestinal colonization of E. cloacae promotes osteolysis by increasing circulating ammonium levels. Elevated ammonium promotes osteoclastogenesis by increasing Trap protein levels in osteoclast precursors and by acetylating and stabilizing CCL3 protein in MM cells. Inhibition of ammonium synthesis, using E. cloacae with a deleted dcd gene, along with probiotic supplementation, alleviated osteolysis in MM. Overall, our work suggests that E. cloacae promotes osteolysis in MM by synthesizing ammonium. This establishes a novel mechanism and potential intervention strategy for managing MM with osteolysis.}, } @article {pmid39780269, year = {2025}, author = {Li, X and Ding, Q and Wan, X and Wu, Q and Ye, S and Lou, Y}, title = {Fecal microbiota transplantation attenuates Alzheimer's disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation.}, journal = {Behavioral and brain functions : BBF}, volume = {21}, number = {1}, pages = {2}, pmid = {39780269}, issn = {1744-9081}, support = {Grant No. Y20220029//Health Project of the Science and Technology Department of Wenzhou/ ; 231104408302408//Industry-university Cooperative education program of Ministry of Education/ ; First Class, Category A//the Key Discipline of Zhejiang Province in Medical Technology/ ; }, mesh = {Animals ; *Fecal Microbiota Transplantation/methods ; *Myeloid Differentiation Factor 88/metabolism ; Mice ; *Alzheimer Disease/therapy/microbiology ; *Mice, Transgenic ; *Toll-Like Receptor 4/metabolism ; *NF-kappa B/metabolism ; *Signal Transduction/physiology ; *Presenilin-1/genetics ; Amyloid beta-Protein Precursor/genetics ; Gastrointestinal Microbiome/physiology ; Inflammation/therapy/metabolism ; Male ; Disease Models, Animal ; Mice, Inbred C57BL ; }, abstract = {Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD. Additionally, disruption of the gut microbiota has been found to be associated with AD, and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach. However, the precise mechanism of FMT in the treatment of AD remains elusive. In this study, FMT was performed by transplanting fecal microbiota from healthy wild-type mice into APP/PS1 mice (APPswe, PSEN1dE9) to assess the effectiveness of FMT in mitigating AD-associated inflammation and to reveal its precise mechanism of action. The results demonstrated that FMT treatment improved cognitive function and reduced the expression levels of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway in mice, which was accompanied by the restoration of gut microbial dysbiosis. These findings suggest that FMT has the potential to ameliorate AD symptoms and delay the disease progression in APP/PS1 mice.}, } @article {pmid39779925, year = {2025}, author = {He, X and Hu, M and Xu, Y and Xia, F and Tan, Y and Wang, Y and Xiang, H and Wu, H and Ji, T and Xu, Q and Wang, L and Huang, Z and Sun, M and Wan, Y and Cui, P and Liang, S and Pan, Y and Xiao, S and He, Y and Song, R and Yan, J and Quan, X and Wei, Y and Hong, C and Liao, W and Li, F and El-Omar, E and Chen, J and Qi, X and Gao, J and Zhou, H}, title = {The gut-brain axis underlying hepatic encephalopathy in liver cirrhosis.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, pmid = {39779925}, issn = {1546-170X}, support = {82372305//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Up to 50-70% of patients with liver cirrhosis develop hepatic encephalopathy (HE), which is closely related to gut microbiota dysbiosis, with an unclear mechanism. Here, by constructing gut-brain modules to assess bacterial neurotoxins from metagenomic datasets, we found that phenylalanine decarboxylase (PDC) genes, mainly from Ruminococcus gnavus, increased approximately tenfold in patients with cirrhosis and higher in patients with HE. Cirrhotic, not healthy, mice colonized with R. gnavus showed brain phenylethylamine (PEA) accumulation, along with memory impairment, symmetrical tremors and cortex-specific neuron loss, typically found in patients with HE. This accumulation of PEA was primarily driven by decreased monoamine oxidase-B activity in both the liver and serum due to cirrhosis. Targeting PDC or PEA reversed the neurological symptoms induced by R. gnavus. Furthermore, fecal microbiota transplantation from patients with HE to germ-free cirrhotic mice replicated these symptoms and further corroborated the efficacy of targeting PDC or PEA. Clinically, high baseline PEA levels were linked to a sevenfold increased risk of HE after intrahepatic portosystemic shunt procedures. Our findings expand the understanding of the gut-liver-brain axis and identify a promising therapeutic and predictive target for HE.}, } @article {pmid39779878, year = {2025}, author = {Keskey, RC and Xiao, J and Hyoju, S and Lam, A and Kim, D and Sidebottom, AM and Zaborin, A and Dijkstra, A and Meltzer, R and Thakur, A and Zhang, K and Chen, HJ and Beloborodova, NV and Pautova, AK and Wolfe, K and Patel, B and Thewissen, R and Zaborina, O and Alverdy, JC}, title = {Enterobactin inhibits microbiota-dependent activation of AhR to promote bacterial sepsis in mice.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {39779878}, issn = {2058-5276}, support = {R01GMO62344-22//U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)/ ; }, abstract = {Sepsis is a major cause of morbidity and mortality, but our understanding of the mechanisms underlying survival or susceptibility is limited. Here, as pathogens often subvert host defence mechanisms, we hypothesized that this might influence the outcome of sepsis. We used microbiota analysis, faecal microbiota transplantation, antibiotic treatment and caecal metabolite analysis to show that gut-microbiota-derived tryptophan metabolites including indoles increased host survival in a mouse model of Serratia marcescens sepsis. Infection in macrophage-specific aryl hydrocarbon receptor (AhR) knockout mice revealed that AhR activation induced transcriptional reprogramming in macrophages and increased bacterial clearance and host survival. However, culture supernatants from multiple bacterial pathogens inhibited AhR activation in vitro. We showed that the secreted siderophore, enterobactin, inhibited AhR activation in vitro and increased sepsis mortality in vivo. By contrast, oral or systemic tryptophan supplementation increased survival. These findings show that sepsis survival depends upon the interplay between pathogen inhibition and the activation of AhR by a microbiota-derived metabolite.}, } @article {pmid39779854, year = {2025}, author = {Won, TH and Arifuzzaman, M and Parkhurst, CN and Miranda, IC and Zhang, B and Hu, E and Kashyap, S and Letourneau, J and Jin, WB and Fu, Y and Guzior, DV and , and Quinn, RA and Guo, CJ and David, LA and Artis, D and Schroeder, FC}, title = {Host metabolism balances microbial regulation of bile acid signalling.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {39779854}, issn = {1476-4687}, abstract = {Metabolites derived from the intestinal microbiota, including bile acids (BA), extensively modulate vertebrate physiology, including development[1], metabolism[2-4], immune responses[5-7] and cognitive function[8]. However, to what extent host responses balance the physiological effects of microbiota-derived metabolites remains unclear[9,10]. Here, using untargeted metabolomics of mouse tissues, we identified a family of BA-methylcysteamine (BA-MCY) conjugates that are abundant in the intestine and dependent on vanin 1 (VNN1), a pantetheinase highly expressed in intestinal tissues. This host-dependent MCY conjugation inverts BA function in the hepatobiliary system. Whereas microbiota-derived free BAs function as agonists of the farnesoid X receptor (FXR) and negatively regulate BA production, BA-MCYs act as potent antagonists of FXR and promote expression of BA biosynthesis genes in vivo. Supplementation with stable-isotope-labelled BA-MCY increased BA production in an FXR-dependent manner, and BA-MCY supplementation in a mouse model of hypercholesteraemia decreased lipid accumulation in the liver, consistent with BA-MCYs acting as intestinal FXR antagonists. The levels of BA-MCY were reduced in microbiota-deficient mice and restored by transplantation of human faecal microbiota. Dietary intervention with inulin fibre further increased levels of both free BAs and BA-MCY levels, indicating that BA-MCY production by the host is regulated by levels of microbiota-derived free BAs. We further show that diverse BA-MCYs are also present in human serum. Together, our results indicate that BA-MCY conjugation by the host balances host-dependent and microbiota-dependent metabolic pathways that regulate FXR-dependent physiology.}, } @article {pmid39779737, year = {2025}, author = {Corcione, S and Ferrocino, I and Lupia, T and Busca, A and Bianco, G and Dellacasa, C and Giaccone, L and Brunello, L and Butera, S and Costa, C and Bruno, B and De Rosa, FG}, title = {Influence of ESBL colonization status on gut microbiota composition during allogenic hematopoietic stem cell transplantation.}, journal = {Scientific reports}, volume = {15}, number = {1}, pages = {1275}, pmid = {39779737}, issn = {2045-2322}, support = {Project no. PE00000007, INF-ACT//EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; Middle Aged ; Adult ; Prospective Studies ; Pilot Projects ; *beta-Lactamases/metabolism ; *Transplantation, Homologous/adverse effects ; Aged ; Feces/microbiology ; Italy ; Anti-Bacterial Agents/therapeutic use/pharmacology ; }, abstract = {After allogeneic HSCT (allo-HSCT), the diversity of the intestinal microbiota significantly decreases. The changes can be rapid and are thought to be caused by chemotherapy, antibiotics, or intestinal inflammation. Most patients are exposed to prophylactic and therapeutic antibiotics during neutropenia and several patients are colonized by ESBL bacteria. We investigated the changes in gut microbiota composition in allo-HSCT, aiming at investigating if the acquisition of ESBL colonization may affect gut microbiome diversity during allo-HSCT. This was a single-center prospective pilot study. All patients consecutively admitted to the Haematological Unit of the City of Health and Science, Molinette Hospital in Turin, Italy, and undergoing allo-HSCT between August 2017 to August 2020 were enrolled in the study. Microbiome analysis on fecal samples were collected every 7 days from hospital admission to discharge and until 1 year after HSCT. 48 patients were enrolled in the study. At baseline 14 patients (29.16%) were colonized by MDR bacteria, mostly extended-spectrum beta-lactamase (ESBL)-producing gram negatives (N = 11; 78.57%). During allo-HSCT, one patient had a positive rectal swab for a carbapenemase-producing Klebsiella pneumoniae and eight patients lost the colonization during the hospital stay. Microbiota composition was compared between patients colonized by ESBL at baseline and non-colonized patients. Patients colonized by ESBL had a greater abundances of Bifidobacterium, Blautia, Clostridium, Coprococcus, L-Ruminococcus Mogibacteriaceae, Peptostreptococceae and Oscillospira, while non-colonized ESBL patients had a greater abundance of Actinomycetales, Staphylococcus and Sutterella. Moreover, microbiota composition of colonized by ESBL that retained colonization after HSCT showed an increased in abundances of Akkermansia, Dialister, Erysipelotrichaceae and Methanobrevibacter when compared with patients that become negative at rectal swabs. From a clinical perspective, the evolution of this prospective pilot study will be to investigate markers of gut barrier functions, SCFA productions and to correlate the predictivity of these parameters with risk of invasive infections and clinical outcomes in allo-HSCT population.}, } @article {pmid39778887, year = {2025}, author = {Pérez-Accino, J and Salavati, M and Glendinning, L and Salavati Schmitz, S}, title = {Effect of a single rectal fecal microbiota transplantation on clinical severity and fecal microbial communities in dogs with chronic inflammatory enteropathy.}, journal = {Journal of veterinary internal medicine}, volume = {39}, number = {1}, pages = {e17264}, pmid = {39778887}, issn = {1939-1676}, support = {//Fiona and Ian Russel Fund/ ; }, mesh = {Animals ; Dogs ; *Dog Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation/veterinary ; *Feces/microbiology ; Male ; Female ; Inflammatory Bowel Diseases/veterinary/therapy/microbiology ; RNA, Ribosomal, 16S/genetics ; Gastrointestinal Microbiome ; Chronic Disease ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been advocated as a treatment for chronic enteropathy (CE) in dogs. However, so far only short-term clinical effects have been reported whereas the effect on the microbiota remains unexplored.

HYPOTHESIS/OBJECTIVES: Assess if a single FMT enema can lead to clinical improvement in dogs with CE when accompanied by presumed favorable microbiota changes. The effect of glycerol as a cryopreservative when storing FMT preparations also was assessed.

ANIMALS: Seven dogs with CE that received FMTs from 2 healthy donor dogs.

MATERIALS AND METHODS: Six dogs received a single FMT, 1 dog received 3 consecutive FMTs. Canine chronic enteropathy clinical activity index (CCECAI) and fecal samples were obtained before (Day 0), and 7, 30 and 90 days after FMT. Samples were stored with and without 10% glycerol. Sequencing of microbiota (16S rRNA, Illumina) was performed and compared by accepted analysis pipelines.

RESULTS: Median CCECAI before FMT was 8 (range, 5-14), decreased to a median of 3 (range, 1-12) within 1 week and a median of 1 (range, 0-12) by Day 30 (P < .01), with an average duration of response of approximately 10 weeks. Significant variation in the donors' microbiota composition was observed across different donations. Recipient microbiota composition or diversity did not change over time. Glycerol addition was associated with a difference in microbiota composition (P ≤ .001).

A single FMT can be considered an appropriate treatment in dogs with CE, but consistent microbiota changes were not observed.}, } @article {pmid39778639, year = {2025}, author = {Chen, C and Wang, J and Cheng, M and Xie, H and Li, W and Zhang, C}, title = {Muribaculum intestinale-derived 3-hydroxybutyric acid from Heterophyllin B attenuated pulmonary fibrosis through IDO1-mediated ferroptosis.}, journal = {Pharmacological research}, volume = {212}, number = {}, pages = {107587}, doi = {10.1016/j.phrs.2025.107587}, pmid = {39778639}, issn = {1096-1186}, abstract = {Pulmonary fibrosis (PF) is a fatal disease with increasing incidence, poor prognosis, and unclear pathogenesis. Our previous research demonstrated the beneficial effects of the natural cyclopeptide Heterophyllin B (HB) in PF. However, the precise mechanism by which HB exerts its effects in PF remains unclear. Our study revealed HB's beneficial effects in alleviating PF symptoms and restoring the intestinal mucosal barrier. Subsequently, the microbiota-dependent antifibrotic efficacy of HB was verified using various delivery routes, antibiotic treatments, and faecal microbiota transplantation. Functionally, 16S rRNA sequencing, untargeted metabolomics, and co-incubation experiments revealed that the antifibrotic efficacy of HB was primarily contingent on the enrichment of Muribaculum intestinale and its metabolite, 3-hydroxybutyric acid. Mechanistically, indoleamine 2,3- dioxygenase 1 (IDO1)-mediated ferroptosis was identified as a pivotal process in initiating PF, and the anti-fibrotic efficacy of HB relies on suppressing IDO1-mediated ferroptosis. Conversely, IDO1 deficiency alleviated the symptoms of bleomycin-induced PF and ferroptosis in mice. Coincidentally, both IDO1 overexpression and ferroptosis were observed in the pulmonary tissue of patients with idiopathic PF. Collectively, this study revealed that HB alleviates PF by eliminating intestinal microecology and metabolism and highlights the feasibility of targeting IDO1 for PF treatment.}, } @article {pmid39777251, year = {2025}, author = {Quaglio, AE and Magro, DO and Imbrizi, M and De Oliveira, EC and Di Stasi, LC and Sassaki, LY}, title = {Creeping fat and gut microbiota in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {31}, number = {1}, pages = {102042}, pmid = {39777251}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology/therapy ; Humans ; *Gastrointestinal Microbiome/physiology/immunology ; *Dysbiosis/immunology ; *Fecal Microbiota Transplantation ; *Intra-Abdominal Fat/immunology ; *Probiotics/therapeutic use ; *Disease Progression ; Prebiotics/administration & dosage ; Fibrosis ; Animals ; Mesentery ; }, abstract = {In this article, we explored the role of adipose tissue, especially mesenteric adipose tissue and creeping fat, and its association with the gut microbiota in the pathophysiology and progression of Crohn's disease (CD). CD is a form of inflammatory bowel disease characterized by chronic inflammation of the gastrointestinal tract, influenced by genetic predisposition, gut microbiota dysbiosis, and environmental factors. Gut microbiota plays a crucial role in modulating immune response and intestinal inflammation and is associated with the onset and progression of CD. Further, visceral adipose tissue, particularly creeping fat, a mesenteric adipose tissue characterized by hypertrophy and fibrosis, has been implicated in CD pathogenesis, inflammation, and fibrosis. The bacteria from the gut microbiota may translocate into mesenteric adipose tissue, contributing to the formation of creeping fat and influencing CD progression. Although creeping fat may be a protective barrier against bacterial invasion, its expansion can damage adjacent tissues, leading to complications. Modulating gut microbiota through interventions such as fecal microbiota transplantation, probiotics, and prebiotics has shown potential in managing CD. However, more research is needed to clarify the mechanisms linking gut dysbiosis, creeping fat, and CD progression and develop targeted therapies for microbiota modulation and fat-related complications in patients with CD.}, } @article {pmid39777148, year = {2024}, author = {An, Y and He, L and Xu, X and Piao, M and Wang, B and Liu, T and Cao, H}, title = {Gut microbiota in post-acute COVID-19 syndrome: not the end of the story.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1500890}, pmid = {39777148}, issn = {1664-302X}, abstract = {The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to major global health concern. However, the focus on immediate effects was assumed as the tip of iceberg due to the symptoms following acute infection, which was defined as post-acute COVID-19 syndrome (PACS). Gut microbiota alterations even after disease resolution and the gastrointestinal symptoms are the key features of PACS. Gut microbiota and derived metabolites disorders may play a crucial role in inflammatory and immune response after SARS-CoV-2 infection through the gut-lung axis. Diet is one of the modifiable factors closely related to gut microbiota and COVID-19. In this review, we described the reciprocal crosstalk between gut and lung, highlighting the participation of diet and gut microbiota in and after COVID-19 by destroying the gut barrier, perturbing the metabolism and regulating the immune system. Therefore, bolstering beneficial species by dietary supplements, probiotics or prebiotics and fecal microbiota transplantation (FMT) may be a novel avenue for COVID-19 and PACS prevention. This review provides a better understanding of the association between gut microbiota and the long-term consequences of COVID-19, which indicates modulating gut dysbiosis may be a potentiality for addressing this multifaceted condition.}, } @article {pmid39776845, year = {2024}, author = {Zhuang, L and You, Y and Zeng, S and Yu, Z and Wang, H and Chen, M and Wen, W}, title = {Fecal microbiota transplantation in severe pneumonia: a case report on overcoming pan-drug resistant Klebsiella pneumoniae infection.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1451751}, pmid = {39776845}, issn = {2296-858X}, abstract = {OBJECTIVE: To evaluate the therapeutic potential of fecal microbiota transplantation (FMT) in treating severe pneumonia patients with concurrent pan-drug resistant Klebsiella pneumoniae infection.

METHODS: A case report of a 95-year-old female patient with severe pneumonia, complicated by pan-resistant bacterial infections, is presented. The patient was diagnosed with severe pneumonia caused by COVID-19, along with co-infections of Staphylococcus hominis, Enterococcus faecalis, Candida tropicalis, Pseudomonas aeruginosa, ESBL-producing pan-drug resistant Klebsiella pneumoniae and pan-resistant Acinetobacter baumannii. During hospitalization, the patient underwent comprehensive treatments, including antimicrobials, mechanical ventilation, and fiberoptic bronchoscopic alveolar lavage. FMT was administered following the failure of conventional treatments to resolve recurrent diarrhea, increased sputum production, and persistent pan-drug resistant Klebsiella pneumoniae infection.

RESULTS: Post-FMT, the patient exhibited significant clinical improvement, including reduced sputum production, cessation of diarrhea, and the normalization of respiratory symptoms. Gut microbiota analysis revealed that FMT enhanced the abundance of beneficial microbiota and suppressed Klebsiella pneumoniae, and the patient was successfully discharged after 133 days of hospitalization.

CONCLUSION: FMT emerged as a pivotal intervention in the management of this severe pneumonia case, suggesting its efficacy in restoring gut microbiota balance and aiding recovery from multi-drug-resistant infections. This case underscores the potential of FMT as a therapeutic option in severe pulmonary infections, especially in the context of antibiotic resistance in severe pneumonia patients.}, } @article {pmid39776440, year = {2024}, author = {Fang, L and Ning, J}, title = {Recent advances in gut microbiota and thyroid disease: pathogenesis and therapeutics in autoimmune, neoplastic, and nodular conditions.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1465928}, pmid = {39776440}, issn = {2235-2988}, mesh = {*Gastrointestinal Microbiome ; Humans ; *Probiotics/therapeutic use ; *Thyroid Diseases/therapy/microbiology ; *Fecal Microbiota Transplantation ; Animals ; Bacteria/classification/metabolism ; Neoplasms/therapy/microbiology ; Dysbiosis/therapy/microbiology ; }, abstract = {This review synthesizes key findings from the past five years of experimental literature, elucidating the gut microbiome's significant influence on the pathogenesis of thyroid diseases. A pronounced shift in the gut microbiota composition has been consistently observed, with a significant reduction in bacteria such as Bifidobacterium, Bacillaceae, Megamonas, and Clostridium, and a notable increase in bacteria, including Bacteroides, Proteobacteria, Actinobacteria, Desulfobacterota, and Klebsiella. These alterations are implicated in the development and progression of thyroid diseases by impacting metabolic pathways including bile acid and cytokine production, including a decrease in short-chain fatty acids (SCFAs) that are crucial for immune regulation and thyroid hormone homeostasis. The review also highlights the therapeutic implications of probiotics in managing thyroid conditions. Evidence suggests that probiotic adjunct therapy can modulate the gut microbiota, leading to improvements in thyroid function and patient outcomes. The use of specific probiotic strains, such as Lactiplantibacillus plantarum 299v and Bifidobacterium longum, has demonstrated potential in enhancing the effects of traditional treatments and possibly restoring a balanced gut microbiota. Notably, fecal microbiota transplantation (FMT) has emerged as a promising intervention in Graves' Disease (GD), demonstrating the potential to recalibrate the gut microbiota, thereby influencing neurotransmitters and trace elements via the gut-brain and gut-thyroid axes. The integration of microbiome-based therapies with traditional treatments is anticipated to usher in a new era of personalized thyroid disease management, offering a more nuanced approach to patient care. By integrating this body of work, the review offers an innovative perspective on the gut microbiome's broad impact on thyroid diseases and the therapeutic applications of probiotics.}, } @article {pmid39775925, year = {2025}, author = {Bloem, MN and Baaleman, DF and Thapar, N and Roberts, SE and Koppen, IJN and Benninga, MA}, title = {Prevalence of functional defecation disorders in European children: A systematic review and meta-analysis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.12437}, pmid = {39775925}, issn = {1536-4801}, support = {//None/ ; }, abstract = {OBJECTIVES: Functional defecation disorders (FDDs) are common among children worldwide. The prevalence of these disorders has not been clearly described in Europe. This study performed a systematic review and meta-analysis on the prevalence of FDD in European children and assessed geographical, age, and sex distribution and associated factors.

METHODS: PubMed, Embase, Psycinfo, Cochrane Library, and Cinahl were searched from 1999 to July 2023. Included studies were (1) prospective or cross-sectional studies of European population-based samples; (2) reporting the prevalence of infant dyschezia (ID) according to Rome II, III, or IV criteria or functional constipation (FC) or functional non-retentive fecal incontinence (FNRFI) according to Rome III or IV criteria; (3) aged 0-18 years; and (4) published in English, Dutch or Spanish. PRISMA guidelines for extracting data and assessing data quality were followed.

RESULTS: Twenty-eight studies were included. Pooled prevalence was 6.9% (95% confidence interval [CI]: 3.1%-11.9%) for ID in infants 0-12 months (9 studies, n = 5611), 8.17% (95% CI: 6.33%-10.22%) for FC in children <4 years (25 studies, n = 35,189), 11.39% (95% CI: 9.34%-14.11%) for FC in children 4-18 years, and 0.24% (95% CI: 0.07%-0.49%) for FNRFI in children 4-18 years (7 studies, n = 16,873). No sex predominance was found for FC. FC prevalence did not differ significantly when diagnosed according to Rome III versus IV. FC prevalence differed between countries, with greatest rates in Italy, Germany, and Spain. No meta-analysis could be performed on other factors associated with FDD.

CONCLUSIONS: FDD is common in European children. Future longitudinal studies are needed to provide better insight into associated factors in pathogenesis.}, } @article {pmid39775370, year = {2025}, author = {Lai, Y and Qiu, R and Zhou, J and Ren, L and Qu, Y and Zhang, G}, title = {Fecal Microbiota Transplantation Alleviates Airway Inflammation in Asthmatic Rats by Increasing the Level of Short-Chain Fatty Acids in the Intestine.}, journal = {Inflammation}, volume = {}, number = {}, pages = {}, pmid = {39775370}, issn = {1573-2576}, support = {(No. 2021JJ30513, No. 2017JJ3245)//Natural Science Foundation of Hunan Province/ ; No. 20B444//Education Department of Hunan Province/ ; (No. 81603705)//National Natural Science Foundation of China/ ; (No. 2017M612567)//Postdoctoral Science Foundation of China/ ; (2024XJZA008)//Hunan University of Chinese Medicine research project/ ; }, abstract = {Asthma is a prevalent chronic inflammatory disorder of the respiratory tract that not only manifests with respiratory symptoms but also often involves intestinal flora disorders and gastrointestinal dysfunction. Recent studies have confirmed the close relationship between the gut and lungs, known as the "gut-lung axis" theory. Fecal microbiota transplantation (FMT), a method for restoring normal intestinal flora, has shown promise in treating common gastrointestinal diseases. The "gut-lung axis" theory suggests that FMT may have significant therapeutic potential for asthma. In this study, we established an Ovalbumin (OVA)-induced rat model of asthma to investigate the protective effect of FMT on airway inflammation and the restoration of intestinal short-chain fatty acids (SCFAs), aiming to explore its underlying mechanism. Rats in the Control group underwent fecal treatment via gavage (Control-FMT, C-FMT group), while rats in the Asthma group underwent fecal treatment via gavage after asthma induction (Asthma-FMT, A-FMT group). Following a two-week period of continuous intragastric administration, various measurements were conducted to assess pulmonary function, peripheral blood neutrophil, lymphocyte, and eosinophil content, lung tissue pathology, and collagen fiber deposition in the lungs. Additionally, neutrophil and eosinophil content in bronchoalveolar lavage fluid (BALF), expression levels of Interleukin-4 (IL-4), IL-5, IL-13, IL-17, IL-33, leukotrienes (LT), thymic stromal lymphopoietin (TSLP), prostaglandin D2 (PGD2) protein and mRNA in lung tissue, and SCFAs content in stool were evaluated. In the C-FMT group, lung function significantly improved, inflammatory cell content in peripheral blood and BALF decreased, lung tissue pathology and collagen fiber deposition significantly improved, the protein and mRNA levels of lung inflammatory factors IL-4, IL-5, IL-13, IL-17, IL-33, LT, TSLP, PGD2 were significantly decreased, and SCFAs such as acetate (C2), propionate (C3), butyrate (C4), isobutyric acid (I-C4), valeric acid (C5), and isovaleric acid (I-C5) content in stool significantly increased. However, the indexes in the A-FMT group did not show significant recovery, and the treatment effect on asthma symptoms in rats was inferior to that in the C-FMT group. Asthma induced intestinal flora disorders in rats, and FMT treatment improved the inflammatory response in asthmatic rat models and corrected their intestinal SCFAs disorders. Encouraging the recovery of intestinal SCFAs may play a significant role, and beneficial bacteria present in feces may improve asthma symptoms by promoting the remodeling of intestinal flora. This experiment provides further scientific evidence supporting the "gut-lung axis" theory.}, } @article {pmid39773995, year = {2024}, author = {Mullish, BH and Innes, AJ and Roberts, LA and Anim-Burton, S and Webber, L and Johnson, NA and Ghani, R and Farshi, P and Khan, AB and Kinsella, F and Kottaridis, P and Krishnamurthy, P and Nicholson, E and Palanicawandar, R and Wheeler, G and Davies, F and Marchesi, JR and Pavlů, J}, title = {Intestinal Microbiota Transplant Prior to Allogeneic Stem Cell Transplant (MAST) trial: study protocol for a multicentre, double-blinded, placebo-controlled, phase IIa trial.}, journal = {BMJ open}, volume = {14}, number = {12}, pages = {e093120}, doi = {10.1136/bmjopen-2024-093120}, pmid = {39773995}, issn = {2044-6055}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hematopoietic Stem Cell Transplantation ; Double-Blind Method ; *Transplantation, Homologous ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; Adult ; Randomized Controlled Trials as Topic ; Transplantation Conditioning/methods ; Fecal Microbiota Transplantation/methods ; Hematologic Neoplasms/therapy ; Female ; Male ; }, abstract = {INTRODUCTION: Lower diversity of the gut microbiome prior to allogeneic haematopoietic cell transplantation (HCT) correlates with reduced survival after the intervention. Most patients undergoing HCT for a haematological malignancy have previously received intensive chemotherapy, resulting in prolonged neutropenic episodes requiring broad-spectrum antibiotics; use of these has been linked to reduced microbiome diversity. Intestinal microbiota transplant (IMT) is a novel treatment approach that restores this diversity. We hypothesised that IMT performed prior to initiation of HCT conditioning restores microbiome diversity during the early stages of HCT, leading to decreased frequency of complications and improved outcomes of HCT.

METHODS AND ANALYSIS: 50 adult patients receiving allogeneic HCT will be recruited into this phase IIa trial and randomised 1:1 to receive capsulised IMT or matched placebo shortly prior to initiation of HCT conditioning and followed for up to 12 months. The primary outcome will be to assess the increase in alpha diversity between pre-IMT and that measured at ~42 days after IMT administration (day +28 of HCT), comparing the difference between patients receiving IMT compared with placebo. Secondary outcomes will include tolerability, the dynamics of gut microbiome diversity metrics and taxonomy over all time points assessed, as well as clinical outcomes (including burden of invasive infections, days of fever, admission to intensive care, development of graft-vs-host disease and mortality).

ETHICS AND DISSEMINATION: This study was approved by a UK Research Ethics Committee (REC reference: 23/NE/0105). Dissemination of results will be in concert with patient and public involvement group input and is expected to be primarily via abstract presentation at conferences and manuscripts in peer-reviewed journals.

TRIAL REGISTRATION NUMBERS: NCT6355583; EudraCT: 2022-003617-10.}, } @article {pmid39773319, year = {2025}, author = {Prince, N and Peralta Marzal, LN and Roussin, L and Monnoye, M and Philippe, C and Maximin, E and Ahmed, S and Salenius, K and Lin, J and Autio, R and Adolfs, Y and Pasterkamp, RJ and Garssen, J and Naudon, L and Rabot, S and Kraneveld, AD and Perez-Pardo, P}, title = {Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447822}, doi = {10.1080/19490976.2024.2447822}, pmid = {39773319}, issn = {1949-0984}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Mice ; Male ; *Mice, Inbred C57BL ; *Brain-Gut Axis/physiology ; *Mice, Inbred BALB C ; Child ; Autism Spectrum Disorder/microbiology ; Dysbiosis/microbiology ; Feces/microbiology ; Disease Models, Animal ; Autistic Disorder/microbiology/physiopathology ; Female ; Social Behavior ; Species Specificity ; Bacteria/classification/isolation & purification/genetics/metabolism ; }, abstract = {Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.}, } @article {pmid39772953, year = {2025}, author = {Teigen, LM and Hoeg, A and Zehra, H and Shah, P and Johnson, R and Hutchison, K and Kocher, M and Lin, AW and Johnson, AJ and Vaughn, BP}, title = {Nutritional optimization of fecal microbiota transplantation in humans: a scoping review.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446378}, doi = {10.1080/19490976.2024.2446378}, pmid = {39772953}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; *Diet ; Clostridium Infections/therapy/microbiology ; Feces/microbiology ; Dietary Supplements ; }, abstract = {Diet constitutes a major source of nutrient flow to the gut microbes. As such, it can be used to help shape the gut microbiome. Fecal microbiota transplantation (FMT) is an increasingly promising therapy in disease states beyond recurrent Clostridioides difficile infection, but diet is largely overlooked for its potential to help optimize this therapy. Therefore, the aim of this scoping review is to present the literature landscape that captures pre- and post-FMT dietary intake in humans, identify research gaps, and provide recommendations for future research. A comprehensive search strategy was developed and searches were run in five databases. Studies were included if they discussed adults who underwent FMT for any recognized treatment indication and had dietary intake as a study objective, this search encompassed studies with interventions that included foods and dietary supplements. The initial screening identified a total of 7721 articles, of which 18 met the inclusion criteria for this review. Studies were heterogeneous, but taken together, they introduce a framework that defines important nutritional considerations for both donors and FMT recipients in the period around FMT dosing. This framework is summarized with this review and highlights the opportunities available to develop FMT-based precision nutrition strategies to optimize its clinical efficacy.}, } @article {pmid39772388, year = {2025}, author = {Wouters, S and Moors, H and Verslegers, M and Leys, N and Malhotra-Kumar, S and Kumar-Singh, S and Mysara, M}, title = {Protocol for fecal microbiota transplantation: A microaerophilic approach for mice housed in a specific pathogen-free facility.}, journal = {STAR protocols}, volume = {6}, number = {1}, pages = {103517}, doi = {10.1016/j.xpro.2024.103517}, pmid = {39772388}, issn = {2666-1667}, abstract = {Recently, studies have emerged exploring the potential application of fecal microbiota transplantation (FMT) in pre-clinical settings. Here, we present a protocol for FMT for mice housed in a specific pathogen-free (SPF) facility. We describe steps for sample collection, microaerophilic processing of freshly collected fecal pellets, and administration through oral gavage. We then detail procedures for the engraftment of the bacterial community. This protocol focuses on age- and gender-matched, healthy donor mice using a mobile and cost-effective alternative to an anoxic cabinet.}, } @article {pmid39771031, year = {2024}, author = {Olga, B and Boicean, A and Fleacă, SR and Blanca, G and Florin, S and Corina, RF and Iulian, RF and Adelaida, S and Sabrina, B and Dura, H and Corina, P and Cristian, A and Onisor, DM}, title = {Importance of Fecal Microbiota Transplantation and Molecular Regulation as Therapeutic Strategies in Inflammatory Bowel Diseases.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/nu16244411}, pmid = {39771031}, issn = {2072-6643}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Inflammatory Bowel Diseases/therapy/microbiology/immunology ; *MicroRNAs/metabolism ; *Gastrointestinal Microbiome ; Gene Expression Regulation ; Animals ; Intestinal Mucosa/microbiology/metabolism/immunology ; }, abstract = {Noncoding RNAs, particularly microRNAs (miRNAs) and small interfering RNAs (siRNAs), have emerged as key players in the pathogenesis and therapeutic strategies for inflammatory bowel disease (IBD). MiRNAs, small endogenous RNA molecules that silence target mRNAs to regulate gene expression, are closely linked to immune responses and inflammatory pathways in IBD. Notably, miR-21, miR-146a, and miR-155 are consistently upregulated in IBD, influencing immune cell modulation, cytokine production, and the intestinal epithelial barrier. These miRNAs serve as biomarkers for disease progression and severity, as well as therapeutic targets for controlling inflammation. This comprehensive review highlights the intricate interplay between the gut microbiota, fecal microbiota transplantation (FMT), and miRNA regulation. It concludes that microbiota and FMT influence miRNA activity, presenting a promising avenue for personalized IBD treatment.}, } @article {pmid39771027, year = {2024}, author = {Gruenbaum, BF and Merchant, KS and Zlotnik, A and Boyko, M}, title = {Gut Microbiome Modulation of Glutamate Dynamics: Implications for Brain Health and Neurotoxicity.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/nu16244405}, pmid = {39771027}, issn = {2072-6643}, mesh = {*Gastrointestinal Microbiome/physiology ; Humans ; *Glutamic Acid/metabolism ; *Brain-Gut Axis/physiology ; *Brain/metabolism ; Animals ; Fecal Microbiota Transplantation ; Blood-Brain Barrier/metabolism ; Neurotoxicity Syndromes/etiology/metabolism ; Depression/metabolism/microbiology ; }, abstract = {The gut-brain axis plays an integral role in maintaining overall health, with growing evidence suggesting its impact on the development of various neuropsychiatric disorders, including depression. This review explores the complex relationship between gut microbiota and glutamate (Glu) regulation, highlighting its effect on brain health, particularly in the context of depression following certain neurological insults. We discuss how microbial populations can either facilitate or limit Glu uptake, influencing its bioavailability and predisposing to neuroinflammation and neurotoxicity. Additionally, we examine the role of gut metabolites and their influence on the blood-brain barrier and neurotransmitter systems involved in mood regulation. The therapeutic potential of microbiome-targeted interventions, such as fecal microbiota transplantation, is also highlighted. While much research has explored the role of Glu in major depressive disorders and other neurological diseases, the contribution of gut microbiota in post-neurological depression remains underexplored. Future research should focus on explaining the mechanisms linking the gut microbiota to neuropsychiatric outcomes, particularly in conditions such as post-stroke depression, post-traumatic brain-injury depression, and epilepsy-associated depression. Systematic reviews and human clinical studies are needed to establish causal relationships and assess the efficacy of microbiome-targeted therapies in improving the neuropsychiatric sequalae after neurological insults.}, } @article {pmid39770958, year = {2024}, author = {Puca, P and Del Gaudio, A and Becherucci, G and Sacchetti, F and Sofo, L and Lopetuso, LR and Papa, A and Cammarota, G and Scaldaferri, F}, title = {Diet and Microbiota Modulation for Chronic Pouchitis: Evidence, Challenges, and Opportunities.}, journal = {Nutrients}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/nu16244337}, pmid = {39770958}, issn = {2072-6643}, mesh = {*Pouchitis/therapy/microbiology ; Humans ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Chronic Disease ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; Colitis, Ulcerative/microbiology/therapy ; Proctocolectomy, Restorative/adverse effects ; Diet/methods ; Diet, Mediterranean ; }, abstract = {Chronic pouchitis occurs in about 50% of patients undergoing a restorative proctocolectomy for ulcerative colitis. This affection represents a significant therapeutic challenge, particularly for symptomatic patients who do not respond to antibiotic treatments and biologic therapies. Several dietary approaches, including low FODMAP diets and the Mediterranean diet, have shown promising results in improving symptoms and disease burden. The rationale for dietary intervention lies in the reduction in inflammation and modulation of gut microbiota. However, conflicting results and methodological heterogeneity jeopardize the transition of these approaches from the field of research to clinical practice. Together with a nutritional approach, innovative methods of microbiota modulation, including probiotics and fecal microbiota transplantation, are emerging as safe and effective strategies in managing chronic pouchitis. This narrative review analyzes recent advancements in nutritional therapies and microbiota modulation as innovative and complementary approaches for managing chronic pouchitis. After examining microbiota modulation strategies, specifically the effectiveness of probiotics, prebiotics, and fecal microbiota transplantation in restoring microbial diversity and their potential role in alleviating symptoms, the review assesses the available clinical evidence concerning dietary interventions and their impact on gut microbiota. A comprehensive understanding of interventions aimed at modulating the microbiota is crucial for enhancing the effectiveness of conventional therapies. Such strategies may lead to significant improvements in patients' quality of life and their perception of the disease. However, the variability in microbiota composition, the use of restrictive diets, and the lack of standardized methods for evaluating these interventions remain significant challenges. Future research is essential to improve our understanding of the underlying mechanisms and optimize clinical application.}, } @article {pmid39770742, year = {2024}, author = {Park, SH and Lee, JH and Lee, S and Shin, J and Cha, B and Hong, JT and Kwon, KS}, title = {Factors for Treatment Failure After Fecal Microbiota Transplantation in Clostridioides difficile Infection.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/microorganisms12122539}, pmid = {39770742}, issn = {2076-2607}, support = {2023AR05//Seoul Clinical Laboratories/ ; }, abstract = {Recently, fecal microbiota transplantation (FMT) has been introduced as an effective treatment option for Clostridioides difficile infection (CDI). However, the risk factors associated with FMT treatment failure have not been well demonstrated. Therefore, we aimed to investigate the risk factors of treatment failure or recurrence after FMT for CDI. This retrospective study included 124 patients with CDI who underwent FMT at Inha University Hospital between November 2017 and August 2021 and were followed up for 8 weeks after FMT for symptoms of CDI. FMT failure was defined as diarrhea recurrence or a positive stool test. We assessed the risk factors for treatment failure, including comorbidities, antibiotic use pre- and post-FMT, and the number of CDI episodes before FMT. Ninety-three patients (75%) experienced symptom improvement <7 days after FMT, while treatment failure occurred in 40 patients (32.3%). Multivariate analysis revealed that males had a lower symptom improvement rate <7 days after FMT (p = 0.049). Patients using antibiotics after FMT showed a higher rate of recurrence or treatment failure in <8 weeks (p = 0.032). Patients requiring antibiotics after FMT should be considered at higher risk of treatment failure. Careful antibiotic stewardship, particularly minimizing non-essential antibiotic use before and after FMT, may significantly enhance treatment outcomes. Further large-scale prospective studies are warranted to confirm these findings and develop targeted antibiotic management protocols for improving the efficacy of FMT in CDI treatment.}, } @article {pmid39770703, year = {2024}, author = {Islam, MZ and Jozipovic, D and Lopez, PA and Krych, L and Correia, BSB and Bertram, HC and Hansen, AK and Hansen, CHF}, title = {Wild-Mouse-Derived Gut Microbiome Transplantation in Laboratory Mice Partly Alleviates House-Dust-Mite-Induced Allergic Airway Inflammation.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/microorganisms12122499}, pmid = {39770703}, issn = {2076-2607}, support = {R288-2018-1123//Lundbeck Foundation/ ; N/A//Sigrid Rigmor Morans Mindefond/ ; }, abstract = {Laboratory mice are instrumental for preclinical research but there are serious concerns that the use of a clean standardized environment for specific-pathogen-free (SPF) mice results in poor bench-to-bedside translation due to their immature immune system. The aim of the present study was to test the importance of the gut microbiota in wild vs. SPF mice for evaluating host immune responses in a house-dust-mite-induced allergic airway inflammation model without the influence of pathogens. The wild mouse microbiome reduced histopathological changes and TNF-α in the lungs and serum when transplanted to microbiota-depleted mice compared to mice transplanted with the microbiome from SPF mice. Moreover, the colonic gene expression of Gata3 was significantly lower in the wild microbiome-associated mice, whereas Muc1 was more highly expressed in both the ileum and colon. Intestinal microbiome and metabolomic analyses revealed distinct profiles associated with the wild-derived microbiome. The wild-mouse microbiome thus partly reduced sensitivity to house-dust-mite-induced allergic airway inflammation compared to the SPF mouse microbiome, and preclinical studies using this model should consider using both 'dirty' rewilded and SPF mice for testing new therapeutic compounds due to the significant effects of their respective microbiomes and derived metabolites on host immune responses.}, } @article {pmid39770634, year = {2024}, author = {Chun, M and Tun, KM and Vongsavath, T and Verma, R and Batra, K and Limsui, D and Jenkins, E}, title = {Fecal Microbiota Transplantation for Chronic Pouchitis: A Systematic Review and Meta-Analysis.}, journal = {Microorganisms}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/microorganisms12122430}, pmid = {39770634}, issn = {2076-2607}, abstract = {Pouchitis is a common complication after ileal-pouch anal anastomosis in patients with medically refractory ulcerative colitis. There has been a lack of high-level evidence focusing on the safety and efficacy outcomes of fecal microbiota transplantation (FMT). We aim to evaluate outcomes and complications of fecal microbiota transplantation (FMT) for chronic pouchitis. Databases were systematically searched to retrieve English-only, original studies, published from inception to 31 March 2024, investigating chronic pouchitis only. Primary outcomes included overall remission, clinical response, remission, relapse, and complications. Seven studies with 94 patients were included. The pooled overall remission rate was 15% (95% CI: 0-29%, p < 0.001), the clinical response rate was 33% (95% CI: 19-46%, p = 0.14), the clinical remission rate was 14% (95% CI: 19-46%, p < 0.001), and the clinical relapse rate was 36% (95% CI: 16-55%, p = 0.11). The pooled proportion of patients with mild adverse events after FMT treatment was 39% (95% CI: 6-71%, p < 0.001). No severe adverse events or deaths were reported. Although FMT is an effective treatment for chronic pouchitis, there is still a high rate of mild adverse events. High-level evidence for FMT is still sparse, limiting recommendations for clinical use.}, } @article {pmid39767682, year = {2024}, author = {Farhadi Rad, H and Tahmasebi, H and Javani, S and Hemati, M and Zakerhamidi, D and Hosseini, M and Alibabaei, F and Banihashemian, SZ and Oksenych, V and Eslami, M}, title = {Microbiota and Cytokine Modulation: Innovations in Enhancing Anticancer Immunity and Personalized Cancer Therapies.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/biomedicines12122776}, pmid = {39767682}, issn = {2227-9059}, abstract = {The gut microbiota plays a crucial role in modulating anticancer immunity, significantly impacting the effectiveness of various cancer therapies, including immunotherapy, chemotherapy, and radiotherapy. Its impact on the development of cancer is complex; certain bacteria, like Fusobacterium nucleatum and Bacteroides fragilis, can stimulate the growth of tumors by causing immunological evasion and inflammation, while advantageous strains, like Faecalibaculum rodentium, have the ability to suppress tumors by modifying immune responses. Cytokine activity and immune system regulation are intimately related. Cytokines including TGF-β, IL-6, and IL-10 promote tumor development by inhibiting efficient immune surveillance. The gut microbiome exhibits a delicate balance between pro- and anti-tumorigenic factors, as evidenced by the enhancement of anti-tumor immunity by cytokines such as IL-12 and IFN-γ. Improved immunotherapy responses are linked to a diverse microbiota, which is correlated with higher tumor infiltration and cytotoxic T-cell activation. Because microbial metabolites, especially short-chain fatty acids, affect cytokine expression and immune cell activation inside the tumor microenvironment, this link highlights the need to maintain microbial balance for optimal treatment effects. Additionally, through stimulating T-cell activation, bacteria like Lactobacillus rhamnosus and Bifidobacterium bifidum increase cytokine production and improve the efficacy of immune checkpoint inhibitors (ICIs). An option for overcoming ICI resistance is fecal microbiota transplantation (FMT), since research suggests that it improves melanoma outcomes by increasing CD8+ T-cell activation. This complex interaction provides an opportunity for novel cancer therapies by highlighting the possibility of microbiome modification as a therapeutic approach in personalized oncology approaches.}, } @article {pmid39767577, year = {2024}, author = {Munteanu, C and Onose, G and Rotariu, M and Poștaru, M and Turnea, M and Galaction, AI}, title = {Role of Microbiota-Derived Hydrogen Sulfide (H2S) in Modulating the Gut-Brain Axis: Implications for Alzheimer's and Parkinson's Disease Pathogenesis.}, journal = {Biomedicines}, volume = {12}, number = {12}, pages = {}, doi = {10.3390/biomedicines12122670}, pmid = {39767577}, issn = {2227-9059}, support = {CNFIS - FDI - 2024 - F - 0099//Supporting the institutional capacity for research and innovation through transdisciplinary biotechnologies (InovBiotech)/ ; }, abstract = {Microbiota-derived hydrogen sulfide (H2S) plays a crucial role in modulating the gut-brain axis, with significant implications for neurodegenerative diseases such as Alzheimer's and Parkinson's. H2S is produced by sulfate-reducing bacteria in the gut and acts as a critical signaling molecule influencing brain health via various pathways, including regulating inflammation, oxidative stress, and immune responses. H2S maintains gut barrier integrity at physiological levels and prevents systemic inflammation, which could impact neuroinflammation. However, as H2S has a dual role or a Janus face, excessive H2S production, often resulting from gut dysbiosis, can compromise the intestinal barrier and exacerbate neurodegenerative processes by promoting neuroinflammation and glial cell dysfunction. This imbalance is linked to the early pathogenesis of Alzheimer's and Parkinson's diseases, where the overproduction of H2S exacerbates beta-amyloid deposition, tau hyperphosphorylation, and alpha-synuclein aggregation, driving neuroinflammatory responses and neuronal damage. Targeting gut microbiota to restore H2S homeostasis through dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation presents a promising therapeutic approach. By rebalancing the microbiota-derived H2S, these strategies may mitigate neurodegeneration and offer novel treatments for Alzheimer's and Parkinson's diseases, underscoring the critical role of the gut-brain axis in maintaining central nervous system health.}, } @article {pmid39766423, year = {2024}, author = {Menezes, AA and Shah, ZA}, title = {A Review of the Consequences of Gut Microbiota in Neurodegenerative Disorders and Aging.}, journal = {Brain sciences}, volume = {14}, number = {12}, pages = {}, doi = {10.3390/brainsci14121224}, pmid = {39766423}, issn = {2076-3425}, support = {R01NS112642/NS/NINDS NIH HHS/United States ; }, abstract = {Age-associated alterations in the brain lead to cognitive deterioration and neurodegenerative disorders (NDDs). This review with a particular focus on Alzheimer's disease (AD), emphasizes the burgeoning significance of the gut microbiota (GMB) in neuroinflammation and its impact on the gut-brain axis (GBA), a communication conduit between the gut and the central nervous system (CNS). Changes in the gut microbiome, including diminished microbial diversity and the prevalence of pro-inflammatory bacteria, are associated with AD pathogenesis. Promising therapies, such as fecal microbiota transplantation (FMT), probiotics, and prebiotics, may restore gut health and enhance cognitive performance. Clinical data remain insufficient, necessitating further research to elucidate causes, enhance therapy, and consider individual variances. This integrative approach may yield innovative therapies aimed at the GMB to improve cognitive function and brain health in older people.}, } @article {pmid39766170, year = {2024}, author = {Ciernikova, S and Sevcikova, A and Novisedlakova, M and Mego, M}, title = {Insights into the Relationship Between the Gut Microbiome and Immune Checkpoint Inhibitors in Solid Tumors.}, journal = {Cancers}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/cancers16244271}, pmid = {39766170}, issn = {2072-6694}, support = {1/0071/24//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 2/0069/22//Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; }, abstract = {Immunotherapy with immune checkpoint inhibitors represents a revolutionary approach to the treatment of solid tumors, including malignant melanoma, lung cancer, and gastrointestinal malignancies. Anti-CTLA-4 and anti-PD-1/PDL-1 therapies provide prolonged survival for cancer patients, but their efficacy and safety are highly variable. This review focuses on the crucial role of the gut microbiome in modulating the efficacy and toxicity of immune checkpoint blockade. Studies suggest that the composition of the gut microbiome may influence the response to immunotherapy, with specific bacterial strains able to promote an anti-tumor immune response. On the other hand, dysbiosis may increase the risk of adverse effects, such as immune-mediated colitis. Interventions aimed at modulating the microbiome, including the use of probiotics, prebiotics, fecal microbial transplantation, or dietary modifications, represent promising strategies to increase treatment efficacy and reduce toxicity. The combination of immunotherapy with the microbiome-based strategy opens up new possibilities for personalized treatment. In addition, factors such as physical activity and nutritional supplementation may indirectly influence the gut ecosystem and consequently improve treatment outcomes in refractory patients, leading to enhanced patient responses and prolonged survival.}, } @article {pmid39766032, year = {2024}, author = {Altrawy, A and Khalifa, MM and Abdelmaksoud, A and Khaled, Y and Saleh, ZM and Sobhy, H and Abdel-Ghany, S and Alqosaibi, A and Al-Muhanna, A and Almulhim, J and El-Hashash, A and Sabit, H and Arneth, B}, title = {Metabolites in the Dance: Deciphering Gut-Microbiota-Mediated Metabolic Reprogramming of the Breast Tumor Microenvironment.}, journal = {Cancers}, volume = {16}, number = {24}, pages = {}, doi = {10.3390/cancers16244132}, pmid = {39766032}, issn = {2072-6694}, abstract = {Breast cancer (BC), a major cause of death among women worldwide, has traditionally been linked to genetic and environmental factors. However, emerging research highlights the gut microbiome's significant role in shaping BC development, progression, and treatment outcomes. This review explores the intricate relationship between the gut microbiota and the breast tumor microenvironment, emphasizing how these microbes influence immune responses, inflammation, and metabolic pathways. Certain bacterial species in the gut either contribute to or hinder BC progression by producing metabolites that affect hormone metabolism, immune system pathways, and cellular signaling. An imbalance in gut bacteria, known as dysbiosis, has been associated with a heightened risk of BC, with metabolites like short-chain fatty acids (SCFAs) and enzymes such as β-glucuronidase playing key roles in this process. Additionally, the gut microbiota can impact the effectiveness of chemotherapy, as certain bacteria can degrade drugs like gemcitabine and irinotecan, leading to reduced treatment efficacy. Understanding the complex interactions between gut bacteria and BC may pave the way for innovative treatment approaches, including personalized microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, offering new hope for more effective prevention, diagnosis, and treatment of BC.}, } @article {pmid39765038, year = {2024}, author = {Wang, C and Peng, M and Gao, Z and Fu, F and Li, G and Su, D and Huang, L and Guo, J and Shan, Y}, title = {Citrus aurantium 'Changshan-huyou' physiological premature fruit drop: A promising prebiotic to tackle obesity.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {136}, number = {}, pages = {156347}, doi = {10.1016/j.phymed.2024.156347}, pmid = {39765038}, issn = {1618-095X}, abstract = {BACKGROUND: Presently, the mitigation and governance of obesity have surfaced as significant public health dilemmas on a global scale. A wealth of studies indicated that the host gut microbiota is instrumental in regulating the interplay between high-fat diet (HFD) intake and the pathogenesis of obesity. Physiological premature fruit drop, a major byproduct of citrus, is rich in a variety of bioactive constituents, yet its potential has remained underutilized for an extended period.

PURPOSE: The objective of this investigation is to examine the chemical constituents of Citrus aurantium'Changshan-huyou' premature fruit drop (HYFD) and investigate its anti-obesity effects, elucidating its potential pathways.

METHODS: Volatile compounds and flavonoids in HYFD were analyzed using chromatographic and mass spectrometric techniques. Furthermore, this study utilized biochemical assays and histopathological examinations to evaluate the effects of HYFD on HFD-fed mice. The impact of HYFD on the gut microbiota of the mice was examined through 16S rRNA gene sequencing, and fecal microbiota transplantation was employed to validate the role of the gut microbial community in host obesity prevention. Concurrently, transcriptome was employed to identify differentially expressed genes, providing further insights into the molecular mechanisms through which HYFD manifests its anti-obesity effects.

RESULTS: Our findings demonstrated that HYFD supplementation significantly alleviated adiposity and ameliorated the dysbiosis of gut microbiota in HFD-induced mice. HYFD rectified the HFD-induced gut microbiota dysregulation, enhanced the presence of beneficial microbial taxa linked to lipid metabolism, including Parabacteroides and Alistipes, and elevated concentrations of the anti-obesity short-chain fatty acids, comprising caproic acid and isocaproic acid. Additionally, transcriptomic analyses confirmed that HYFD prevented obesity in mice by enhancing fatty acid catabolism via the activation of the AMPK/PPARα/CPT1a signaling pathway.

CONCLUSION: Our results provided novel insights into the mechanism of citrus physiological premature fruit drop and its potential role in preventing obesity, while sparking greater interest in leveraging more biomass waste.}, } @article {pmid39764653, year = {2024}, author = {Mao, Y and Huang, Y and Zhang, W and Liang, H and Liu, F and Luo, Q and Xu, C and Qin, Y and Liu, J and Tang, S and Liu, H and Ge, X}, title = {FMT reduces systemic inflammatory response in severe acute pancreatitis by increasing the abundance of intestinal Bifidobacteria and fecal bacteria.}, journal = {Biomolecules & biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2024.11445}, pmid = {39764653}, issn = {2831-090X}, abstract = {Severe acute pancreatitis (SAP) is one of the leading causes of hospital admissions for gastrointestinal diseases, with a rising incidence worldwide. Intestinal microbiota dysbiosis caused by SAP exacerbates systemic inflammatory response syndrome and organ dysfunction. Fecal microbiota transplantation (FMT) has emerged as a promising therapeutic option for gastrointestinal diseases. In this study, fecal samples from healthy, control, and FMT-treated groups were analyzed using 16S rRNA sequencing to assess microbiome abundance and diversity. Composition and functional prediction analyses were conducted to explore the mechanisms underlying FMT in SAP. FMT significantly improved clinical parameters in SAP patients, including leukocyte count, C-reactive protein (CRP), neutrophil granulocyte count, lactate dehydrogenase (LDH), and calcitonin (P < 0.05). Organ failure rates significantly increased in the control group but decreased in the FMT group after treatment (P < 0.05). Fecal microbiota sequencing revealed that FMT significantly upregulated the abundance of Bifidobacterium longum among all SAP patients (P < 0.05). Receiver operating characteristic (ROC) curve analysis indicated that Bifidobacterium longum might play a critical role in the efficacy of FMT, with an area under the curve (AUC) value of 0.84. Additionally, there was a negative correlation between Bifidobacterium longum abundance and procalcitonin (PCT) levels, as well as a negative correlation between Escherichia coli abundance and both CT and Ca values (P < 0.05). The relative abundances of Bifidobacterium longum and Escherichia coli were significantly higher in the FMT group compared to the Bifidobacterium triple viable group (P < 0.05). In conclusion, this research supports FMT as a safe and effective intervention for treating SAP patients.}, } @article {pmid39764615, year = {2025}, author = {Harris, SC and Bajaj, JS}, title = {Interaction of the Gut-Liver-Brain Axis and the sterolbiome with sexual dysfunction in patients with cirrhosis.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446390}, doi = {10.1080/19490976.2024.2446390}, pmid = {39764615}, issn = {1949-0984}, mesh = {Humans ; *Liver Cirrhosis/complications/metabolism ; *Gastrointestinal Microbiome ; *Brain-Gut Axis/physiology ; *Sexual Dysfunction, Physiological/metabolism/etiology/physiopathology ; *Liver/metabolism ; Sterols/metabolism ; Brain/metabolism ; Gonadal Steroid Hormones/metabolism ; Animals ; Quality of Life ; }, abstract = {There is a complex interplay between the gut microbes, liver, and central nervous system, a gut-liver-brain axis, where the brain impacts intestinal and hepatic function while the gut and liver can impact cognition and mental status. Dysregulation of this axis can be seen in numerous diseases. Hepatic encephalopathy, a consequence of cirrhosis, is perhaps the best studied perturbation of this system. However, patients with cirrhosis have been shown to have increased incidence of other disorders of mental health which may be otherwise less clinically identifiable. Sexual dysfunction affects a large proportion of patients with cirrhosis and is associated with decreased quality of life. Screening for sexual dysfunction in patients with cirrhosis is often overlooked, and even when identified, treatment options are limited, particularly in patients with advanced liver disease. The mechanism by which patients with cirrhosis develop sexual dysfunction is multifactorial, but a key driver of this clinical manifestation is alterations in circulating sex hormones. In patients with cirrhosis, low serum sex hormones have been shown to be associated with higher mortality regardless of MELD score. The gut microbiome has been shown to have an immense metabolic capacity to metabolize steroid hormones. This "sterolbiome" has already been implicated in other disease processes and has been linked to low circulating sex hormones, suggesting a new mechanism by which sex hormones may be altered in disease states where the gut-liver-brain axis is disrupted. The aim of this review is to cover sex hormone changes and sexual dysfunction in cirrhosis, examine the gut microbiome and its metabolic capacity, particularly for steroid hormones, and consider how microbial changes using fecal microbiota transplant could modulate sexual dysfunction.}, } @article {pmid39764447, year = {2024}, author = {Wang, J and Zhuang, P and Lin, B and Zheng, J and Li, H and Tang, W and Ye, W and Chen, X and Zheng, M}, title = {Comparative analysis of gut microbiota in metabolic syndrome and obese children from Southeastern China.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1503302}, pmid = {39764447}, issn = {1664-302X}, abstract = {The prevalence of childhood obesity is rising globally, with some obese children progressing to develop metabolic syndrome (MS). However, the specific differences between these groups remain unclear. To investigate the differences in gut microbiota, we conducted physiological and biochemical assessments, alongside 16S rRNA sequencing, in a cohort of 32 children from Southeastern China, which included 4 normal-weight children, 5 with mild obesity, 9 with moderate obesity, 9 with severe obesity, and 5 with metabolic syndrome. Our results indicated that waist circumference, serum triglycerides, total cholesterol, non-HDL levels, and the prevalence of fatty liver were significantly elevated in both obese and MS children compared to their normal-weight peers, with the MS group exhibiting more pronounced abnormalities. Conversely, HDL levels showed a contrasting trend. Additionally, alpha diversity of gut microbiota increased with weight, while beta diversity analysis revealed significant compositional differences between children with MS and those who were normal weight or obese. At the class and genus levels, we found that the relative abundance of c_Gammaproteobacteria increased with weight, whereas c_Bacteroidia and g_Bacteroides decreased. Notably, g_Faecalibacterium was significantly less abundant in the MS group compared to the other cohorts. LEfSe and functional analyses identified distinct gut microbiota and functional differences between children with MS and those with normal weight or obesity. Furthermore, gavage experiments in mice showed that gut microbiota from obese and MS subjects significantly increased serum triglycerides and cholesterol levels, leading to hepatocellular damage. In contrast, fecal gavage from normal-weight individuals into obese model mice significantly reduced serum triglycerides and the number of degenerative liver cells, as well as the extent of fat accumulation. These findings provide critical insights into the understanding and management of obesity and metabolic syndrome in pediatric populations.}, } @article {pmid39762283, year = {2025}, author = {Feng, C and Wu, Y and Zhang, X and Wang, S and Wang, J and Yang, H}, title = {Maternal milk fat globule membrane enriched gut L. murinus and circulating SCFAs to improve placental efficiency and fetal development in intrauterine growth restricted mice model.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2449095}, doi = {10.1080/19490976.2024.2449095}, pmid = {39762283}, issn = {1949-0984}, mesh = {Animals ; Female ; Pregnancy ; *Gastrointestinal Microbiome/drug effects ; Mice ; *Placenta/metabolism ; *Fetal Growth Retardation/metabolism ; *Glycoproteins/metabolism ; *Fatty Acids, Volatile/metabolism ; *Lipid Droplets/metabolism ; *Glycolipids/metabolism ; *Fetal Development/drug effects ; *Disease Models, Animal ; Lactobacillus ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; }, abstract = {Intrauterine growth restriction (IUGR) caused by placental dysfunctions leads to fetal growth defects. Maternal microbiome and its metabolites have been reported to promote placental development. Milk fat globule membrane (MFGM) is known for its diverse bioactive functions, while the effects of gestational MFGM supplementation on the maternal gut microbiota, placental efficiency, and fetal development remained unclear. In this study, low protein diet-induced IUGR decreased the litter birth weight, fetal birth weight, and the fetal/placental ratio in pregnant mice, while gestational MFGM supplementation restored these impairments. Meanwhile, MFGM supplementation during gestation enriched intestinal Lactobacillus murinus (L. murinus) and increased luminal and circulating short chain fatty acids (SCFAs) in IUGR pregnant mice, which improved placental efficiency and fetal development due to an enhanced antioxidant capacity and a decreased inflammation. In addition, fecal microbiota transplantation (FMT) with MFGM-derived microbiota reprinted the promoted phenotypes of maternal litter characteristics, gut L. murinus enrichment, placental efficiency, and fetal gut development in MFGM-fed pregnant mice, which were also recapitulated by exogenous administration with L. murinus or SCFAs cocktail. Mechanically, MFGM, MFGM-derived microbiota, L. murinus, or SCFAs cocktail activated IUGR-induced depressive phosphorylation of PI3K-Akt signaling in the placenta. Moreover, in vitro placental cells cultivation under amino acid shortage model (AAS) or oxygen-glucose shortage model (OGS) was used to validate that MFGM-derived key microbial and circulating SCFAs cocktails can alleviate placental oxidative stress and inflammation via activating PI3K/Akt signaling. Taken together, gestational MFGM supplementation enriched intestinal L. murinus and circulating SCFAs of IUGR pregnant mice, thereby improving placental efficiency, fetal growth, and intestinal functions of IUGR fetus. Our findings will provide theoretical support for the application of MFGM in the maternal-placental-fetal nutrition to address pregnancy malnutrition-induced IUGR.}, } @article {pmid39762111, year = {2025}, author = {Al-Shakhshir, S and Quraishi, MN and Mullish, B and Patel, A and Vince, A and Rowe, A and Homer, V and Jackson, N and Gyimah, D and Shabir, S and Manzoor, S and Cooney, R and Alrubaiy, L and Quince, C and van Schaik, W and Hares, M and Beggs, AD and Efstathiou, E and Rimmer, P and Weston, C and Iqbal, T and Trivedi, PJ}, title = {FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial.}, journal = {BMJ open}, volume = {15}, number = {1}, pages = {e095392}, doi = {10.1136/bmjopen-2024-095392}, pmid = {39762111}, issn = {2044-6055}, mesh = {Adult ; Female ; Humans ; Male ; *Cholangitis, Sclerosing/therapy ; Clinical Trials, Phase II as Topic ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Inflammatory Bowel Diseases/therapy/microbiology ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {INTRODUCTION: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity. However, the longevity of such changes and the impact on markers of disease activity and disease progression have not been studied. The aim of this clinical trial is to determine the effects of repeated FMT as a treatment for PSC-IBD.

METHODS AND ANALYSIS: FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO) is a phase IIa randomised placebo-controlled trial to assess the efficacy and safety of repeated colonic administration of FMT in patients with non-cirrhotic PSC-IBD. Fifty-eight patients will be recruited from six sites across England and randomised in a 1:1 ratio between active FMT or FMT placebo arms. FMT will be manufactured by the University of Birmingham Microbiome Treatment Centre, using stool collected from rigorously screened healthy donors. A total of 8 weekly treatments will be delivered; the first through colonoscopic administration (week 1) and the remaining seven via once-weekly enema (up to week 8). Participants will then be followed on a 12-weekly basis until week 48 from the first treatment visit. The primary efficacy outcome will be to determine the effect of FMT on serum alkaline phosphatase values over time (end of study at 48 weeks). Key secondary outcomes will be to evaluate the impact of FMT on other liver biochemical parameters, PSC risk scores, circulating and imaging markers of liver fibrosis, health-related quality of life measures, IBD activity and the incidence of PSC-related clinical events. Key translational objectives will be to identify mucosal metagenomic, metatranscriptomic, metabolomic and immunological pathways associated with the administration of FMT.

ETHICS AND DISSEMINATION: The protocol was approved by the South Central-Hampshire B Research Ethics Committee (REC 23/SC/0147). Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

TRIAL REGISTRATION NUMBER: The trial was registered at ClinicalTrials.gov on 23 February 2024 (NCT06286709). Weblink: Study Details | FAecal Microbiota Transplantation in primaRy sclerosinG chOlangitis | ClinicalTrials.gov.}, } @article {pmid39761011, year = {2024}, author = {Jain, V and Dalby, MJ and Alexander, EC and Burford, C and Acford-Palmer, H and Serghiou, IR and Teng, NMY and Kiu, R and Gerasimidis, K and Zafeiropoulou, K and Logan, M and Verma, A and Davenport, M and Hall, LJ and Dhawan, A}, title = {Association of gut microbiota and gut metabolites and adverse outcomes in biliary atresia: A longitudinal prospective study.}, journal = {Hepatology communications}, volume = {8}, number = {11}, pages = {}, pmid = {39761011}, issn = {2471-254X}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Biliary Atresia/surgery/microbiology/metabolism ; *Feces/microbiology ; Male ; Female ; Prospective Studies ; Infant ; Longitudinal Studies ; Portoenterostomy, Hepatic ; RNA, Ribosomal, 16S/genetics ; Enterococcus ; Case-Control Studies ; Infant, Newborn ; Bifidobacterium/isolation & purification ; }, abstract = {BACKGROUND: The Kasai portoenterostomy (KPE) aims to re-establish bile flow in biliary atresia (BA); however, BA remains the commonest indication for liver transplantation in pediatrics. Gut microbiota-host interplay is increasingly associated with outcomes in chronic liver disease. This study characterized fecal microbiota and fatty acid metabolites in BA.

METHODS: Fecal samples were prospectively collected in newly diagnosed BA infants (n = 55) before and after KPE. Age-matched healthy control (n = 19) and cholestatic control (n = 21) fecal samples were collected. Fecal 16S rRNA gene amplicon sequencing for gut microbiota and gas chromatography for fecal fatty acids was performed.

RESULTS: Increased abundance of Enterococcus in pre-KPE BA and cholestatic control infants, compared to healthy infants, was demonstrated. At the early post-KPE time points, increased alpha diversity was revealed in BA versus healthy cohorts. A lower relative abundance of Bifidobacterium and increased Enterococcus, Clostridium, Fusobacterium, and Pseudomonas was seen in infants with BA. Fecal acetate was reduced, and fecal butyrate and propionate were elevated in early post-KPE BA infants. Higher post-KPE alpha diversity was associated with nonfavorable clinical outcomes (6-month jaundice and liver transplantation). A higher relative abundance of post-KPE Streptococcus and Fusobacterium and a lower relative abundance of Dorea, Blautia, and Oscillospira were associated with nonfavorable clinical outcomes. Blautia inversely correlated to liver disease severity, and Bifidobacterium inversely correlated to fibrosis biomarkers. Bifidobacterium abundance was significantly lower in infants experiencing cholangitis within 6 months after KPE.

CONCLUSIONS: Increased diversity, enrichment of pathogenic, and depletion of beneficial microbiota early post-KPE are all factors associated with nonfavorable BA outcomes. Manipulation of gut microbiota in the early postsurgical period could provide therapeutic potential.}, } @article {pmid39760535, year = {2025}, author = {Saha, S and Schnabl, B}, title = {Modulating the microbiome in chronic liver diseases- current evidence on the role of fecal microbiota transplantation.}, journal = {Expert review of gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1080/17474124.2025.2450707}, pmid = {39760535}, issn = {1747-4132}, abstract = {INTRODUCTION: The gut microbiota has a complex relationship with the human host and is key to maintaining health. Disruption of the healthy diverse gut microbial milieu plays an important role in the pathogenesis of several diseases including Clostridioides difficile infection (CDI), inflammatory bowel disease, irritable bowel syndrome, alcohol-related liver disease and metabolic-dysfunction associated steatotic liver disease (MASLD). Fecal microbiota transplantation (FMT) is highly effective in treating CDI, though its utility in other diseases is still being explored.

AREAS COVERED: In this narrative review, we explore the role of gut microbiota in liver diseases, focusing on key changes in the microbial composition and function. We summarize current evidence on the role of FMT, identifying gaps in current research and outlining future directions for investigation. We comprehensively searched PubMed through 15 October 2024 to identify relevant studies.

EXPERT OPINION: While data from available studies shows promise, more research is necessary before we can use FMT for liver diseases. Key areas that require further study are- determining the optimal FMT regimen for each disease, establishing efficacy and safety with larger clinical trials, ensuring safe and equitable access to the FMT product and mechanistic insights into the reasons for success or failure of FMT.}, } @article {pmid39759692, year = {2024}, author = {Muzaffer, M and Masarath, A and Mohammed, F}, title = {Biliary Atresia: A Case Report.}, journal = {Cureus}, volume = {16}, number = {12}, pages = {e75087}, pmid = {39759692}, issn = {2168-8184}, abstract = {Biliary atresia (BA) is a serious hepatobiliary disorder that occurs due to progressive inflammation and scarring obstruction in the bile ducts, posing a threat to life. This condition usually appears in infants, and timely identification is fundamental for a better prognosis. If left untreated, individuals will inevitably experience liver damage and mortality. This case report describes a nine-month-old female infant presenting with jaundice, icteric sclera, yellowish skin, acholic feces, and hepatomegaly. Elevated liver enzymes and a hepatobiliary iminodiacetic acid (HIDA) scan confirmed BA. Histopathological examination revealed fibrosis, cholestatic disease, and an atretic gallbladder. A modified Kasai portoenterostomy (KPE) with Roux-en-Y jejunojejunostomy was performed, and the infant was discharged with supportive care. However, seven months post-Kasai portoenterostomy, the infant presented with persistent jaundice and progressive deterioration of liver function, indicative of a failed Kasai procedure. Consequently, she was scheduled to undergo liver transplantation (LT) as a definitive treatment. BA is a rare disorder that is observed across nearly all ethnic groups, though the incidence rates vary significantly. This case highlights the efficacy of liver transplantation in treating failed Kasai procedures and demonstrates the potential for enhanced outcomes in infants with end-stage liver disease.}, } @article {pmid39758967, year = {2025}, author = {Thorndal, C and Kragsnaes, MS and Nilsson, AC and Holm, DK and dePont Christensen, R and Ellingsen, T and Kjeldsen, J and Bjørsum-Meyer, T}, title = {Safety and efficacy of faecal microbiota transplantation in patients with acute uncomplicated diverticulitis: study protocol for a randomised placebo-controlled trial.}, journal = {Therapeutic advances in gastroenterology}, volume = {18}, number = {}, pages = {17562848241309868}, pmid = {39758967}, issn = {1756-283X}, abstract = {BACKGROUND: Little is known about the involvement of gut microbiota in the disease course of diverticulitis and the potential benefits of manipulating the gut milieu. We propose to conduct a randomised placebo-controlled feasibility trial of faecal microbiota transplantation (FMT) given as capsules to patients with acute uncomplicated diverticulitis.

OBJECTIVES: The objective is primarily to investigate the feasibility of clinical safety, explore efficacy associated with FMT in this patient population, and examine changes in patient-reported quality of life and the composition and function of the gut microbiota.

DESIGN: Study protocol for a randomised placebo-controlled trial.

METHODS AND ANALYSIS: Participants with acute, uncomplicated diverticulitis, as confirmed by computed tomography (CT) scan, will be recruited from Odense University Hospital (Denmark) and randomly assigned to either the intervention group or the control group. The intervention group will consist of 20 patients who receive encapsulated FMT. The control group will also consist of 20 patients, receiving placebo capsules. Primary safety endpoint: Patient safety is monitored by (a) the number of re-admissions and (b) the number of adverse events within 3 months of FMT/placebo; Primary efficacy endpoint: Reduction in the proportion of patients treated with antibiotics within 3 months following FMT/placebo; Secondary outcome: Change from baseline to 3 months in the GI-QLI questionnaire. Results will be analysed using an intention-to-treat approach. Adverse events or unintended consequences will be reported.

ETHICS AND DISCUSSION: This is the first study to investigate the safety and efficacy of FMT in patients with acute uncomplicated diverticulitis. The project has the potential to broaden the knowledge and literature on the role of the intestinal microbiota in diverticulitis, and we believe it will elevate our understanding of cause and effect.

TRIAL REGISTRATION: Informed consent is obtained from all participants. The study is approved by the regional ethics committee (ref. S-20230023) and the Danish Data Protection Agency (ref. 24/2435). The trial was registered on clinicaltrials.gov (NCT06254625) on 10th February 2024.}, } @article {pmid39758313, year = {2024}, author = {Liu, B and Zhang, Z and Zhao, J and Li, X and Wang, Y and Liu, L and Qiao, W and Chen, L}, title = {Lactiplantibacillus plantarum HM-P2 influences gestational gut microbiome and microbial metabolism.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1489359}, pmid = {39758313}, issn = {2296-861X}, abstract = {INTRODUCTION: Human milk-derived probiotics are beneficial bacteria that provide gestational health benefits, for both pregnant women and their offspring. The study aims to investigate whether the administration of human milk-derived probiotic L. plantarum HM-P2 could effectively influence gestational health.

METHODS: The gestational humanized microbiome model was built by fecal microbiome transplant from gestational women into germ-free (GF) mice.

RESULTS: HM-P2 was successfully planted and increased the top crypt depth of the colon, and microbes such as L. reuteri, Anaerofilum sp. An201, and Gemmiger were up-regulated in the HM-P2 group throughout gestation. HM-P2 significantly promoted the contents of intestinal caproic acid, bile acids, and tryptophan catabolites such as serotonin. Gut microbes were associated with these bile acids and tryptophans.

DISCUSSION: HM-P2 could modulate the microbial community and microbial metabolites in gestational humanized GF mice. This probiotic strain could be a potential gestational dietary supplement with health benefits.}, } @article {pmid39757809, year = {2025}, author = {Huang, ST and Hu, YH and Gao, YC and Zhou, DD and Chen, MY and Wang, L and Song, JY and Zhou, HH and Zhang, W and Huang, WH}, title = {Hypoglycemic Effect of Ginsenoside Compound K Mediated by N-Acetylserotonin Derived From Gut Microbiota.}, journal = {Phytotherapy research : PTR}, volume = {}, number = {}, pages = {}, doi = {10.1002/ptr.8385}, pmid = {39757809}, issn = {1099-1573}, support = {82074000//National Natural Science Foundation of China/ ; 82073945//National Natural Science Foundation of China/ ; 81874329//National Natural Science Foundation of China/ ; 2023YFC3405200//National Key Research and Development Program of China/ ; 2021YFA1301200//National Key Research and Development Program of China/ ; 2024JJ5585//Hunan Provincial Natural Science Foundation of China/ ; 2023SK2083//Scientific Research Project of Furong Laboratory of Central South University/ ; }, abstract = {Ginsenoside compound K (GCK) has been proved to have great hypoglycemic effect pertinent to gut microbiota. However, the improvement of high-fat-diet (HFD)-induced type 2 diabetes (T2D) as well as the mechanism of GCK mediated by gut microbiota is not well-known. This study aimed to investigate the hypoglycemic effects and mechanism of GCK on a HFD-induced diabetic mouse model. HFD-induced pseudo-germ free (GF) T2D mice model and fecal microbiota transplantation (FMT) experiments were performed to clarify the role of gut microbiota in the hypoglycemic effect of GCK. Differential metabolites were screened by untargeted metabolomics analysis and their functions were verified by suppling to T2D mice. The level of glucagon-like peptide-1 (GLP-1) in plasma was detected by ELISA analysis to explore the potential hypoglycemic mechanism of GCK. The results showed GCK alleviated metabolic disorders and altered gut microbiota in HFD-induced diabetic mice, which was transmitted to pseudo-GF diabetic mice via FMT experiment to reproduce the hypoglycemic effect. Non-targeted metabolites analysis on cecal content samples indicated that N-acetylserotonin (NAS) was markedly increased after GCK treatment. Moreover, gavage with NAS improved insulin sensitivity and increased the secretion of GLP-1 in HFD mice. Our study showed that GCK had hypoglycemic effect through modifying gut microbiota profiling.}, } @article {pmid39757609, year = {2024}, author = {Bhat, MM and Hussain, MS and Bisht, AS and Agrawal, M and Sultana, A and Khurrana, N and Kumar, R}, title = {Frontiers in Pulmonary Hypertension: A Comprehensive Insight of Etiological Advances.}, journal = {Current reviews in clinical and experimental pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724328325178241210174545}, pmid = {39757609}, issn = {2772-4336}, abstract = {Pulmonary hypertension (PH) is a severe, progressive disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular failure and increased mortality. Despite advancements in management, the median survival for PH patients remains 5-7 years, with an inhospital mortality rate of approximately 6%. The core pathological feature of PH is pulmonary vascular remodeling (PVR), a multifactorial process involving endothelial dysfunction, inflammation, and aberrant immune responses. While current therapies target endothelial dysfunction, they fall short of preventing PVR or halting disease progression. Emerging research highlights the potential of immune-inflammatory pathways, oxygen-sensing mechanisms, and gut microbiota modulation as therapeutic targets. Integrating nutritional strategies, probiotics, and fecal microbiota transplantation (FMT) as adjunctive therapies also shows promise. These factors may collectively influence PVR, offering novel insights into therapeutic avenues for PH management in the future.}, } @article {pmid39756658, year = {2025}, author = {Chen, Q and Liu, F and Zhang, G and Qu, Q and Chen, Y and Li, M and Huang, Q and Fu, H and Zhu, X and He, Y and Huang, X and Zhang, X}, title = {Progesterone Regulates Gut Microbiota Mediating Bone Marrow MSCs Injury in ITP Patients during Pregnancy.}, journal = {Journal of thrombosis and haemostasis : JTH}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jtha.2024.12.027}, pmid = {39756658}, issn = {1538-7836}, abstract = {BACKGROUND: Immune thrombocytopenia during pregnancy (PITP) is the most common cause of platelet reduction in early and mid-pregnancy. However, the pathogenesis of PITP is still unclear.

OBJECTIVES: To determine the characteristics of bone marrow mesenchymal stem cells (BM-MSCs) in PITP patients and to explore the associations between metabolites, the gut microbiota, and BM-MSCs in PITP.

METHODS: The characteristics of BM-MSCs were detected through in vitro and in vivo experiments. Non-targeted metabolomics was used to screen metabolites. The features of the gut microbiota were analyzed by 16S rDNA sequencing. PITP and a fecal microbiota transplantation (FMT) mouse model were established to explore the associations between metabolites, the gut microbiota, and BM-MSCs.

RESULTS: BM-MSCs from PITP patients had significant senescence and apoptosis, as well as impaired immunoregulatory function. Metabolomic analysis indicated that progesterone was the most significant specific metabolite in PITP patients. In vivo studies showed that progesterone mediated the MSCs injury. Further analysis of the gut microbiota and FMT experiments revealed that progesterone mediated BM-MSCs injury by regulating the the composition of the gut microbiota in the PITP. RNA-seq analysis of BM-MSCs from FMT mice revealed abnormal expression of genes related to cell aging and the NOD-like receptor signaling pathway.

CONCLUSION: In conclusion, BM-MSCs in the PITP were significantly impaired, which was associated with increased progesterone and changes in the gut microbiota regulated by progesterone. Intervening with the gut microbiota may become a new treatment for PITP.}, } @article {pmid39754054, year = {2025}, author = {Azhar Ud Din, M and Lin, Y and Lyu, C and Yi, C and Fang, A and Mao, F}, title = {Advancing therapeutic strategies for graft-versus-host disease by targeting gut microbiome dynamics in allogeneic hematopoietic stem cell transplantation: current evidence and future directions.}, journal = {Molecular medicine (Cambridge, Mass.)}, volume = {31}, number = {1}, pages = {2}, pmid = {39754054}, issn = {1528-3658}, mesh = {*Graft vs Host Disease/etiology/microbiology ; Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome ; *Transplantation, Homologous ; Animals ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; }, abstract = {Hematopoietic stem cell transplantation (HSCT) is a highly effective therapy for malignant blood illnesses that pose a high risk, as well as diseases that are at risk due to other variables, such as genetics. However, the prevalence of graft-versus-host disease (GVHD) has impeded its widespread use. Ensuring the stability of microbial varieties and associated metabolites is crucial for supporting metabolic processes, preventing pathogen intrusion, and modulating the immune system. Consequently, it significantly affects the overall well-being and susceptibility of the host to disease. Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) may experience a disruption in the balance between the immune system and gut bacteria when treated with medicines and foreign cells. This can lead to secondary intestinal inflammation and GVHD. Thus, GM is both a reliable indicator of post-transplant mortality and a means of enhancing GVHD prevention and treatment after allo-HSCT. This can be achieved through various strategies, including nutritional support, probiotics, selective use of antibiotics, and fecal microbiota transplantation (FMT) to target gut microbes. This review examines research advancements and the practical use of intestinal bacteria in GVHD following allo-HSCT. These findings may offer novel insights into the prevention and treatment of GVHD after allo-HSCT.}, } @article {pmid39747695, year = {2025}, author = {Wang, X and Fang, Y and Liang, W and Cai, Y and Wong, CC and Wang, J and Wang, N and Lau, HC and Jiao, Y and Zhou, X and Ye, L and Mo, M and Yang, T and Fan, M and Song, L and Zhou, H and Zhao, Q and Chu, ES and Liang, M and Liu, W and Liu, X and Zhang, S and Shang, H and Wei, H and Li, X and Xu, L and Liao, B and Sung, JJY and Kuang, M and Yu, J}, title = {Gut-liver translocation of pathogen Klebsiella pneumoniae promotes hepatocellular carcinoma in mice.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, pmid = {39747695}, issn = {2058-5276}, support = {82173191//National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund)/ ; }, abstract = {Hepatocellular carcinoma (HCC) is accompanied by an altered gut microbiota but whether the latter contributes to carcinogenesis is unclear. Here we show that faecal microbiota transplantation (FMT) using stool samples from patients with HCC spontaneously initiate liver inflammation, fibrosis and dysplasia in wild-type mice, and accelerate disease progression in a mouse model of HCC. We find that HCC-FMT results in gut barrier injury and translocation of live bacteria to the liver. Metagenomic analyses and bacterial culture of liver tissues reveal enrichment of the gut pathogen Klebsiella pneumoniae in patients with HCC and mice transplanted with the HCC microbiota. Moreover, K. pneumoniae monocolonization recapitulates the effect of HCC-FMT in promoting liver inflammation and hepatocarcinogenesis. Mechanistically, K. pneumoniae surface protein PBP1B interacts with and activates TLR4 on HCC cells, leading to increased cell proliferation and activation of oncogenic signalling. Targeting gut colonization using K. oxytoca or TLR4 inhibition represses K. pneumoniae-induced HCC progression. These findings indicate a role for an altered gut microbiota in hepatocarcinogenesis.}, } @article {pmid39746875, year = {2025}, author = {Faith, JJ}, title = {Assessing live microbial therapeutic transmission.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2447836}, doi = {10.1080/19490976.2024.2447836}, pmid = {39746875}, issn = {1949-0984}, mesh = {Humans ; *Fecal Microbiota Transplantation ; *Clostridium Infections/microbiology/therapy/drug therapy ; *Clostridioides difficile/drug effects/physiology/genetics ; *Gastrointestinal Microbiome ; Feces/microbiology ; Animals ; }, abstract = {The development of fecal microbiota transplantation and defined live biotherapeutic products for the treatment of human disease has been an empirically driven process yielding a notable success of approved drugs for the treatment of recurrent Clostridioides difficile infection. Assessing the potential of this therapeutic modality in other indications with mixed clinical results would benefit from consistent quantitative frameworks to characterize drug potency and composition and to assess the impact of dose and composition on the frequency and duration of strain engraftment. Monitoring these drug properties and engraftment outcomes would help identify minimally sufficient sets of microbial strains to treat disease and provide insights into the intersection between microbial function and host physiology. Broad and correct usage of strain detection methods is essential to this advancement. This article describes strain detection approaches, where they are best applied, what data they require, and clinical trial designs that are best suited to their application.}, } @article {pmid39746695, year = {2024}, author = {He, H and Zhang, JP and Wei, ZJ and Lu, Y and Zhao, YL and Sun, RJ}, title = {[Role of human herpesvirus infection in refractory gastrointestinal graft-versus-host-disease after hematopoietic stem cell transplantation and the diagnosis and treatment thereof].}, journal = {Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi}, volume = {45}, number = {11}, pages = {1016-1021}, doi = {10.3760/cma.j.cn121090-20240906-00339}, pmid = {39746695}, issn = {0253-2727}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Male ; Female ; Adult ; Middle Aged ; *Graft vs Host Disease/diagnosis/etiology ; Retrospective Studies ; Adolescent ; Young Adult ; Child ; Child, Preschool ; Infant ; Herpesviridae Infections/diagnosis ; Transplantation, Homologous ; Cytomegalovirus/isolation & purification ; Herpesvirus 6, Human/isolation & purification ; }, abstract = {Objective: This study aimed to investigate the role of human herpesvirus (HHV) infection in refractory intestinal graft-versus-host disease (GI-GVHD) after hematopoietic stem cell transplantation (HSCT) and its diagnosis and treatment. Methods: This study retrospectively analyzed patients presenting with refractory GI-GVHD after allogeneic HSCT (allo-HSCT) with concomitant colonoscopy and mucosal biopsy at Lu Daopei Hospital, Yanda, Hebei, from March 2022 to July 2024. Human herpesvirus 6 (HHV6), HHV7, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) detection with the RQ-PCR method. The intestinal mucosa was pathologically assessed and immunohistochemistry was utilized to detect the CMV early antigen, CMV late antigen, and EBV by in situ hybridization. Results: This study included 42 patients, consisting of 25 males and 17 females with a median age of 26 (1-59) years. All were histopathologically diagnosed as GI-GVHD. Among them, 34 (81.0%) cases had combined viral enteritis, with 52.4% positive for EBV, 38.1% positive for HHV6, 26.2% positive for CMV, and 14.3% positive for HHV7. Further, 17 (40.5%) cases had mixed viral infections, including 5 EBV+ HHV6, 3 CMV+HHV6, 3 CMV+EBV, 2 CMV+EBV+HHV6, 2 EBV+HHV6+HHV7, 1 EBV+HHV7, and 1 HHV6 + HHV7 cases. Furthermore, 17 (40.5%) had a single viral infection, including 9 EBV, 3 CMV, 3 HHV6, and 2 HHV7 cases. Moreover, 17 (40.5%) patients exhibited a positive histopathological viral test, including 7 (16.6%) CMV-positive and 12 (28.5%) EBV-positive cases. The same positive virus was detected in the feces of all 34 patients with positive tissue homogenate virus, and the positive rate of the same virus in the blood was 17.6%. Tissue homogenized virus testing was utilized as the diagnostic criterion for enterocolitis: blood tests for CMV, EBV, HHV6, and HHV7 demonstrated a sensitivity of 45.4%, 4.5%, 6.3%, and 0%, and specificity of 90.3%, 95%, 100%, and 110%, respectively. Additionally, fecal tests for CMV, EBV, HHV6, and HHV7 demonstrated a sensitivity and specificity of 100%. Treatment based on etiology caused ORR and CR rates for diarrhea of 76.1% (32/42) and 66.6% (28/42), respectively. The median follow-up of 42 patients was 13 (1 - 49) months, and 28 patients survived, with an expected 2-year survival rate of 61.9%. Conclusion: In addition to GVHD itself, intestinal human herpesvirus infection is one of the reasons for the refractory nature of GI-GVHD. Viral testing in blood and tissues reveals significant segregation, and the possibility of comorbid viral enteritis cannot be excluded even if a patient with GI-GVHD tests negative for blood viruses.}, } @article {pmid39744736, year = {2024}, author = {Jeyaraman, N and Jeyaraman, M and Dhanpal, P and Ramasubramanian, S and Ragavanandam, L and Muthu, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Gut microbiome and orthopaedic health: Bridging the divide between digestion and bone integrity.}, journal = {World journal of orthopedics}, volume = {15}, number = {12}, pages = {1135-1145}, pmid = {39744736}, issn = {2218-5836}, abstract = {The gut microbiome, a complex ecosystem of microorganisms in the digestive tract, has emerged as a critical factor in human health, influencing metabolic, immune, and neurological functions. This review explores the connection between the gut microbiome and orthopedic health, examining how gut microbes impact bone density, joint integrity, and skeletal health. It highlights mechanisms linking gut dysbiosis to inflammation in conditions such as rheumatoid arthritis and osteoarthritis, suggesting microbiome modulation as a potential therapeutic strategy. Key findings include the microbiome's role in bone metabolism through hormone regulation and production of short-chain fatty acids, crucial for mineral absorption. The review also considers the effects of diet, probiotics, and fecal microbiota transplantation on gut microbiome composition and their implications for orthopedic health. While promising, challenges in translating microbiome research into clinical practice persist, necessitating further exploration and ethical consideration of microbiome-based therapies. This interdisciplinary research aims to link digestive health with musculoskeletal integrity, offering new insights into the prevention and management of bone and joint diseases.}, } @article {pmid39744230, year = {2025}, author = {Singh, A and Chandrasekar, SV and Valappil, VT and Scaria, J and Ranjan, A}, title = {Tumor immunomodulation by nanoparticle and focused ultrasound alters gut microbiome in a sexually dimorphic manner.}, journal = {Theranostics}, volume = {15}, number = {1}, pages = {216-232}, pmid = {39744230}, issn = {1838-7640}, mesh = {Animals ; Female ; Male ; *Gastrointestinal Microbiome/immunology ; Mice ; *Nanoparticles/administration & dosage ; *Immunomodulation ; Calreticulin/metabolism ; Cell Line, Tumor ; Immunogenic Cell Death/drug effects ; Mice, Inbred C57BL ; Mouth Neoplasms/immunology/microbiology/therapy ; Sex Characteristics ; Cytokines/metabolism ; }, abstract = {Background: Local immunomodulation with nanoparticles (NPs) and focused ultrasound (FUS) is recognized for triggering anti-tumor immunity. However, the impact of these tumor immunomodulations on sex-specific microbiome diversity at distant sites and their correlation with therapeutic effectiveness remains unknown. Here, we conducted local intratumoral therapy using immunogenic cell death-enhancing Calreticulin-Nanoparticles (CRT-NPs) and FUS in male and female mice. We identified immune-related microbiome populations, aiming to translate our findings into clinical applications. Methods: CRT-NPs were synthesized by loading CRT-delivering plasmids into cationic liposomes. Local tumor therapy was performed using CRT-NP and FUS-based histotripsy (HT) on poorly immunogenic Mouse Oral Squamous Cell Carcinoma (MOC2) in the flank regions of male and female mice. Fecal samples were collected and analyzed before and three weeks post-treatment. The microbiome features were then correlated with immune cell dynamics within tumors and systemic cytokine responses to identify prognostic biomarkers in both male and female subjects. Results: Intratumorally administered CRT-NP induced tumor remission and immune cell activation in both male and female mice, whereas HT was ineffective in males and showed efficacy only in females. Turicibacter and Peptococcus inversely correlated with tumor growth, while Enterorhabdus, Subdologranulum, Desulfovibrio, and Aldercreutzia-Asaccharobacter showed direct correlations with tumor growth. HT induced higher levels of Turicibacter in MOC2-bearing females, while males displayed increased Enterorhabdus and Streptococcus populations. Independent of sex, treatments promoting CD4+ T helper cells, functional CD8+ T cells, and total macrophage infiltration correlated with higher levels of Gastrophilales, Romboutsia, Turicibacter, and Peptococcus. Alternatively, Enterorhabdus, Desulfovibrio, Streptococcus, and Staphylococcus corresponded to poor treatment outcomes in both sexes. Conclusion: An enhanced abundance of Enterorhabdus, Desulfovibrio, Streptococcus, and Staphylococcus in response to immunomodulatory therapies could serve as predictive biomarkers in a sex-independent manner. These findings could also be potentially extended to the realm of personalized interventions through fecal transplantations to reverse immunosuppressive phenotypes in males and improve patient outcomes.}, } @article {pmid39741383, year = {2024}, author = {van Rheenen, PF and Kolho, KL and Russell, RK and Aloi, M and Deganello, A and Hussey, S and Junge, N and De Laffolie, J and Deneau, MR and Fitzpatrick, E and Griffiths, AM and Hojsak, I and Nicastro, E and Nita, A and Pakarinen, M and Ricciuto, A and de Ridder, L and Sonzogni, A and Tenca, A and Samyn, M and Indolfi, G}, title = {Primary sclerosing cholangitis in children with inflammatory bowel disease: An ESPGHAN position paper from the Hepatology Committee and the IBD Porto group.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.12378}, pmid = {39741383}, issn = {1536-4801}, support = {//European Society for Paediatric Gastroenterology Hepatology and Nutrition/ ; }, abstract = {OBJECTIVE: We aimed to provide an evidence-supported approach to diagnose, monitor, and treat children with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC).

METHODS: The core group formulated seven PICO-structured clinical questions. A systematic literature search from inception to December 2022 was conducted by a medical librarian using MEDLINE and EMBASE. Core messages from the literature were phrased as position statements and then circulated to a sounding board composed of international experts in pediatric gastroenterology and hepatology, histopathology, adult gastroenterology and hepatology, radiology, and surgery. Statements reaching at least 80% agreement were considered as final. The other statements were refined and then subjected to a second online vote or rejection.

RESULTS: Regular screening for gamma-glutamyltransferase (GGT) is essential for detecting possible biliary disease in children with IBD. MR cholangiopancreatography is the radiological modality of choice for establishing the diagnosis of PSC. Liver biopsy is relevant in the evaluation of small duct PSC or autoimmune hepatitis. Children who do not have known IBD at the time of PSC diagnosis should undergo initial screening with fecal calprotectin for asymptomatic colitis, and then at least once yearly thereafter. Children with a cholestatic liver enzyme profile can be considered for treatment with ursodeoxycholic acid and can continue if there is a meaningful reduction or normalization in GGT. Oral vancomycin may have a beneficial effect on GGT and intestinal inflammation, but judicious use is recommended due to the lack of long-term studies. Children with PSC-IBD combined with convincing features of autoimmune hepatitis may benefit from corticosteroids and antimetabolites.

CONCLUSIONS: We present state-of-the-art guidance on the diagnostic criteria, follow-up strategies, and therapeutic strategies and point out research gaps in children and adolescents with PSC-IBD.}, } @article {pmid39739648, year = {2024}, author = {Lei, J and Lv, L and Zhong, L and Xu, F and Su, W and Chen, Y and Wu, Z and He, S and Chen, Y}, title = {The Gut Microbiota Affects Anti-TNF Responsiveness by Activating the NAD[+] Salvage Pathway in Ulcerative Colitis.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2413128}, doi = {10.1002/advs.202413128}, pmid = {39739648}, issn = {2198-3844}, support = {82100548//National Natural Science Foundation of China/ ; CSTB2022NSCQ-MSX0094//Natural Science Foundation of Chongqing Municipality/ ; }, abstract = {Approximately 50% of the patients with ulcerative colitis (UC) are primarily nonresponsive to anti-tumor necrosis factor (TNF) therapy or lose their responsiveness over time. The gut microbiota plays an important role in the resistance of UC to anti-TNF therapy; however, the underlying mechanism remains unknown. Here, it is found that the transplantation of gut fecal microbiota from patients with UC alters the diversity of the gut microbiota in dextran sulfate sodium-induced colitis mice and may affect the therapeutic responsiveness of mice to infliximab. Furthermore, the abundances of Romboutsia and Fusobacterium increase in the tissues of patients with UC who do not respond to anti-TNF therapy. Differentially abundant metabolites are mainly enriched in nicotinate and nicotinamide metabolism in NCM460 cells after Fusobacterium nucleatum infection. Mechanistically, F. nucleatum promotes the nicotinamide adenine dinucleotide (NAD[+]) salvage pathway by upregulating NAMPT expression, which subsequently leads to the activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway and promotes the secretion of inflammatory factors, ultimately inhibiting the therapeutic response to anti-TNF drugs. These findings demonstrate that the gut microbiota can influence the response to anti-TNF therapy in patients with UC and highlight the therapeutic potential of targeting F. nucleatum and its associated pathways for preventing and treating drug resistance in UC.}, } @article {pmid39738016, year = {2024}, author = {Li, Z and Gu, M and Zaparte, A and Fu, X and Mahen, K and Mrdjen, M and Li, XS and Yang, Z and Ma, J and Thoudam, T and Chandler, K and Hesler, M and Heathers, L and Gorse, K and Van, TT and Wong, D and Gibson, AM and Wang, Z and Taylor, CM and Quijada, P and Makarewich, CA and Hazen, SL and Liangpunsakul, S and Brown, JM and Lefer, DJ and Welsh, DA and Sharp, TE}, title = {Alcohol-induced gut microbial reorganization and associated overproduction of phenylacetylglutamine promotes cardiovascular disease.}, journal = {Nature communications}, volume = {15}, number = {1}, pages = {10788}, pmid = {39738016}, issn = {2041-1723}, support = {R01 AA029984/AA/NIAAA NIH HHS/United States ; P50 AA024333/AA/NIAAA NIH HHS/United States ; UH2 AA026226/AA/NIAAA NIH HHS/United States ; P60 AA009803/AA/NIAAA NIH HHS/United States ; R21 AA027199/AA/NIAAA NIH HHS/United States ; U01 AA026917/AA/NIAAA NIH HHS/United States ; UH3 AA026903/AA/NIAAA NIH HHS/United States ; R01AA030312//U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)/ ; T32 AR065972/AR/NIAMS NIH HHS/United States ; T32 HL069766/HL/NHLBI NIH HHS/United States ; R25 HL145817/HL/NHLBI NIH HHS/United States ; HL160569//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; HL171221//U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)/ ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL167831/HL/NHLBI NIH HHS/United States ; P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL146098/HL/NHLBI NIH HHS/United States ; R01 HL146514/HL/NHLBI NIH HHS/United States ; R01 HL151398/HL/NHLBI NIH HHS/United States ; NSF 2018936//National Science Foundation (NSF)/ ; RF1 NS133812/NS/NINDS NIH HHS/United States ; P20 GM103424/GM/NIGMS NIH HHS/United States ; U54 GM104940/GM/NIGMS NIH HHS/United States ; U24 DK1132746//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; R01 DK130227/DK/NIDDK NIH HHS/United States ; R01 DK120679/DK/NIDDK NIH HHS/United States ; KC2210163//U.S. Department of Defense (United States Department of Defense)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; Male ; *Glutamine/metabolism/analogs & derivatives ; *Cardiovascular Diseases/metabolism/microbiology/etiology ; Mice ; Humans ; Mice, Inbred C57BL ; Myocytes, Cardiac/metabolism/drug effects ; Ethanol/pharmacology/metabolism ; Oxidative Stress/drug effects ; Fecal Microbiota Transplantation ; Alcoholism/metabolism ; Disease Models, Animal ; Female ; Glutamates/metabolism ; Endothelial Cells/metabolism/drug effects ; Middle Aged ; }, abstract = {The mechanism(s) underlying gut microbial metabolite (GMM) contribution towards alcohol-mediated cardiovascular disease (CVD) is unknown. Herein we observe elevation in circulating phenylacetylglutamine (PAGln), a known CVD-associated GMM, in individuals living with alcohol use disorder. In a male murine binge-on-chronic alcohol model, we confirm gut microbial reorganization, elevation in PAGln levels, and the presence of cardiovascular pathophysiology. Fecal microbiota transplantation from pair-/alcohol-fed mice into naïve male mice demonstrates the transmissibility of PAGln production and the CVD phenotype. Independent of alcohol exposure, pharmacological-mediated increases in PAGln elicits direct cardiac and vascular dysfunction. PAGln induced hypercontractility and altered calcium cycling in isolated cardiomyocytes providing evidence of improper relaxation which corresponds to elevated filling pressures observed in vivo. Furthermore, PAGln directly induces vascular endothelial cell activation through induction of oxidative stress leading to endothelial cell dysfunction. We thus reveal that the alcohol-induced microbial reorganization and resultant GMM elevation, specifically PAGln, directly contributes to CVD.}, } @article {pmid39736988, year = {2024}, author = {Wang, F and Wang, Z and Qu, L}, title = {The changes of intestinal flora and metabolites in atopic dermatitis mice.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1462491}, pmid = {39736988}, issn = {1664-302X}, abstract = {INTRODUCTION: Atopic dermatitis (AD) is an allergic disease caused by various factors that can affect an individual's appearance and cause psychological stress. Therefore, it is necessary to investigate the underlying mechanisms and develop effective treatment strategies. The gut microbiota and bacterial metabolism play crucial roles in human diseases. However, their specific role in AD remains unclear.

METHODS: In this study, we established a mouse model of AD and found that 2,4-dinitrofluorobenzene disrupted the skin barrier in mice. The species composition of intestinal bacteria was then analyzed by fecal 16s rRNA sequencing. The metabolic level of mice was analyzed by untargeted and targeted metabolomics in stool.

RESULTS: The levels of filaggrin and aquaporin 3 proteins in the model mice and total superoxide dismutase, catalase and malondialdehyde levels were significantly altered. Additionally, inflammatory factors such as tumor necrosis factor-alpha showed a significant increase. Using 16S rRNA gene sequencing, we identified 270 bacterial species with altered abundances of Ruminococcaceae and Bifidobacteriaceae. The untargeted metabolomic analysis detected 1,299 metabolites. Targeted analysis of free fatty acids revealed 49 metabolites with notable increases in linoleic and linolenic acid levels. Fecal bacterial transplantation experiments have demonstrated that oxidative stress, inflammation, and skin barrier damage were alleviated after transplantation.

DISCUSSION: These findings suggested that the metabolite linoleic acid negatively correlated with Ruminococcaceae and Bifidobacteriaceae may influence AD development. Perturbations in the intestinal bacteria and flora contributed to the development of AD, and the mouse model could serve as a valuable tool for further investigation of therapeutic approaches for managing ADS.}, } @article {pmid39736924, year = {2025}, author = {Yuan, C}, title = {Molecular mechanisms and therapeutic strategies of gut microbiota modulation in Sarcopenia (Review).}, journal = {Oncology letters}, volume = {29}, number = {3}, pages = {104}, pmid = {39736924}, issn = {1792-1082}, abstract = {Sarcopenia is an age-related disease that is characterized by a decline in muscle mass and function with significant epidemiological and clinical implications. In recent years, gut microbiota has gained attention as an important regulatory factor in human health. To the best of our knowledge, this is the first study to introduce the definition and epidemiological background of sarcopenia and analyze the potential impact of the gut microbiota on muscle metabolism and growth, including aspects such as gut microbiota metabolites, muscle protein synthesis and energy metabolism. Additionally, this article summarizes the current research progress in gut microbiota interventions for the treatment of sarcopenia, such as probiotics, prebiotics and fecal microbiota transplantation and discusses future research directions and potential therapeutic strategies.}, } @article {pmid39735707, year = {2024}, author = {Chu, C and Behera, TR and Huang, Y and Qiu, W and Chen, J and Shen, Q}, title = {Research progress of gut microbiome and diabetic nephropathy.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1490314}, pmid = {39735707}, issn = {2296-858X}, abstract = {Diabetic nephropathy is an important complication of diabetic microvascular injury, and it is also an important cause of end-stage renal disease. Its high prevalence and disability rate significantly impacts patients' quality of life while imposing substantial social and economic burdens. Gut microbiota affects host metabolism, multiple organ functions, and regulates host health throughout the life cycle. With the rapid development of technology, researchers have found that gut microbiota is closely related to the progression of diabetic kidney disease. This review explores the role of gut microbiome in diabetic nephropathy summarizing proposed mechanisms of progression and focusing on microbial metabolites, intestinal barrier disruption, inflammation, filtration barrier damage and renal fibrosis. This review also examines the mechanism and limitations of current treatments, including drugs, fecal microbiota transplantation, and lifestyle changes, offering new perspectives on prevention and treatment.}, } @article {pmid39735647, year = {2024}, author = {Wang, H and Li, S and Zhang, L and Zhang, N}, title = {The role of fecal microbiota transplantation in type 2 diabetes mellitus treatment.}, journal = {Frontiers in endocrinology}, volume = {15}, number = {}, pages = {1469165}, pmid = {39735647}, issn = {1664-2392}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Diabetes Mellitus, Type 2/therapy/microbiology ; *Gastrointestinal Microbiome ; Animals ; }, abstract = {In contemporary microbial research, the exploration of interactions between microorganisms and multicellular hosts constitutes a burgeoning field. The gut microbiota is increasingly acknowledged as a pivotal contributor to various disorders within the endocrine system, encompassing conditions such as diabetes and thyroid diseases. A surge in research activities has been witnessed in recent years, elucidating the intricate interplay between the gut microbiota and disorders of the endocrine system. Simultaneously, fecal microbiota transplantation (FMT) has emerged as a focal point, garnering substantial attention in both biomedical and clinical spheres. Research endeavors have uncovered the remarkable therapeutic efficacy of FMT across diverse diseases, with particular emphasis on its application in addressing type 2 diabetes mellitus (T2DM) and associated com-plications. Consequently, this manuscript accentuates the intimate connection between the gut microbiota and disorders within the endocrine system, with a specific focus on exploring the potential of FMT as an intervention in the therapeutic landscape of T2DM and its complications. Furthermore, the article scrutinizes concerns inherent in treatment modalities centered around the gut microbiota, proposing viable solutions to address these issues.}, } @article {pmid39735273, year = {2024}, author = {Patnaik, S and Durairajan, SSK and Singh, AK and Krishnamoorthi, S and Iyaswamy, A and Mandavi, SP and Jeewon, R and Williams, LL}, title = {Role of Candida species in pathogenesis, immune regulation, and prognostic tools for managing ulcerative colitis and Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {48}, pages = {5212-5220}, pmid = {39735273}, issn = {2219-2840}, mesh = {Humans ; *Crohn Disease/immunology/microbiology/therapy ; *Gastrointestinal Microbiome/immunology ; *Colitis, Ulcerative/microbiology/immunology/diagnosis/therapy ; *Dysbiosis/immunology/microbiology ; Prognosis ; Candida albicans/immunology/pathogenicity/isolation & purification ; Immunity, Mucosal ; Candida/immunology/pathogenicity/isolation & purification ; Candidiasis/immunology/microbiology/diagnosis ; Host-Pathogen Interactions ; Intestinal Mucosa/microbiology/immunology ; }, abstract = {The gut microbiome plays a key role in the pathogenesis and disease activity of inflammatory bowel disease (IBD). While research has focused on the bacterial microbiome, recent studies have shifted towards host genetics and host-fungal interactions. The mycobiota is a vital component of the gastrointestinal microbial community and plays a significant role in immune regulation. Among fungi, Candida species, particularly Candida albicans (C. albicans), have been extensively studied due to their dual role as gut commensals and invasive pathogens. Recent findings indicate that various strains of C. albicans exhibit considerable differences in virulence factors, impacting IBD's pathophysiology. Intestinal fungal dysbiosis and antifungal mucosal immunity may be associated to IBD, especially Crohn's disease (CD). This article discusses intestinal fungal dysbiosis and antifungal immunity in healthy individuals and CD patients. It discusses factors influencing the mycobiome's role in IBD pathogenesis and highlights significant contributions from the scientific community aimed at enhancing understanding of the mycobiome and encouraging further research and targeted intervention studies on specific fungal populations. Our article also provided insights into a recent study by Wu et al in the World Journal of Gastroenterology regarding the role of the gut microbiota in the pathogenesis of CD.}, } @article {pmid39735176, year = {2025}, author = {Bhatia, Z and Kumar, S and Seshadri, S}, title = {Fecal microbiota transplantation as a potential therapeutic approach to improve impaired glucose tolerance via gut microbiota modulation in rat model.}, journal = {Journal of diabetes and metabolic disorders}, volume = {24}, number = {1}, pages = {28}, pmid = {39735176}, issn = {2251-6581}, abstract = {OBJECTIVES: To investigate the impact of diet-induced gut microbiota alterations on type 2 diabetes and assess the therapeutic potential of Fecal Microbiota Transplantation (FMT) in restoring a balanced gut microenvironment.

METHODS: To induce type 2 diabetes, rats were fed a high-sugar high-fat diet (HSFD) for 90 days. After diabetes induction, animals were divided into an HSFD control group, a metformin group (100 mg/kg), and an FMT group (100 mg/kg), receiving treatment for an additional 90 days. Fasting blood glucose levels, glucose tolerance, serum markers (HbA1C, free fatty acids, lipopolysaccharides, pro-inflammatory and anti-inflammatory cytokines), and gut microbiota profiles via cecal metagenome sequencing were analyzed post-treatment.

RESULTS: FMT effectively restored gut microbiota composition to a profile similar to healthy controls, rebalancing the Firmicutes/Bacteroidetes ratio and increasing beneficial taxa, including Prevotella ruminicola, Akkermansia muciniphila, Roseburia, and Faecalibacterium prausnitzii. These microbial shifts corresponded with significant metabolic improvements: FMT reduced inflammatory markers (LPS and FFA), lowered HbA1c, and improved glucose tolerance. Enhanced gut barrier integrity observed in FMT-treated animals likely contributed to reduced endotoxemia and systemic inflammation, distinguishing FMT's metabolic effects from those of metformin. Notably, FMT addressed the dysbiosis associated with HSFD, promoting microbial resilience and mitigating the metabolic disruptions linked to type 2 diabetes.

CONCLUSION: These findings underscore the potential of FMT as a targeted therapeutic approach to modulate gut microbiota composition and mitigate metabolic dysregulation induced by high sugar high fat diet.}, } @article {pmid39733842, year = {2024}, author = {Mamun, AA and Geng, P and Wang, S and Shao, C and Xiao, J}, title = {IUPHAR review: Targeted therapies of signaling pathways based on the gut microbiome in autism spectrum disorders: Mechanistic and therapeutic applications.}, journal = {Pharmacological research}, volume = {211}, number = {}, pages = {107559}, doi = {10.1016/j.phrs.2024.107559}, pmid = {39733842}, issn = {1096-1186}, abstract = {Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by impairments in social interaction, communication and repetitive activities. Gut microbiota significantly influences behavior and neurodevelopment by regulating the gut-brain axis. This review explores gut microbiota-influenced treatments for ASD, focusing on their therapeutic applications and mechanistic insights. In addition, this review discusses the interactions between gut microbiota and the immune, metabolic and neuroendocrine systems, focusing on crucial microbial metabolites including short-chain fatty acids (SCFAs) and several neurotransmitters. Furthermore, the review explores various therapy methods including fecal microbiota transplantation, dietary modifications, probiotics and prebiotics and evaluates their safety and efficacy in reducing ASD symptoms. The discussion shows the potential of customized microbiome-based therapeutics and the integration of multi-omics methods to understand the underlying mechanisms. Moreover, the review explores the intricate relationship between gut microbiota and ASD, aiming to develop innovative therapies that utilize the gut microbiome to improve the clinical outcomes of ASD patients. Microbial metabolites such as neurotransmitter precursors, tryptophan metabolites and SCFAs affect brain development and behavior. Symptoms of ASD are linked to changes in these metabolites. Dysbiosis in the gut microbiome may impact neuroinflammatory processes linked to autism, negatively affecting immune signaling pathways. Research indicates that probiotics and prebiotics can improve gut microbiota and alleviate symptoms in ASD patients. Fecal microbiota transplantation may also improve behavioral symptoms and restore gut microbiota balance. The review emphasizes the need for further research on gut microbiota modification as a potential therapeutic approach for ASD, highlighting its potential in clinical settings.}, } @article {pmid39733798, year = {2024}, author = {Luo, Y and Li, M and Luo, D and Tang, B}, title = {Gut Microbiota: An Important Participant in Childhood Obesity.}, journal = {Advances in nutrition (Bethesda, Md.)}, volume = {}, number = {}, pages = {100362}, doi = {10.1016/j.advnut.2024.100362}, pmid = {39733798}, issn = {2156-5376}, abstract = {Increasing prevalence of childhood obesity has emerged as a critical global public health concern. Recent studies have challenged the previous belief that obesity was solely a result of excessive caloric intake. Alterations in early-life gut microbiota can contribute to childhood obesity through their influence on nutrient absorption and metabolism, initiation of inflammatory responses, and regulation of gut-brain communication. The gut microbiota is increasingly acknowledged to play a crucial role in human health, as certain beneficial bacteria have been scientifically proven to possess the capacity to reduce body fat content and enhance intestinal barrier function, and their metabolic products to exhibit anti-inflammatory effect. Examples of such microbes include bifidobacteria, Akkermansia muciniphila, and Lactobacillus reuteri. In contrast, an increase in Enterobacteriaceae and Propionate-producing bacteria (Prevotellaceae and Veillonellaceae) has been implicated in the induction of low-grade systemic inflammation and disturbances in lipid metabolism, which can predispose individuals to obesity. Studies have demonstrated that modulating the gut microbiota through diet, lifestyle changes, prebiotics, probiotics, or fecal microbiota transplantation may contribute to gut homeostasis and the management of obesity and its associated comorbidities. This review elucidates the impact of alterations in gut microbiota composition during early-life on childhood obesity and explores the mechanisms by which gut microbiota contributes to the pathogenesis of obesity, and specifically focuses on recent advances in utilizing short-chain fatty acids for regulating gut microbiota and ameliorating obesity. Additionally, it discusses the therapeutic strategies for childhood obesity from the perspective of gut microbiota, aiming to provide a theoretical foundation for interventions targeting pediatric obesity based on gut microbiota. Statement of Significance: We provide a summary of the factors, mechanisms, and therapeutic strategies pertaining to the impact of gut microbiota alterations on childhood obesity, with particularly emphasis recent advancements in leveraging short-chain fatty acids for modulating gut microbiota composition and ameliorating obesity-related concerns.}, } @article {pmid39732757, year = {2024}, author = {Jasiński, M and Biliński, J and Maciejewska, M and Ostrowska, K and Rusicka-Krzewska, P and Konarski, W and Podsiadły, E and Snarski, E and Basak, GW}, title = {Impact of gut colonization by antibiotic-resistant bacteria on the outcomes of autologous stem cell transplantation in multiple myeloma.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {31221}, pmid = {39732757}, issn = {2045-2322}, mesh = {Humans ; *Multiple Myeloma/therapy/microbiology ; Male ; Middle Aged ; Female ; *Transplantation, Autologous ; Aged ; Retrospective Studies ; *Gastrointestinal Microbiome ; Adult ; *Hematopoietic Stem Cell Transplantation/adverse effects ; Anti-Bacterial Agents/therapeutic use/pharmacology ; Drug Resistance, Bacterial ; Treatment Outcome ; }, abstract = {Patients undergoing autologous stem cell transplantation (auto-SCT) face elevated risks of infections. Additionally, patients colonized in the gastrointestinal tract with antibiotic-resistant bacteria (ARB) are at higher risk of infection with ARB and other infections. Therefore, patients colonized with ARB before auto-SCT should present with an exceptionally high incidence of infections. According to current literature, ARB colonization is the surrogate marker for dysbiosis, which is known to be associated with a diagnosis of multiple myeloma (MM). Given that, this retrospective study aimed to assess the influence of ARB colonization on infection rates, hematopoiesis regeneration, mucositis, overall survival, and progression-free survival following auto-SCT in MM. Data from 138 MM patients undergoing 141 auto-SCT were analyzed, with 15% showing ARB colonization. Among colonized patients, ESBL-producing gram-negative rods predominated. Patients with gut ARB colonization had significantly higher infection rates than non-colonized individuals (52 vs. 26%, P = 0.02), particularly bloodstream infections (43% vs. 14%, P = 0.004). Colonized patients also tended to exhibit shorter survival rates although there was no statistical significance (1-year and 2-year OS; non-colonized vs. colonized; 97 and 92% vs. 90 and 86%; p = 0.054). Based on our results, gut colonization before auto-SCT negatively affects treatment outcomes.}, } @article {pmid39732731, year = {2024}, author = {Lu, Y and Huangfu, S and Ma, C and Ding, Y and Zhang, Y and Zhou, C and Liao, L and Li, M and You, J and Chen, Y and Wang, D and Chen, A and Jiang, B}, title = {Exosomes derived from umbilical cord mesenchymal stem cells promote healing of complex perianal fistulas in rats.}, journal = {Stem cell research & therapy}, volume = {15}, number = {1}, pages = {414}, pmid = {39732731}, issn = {1757-6512}, support = {BE2022674//General Program of Jiangsu Province Social Development-oriented Special Fund Project/ ; No. 82004365//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Exosomes/metabolism ; Rats ; *Mesenchymal Stem Cells/metabolism/cytology ; *Wound Healing ; *Rats, Sprague-Dawley ; *Umbilical Cord/cytology ; *Rectal Fistula/therapy/metabolism ; Humans ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; Disease Models, Animal ; Male ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/genetics ; Mesenchymal Stem Cell Transplantation/methods ; }, abstract = {BACKGROUND: Complex perianal fistulas, challenging to treat and prone to recurrence, often require surgical intervention that may cause fecal incontinence and lower quality of life due to large surgical wounds and potential sphincter damage. Human umbilical cord-derived MSCs (hUC-MSCs) and their exosomes (hUCMSCs-Exo) may promote wound healing.

METHODS: This study assessed the efficacy, mechanisms, and safety of these exosomes in treating complex perianal fistulas in SD rats. We established a rat model, divided rats with fistulas into the control and the exosome groups. We assessed treatment efficacy through ultrasound, clinical observations, and histopathological analysis. We also evaluated the activation of the HIF-1α/TGF-β/Smad signaling pathway via PCR and Western blot and assessed serological markers for HIF-1α and inflammatory indices through ELISA. We analyzed gut microbiota and the systemic metabolic environment via untargeted metabolomics.

RESULTS: The hUCMSCs-Exo effectively promoted healing of wound, regulated the immune balance enhanced collagen synthesis and angiogenesis in the perianal fistulas model of rats, and regulated the gut microbiota and metabolomic profiles. Results of PCR and Western blot analyses indicated that the exosomes activated HIF-1α/TGF-β/Smad signaling pathways. To the dosages tested, the 10ug/100ul concentration (medium dose) was found to be the most effective to the treatment of complex perianal fistulas.

CONCLUSIONS: The hUCMSCs-Exo significantly promoted the healing of wound in perianal fistulas of rats and demonstrated higher safety. The underlying mechanism facilitating the healing process was likely associated with the activation of the HIF-1α/TGF-β/Smad signaling pathway.}, } @article {pmid39732352, year = {2024}, author = {Kamath, S and Sokolenko, E and Collins, K and Chan, NSL and Mills, N and Clark, SR and Marques, FZ and Joyce, P}, title = {IUPHAR themed review: The gut microbiome in schizophrenia.}, journal = {Pharmacological research}, volume = {211}, number = {}, pages = {107561}, doi = {10.1016/j.phrs.2024.107561}, pmid = {39732352}, issn = {1096-1186}, abstract = {Gut microbial dysbiosis or altered gut microbial consortium, in schizophrenia suggests a pathogenic role through the gut-brain axis, influencing neuroinflammatory and neurotransmitter pathways critical to psychotic, affective, and cognitive symptoms. Paradoxically, conventional psychotropic interventions may exacerbate this dysbiosis, with antipsychotics, particularly olanzapine, demonstrating profound effects on microbial architecture through disruption of bacterial phyla ratios, diminished taxonomic diversity, and attenuated short-chain fatty acid synthesis. To address these challenges, novel therapeutic strategies targeting the gut microbiome, encompassing probiotic supplementation, prebiotic compounds, faecal microbiota transplantation, and rationalised co-pharmacotherapy, show promise in attenuating antipsychotic-induced metabolic disruptions while enhancing therapeutic efficacy. Harnessing such insights, precision medicine approaches promise to transform antipsychotic prescribing practices by identifying patients at risk of metabolic side effects based on their microbial profiles. This IUPHAR review collates the current literature landscape of the gut-brain axis and its intricate relationship with schizophrenia while advocating for integrating microbiome assessments and therapeutic management. Such a fundamental shift in proposing microbiome-informed psychotropic prescriptions to optimise therapeutic efficacy and reduce adverse metabolic impacts would align antipsychotic treatments with microbiome safety, prioritising 'gut-neutral' or gut-favourable drugs to safeguard long-term patient outcomes in schizophrenia therapy.}, } @article {pmid39731142, year = {2024}, author = {Yang, Y and Wang, L and Zhuang, T and Xu, T and Ji, M and Wang, Q}, title = {Washed microbiota transplantation stopped recurrent sepsis in a patient with myelofibrosis: a case report.}, journal = {Gut pathogens}, volume = {16}, number = {1}, pages = {78}, pmid = {39731142}, issn = {1757-4749}, abstract = {BACKGROUND: Sepsis represents the most prevalent infectious complication and the primary cause of mortality in myeloproliferative neoplasms (MPN). The risk of sepsis and the difficulty of treatment are significantly increased in MPN patients due to the need for immunomodulators and antibiotics.

CASE PRESENTATION: On June 9, 2023, a 69-year-old male was admitted to the hospital. Following a battery of tests, the diagnosis of sepsis due to Escherichia coli was ultimately established. The patient was administered amoxicillin clavulanate potassium intravenously. In light of the patient's recurrent sepsis and the likelihood that the source of infection is the intestinal tract, we advised that the patient undergo washed microbiota transplantation (WMT) via a colonic transendoscopic enteral tube (TET).

CONCLUSIONS: WMT as the new method of fecal microbiota transplantation (FMT) successfully cured the recurrent sepsis in this case, indicating the novel option for challenging the refractory or serious infections.}, } @article {pmid39729440, year = {2024}, author = {Cibulkova, I and Rehorova, V and Soukupova, H and Waldauf, P and Cahova, M and Manak, J and Matejovic, M and Duska, F}, title = {Allogenic faecal microbiota transplantation for antibiotic-associated diarrhoea in critically ill patients (FEBATRICE)-Study protocol for a multi-centre randomised controlled trial (phase II).}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0310180}, pmid = {39729440}, issn = {1932-6203}, mesh = {Female ; Humans ; Male ; *Anti-Bacterial Agents/adverse effects/therapeutic use ; *Critical Illness ; *Diarrhea/therapy/microbiology ; Dysbiosis/therapy/microbiology ; *Fecal Microbiota Transplantation/methods/adverse effects ; Feces/microbiology ; *Gastrointestinal Microbiome/drug effects ; Prospective Studies ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; }, abstract = {BACKGROUND: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea.

METHODS: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota.

DISCUSSION: Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims.

TRIAL REGISTRATION: www.clinicaltrials.gov (NCT05430269).}, } @article {pmid39728458, year = {2024}, author = {Voziki, A and Deda, O and Kachrimanidou, M}, title = {The Efficacy of Fecal Microbiota Transplantation in Mouse Models Infected with Clostridioides difficile from the Perspective of Metabolic Profiling: A Systematic Review.}, journal = {Metabolites}, volume = {14}, number = {12}, pages = {}, pmid = {39728458}, issn = {2218-1989}, abstract = {Objectives: This systematic review evaluates the effectiveness of fecal microbiota transplantation (FMT) in treating Clostridioides difficile infection (CDI) in mouse models using a metabolomics-based approach. Methods: A comprehensive search was conducted in three databases (PubMed, Scopus, Google Scholar) from 10 April 2024 to 17 June 2024. Out of the 460 research studies reviewed and subjected to exclusion criteria, only 5 studies met all the inclusion criteria and were analyzed. Results: These studies consistently showed that FMT effectively restored gut microbiota and altered metabolic profiles, particularly increasing short-chain fatty acids (SCFAs) and secondary bile acids, which inhibited C. difficile growth. FMT proved superior to antibiotic and probiotic treatments in re-establishing a healthy gut microbiome, as evidenced by significant changes in the amino acid and carbohydrate levels. Despite its promise, variability in the outcomes-due to factors such as immune status, treatment protocols, and donor microbiome differences-underscores the need for standardization. Rather than pursuing immediate standardization, the documentation of factors such as donor and recipient microbiome profiles, preparation methods, and administration details could help identify optimal configurations for specific contexts and patient needs. In all the studies, FMT was successful in restoring the metabolic profile in mice. Conclusions: These findings align with the clinical data from CDI patients, suggesting that FMT holds potential as a therapeutic strategy for gut health restoration and CDI management. Further studies could pave the way for adoption in clinical practice.}, } @article {pmid39726974, year = {2024}, author = {Ebrahimi, R and Farsi, Y and Nejadghaderi, SA}, title = {Fecal microbiota transplantation for glaucoma; a potential emerging treatment strategy.}, journal = {Current research in microbial sciences}, volume = {7}, number = {}, pages = {100314}, pmid = {39726974}, issn = {2666-5174}, abstract = {Glaucoma is the primary cause of irreversible blindness globally. Different glaucoma subtypes are identified by their underlying mechanisms, and treatment options differ by its pathogenesis. Current management includes topical medications to lower intraocular pressure and surgical procedures like trabeculoplasty and glaucoma drainage implants. Fecal microbiota transplantation (FMT) is an almost effective and safe treatment option for recurrent Clostridium difficile infection. The relationship between bacterial populations, metabolites, and inflammatory pathways in retinal diseases indicates possible therapeutic strategies. Thus, incorporating host microbiota-based therapies could offer an additional treatment option for glaucoma patients. Here, we propose that combining FMT with standard glaucoma treatments may benefit those affected by this condition. Also, the potential safety, efficacy, cost-effectiveness and clinical applications are discussed.}, } @article {pmid39726854, year = {2025}, author = {Minerbi, A and Khoutorsky, A and Shir, Y}, title = {Decoding the connection: unraveling the role of gut microbiome in fibromyalgia.}, journal = {Pain reports}, volume = {10}, number = {1}, pages = {e1224}, pmid = {39726854}, issn = {2471-2531}, abstract = {The gut microbiome is emerging as a critical player in the pathophysiology of fibromyalgia, offering mechanistic insights as well as potential diagnostic and therapeutic applications.}, } @article {pmid39725607, year = {2025}, author = {Wang, P and Wang, R and Zhao, W and Zhao, Y and Wang, D and Zhao, S and Ge, Z and Ma, Y and Zhao, X}, title = {Gut microbiota-derived 4-hydroxyphenylacetic acid from resveratrol supplementation prevents obesity through SIRT1 signaling activation.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2446391}, doi = {10.1080/19490976.2024.2446391}, pmid = {39725607}, issn = {1949-0984}, mesh = {*Gastrointestinal Microbiome/drug effects ; Animals ; *Sirtuin 1/metabolism ; *Obesity/metabolism/prevention & control/microbiology ; *Resveratrol/pharmacology/administration & dosage ; Mice ; *Phenylacetates/pharmacology/metabolism ; *Signal Transduction/drug effects ; *Diet, High-Fat/adverse effects ; Male ; *Mice, Inbred C57BL ; Dysbiosis/microbiology/prevention & control ; Adipose Tissue, White/metabolism/drug effects ; Anti-Obesity Agents/pharmacology/administration & dosage ; Dietary Supplements ; Bacteria/classification/metabolism/drug effects/genetics ; Fecal Microbiota Transplantation ; }, abstract = {Resveratrol (RSV), a natural polyphenol, has been suggested to influence glucose and lipid metabolism. However, the underlying molecular mechanism of its action remains largely unknown due to its multiple biological targets and low bioavailability. In this study, we demonstrate that RSV supplementation ameliorates high-fat-diet (HFD)-induced gut microbiota dysbiosis, enhancing the abundance of anti-obesity bacterial strains such as Akkermansia, Bacteroides and Blautia. The critical role of gut microbiota in RSV-mediated anti-obesity effects was confirmed through antibiotic-induced microbiome depletion and fecal microbiota transplantation (FMT), which showed that RSV treatment effectively mitigates body weight, histopathological damage, glucose dysregulation and systematic inflammation associated with HFD. Metabolomics analysis revealed that RSV supplementation significantly increases the levels of the gut microbial flavonoid catabolite 4-hydroxyphenylacetic acid (4-HPA). Notably, 4-HPA was sufficient to reverse obesity and glucose intolerance in HFD-fed mice. Mechanistically,4-HPA treatment markedly regulates SIRT1 signaling pathways and induces the expression of beige fat and thermogenesis-specific markers in white adipose tissue (WAT). These beneficial effects of 4-HPA are partially abolished by EX527, a known SIRT1 inhibitor. Collectively, our findings indicate that RSV improve obesity through a gut microbiota-derived 4-HPA-SIRT1 axis, highlighting gut microbiota metabolites as a promising target for obesity prevention.}, } @article {pmid39725475, year = {2024}, author = {Yang, RF and Wu, W and Zhang, P}, title = {Research Progress on Obesity-Associated Kidney Diseases.}, journal = {Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae}, volume = {}, number = {}, pages = {}, doi = {10.3881/j.issn.1000-503X.16098}, pmid = {39725475}, issn = {1000-503X}, abstract = {The pathogenesis of obesity-associated kidney disease (OAKD) involves many aspects,including the overactivation of the renin-angiotensin-aldosterone system,insulin resistance,chronic inflammation,disorder of lipid metabolism and imbalance of gut microecology.Treatment strategies for OAKD focus on lifestyle adjustments,pharmacotherapy,bariatric surgery,and fecal microbiota transplantation.A deeper understanding of the hazards of OAKD and its pathogenesis will contribute to the development of personalized and precise strategies for prevention,diagnosis and treatment of OAKD in the future.}, } @article {pmid39724461, year = {2024}, author = {Mahmoudian, F and Gheshlagh, SR and Hemati, M and Farhadi, S and Eslami, M}, title = {The influence of microbiota on the efficacy and toxicity of immunotherapy in cancer treatment.}, journal = {Molecular biology reports}, volume = {52}, number = {1}, pages = {86}, pmid = {39724461}, issn = {1573-4978}, mesh = {Animals ; Humans ; *Dysbiosis/immunology/microbiology/therapy ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome/immunology ; *Immunotherapy/methods/adverse effects ; *Neoplasms/immunology/microbiology/therapy ; }, abstract = {Immunotherapy, which uses the body's immune system to fight cancer cells, has gained attention recently as a breakthrough in cancer treatment. Although significant progress has been made, obstacles still exist since cancers are skilled at avoiding immune monitoring. The gut microbiota is being looked at more and more in modern research as a critical component in improving the results of immunotherapy. Through modulating both innate and adaptive immune responses, the gut microbiome has a significant impact on cancer immunotherapy. The effectiveness of treatment and the way the immune system responds are significantly influenced by some microorganisms and the metabolites they produce, especially short-chain fatty acids. On the other hand, dysbiosis and persistent inflammation in the gut environment might unintentionally accelerate the growth of tumors, which makes the complex relationship between the makeup of the microbiota and cancer treatment more challenging. Gut microbiota plays a crucial role in immunotherapy effectiveness. Improved microbial diversity leads to better treatment responses, with some taxa like Bacteroides and Ruminococcaceae being linked to better responses to immune checkpoint inhibitors. Dysbiotic conditions can worsen immune-related side effects and reduce treatment effectiveness. Strategies manipulating gut microbiota, such as fecal microbiota transplantation, antibiotic therapies, and dietary interventions, could optimize immunotherapy response and prognosis. However, standardizing these interventions for different cancer types and patient populations is challenging due to individual microbiome differences. Future research should combine microbiome research with AI and rigorous clinical trials for individualized cancer treatments.}, } @article {pmid39717506, year = {2025}, author = {Bloom, PP and Chung, RT}, title = {The future of clinical trials of gut microbiome therapeutics in cirrhosis.}, journal = {JHEP reports : innovation in hepatology}, volume = {7}, number = {1}, pages = {101234}, pmid = {39717506}, issn = {2589-5559}, abstract = {The last two decades have witnessed an explosion of microbiome research, including in hepatology, with studies demonstrating altered microbial composition in liver disease. More recently, efforts have been made to understand the association of microbiome features with clinical outcomes and to develop therapeutics targeting the microbiome. While microbiome therapeutics hold much promise, their unique features pose certain challenges for the design and conduct of clinical trials. Herein, we will briefly review indications for microbiome therapeutics in cirrhosis, currently available microbiome therapeutics, and the biological pathways targeted by these therapies. We will then focus on the best practices and important considerations for clinical trials of gut microbiome therapeutics in cirrhosis.}, } @article {pmid39716346, year = {2024}, author = {Li, Y and Wang, K and Shen, D and Liu, J and Li, S and Liu, L and Nagaoka, K and Li, C}, title = {Mogroside V protects Lipopolysaccharides-induced lung inflammation chicken via suppressing inflammation mediated by the Th17 through the gut-lung axis.}, journal = {Journal of animal science}, volume = {}, number = {}, pages = {}, doi = {10.1093/jas/skae388}, pmid = {39716346}, issn = {1525-3163}, abstract = {Lipopolysaccharide (LPS) exposure triggers pulmonary inflammation, leading to compromised lung function in broiler. As amplified by policy restrictions on antibiotic usage, seeking antibiotic alternatives has become imperative. Mogroside V (MGV) has been reported to have a beneficial role in livestock and poultry production due to its remarkable anti-inflammatory effects. Despite evidence showcasing MGV's efficacy against LPS-triggered lung inflammation, its precise mechanism of action remains elusive. In this study, we transplanted normal fecal microbiota (CF), fecal microbiota modified by MGV (MF), and sterile fecal filtrate (MS) into broiler with LPS-induced pneumonia. The results showed that through fecal microbiota transplantation, transplanting MGV-induced microbial populations significantly mitigated tissue damage induced by LPS and enhanced the mRNA level of pulmonary tight junction proteins and mucoprotein (P < 0.01). The expression levels of RORα (P < 0.001), Foxp3 (P < 0.01) and PD-L1 (P < 0.01) were significantly increased in the MF group than CF group. The concentrations of IL-6 and IL-17 in broilers lung tissue of MF group were lower than those in broilers of CF group (P < 0.05). Furthermore, the concentration of TGF-β in broilers serum of MS and MF groups was higher than those in broilers of control group (P < 0.05). Microbial community analysis demonstrated that at genus level, the harmful bacterial populations Escherichia-shigella and Helicobacter following FMT treatment was significantly reduced in MF group (P < 0.05), potentially mediating its protective effects. Compared with CF group, valerate content and FFAR2 mRNA expression levels in MF group were significantly increased (P < 0.05). The study suggests that MGV via the gut-lung axis, attenuates Th17-mediated inflammation, offering promise as a therapeutic strategy against LPS-induced lung inflammation in chickens.}, } @article {pmid39715825, year = {2024}, author = {Bornbusch, SL and Crosier, A and Gentry, L and Delaski, KM and Maslanka, M and Muletz-Wolz, CR}, title = {Fecal microbiota transplants facilitate post-antibiotic recovery of gut microbiota in cheetahs (Acinonyx jubatus).}, journal = {Communications biology}, volume = {7}, number = {1}, pages = {1689}, pmid = {39715825}, issn = {2399-3642}, support = {NSF IOS-2131060//National Science Foundation (NSF)/ ; }, mesh = {*Acinonyx ; *Gastrointestinal Microbiome ; Animals ; *Anti-Bacterial Agents/pharmacology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Male ; Female ; }, abstract = {Burgeoning study of host-associated microbiomes has accelerated the development of microbial therapies, including fecal microbiota transplants (FMTs). FMTs provide host-specific microbial supplementation, with applicability across host species. Studying FMTs can simultaneously provide comparative frameworks for understanding microbial therapies in diverse microbial systems and improve the health of managed wildlife. Ex-situ carnivores, including cheetahs (Acinonyx jubatus), often suffer from intractable gut infections similar to those treated with antibiotics and FMTs in humans, providing a valuable system for testing FMT efficacy. Using an experimental approach in 21 cheetahs, we tested whether autologous FMTs facilitated post-antibiotic recovery of gut microbiota. We used 16S rRNA sequencing and microbial source tracking to characterize antibiotic-induced microbial extirpations and signatures of FMT engraftment for single versus multiple FMTs. We found that antibiotics extirpated abundant bacteria and FMTs quickened post-antibiotic recovery via engraftment of bacteria that may facilitate protein digestion and butyrate production (Fusobacterium). Although multiple FMTs better sustained microbial recovery compared to a single FMT, one FMT improved recovery compared to antibiotics alone. This study elucidated the dynamics of microbiome modulation in a non-model system and improves foundations for reproducible, low-cost, low-dose, and minimally invasive FMT protocols, emphasizing the scientific and applied value of FMTs across species.}, } @article {pmid39715151, year = {2024}, author = {Nie, P and Hu, L and You, T and Jia, T and Xu, H}, title = {Lead Mediated Lipopolysaccharides Exacerbates Fatty Liver Processes in High-Fat Diets-Induced Mice.}, journal = {Environmental toxicology}, volume = {}, number = {}, pages = {}, doi = {10.1002/tox.24463}, pmid = {39715151}, issn = {1522-7278}, support = {82060606//National Natural Science Foundation of China/ ; }, abstract = {Obesity leads to a variety of health risks, and lead, which is ranked second in Agency for Toxic Substances and Disease Registry's priority list of harmful substances, may be more harmful to individuals that are obese. C57BL/6 mice were fed a normal diet or a high-fat diet with or without exposure to 1 g/L lead exposure in drinking water for 8 consecutive weeks. Serum and hepatic biochemistry analysis, histopathological observation, and RT-qPCR were used to explore the potential mechanism of liver damage in obese individuals after Pb exposure, and fecal microbiota transplantation was performed to investigate the role of the gut microbiota in the progression of fatty liver disease. We found that the progression of fatty liver disease induced by high-fat diets was accelerated by chronic lead intake. In addition, the occurrences of liver injury in recipient mice suggested the role of the gut microbiota. These findings indicated that the combination of lead and a HFD exacerbated hepatic lipotoxicity by activating LPS-mediated inflammation, and that gut microbiota disorders and impaired intestinal barrier function play pivotal roles in the progression of fatty liver disease.}, } @article {pmid39714951, year = {2024}, author = {Li, W and Wang, Y and Shi, Y and He, F and Zhao, Z and Liu, J and Gao, Z and Zhang, J and Shen, X}, title = {The gut microbiota mediates memory impairment under high-altitude hypoxia via the gut-brain axis in mice.}, journal = {The FEBS journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/febs.17365}, pmid = {39714951}, issn = {1742-4658}, support = {81973073//National Natural Science Foundation of China/ ; 82173481//National Natural Science Foundation of China/ ; 82204089//National Natural Science Foundation of China/ ; }, abstract = {Hypoxia is a predominant risk factor at high altitudes, and evidence suggests that high-altitude hypoxia alters the gut microbiota, which plays an essential regulatory role in memory function. However, the causal relationship between the gut microbiota and memory impairment under hypoxic conditions remains unclear. In this study, we employed a high-altitude hypoxia model combined with fecal microbiota transplantation (FMT) approach in mice to explore the effects of the gut microbiota on memory impairment in a hypoxic environment. We observed that high-altitude hypoxia exposure reduced short- and long-term memory and hippocampus-dependent fear memory abilities, along with decreased relative abundance of Ligilactobacillus and Muribaculum. Moreover, hypoxic conditions increased intestinal and blood-brain barrier permeability. FMT from hypoxia-exposed mice into naïve antibiotic-treated mice resulted in similar memory impairments, Ligilactobacillus and Muribaculum abundance changes, and increased intestinal/blood-brain barrier permeability. Correlation analysis showed a robust positive association between Ligilactobacillus and Muribaculum with hippocampus-dependent contextual fear memory. Likewise, Ligilactobacillus was positively correlated with short-term memory. Therefore, Ligilactobacillus and Muribaculum may be key microbes in reducing memory ability in hypoxia, with the intestinal and blood-brain barriers as primary pathways. Our findings provide further evidence for the potential regulatory mechanism by which gut microbiota dysbiosis may contribute to memory impairment in a high-altitude environment.}, } @article {pmid39712898, year = {2024}, author = {Tang, M and Wu, Y and Liang, J and Yang, S and Huang, Z and Hu, J and Yang, Q and Liu, F and Li, S}, title = {Gut microbiota has important roles in the obstructive sleep apnea-induced inflammation and consequent neurocognitive impairment.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1457348}, pmid = {39712898}, issn = {1664-302X}, abstract = {Obstructive sleep apnea (OSA) is a state of sleep disorder, characterized by repetitive episodes of apnea and chronic intermittent hypoxia. OSA has an extremely high prevalence worldwide and represents a serious challenge to public health, yet its severity is frequently underestimated. It is now well established that neurocognitive dysfunction, manifested as deficits in attention, memory, and executive functions, is a common complication observed in patients with OSA, whereas the specific pathogenesis remains poorly understood, despite the likelihood of involvement of inflammation. Here, we provide an overview of the current state of the art, demonstrating the intimacy of OSA with inflammation and cognitive impairment. Subsequently, we present the recent findings on the investigation of gut microbiota alteration in the OSA conditions, based on both patients-based clinical studies and animal models of OSA. We present an insightful discussion on the role of changes in the abundance of specific gut microbial members, including short-chain fatty acid (SCFA)-producers and/or microbes with pathogenic potential, in the pathogenesis of inflammation and further cognitive dysfunction. The transplantation of fecal microbiota from the mouse model of OSA can elicit inflammation and neurobehavioral disorders in naïve mice, thereby validating the causal relationship to inflammation and cognitive abnormality. This work calls for greater attention on OSA and the associated inflammation, which require timely and effective therapy to protect the brain from irreversible damage. This work also suggests that modification of the gut microbiota using prebiotics, probiotics or fecal microbiota transplantation may represent a potential adjuvant therapy for OSA.}, } @article {pmid39712559, year = {2024}, author = {Özdemir, Ö}, title = {Relation between dysbiosis and inborn errors of immunity.}, journal = {World journal of methodology}, volume = {14}, number = {4}, pages = {96380}, pmid = {39712559}, issn = {2222-0682}, abstract = {Inborn errors of immunity (IEI) disorders, formerly primary immune deficiency diseases, are a heterogeneous group of disorders with variable hereditary transitions, clinical manifestations, complications and varying disease severity. Many of the clinical symptoms, signs and complications in IEI patients can be attributed to inflammatory and immune dysregulatory processes due to loss of microbial diversity (dysbiosis). For example, in common variable immunodeficiency patients, the diversity of bacteria, but not fungi, in the gut microbiota has been found to be reduced and significantly altered. Again, this was associated with a more severe disease phenotype. Compromise of the STAT3/Th17 pathway in hyper-IgE syndrome may lead to dysbiosis of the oral microbiota in these patients, causing Candida albicans to switch from commensal to pathogenic. Modification of the microbiota can be used as a therapeutic approach in patients with IEI. Prebiotics, probiotics, postbiotics and fecal microbiota transplantation can be used to restore the balance of the gut microbiota and reduce pathogenicity in IEI patients. Clinical trials are currently underway to understand the impact of this dysbiosis on the phenotype of IEI diseases and its role in their treatment.}, } @article {pmid39712189, year = {2024}, author = {Lusk, S and Memos, NK and Rauschmayer, A and Ray, RS}, title = {The microbiome is dispensable for normal respiratory function and chemoreflexes in mice.}, journal = {Frontiers in physiology}, volume = {15}, number = {}, pages = {1481394}, pmid = {39712189}, issn = {1664-042X}, abstract = {Increasing evidence indicates an association between microbiome composition and respiratory homeostasis and disease, particularly disordered breathing, such as obstructive sleep apnea. Previous work showing respiratory disruption is limited by the methodology employed to disrupt, eliminate, or remove the microbiome by antibiotic depletion. Our work utilized germ-free mice born without a microbiome and described respiratory alterations. We used whole-body flow through barometric plethysmography to assay conscious and unrestrained C57BL/6J germ-free (GF, n = 24) and specific-pathogen-free (SPF, n = 28) adult mice (with an intact microbiome) in normoxic (21% O2,79% N2) conditions and during challenges in hypercapnic (5% CO2, 21% O2, 74% N2) and hypoxic (10% O2, 90% N2) environments. Following initial plethysmography analysis, we performed fecal transplants to test the ability of gut microbiome establishment to rescue any observed phenotypes. Data were comprehensively analyzed using our newly published respiratory analysis software, Breathe Easy, to identify alterations in respiratory parameters, including ventilatory frequency, tidal volume, ventilation, apnea frequency, and sigh frequency. We also considered possible metabolic changes by analyzing oxygen consumption, carbon dioxide production, and ventilatory equivalents of oxygen. We also assayed GF and SPF neonates in an autoresuscitation assay to understand the effects of the microbiome on cardiorespiratory stressors in early development. We found several differences in baseline and recovery cardiorespiratory parameters in the neonates and differences in body weight at both ages studied. However, there was no difference in the overall survival of the neonates, and in contrast to prior studies utilizing gut microbial depletion, we found no consequential respiratory alterations in GF versus SPF adult mice at baseline or following fecal transplant in any groups. Interestingly, we did see alterations in oxygen consumption in the GF adult mice, which suggests an altered metabolic demand. Results from this study suggest that microbiome alteration in mice may not play as large a role in respiratory outcomes when a less severe methodology to eliminate the microbiome is utilized.}, } @article {pmid39711145, year = {2024}, author = {Qian, M and Jiang, Z and Xu, C and Wang, L and Hu, N}, title = {Changes in the gut microbiota and derived fecal metabolites may play a role in tacrolimus-induced diabetes in mice.}, journal = {Future microbiology}, volume = {}, number = {}, pages = {1-10}, doi = {10.1080/17460913.2024.2444761}, pmid = {39711145}, issn = {1746-0921}, abstract = {AIMS: A notable scarcity of research has focused on examining alterations in gut microbiota and its metabolites within tacrolimus (TAC)-induced diabetes models.

METHODS: Tacrolimus-induced changes in glucose and lipid metabolism indices were analyzed through different routes of administration. The potential role of gut microbiota and its metabolites in TAC-induced diabetes was investigated using 16S rRNA sequencing and non-targeted metabolomics.

RESULTS: After intraperitoneal(ip) and oral(po) administration of TAC, the α-diversity index of gut microbiota was significantly increased. The gut microbiota of the three groups of mice was significantly separated, and there were significant changes in composition and functional genes. Fecal metabolites changed significantly after TAC administration by different routes, and 53 metabolites (38 down-regulated and 15 up-regulated) were identified (CON vs. TACip). Similarly, 29 metabolites (8 down-regulated and 21 up-regulated) were identified (CON vs. TACpo). KEGG pathway analysis identified 4 and 13 significantly altered metabolic pathways, respectively. Correlation analysis suggested that microbiota and metabolites were involved in the pathogenesis of TAC-induced diabetes.

CONCLUSION: This study investigated the alterations in gut microbiota and fecal metabolites in TAC-induced diabetic mice and evaluated the correlation between these changes. These findings provide valuable insights into potential biomarkers in the development of TAC-induced diabetes.}, } @article {pmid39710789, year = {2024}, author = {Wang, Y and Bai, M and Peng, Q and Li, L and Tian, F and Guo, Y and Jing, C}, title = {Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease.}, journal = {European journal of medical research}, volume = {29}, number = {1}, pages = {614}, pmid = {39710789}, issn = {2047-783X}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Neovascularization, Pathologic/metabolism/microbiology ; Neoplasms/microbiology/metabolism/immunology ; Inflammation/metabolism ; Cardiovascular Diseases/microbiology/metabolism/etiology ; Animals ; Neurodegenerative Diseases/microbiology/metabolism ; Angiogenesis ; }, abstract = {The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator. This abstract aims to elucidate the connection between the gut microbiota and angiogenesis in various diseases. The gut microbiota influences angiogenesis through various mechanisms, including the production of metabolites that directly or indirectly affect vascularization. For example, short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are known to regulate immune responses and inflammation, thereby affecting angiogenesis. In the context of cardiovascular diseases, the gut microbiota promotes atherosclerosis and vascular dysfunction by producing trimethylamine N-oxide (TMAO) and other metabolites that promote inflammation and endothelial dysfunction. Similarly, in neurodegenerative diseases, the gut microbiota may influence neuroinflammation and the integrity of the blood-brain barrier, thereby affecting angiogenesis. In cases of fractures and wound healing, the gut microbiota promotes angiogenesis by activating inflammatory responses and immune effects, facilitating the healing of tissue damage. In cancer, the gut microbiota can either inhibit or promote tumor growth and angiogenesis, depending on the specific bacterial composition and their metabolites. For instance, some bacteria can activate inflammasomes, leading to the production of inflammatory factors that alter the tumor immune microenvironment and activate angiogenesis-related signaling pathways, affecting tumor angiogenesis and metastasis. Some bacteria can directly interact with tumor cells, activating angiogenesis-related signaling pathways. Diet, as a modifiable factor, significantly influences angiogenesis through diet-derived microbial metabolites. Diet can rapidly alter the composition of the microbiota and its metabolic activity, thereby changing the concentration of microbial-derived metabolites and profoundly affecting the host's immune response and angiogenesis. For example, a high animal protein diet promotes the production of pro-atherogenic metabolites like TMAO, activating inflammatory pathways and interfering with platelet function, which is associated with the severity of coronary artery plaques, peripheral artery disease, and cardiovascular diseases. A diet rich in dietary fiber promotes the production of SCFAs, which act as ligands for cell surface or intracellular receptors, regulating various biological processes, including inflammation, tissue homeostasis, and immune responses, thereby influencing angiogenesis. In summary, the role of the gut microbiota in angiogenesis is multifaceted, playing an important role in disease progression by affecting various biological processes such as inflammation, immune responses, and multiple signaling pathways. Diet-derived microbial metabolites play a crucial role in linking the gut microbiota and angiogenesis. Understanding the complex interactions between diet, the gut microbiota, and angiogenesis has the potential to uncover novel therapeutic targets for managing these conditions. Therefore, interventions targeting the gut microbiota and its metabolites, such as through fecal microbiota transplantation (FMT) and the application of probiotics to alter the composition of the gut microbiota and enhance the production of beneficial metabolites, present a promising therapeutic strategy.}, } @article {pmid39710683, year = {2024}, author = {Yarahmadi, A and Afkhami, H and Javadi, A and Kashfi, M}, title = {Understanding the complex function of gut microbiota: its impact on the pathogenesis of obesity and beyond: a comprehensive review.}, journal = {Diabetology & metabolic syndrome}, volume = {16}, number = {1}, pages = {308}, pmid = {39710683}, issn = {1758-5996}, abstract = {Obesity is a multifactorial condition influenced by genetic, environmental, and microbiome-related factors. The gut microbiome plays a vital role in maintaining intestinal health, increasing mucus creation, helping the intestinal epithelium mend, and regulating short-chain fatty acid (SCFA) production. These tasks are vital for managing metabolism and maintaining energy balance. Dysbiosis-an imbalance in the microbiome-leads to increased appetite and the rise of metabolic disorders, both fuel obesity and its issues. Furthermore, childhood obesity connects with unique shifts in gut microbiota makeup. For instance, there is a surge in pro-inflammatory bacteria compared to children who are not obese. Considering the intricate nature and variety of the gut microbiota, additional investigations are necessary to clarify its exact involvement in the beginnings and advancement of obesity and related metabolic dilemmas. Currently, therapeutic methods like probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), dietary interventions like Mediterranean and ketogenic diets, and physical activity show potential in adjusting the gut microbiome to fight obesity and aid weight loss. Furthermore, the review underscores the integration of microbial metabolites with pharmacological agents such as orlistat and semaglutide in restoring microbial homeostasis. However, more clinical tests are essential to refine the doses, frequency, and lasting effectiveness of these treatments. This narrative overview compiles the existing knowledge on the multifaceted role of gut microbiota in obesity and much more, showcasing possible treatment strategies for addressing these health challenges.}, } @article {pmid39706182, year = {2024}, author = {Jiang, Y and Huang, Z and Sun, W and Huang, J and Xu, Y and Liao, Y and Jin, T and Li, Q and Ho, IHT and Zou, Y and Zhu, W and Li, Q and Qin, F and Zhang, X and Shi, S and Zhang, N and Yang, S and Xie, W and Wu, S and Tan, L and Zhang, L and Chen, H and Gin, T and Chan, MTV and Wu, WKK and Xiao, L and Liu, X}, title = {Roseburia intestinalis-derived butyrate alleviates neuropathic pain.}, journal = {Cell host & microbe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.chom.2024.11.013}, pmid = {39706182}, issn = {1934-6069}, abstract = {Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles. Functionally, fecal microbiota transplantation from patients with PHN to mice heightened pain sensitivity. Administration of Roseburia intestinalis, a bacterium both depleted in patients with shingles and PHN, alleviated peripheral nerve injury-induced pain in mice. R. intestinalis enhanced vagal neurotransmission to the nucleus tractus solitarius (NTS) to suppress the central amygdala (CeA), a brain region involved in pain perception. R. intestinalis-generated butyrate activated vagal neurons through the receptor, G protein-coupled receptor 41 (GPR41). Vagal knockout of Gpr41 abolished the effects of R. intestinalis on the NTS-CeA circuit and reduced pain behaviors. Overall, we established a microbiota-based model for PHN risk assessment and identified R. intestinalis as a potential pain-alleviating probiotic.}, } @article {pmid39703540, year = {2024}, author = {Finnegan, YE and Neill, HR and Prpa, EJ and Pot, B}, title = {"Gut" to grips with the science of the microbiome - a symposium report.}, journal = {Gut microbiome (Cambridge, England)}, volume = {5}, number = {}, pages = {e11}, pmid = {39703540}, issn = {2632-2897}, abstract = {The latest Yakult Science Study Day was held virtually on 2 November 2023. Aimed at healthcare professionals, researchers, and students, a variety of experts explored the latest gut microbiome research and what it means in practice. The morning sessions discussed the role of the microbiome in health and disease, the rapid advancements in DNA sequencing and implications for personalised nutrition, the current state of evidence on health benefits associated with fermented foods, prebiotics and probiotics and the challenges involved in interpreting research in this area. The afternoon session considered the emerging research on the microbiota-gut-brain axis in mediating effects of food on mood, the bidirectional impact of menopause on the gut microbiota, and the interplay between the gut and skin with implications for the treatment of rare and common skin disorders. The session ended with an update on the use of faecal microbiota transplant in both research and clinical practice. Undoubtedly, the gut microbiome is emerging as a key conductor of human health, both in relation to gastrointestinal and non-gastrointestinal outcomes. As research continues to elucidate mechanisms of action and confirm their effects in human trials, the gut microbiome should be a key consideration within a holistic approach to health moving forward.}, } @article {pmid39703374, year = {2024}, author = {Chen, T and Wang, N and Hao, Y and Fu, L}, title = {Fecal microbiota transplantation from postmenopausal osteoporosis human donors accelerated bone mass loss in mice.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1488017}, pmid = {39703374}, issn = {2235-2988}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Humans ; Mice ; *Gastrointestinal Microbiome ; Female ; *Feces/microbiology ; *Osteoporosis, Postmenopausal/microbiology ; Disease Models, Animal ; Bacteria/classification/isolation & purification/genetics ; Bone Density ; Middle Aged ; Zonula Occludens-1 Protein/metabolism ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVES: To investigate the effect of gut microbiota from postmenopausal osteoporosis patients on bone mass in mice.

METHODS: Fecal samples were collected from postmenopausal women with normal bone mass (Con, n=5) and postmenopausal women with osteoporosis (Op, n=5). Microbial composition was identified by shallow shotgun sequencing. Then fecal samples were transplanted into pseudo-sterile mice previously treated with antibiotics for 4 weeks. These mice were categorized into two groups: the Vehicle group (n=7) received fecal samples from individuals with normal bone mass, and the FMT group (n=7) received fecal samples from individuals with osteoporosis. After 8 weeks, bone mass, intestinal microbial composition, intestinal permeability and inflammation were assessed, followed by a correlation analysis.

RESULTS: The bone mass was significantly reduced in the FMT group. Microbiota sequencing showed that Shannon index (p < 0.05) and Simpson index (p < 0.05) were significantly increased in Op groups, and β diversity showed significant differences. the recipient mice were similar. linear discriminant analysis effect size (LEfSe) analysis of mice showed that Halobiforma, Enterorhabdus, Alistipes, and Butyricimonas were significantly enriched in the FMT group. Lachnospiraceae and Oscillibacter were significantly enriched in the Vehicle group. H&E staining of intestinal tissues showed obvious intestinal mucosal injury in mice. Intestinal immunohistochemistry showed that the expression of Claudin and ZO-1 in the intestinal tissue of the FMT group mice was decreased. The FITC-Dextran (FD-4) absorption rate and serum soluble CD14 (sCD14) content were increased in FMT mice. Correlation analysis showed that these dominant genera were significantly associated with bone metabolism and intestinal permeability, and were associated with the enrichment of specific enzymes. Serum and bone tissue inflammatory cytokines detection showed that the expression of TNF-α and IL-17A in the FMT group were significantly increased.

CONCLUSION: Overall, our findings suggested gut microbiota from postmenopausal osteoporosis patients accelerate bone mass loss in mice. Aberrant gut microbiota might play a causal role in the process of bone mass loss mediated by inflammation after the destruction of the intestinal barrier.}, } @article {pmid39702789, year = {2024}, author = {Kaur, S and Patel, BCK and Collen, A and Malhotra, R}, title = {The microbiome and the eye: a new era in ophthalmology.}, journal = {Eye (London, England)}, volume = {}, number = {}, pages = {}, pmid = {39702789}, issn = {1476-5454}, abstract = {The human microbiome has progressively been recognised for its role in various disease processes. In ophthalmology, complex interactions between the gut and distinct ocular microbiota within each structure and microenvironment of the eye has advanced our knowledge on the multi-directional relationships of these ecosystems. Increasingly, studies have shown that modulation of the microbiome can be achieved through faecal microbiota transplantation and synbiotics producing favourable outcomes for ophthalmic diseases. As ophthalmologists, we are obliged to educate our patients on measures to cultivate a healthy gut microbiome through a range of holistic measures. Further integrative studies combining microbial metagenomics, metatranscriptomics and metabolomics are necessary to fully characterise the human microbiome and enable targeted therapeutic interventions.}, } @article {pmid38659831, year = {2024}, author = {Sall, IJ and Foxall, R and Felth, L and Maret, S and Rosa, Z and Gaur, A and Calawa, J and Pavlik, N and Whistler, J and Whistler, CA}, title = {Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.04.15.589671}, pmid = {38659831}, issn = {2692-8205}, support = {F31 DA056222/DA/NIDA NIH HHS/United States ; P20 GM103506/GM/NIGMS NIH HHS/United States ; R15 DA058187/DA/NIDA NIH HHS/United States ; R21 DA049565/DA/NIDA NIH HHS/United States ; }, abstract = {The therapeutic benefits of opioids are compromised by the development of analgesic tolerance, which necessitates higher dosing for pain management thereby increasing the liability for drug dependence and addiction. Rodent models indicate opposing roles of the gut microbiota in tolerance: morphine-induced gut dysbiosis exacerbates tolerance, whereas probiotics ameliorate tolerance. Not all individuals develop tolerance which could be influenced by differences in microbiota, and yet no study design has capitalized upon this natural variation. We leveraged natural behavioral variation in a murine model of voluntary oral morphine self-administration to elucidate the mechanisms by which microbiota influences tolerance. Although all mice shared similar morphine-driven microbiota changes that largely masked informative associations with variability in tolerance, our high-resolution temporal analyses revealed a divergence in the progression of dysbiosis that best explained sustained antinociception. Mice that did not develop tolerance maintained a higher capacity for production of the short-chain fatty acid (SCFA) butyrate known to bolster intestinal barriers and promote neuronal homeostasis. Both fecal microbial transplantation (FMT) from donor mice that did not develop tolerance and dietary butyrate supplementation significantly reduced the development of tolerance independently of suppression of systemic inflammation. These findings could inform immediate therapies to extend the analgesic efficacy of opioids.}, } @article {pmid39701930, year = {2024}, author = {Wen, J and Wang, S and Sun, K and Wang, H and Yuan, Z and Deng, W}, title = {Chang-Wei-Qing Combined with PD-1 Inhibitor Alleviates Colitis-Associated Colorectal Tumorigenesis by Modulating the Gut Microbiota and Restoring Intestinal Barrier.}, journal = {Biological procedures online}, volume = {26}, number = {1}, pages = {32}, pmid = {39701930}, issn = {1480-9222}, support = {ptkwws202002//Shanghai Putuo District Health and Health System Science and Technology Innovation Project/ ; 2021tszk01//Shanghai Putuo District Health and Health System Clinical Specialty Construction Project/ ; ZY[2021-2023]-0302//Shanghai Municipal Health Commission's Shanghai Further Accelerating Traditional Chinese Medicine Development Three-Year Action Plan Project/ ; }, abstract = {Chang-Wei-Qing (CWQ) is a widely recognized Traditional Chinese Medicine (TCM) formulation composed of Astragalus, Codonopsis, Atractylodes, Poria, Coix seed, Akebia trifoliata Koidz, Sargentodoxa cuneata, and Vitis quinquangularis Rehd. This formulation has garnered significant interest for its positive effects in mitigating colorectal cancer, and when combined with PD-1, it affects some gut microbiota associated with tumor infiltrating lymphocytes cells. However, the biological rationale underlying the suppression of colitis-associated colorectal cancer (CAC) in AOM/DSS-treated mice by CWQ combined with PD-1 inhibitor remains to be explored. Our aim is to explore the chemopreventive effect of CWQ combined with PD-1 inhibitor on CAC, with a focus on modulating the gut microbiota. A mouse model of CAC was established using azoxymethane (AOM) and dextran sulfate sodium (DSS) treatment. Pathological evaluation of tissue samples included immunohistochemistry and hematoxylin and eosin staining. Intestinal barrier function was assessed by transmission electron microscopy. Fecal microbiota and metabolites were analyzed through 16 S rRNA gene sequencing and liquid chromatography-mass spectrometry, respectively. Mice treated with antibiotics served as models for fecal microbiota transplantation. CWQ combined with PD-1 inhibitor suppressed CAC in AOM/DSS-treated mice. This combined therapy effectively alleviated gut dysbiosis in the CAC model by increasing microbial diversity, enriching probiotic populations such as Limosilactobacillus and Bifidobacterium, and reducing pathogenic bacteria like Desulfovibrio. Additionally, CWQ combined with PD-1 inhibitor downregulated metabolites associated with the NF-kappa B signaling pathway. The combined treatment also significantly improved intestinal barrier function in CAC mice. Transmission electron microscopy of the CWQ combined with PD-1 inhibitor group showed enhanced cellular integrity, a relatively normal mitochondrial structure with intact membranes, and a more abundant, unexpanded endoplasmic reticulum, underscoring the protective effects of this combination on intestinal barrier integrity. Transcriptomic analysis further demonstrated that the combined therapy upregulated genes involved in tight and adherens junctions, while downregulating genes linked to innate immune responses. CWQ combined with PD-1 inhibitor can ameliorate dysbiosis in the AOM/DSS mouse model, with the metabolites of the gut microbiome potentially possessing anti-inflammatory activity. Moreover, CWQ combined with PD-1 inhibitor improves intestinal barrier function, thereby effectively inhibiting the occurrence and development of CAC.}, } @article {pmid39699275, year = {2024}, author = {Wang, Y and Xue, Y and Xu, H and Zhu, Q and Qin, K and He, Z and Huang, A and Mu, M and Tao, X}, title = {Pediococcus acidilactici Y01 reduces HFD-induced obesity via altering gut microbiota and metabolomic profiles and modulating adipose tissue macrophage M1/M2 polarization.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo04301d}, pmid = {39699275}, issn = {2042-650X}, abstract = {Obesity-related metabolic syndrome is intimately associated with infiltrated adipose tissue macrophages (ATMs), gut microbiota, and metabolic disorders. Pediococcus acidilactici holds the potential to mitigate obesity; however, there exist strain-specific functionalities and diverse mechanisms, which deserve extensive exploration. This study aims to explore the potential of P. acidilactici Y01, isolated from traditional sour whey, in alleviating HFD-induced metabolic syndrome in mice and elucidating its underlying mechanism. The results showed that P. acidilactici Y01 could inhibit the increase of body weight gain, the deposition of fat, lipid disorders and chronic low-grade inflammation, improve glucose tolerance and insulin resistance, and could reduce adipose tissue inflammation by decreasing M1-type ATMs and increasing M2-type ATMs. Meanwhile, P. acidilactici Y01 significantly increased the abundance of potentially beneficial intestinal bacteria, such as Akkermansia, Alistipes, Bifidobacterium, Lachnospiraceae_NK4A136_group, Lactobacillus, norank_f__Muribaculaceae, and Parabacteroides, and partially restored the levels of metabolites, such as phosphatidylcholines, glycerophosphocholines, sphingolipids and unsaturated fatty acids. The fecal microbiota transplantation experiment demonstrated that P. acidilactici Y01 ameliorated obesity-related metabolic syndrome by modulating the polarization of M1/M2 ATMs mediated by gut microbiota. Overall, as a dietary supplement, P. acidilactici Y01 has good potential in the prevention and treatment of obesity.}, } @article {pmid39699220, year = {2024}, author = {Li, T and Hu, G and Fu, S and Qin, D and Song, Z}, title = {Phillyrin ameliorates DSS-induced colitis in mice via modulating the gut microbiota and inhibiting the NF-κB/MLCK pathway.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0200624}, doi = {10.1128/spectrum.02006-24}, pmid = {39699220}, issn = {2165-0497}, abstract = {Phillyrin (PHY), also known as forsythin, is an active constituent isolated from the fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae). It exhibits anti-inflammatory, anti-viral, and antioxidant properties. However, the precise impact of PHY on colitis induced by dextran sodium sulfate (DSS) and its mechanism remain elusive. The present investigation revealed that PHY (12.5, 25.0, and 50.0 mg/kg) exhibited significant therapeutic efficacy in protecting mice against DSS-induced colitis. This effect was manifested as reduced weight loss, a shortened colon, increased secretion of inflammatory factors, increased intestinal permeability, and an enhanced disease activity index in mice with ulcerative colitis (UC). Molecular investigations have determined that PHY mitigates the nuclear translocation of nuclear factor kappa B, thereby downregulating myosin light-chain kinase-driven myosin light-chain phosphorylation. This mechanism results in the preservation of the integrity of the intestinal barrier. The outcomes of 16S rRNA sequencing suggest that PHY (50 mg/kg) augmented the relative abundance of certain probiotic strains, including Lactobacillaceae and Lachnospiraceae. Additionally, PHY supplementation elevated the short-chain fatty acid contents within the intestinal contents of mice with UC. In conclusion, pre-treatment with PHY may ameliorate the DSS-induced UC in mice by lowering the expression of inflammatory factors, protecting intestinal barrier function, and enhancing the structure of the intestinal flora.IMPORTANCEThe protective effect of phillyrin on DSS-induced colitis was explained for the first time, and the anti-inflammatory effect of phillyrin was demonstrated by fecal microbiota transplantation experiments mainly through intestinal flora.}, } @article {pmid39694919, year = {2025}, author = {Zhang, Y and Ji, X and Chang, K and Yin, H and Zhao, M and Zhao, L}, title = {The regulatory effect of chitooligosaccharides on islet inflammation in T2D individuals after islet cell transplantation: the mechanism behind Candida albicans abundance and macrophage polarization.}, journal = {Gut microbes}, volume = {17}, number = {1}, pages = {2442051}, pmid = {39694919}, issn = {1949-0984}, mesh = {Animals ; *Candida albicans/drug effects ; *Oligosaccharides/pharmacology ; Mice ; *Gastrointestinal Microbiome/drug effects ; Humans ; *Macrophages/drug effects/immunology ; *Diabetes Mellitus, Type 2/microbiology ; *Islets of Langerhans Transplantation ; *Myeloid Differentiation Factor 88/metabolism/genetics ; *Inflammation ; Male ; Mice, Inbred C57BL ; Chitosan/pharmacology ; Islets of Langerhans/drug effects ; STAT6 Transcription Factor/metabolism/genetics ; NF-kappa B/metabolism/genetics ; }, abstract = {Islet cell transplantation (ICT) represents a promising therapeutic approach for addressing diabetes mellitus. However, the islet inflammation during transplantation significantly reduces the surgical outcome rate, which is related to the polarization of macrophages. Chitooligosaccharides (COS) was previously reported which could modulate the immune system, alleviate inflammation, regulate gut microecology, and repair the intestinal barrier. Therefore, we hypothesized COS could relieve pancreatic inflammation by regulating macrophage polarization and gut microbiota. First, 18S rDNA gene sequencing was performed on fecal samples from the ICT population, showing abnormally increased amount of Candida albicans, possibly causing pancreatic inflammation. Functional oligosaccharides responsible for regulating macrophage polarization and inhibiting the growth of Candida albicans were screened. Afterwards, human flora-associated T2D (HMA-T2D) mouse models of gut microbiota were established, and the ability of the selected oligosaccharides were validated in vivo to alleviate inflammation and regulate gut microbiota. The results indicated that ICT significantly decreased the alpha diversity of gut fungal, altered fungal community structures, and increased Candida albicans abundance. Moreover, Candida albicans promoted M1 macrophage polarization, leading to islet inflammation. COS inhibited Candida albicans growth, suppressed the MyD88-NF-κB pathway, activated STAT6, inhibited M1, and promoted M2 macrophage polarization. Furthermore, COS-treated HMA-T2D mice displayed lower M1 macrophage differentiation and higher M2 macrophage numbers. Additionally, COS also enhanced ZO-1 and Occludin mRNA expression, reduced Candida albicans abundance, and balanced gut microecology. This study illustrated that COS modulated macrophage polarization via the MyD88/NF-κB and STAT6 pathways, repaired the intestinal barrier, and reduced Candida albicans abundance to alleviate islet inflammation.}, } @article {pmid39691426, year = {2024}, author = {Yu, J and Chen, YX and Wang, JW and Wu, HT}, title = {Research progress on the relationship between traumatic brain injury and brain-gut-microbial axis.}, journal = {Ibrain}, volume = {10}, number = {4}, pages = {477-487}, pmid = {39691426}, issn = {2769-2795}, abstract = {Traumatic brain injury (TBI) is a common disease with a high rate of death and disability, which poses a serious threat to human health; thus, the effective treatment of TBI has been a high priority. The brain-gut-microbial (BGM) axis, as a bidirectional communication network for information exchange between the brain and gut, plays a crucial role in neurological diseases. This article comprehensively explores the interrelationship between the BGM axis and TBI, including its physiological effects, basic pathophysiology, and potential therapeutic strategies. It highlights how the bidirectional regulatory pathways of the BGM axis could provide new insights into clinical TBI treatment and underscores the necessity for advanced research and development of innovative clinical treatments for TBI.}, } @article {pmid39686442, year = {2024}, author = {Liu, F and Zhang, H and Fan, L and Yu, Q and Wang, S}, title = {Hotspots and development trends of gut microbiota in atopic dermatitis: A bibliometric analysis from 1988 to 2024.}, journal = {Medicine}, volume = {103}, number = {50}, pages = {e40931}, pmid = {39686442}, issn = {1536-5964}, mesh = {*Dermatitis, Atopic/microbiology/therapy ; *Gastrointestinal Microbiome ; Humans ; *Bibliometrics ; Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {BACKGROUND: Atopic dermatitis (AD) is a prevalent inflammatory skin condition that commonly occurs in children. More and more scientific evidence suggests that gut microbiota plays an important role in the pathogenesis of AD, whereas there is no article providing a comprehensive summary and analysis. We aimed to analyze documents on AD and gut microbiota and identify hotspots and development trends in this field.

METHODS: Articles and reviews in the field of AD and gut microbiota from January 1, 1988 to October 20, 2024 were obtained from the Web of Science Core Collection database. Biblioshiny was utilized for evaluating and visualizing the core authors, journals, countries, documents, trend topics, and hotspots in this field.

RESULTS: Among 1672 documents, it indicated that the number of annual publications generally increased. The United States had the highest production, impact, and international collaboration. Journal of Allergy and Clinical Immunology was the journal of the maximum publications. Based on keyword co-occurrence and clustering analysis, "stratum-corneum lipids," "probiotics," "prebiotics," "fecal microbiota transplantation," "phage therapy," "short chain fatty-acids," "biologic therapy," and "skin inflammation" represented current trend topics. The pathological and molecular mechanisms and associated therapeutic methods for AD and gut microbiota were the research hotspots. The incorporation of microbiota-based therapies alongside conventional treatments can contribute to better clinical outcomes.

CONCLUSION: We highlighted that gut microbiota may exacerbate symptoms of AD through various aspects, including immunity, metabolites, and neuroendocrine pathways. More efforts are required to investigate the safety and efficacy of gut microbial management methods for the prevention and treatment of AD.}, } @article {pmid39684918, year = {2024}, author = {Li, C and Chen, S and Wang, Y and Su, Q}, title = {Microbiome-Based Therapeutics for Insomnia.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684918}, issn = {1422-0067}, mesh = {Humans ; *Sleep Initiation and Maintenance Disorders/therapy/microbiology ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation/methods ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; Animals ; Synbiotics ; }, abstract = {Insomnia poses considerable risks to both physical and mental health, leading to cognitive impairment, weakened immune function, metabolic dysfunction, cardiovascular issues, and reduced quality of life. Given the significant global increase in insomnia and the growing scientific evidence connecting gut microbiota to this disorder, targeting gut microbiota as an intervention for insomnia has gained popularity. In this review, we summarize current microbiome-based therapeutics for insomnia, including dietary modifications; probiotic, prebiotic, postbiotic, and synbiotic interventions; and fecal microbiota transplantation. Moreover, we assess the capabilities and weaknesses of these technologies to offer valuable insights for future studies.}, } @article {pmid39684788, year = {2024}, author = {Moreno, RJ and Ashwood, P}, title = {An Update on Microbial Interventions in Autism Spectrum Disorder with Gastrointestinal Symptoms.}, journal = {International journal of molecular sciences}, volume = {25}, number = {23}, pages = {}, pmid = {39684788}, issn = {1422-0067}, support = {HD090214/HD/NICHD NIH HHS/United States ; }, mesh = {Humans ; *Autism Spectrum Disorder/therapy/microbiology ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; *Fecal Microbiota Transplantation/methods ; *Dysbiosis/therapy/microbiology ; *Prebiotics ; Gastrointestinal Diseases/therapy/microbiology ; Anti-Bacterial Agents/therapeutic use ; Animals ; }, abstract = {In the United States, autism spectrum disorder (ASD) affects 1 in 33 children and is characterized by atypical social interactions, communication difficulties, and intense, restricted interests. Microbial dysbiosis in the gastrointestinal (GI) tract is frequently observed in individuals with ASD, potentially contributing to behavioral manifestations and correlating with worsening severity. Moreover, dysbiosis may contribute to the increased prevalence of GI comorbidities in the ASD population and exacerbate immune dysregulation, further worsening dysbiosis. Over the past 25 years, research on the impact of microbial manipulation on ASD outcomes has gained substantial interest. Various approaches to microbial manipulation have been preclinically and clinically tested, including antibiotic treatment, dietary modifications, prebiotics, probiotics, and fecal microbiota transplantation. Each method has shown varying degrees of success in reducing the severity of ASD behaviors and/or GI symptoms and varying long-term efficacy. In this review, we discuss these microbiome manipulation methods and their outcomes. We also discuss potential microbiome manipulation early in life, as this is a critical period for neurodevelopment.}, } @article {pmid39682952, year = {2024}, author = {Ma, H and Mueed, A and Ma, Y and Ibrahim, M and Su, L and Wang, Q}, title = {Fecal Microbiota Transplantation Activity of Floccularia luteovirens Polysaccharides and Their Protective Effect on Cyclophosphamide-Induced Immunosuppression and Intestinal Injury in Mice.}, journal = {Foods (Basel, Switzerland)}, volume = {13}, number = {23}, pages = {}, pmid = {39682952}, issn = {2304-8158}, support = {2021YFD1600401//National Key Research and Development Program of China/ ; }, abstract = {Floccularia luteovirens polysaccharides (FLP1s) have potential biological activities. Our previous study showed that FLP1s positively regulated gut immunity and microbiota. However, it is still unclear whether FLP1s mediate gut microbiota in immunosuppressed mice. This research aims to explore the relationship between FLP1-mediated gut microbes and intestinal immunity in immunosuppressed mice through fecal microbiota transplantation (FMT). The results demonstrated that FLP1s exhibited prebiotic and anti-immunosuppressive effects on CTX-induced immunosuppressed mice. FFLP1 treatment (microbiota transplantation from the fecal sample) remarkably elevated the production of sIgA and secretion of the anti-inflammatory cytokines IL-4, TNF-α, and IFN-γ in the intestine of CTX-treated mice, inducing activation of the MAPK pathway. Moreover, FFLP1s mitigated oxidative stress by activating the Nrf2/Keap1 signaling pathway and strengthened the intestinal barrier function by upregulating the expression level of tight junction proteins (occludin, claudin-1, MUC-2, and ZO-1). Furthermore, FFPL1s restored gut dysbiosis in CTX-treated immunosuppressed mice by increasing the abundance of Alloprevotella, Lachnospiraceae, and Bacteroides. They also modified the composition of fecal metabolites, leading to enhanced regulation of lipolysis in adipocytes, the cGMP-PKG pathway, the Rap1 signaling pathway, and ovarian steroidogenesis, as indicated by KEGG pathway analysis. These findings indicate that FLP1s could modulate the response of the intestinal immune system through regulation of the gut microbiota, thus promoting immune activation in CTX-treated immunosuppressed mice. FLP1s can serve as a natural protective agent against CTX-induced immune injury.}, } @article {pmid39682542, year = {2024}, author = {Morales, C and Ballestero, L and Del Río, P and Barbero-Herranz, R and Olavarrieta, L and Gómez-Artíguez, L and Galeano, J and Avendaño-Ortiz, J and Basterra, J and Del Campo, R}, title = {Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor?.}, journal = {Diagnostics (Basel, Switzerland)}, volume = {14}, number = {23}, pages = {}, pmid = {39682542}, issn = {2075-4418}, support = {XX//Mikrobiomik/ ; }, abstract = {BACKGROUND/OBJECTIVES: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent Clostridioides difficile infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification. However, despite the high amount of data generated from the ongoing research studies relating microbiota and health, there is not yet a consensus defining what is a "healthy" microbiota. To date, knowledge of the composition of the microbiota is not a requirement to be a faecal donor. The aim of this work was to evaluate whether the analysis of the composition of the microbiota by massive sequencing of 16S rDNA could be useful in the selection of the faecal donors.

METHODS: Samples from 10 certified donors from Mikrobiomik Healthcare Company were collected and sequenced using 16S rDNA in a MiSeq (Illumina) platform. Alpha (Chao1 and Shannon indices) and beta diversity (Bray-Curtis) were performed using the bioinformatic web server Microbiome Analyst. The differences in microbial composition at the genera and phyla levels among the donors were evaluated.

RESULTS: The microbial diversity metric by alpha diversity indexes showed that most donors exhibited a similar microbial diversity and richness, whereas beta diversity by 16S rDNA sequencing revealed significant inter-donor differences, with a more stable microbial composition over time in some donors. The phyla Bacillota and Bacteroidota were predominant in all donors, while the density of other phyla, such as Actinomycota and Pseudomonota, varied among individuals. Each donor exhibited a characteristic genera distribution pattern; however, it was possible to define a microbiome core consisting of the genera Agathobacter, Eubacterium, Bacteroides, Clostridia UCG-014 and Akkermansia. Conclusions: The results suggest that donor certification does not need to rely exclusively on their microbiota composition, as it is unique to each donor. While one donor showed greater microbial diversity and richness, clear criteria for microbial normality and health have yet to be established. Therefore, donor certification should focus more on clinical and lifestyle aspects.}, } @article {pmid39681213, year = {2024}, author = {Liu, X and Tan, X and Yu, Y and Niu, J and Zhao, B and Wang, Q}, title = {Short chain fatty acids mediates complement C1q pathway alleviation of perioperative neurocognitive disorders.}, journal = {Neuropharmacology}, volume = {}, number = {}, pages = {110266}, doi = {10.1016/j.neuropharm.2024.110266}, pmid = {39681213}, issn = {1873-7064}, abstract = {Perioperative neurocognitive disorders (PND) is one of the most common postoperative complications, which can lead to a harmful impact on self-dependence, longer hospital stays, increased medical costs, morbidity, and mortality amongst older adults. Microglia can modulate synapse elimination involved in the complement component protein 1q (C1q) pathway to induce cognitive dysfunction, which is significantly improved by short chain fatty acids (SCFAs) treatment. Here we investigate the effects of SCFAs treatment on PND via mediating C1q complement pathway. High-throughput sequencing of 16S rDNA from fecal samples of male SD rats was applied to assess the changes in gut microbiota. Fecal microbiota transplantation (FMT) was performed to investigate whether gut microbiota from PND rats could alter cognitive impairment. The blood from the rat tail vein was collected to measure the SCFAs concentrations. Hippocampal and brain tissue samples were obtained to perform Western blots, Golgi and immunofluorescence staining. Primary microglia treated with SCFAs or Histone deacetylase inhibitor were cultured to measure microglial activation states and the expression of acetylated histone. The 16S rDNA sequencing results showed that PND rats had the significant changes in the species diversity of the gut microbiota and the metabolite of specifc species. Gut microbiota from PND rats could alter spatial learning and memory, and meanwhile, the changed SCFAs concentrations in plasma were involved. The synapse elimination in PND rats was strikingly reversed by SCFAs treatment involved in modulation complement C1q via suppressing neuroinflammation. This suggests that a link between gut microbiota dysbiosis and cognitive function impairment is involved in synapse elimination via mediating complement C1q pathway. SCFAs treatment can alleviate PND, the mechanisms of which may be associated with regulating complement C1q pathway.}, } @article {pmid39680691, year = {2024}, author = {Yang, JC and Lagishetty, V and Aja, E and Arias-Jayo, N and Chang, C and Hauer, M and Katzka, W and Zhou, Y and Sedighian, F and Koletic, C and Liang, F and Dong, TS and Situ, J and Troutman, R and Buri, H and Bhute, S and Simpson, CA and Braun, J and Jacob, N and Jacobs, JP}, title = {Biogeographical distribution of gut microbiome composition and function is partially recapitulated by fecal transplantation into germ-free mice.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ismejo/wrae250}, pmid = {39680691}, issn = {1751-7370}, abstract = {Fecal microbiota transplantation has been vital for establishing whether host phenotypes can be conferred through the microbiome. However, whether the existing microbial ecology along the mouse gastrointestinal tract can be recapitulated in germ-free mice colonized with stool remains unknown. We first identified microbes and their predicted functions specific to each of six intestinal regions in three cohorts of specific pathogen-free mice spanning two facilities. Of these region-specific microbes, the health-linked genus Akkermansia was consistently enriched in the lumen of the small intestine compared to the colon. Predictive functional modeling on 16S rRNA gene amplicon sequencing data recapitulated in shotgun sequencing data revealed increased microbial central metabolism, lipolytic fermentation, and cross-feeding in the small intestine, whereas butyrate synthesis was colon-enriched. Neuroactive compound metabolism also demonstrated regional specificity, including small intestine-enriched gamma-aminobutyric acid degradation and colon-enriched tryptophan degradation. Specifically, the jejunum and ileum stood out as sites with high predicted metabolic and neuromodulation activity. Differences between luminal and mucosal microbiomes within each site of the gastrointestinal tract were largely facility-specific, though there were a few consistent patterns in microbial metabolism in specific pathogen-free mice. These included luminal enrichment of central metabolism and cross-feeding within both the small intestine and the colon, and mucosal enrichment of butyrate synthesis within the colon. Across three cohorts of germ-free mice colonized with mice or human stool, compositional and functional region specificity were inconsistently reproduced. These results underscore the importance of investigating the spatial variation of the gut microbiome to better understand its impact on host physiology.}, } @article {pmid39680624, year = {2024}, author = {Zuo, H and Jiang, W and Gao, J and Ma, Z and Li, C and Peng, Y and Jin, J and Zhan, X and Lv, W and Liu, X and Hu, J and Zhang, M and Jia, Y and Xu, Z and Tang, J and Zheng, R and Zuo, B}, title = {SYISL Knockout Promotes Embryonic Muscle Development of Offspring by Modulating Maternal Gut Microbiota and Fetal Myogenic Cell Dynamics.}, journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)}, volume = {}, number = {}, pages = {e2410953}, doi = {10.1002/advs.202410953}, pmid = {39680624}, issn = {2198-3844}, support = {32221005//National Natural Science Foundation of China/ ; 31900448//National Natural Science Foundation of China/ ; 2021YFA0805903//National Key Research and Development Program of China/ ; 2021CFA018//Natural Science Foundation of Hubei Province/ ; 2021-620-000-001-030//Agricultural Innovation Fund of Hubei Province/ ; 2022ESOF007//Open Fund of Hubei Key Laboratory of Embryonic Stem Cell Research/ ; 2023ZD04072//Biological Breeding-National Science and Technology Major Project/ ; }, abstract = {Embryonic muscle fiber formation determines post-birth muscle fiber totals. The previous research shows SYISL knockout significantly increases muscle fiber numbers and mass in mice, but the mechanism remains unclear. This study confirms that the SYISL gene, maternal gut microbiota, and their interaction significantly affect the number of muscle fibers in mouse embryos through distinct mechanisms, as SYISL knockout alters maternal gut microbiota composition and boosts butyrate levels in embryonic serum. Both fecal microbiota transplantation and butyrate feeding significantly increase muscle fiber numbers in offspring, with butyrate inhibiting histone deacetylases and increasing histone acetylation in embryonic muscle. Combined analysis of RNA-seq between wild-type and SYISL knockout mice with ChIP-seq for H3K9ac and H3K27ac reveals that SYISL and maternal microbiota interaction regulates myogenesis via the butyrate-HDAC-H3K9ac/H3K27ac pathway. Furthermore, scRNA-seq analysis shows that SYISL knockout alone significantly increases the number and proportion of myogenic cells and their dynamics, independently of regulating histone acetylation levels. Cell communication analysis suggests that this may be due to the downregulation of signaling pathways such as MSTN and TGFβ. Overall, multiple pathways are highlighted through which SYISL influences embryonic muscle development, offering valuable insights for treating muscle diseases and improving livestock production.}, } @article {pmid39679941, year = {2024}, author = {Wu, Q and Wang, J and Tu, C and Chen, P and Deng, Y and Yu, L and Xu, X and Fang, X and Li, W}, title = {Gut microbiota of patients insusceptible to olanzapine-induced fatty liver disease relieves hepatic steatosis in rat.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {}, number = {}, pages = {}, doi = {10.1152/ajpgi.00167.2024}, pmid = {39679941}, issn = {1522-1547}, support = {82173903//MOST | National Natural Science Foundation of China (NSFC)/ ; 81903686//Natural Science Foundation for Young Scientists of Shanxi Province (Young Scientists Fund of the National Natural Science Foundation of China)/ ; }, abstract = {Olanzapine-induced fatty liver disease continues to pose vital therapeutic challenges in the treatment of psychiatric disorders. In addition, we observed that some patients were less prone to hepatic steatosis induced by olanzapine. Therefore, we aimed to investigate the role and the underlying mechanism of the intestinal flora in olanzapine-mediated hepatic side effects and explore the possible countermeasures. Our results showed that patients with different susceptibilities to olanzapine-induced fatty liver disease had different gut microbial diversity and composition. Furthermore, we performed fecal microbiota treatment (FMT), and confirmed that the gut microbiome of patients less prone to the fatty liver caused by olanzapine exhibited an alleviation against fatty liver disease in rats. In terms of mechanism, we revealed that the crosstalk of leptin with the gut-short-chain fatty acid (SCFA)-liver axis play a critical role in olanzapine-related fatty degeneration in liver. These findings propose a promising strategy for overcoming the issues associated with olanzapine application and will hopefully inspire future in-depth research of fecal microbiota-based therapy in olanzapine-induced fatty liver disease.}, } @article {pmid39679465, year = {2024}, author = {Wang, M and Ma, Y and Zeng, B and Yang, W and Huang, C and Tang, B}, title = {Influence of the Gut Microbiota, Metabolism and Environment on Neuropsychiatric Disorders.}, journal = {Current reviews in clinical and experimental pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.2174/0127724328335219241202142003}, pmid = {39679465}, issn = {2772-4336}, abstract = {The two-way communication between intestinal microbiota and the central nervous system (the microbiota-gut-brain axis) is involved in the regulation of brain function, neurodevelopment, and aging. The microbiota-gut-brain axis dysfunction may be a predisposition factor for Parkinson's disease (PD), Alzheimer's disease (AD), Autism spectrum disorder (ASD), and other neurological diseases. However, it is not clear whether gut microbiota dysfunction contributes to neuropsychiatric disorders. Changes in the gut microbiota may modulate or modify the effects of environmental factors on neuropsychiatric disorders. Factors that impact neuropsychiatric disorders also influence the gut microbiota, including diet patterns, exercise, stress and functional gastrointestinal disorders. These factors change microbiome composition and function, along with the metabolism and immune responses that cause neuropsychiatric disorders. In this review, we summarized epidemiological and laboratory evidence for the influence of the gut microbiota, metabolism and environmental factors on neuropsychiatric disorders incidence and outcomes. Furthermore, the role of gut microbiota in the two-way interaction between the gut and the brain was also reviewed, including the vagus nerve, microbial metabolism, and immuno-inflammatory responses. We also considered the therapeutic strategies that target gut microbiota in the treatment of neuropsychiatric disorders, including prebiotics, probiotics, Fecal microbiota transplant (FMT), and antibiotics. Based on these data, possible strategies for microbiota-targeted intervention could improve people's lives and prevent neuropsychiatric disorders in the future.}, } @article {pmid39679306, year = {2024}, author = {Hasnaoui, A and Trigui, R and Giuffrida, M}, title = {Gut microbiota and mesenteric adipose tissue interactions in shaping phenotypes and treatment strategies for Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {46}, pages = {4969-4976}, pmid = {39679306}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology/therapy ; Humans ; *Gastrointestinal Microbiome/immunology ; *Dysbiosis/immunology ; *Fecal Microbiota Transplantation ; *Phenotype ; *Mesentery ; Adipose Tissue/immunology/microbiology/metabolism ; Bacterial Translocation ; Cytokines/metabolism ; }, abstract = {In this letter, we commented on the article by Wu et al. We examined the interactions between mesenteric adipose tissue, creeping fat, and gut microbiota in Crohn's disease (CD), a condition marked by chronic gastrointestinal inflammation with a rising global incidence. The pathogenesis of CD involves complex genetic, environmental, and microbial factors. Dysbiosis, which is an imbalance in gut microbial communities, is frequently observed in CD patients, highlighting the pivotal role of the gut microbiota in disease progression and the inflammatory response. Recent studies have shown that mesenteric adipose tissue and creeping fat actively contribute to inflammation by producing proinflammatory cytokines. The relationship between creeping fat and altered microbiota can shift from a potentially protective role to one that encourages bacterial translocation, further complicating disease management. Recent research has suggested that fecal microbiota transplantation could help restore microbial balance, offering a promising therapeutic strategy to improve clinical disease response.}, } @article {pmid39265742, year = {2025}, author = {Herner, A and Nennstiel, S and Ramser, M and Turina, M and Schlag, C}, title = {New therapeutic approach for anastomotic leaks after ileoanal J-pouch construction in patients with ulcerative colitis.}, journal = {Gastrointestinal endoscopy}, volume = {101}, number = {1}, pages = {222-223}, doi = {10.1016/j.gie.2024.09.004}, pmid = {39265742}, issn = {1097-6779}, } @article {pmid39679283, year = {2024}, author = {Chen, J and Yang, H and Qin, Y and Zhou, X and Ma, Q}, title = {Tryptophan Ameliorates Metabolic Syndrome by Inhibiting Intestinal Farnesoid X Receptor Signaling: The Role of Gut Microbiota-Bile Acid Crosstalk.}, journal = {Research (Washington, D.C.)}, volume = {7}, number = {}, pages = {0515}, pmid = {39679283}, issn = {2639-5274}, abstract = {Background and Aims: Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood. Methods and Results: In this study, experiments involving a high-fat diet (HFD) and fecal microbiota transplantation (FMT) were conducted to investigate the role of Trp in regulating metabolic disorders. In a mouse model, Trp supplementation inhibited intestinal farnesoid X receptor (FXR) signaling and promoted hepatic bile acid (BA) synthesis and excretion, accompanied by elevated levels of conjugated BAs and the ratio of non-12-OH to 12-OH BAs in hepatic and fecal BA profiles. As Trp alters the gut microbiota and the abundance of bile salt hydrolase (BSH)-enriched microbes, we collected fresh feces from Trp-supplemented mice and performed FMT and sterile fecal filtrate (SFF) inoculations in HFD-treated mice. FMT and SFF not only displayed lipid-lowering properties but also inhibited intestinal FXR signaling and increased hepatic BA synthesis. This suggests that the gut microbiota play a beneficial role in improving BA metabolism through Trp. Furthermore, fexaramine (a gut-specific FXR agonist) reversed the therapeutic effects of Trp, suggesting that Trp acts through the FXR signaling pathway. Finally, validation in a finishing pig model revealed that Trp improved lipid metabolism, enlarged the hepatic BA pool, and altered numerous glycerophospholipid molecules in the hepatic lipid profile. Conclusion: Our studies suggest that Trp inhibits intestinal FXR signaling mediated by the gut microbiota-BA crosstalk, which in turn promotes hepatic BA synthesis, thereby ameliorating MS.}, } @article {pmid39679259, year = {2024}, author = {Feng, M and Zou, Z and Shou, P and Peng, W and Liu, M and Li, X}, title = {Gut microbiota and Parkinson's disease: potential links and the role of fecal microbiota transplantation.}, journal = {Frontiers in aging neuroscience}, volume = {16}, number = {}, pages = {1479343}, pmid = {39679259}, issn = {1663-4365}, abstract = {Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and seriously affects the quality of life of elderly patients. PD is characterized by the loss of dopaminergic neurons in the substantia nigra as well as abnormal accumulation of α-synuclein in neurons. Recent research has deepened our understanding of the gut microbiota, revealing that it participates in the pathological process of PD through the gut-brain axis, suggesting that the gut may be the source of PD. Therefore, studying the relationship between gut microbiota and PD is crucial for improving our understanding of the disease's prevention, diagnosis, and treatment. In this review, we first describe the bidirectional regulation of the gut-brain axis by the gut microbiota and the mechanisms underlying the involvement of gut microbiota and their metabolites in PD. We then summarize the different species of gut microbiota found in patients with PD and their correlations with clinical symptoms. Finally, we review the most comprehensive animal and human studies on treating PD through fecal microbiota transplantation (FMT), discussing the challenges and considerations associated with this treatment approach.}, } @article {pmid39677507, year = {2024}, author = {Li, Y and Xiao, P and Ding, H and Wang, H and Xu, Q and Wang, R and Zheng, L and Song, X and Wang, Y and Zhang, T}, title = {Fecal Microbiota Transplantation in Children with Autism.}, journal = {Neuropsychiatric disease and treatment}, volume = {20}, number = {}, pages = {2391-2400}, pmid = {39677507}, issn = {1176-6328}, abstract = {PURPOSE: This research aimed to explore the clinical efficacy of fecal microbiota transplantation (FMT) in treating children with autism spectrum disorder (ASD).

METHODS: In this single-arm prospective study, every participant received FMT therapy, followed by an 8-week follow-up. Children unable to swallow lyophilized capsules (Caps) received fecal solution through transendoscopic enteral tube (TET) or nasal jejunal tube (NJT) approaches. All participants underwent assessments of ASD core symptoms, gastrointestinal (GI) symptoms and sleep status initially, after treatment and during follow-up. The study outcomes included the changes in scores of the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Gastrointestinal Symptoms Rating Scale (GSRS) and Sleep Disturbance Scale for Children (SDSC), as well as the adverse events (AEs).

RESULTS: 98 participants were involved, consisting of 80 males and 18 females, with a median age of 7 years. 73 children received the FMT in the form of Caps, while 13 patients underwent the procedure through TET and 12 patients via NJT. Improvements were observed in all outcome measures for Caps and NJT groups at both the post-treatment and 8-week follow-up evaluations. Adjusted between-group analyses at post-treatment and follow-up showed that Caps and NJT group had greater reduction in ABC, CARS and SRS scores compared with TET group, while NJT group had greater reduction in SDSC scores compared with Caps and TET group. The incidence of AEs was 8.2% in the Caps group, 23.1% in the TET group, and 8.3% in the NJT group, with no serious AEs reported.

CONCLUSION: FMT treatment can improve the core symptoms, GI symptoms and sleep disturbances in children with ASD. The upper GI tract routes, including Caps and NJT, may be more effective and safe compared to the lower GI tract route of TET.}, } @article {pmid39674485, year = {2024}, author = {Ni, Z and Chen, L and Qian, X and Yong, Y and Wu, M and Yihao, L and Li, J and Wang, Y and Li, L and Shao, Y and Chen, A}, title = {Preliminary characterization of Ramaria botrytoides polysaccharide RB-P1-1 and analysis of its hypoglycemic effects by altering the gut microbiota and metabolites in mice with type 2 diabetes mellitus.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {138774}, doi = {10.1016/j.ijbiomac.2024.138774}, pmid = {39674485}, issn = {1879-0003}, abstract = {Gut microbiota has a symbiotic relationship with the host and is closely linked to the development of type 2 diabetes mellitus (T2DM). Polysaccharides are natural bioactive compounds with beneficial effects on T2DM; however, the mechanisms underlying their effects remain unclear. This study investigated the hypoglycemic effects of a purified polysaccharide, RB-P1-1, from Ramaria botrytoides and assessed its association with gut microbiota and metabolite changes using 16S rDNA sequencing and liquid chromatography-mass spectrometry, respectively. Hypoglycemic effects were evaluated after microbial community restoration via fecal microbiota transplantation. RB-P1-1 significantly improved hyperglycemia profiles and reshaped gut microbiota, increasing the abundance of Alistipes, Bacteroides, Ruminococcus, Odoribacter, Akkermansia, and Turicibacter. RB-P1-1 modulated microbiota metabolites associated with hypoglycemic effects, including pyridoxamine, L-histidine, quercetin, 3-phosphonopropionic acid, oleoylethanolamide, 3-ketocholanic acid, 4-phenylbutyric acid, LysoPC(P-16:0/0:0), LysoPC(18:2), and short-chain fatty acids, and altered various metabolic pathways involved in T2DM development. Gut microbiota that showed altered abundance were correlated with metabolites that showed altered concentration. Gut microbiota isolated from the RB-P1-1-treated group alleviated the symptoms associated with T2DM. These results suggest RB-P1-1 is an effective active ingredient in the treatment of T2DM by modulating gut microbiota and metabolites.}, } @article {pmid39674267, year = {2024}, author = {Cheng, X and Yang, J and Wang, Z and Zhou, K and An, X and Xu, ZZ and Lu, H}, title = {Modulating intestinal viruses: A potential avenue for improving metabolic diseases with unresolved challenges.}, journal = {Life sciences}, volume = {}, number = {}, pages = {123309}, doi = {10.1016/j.lfs.2024.123309}, pmid = {39674267}, issn = {1879-0631}, abstract = {The gut microbiome affects the occurrence and development of metabolic diseases, with a significant amount of research focused on intestinal bacteria. As an important part of the gut microbiome, gut viruses were studied recently, particularly through fecal virome transplantation (FVT), revealing manipulating the gut virus could reverse overweight and glucose intolerance in mice. And human cohort studies found gut virome changed significantly in patients with metabolic disease. By summarizing those studies, we compared the research and analytical methods, as well as the similarities and differences in their results, and analyzed the reasons for these discrepancies. FVT provided potential value to improve metabolic diseases, but the mechanisms involved and the effect of FVT on humans should be investigated further. The potential methods of regulating intestinal virome composition and the possible mechanisms of intestinal virome changes affecting metabolic diseases were also discussed.}, } @article {pmid39672770, year = {2024}, author = {Facchin, S and Cardin, R and Patuzzi, I and Carlotto, C and Minotto, M and Barberio, B and Zingone, F and Besutti, VM and Castagliuolo, I and Cattelan, A and Savarino, EV}, title = {Long-term stability and efficacy of frozen fecal microbiota transplant (FMT) product at 24 months.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.dld.2024.11.025}, pmid = {39672770}, issn = {1878-3562}, abstract = {BACKGROUND: Freezing donor fecal microbiota has improved fecal microbiota transplantation (FMT) for recurrent C. difficile infection (CDI), achieving short-term effectiveness similar to fresh-samples. Research shows frozen fecal matter remains effective for up to 12-months at -80 °C.

OBJECTIVE: To assess how long-term-freezing and thawing affect the viability, microbial composition, and clinical efficacy of frozen-stools for FMT.

METHODS: Stool samples from three donors were processed into 18 aliquots, thawed at intervals over two years, and analyzed for cell viability and microbial load. Microbiota composition was assessed through 16S-sequencing, with diversity evaluated using the Shannon-index and Principal-Coordinates-Analysis based on Bray-Curtis-distance (α/β-diversity). The same donors provided fecal material for a total of 23 FMT procedures, including 15 for CDI and 8 off-label.

RESULTS: We found that donor stools frozen for two years contained viable bacteria comparable to fresh samples, with anaerobic and aerobic species remaining viable for 24 months. Despite a reduction in colony-forming-units, FMT was successful in 71.4 % and 100 % of the cases at one year and at the end of follow-up, respectively. Most bacterial changes occurred among anaerobic species (Blautia producta and Bifidobacterium adolescentis), increasing post-thawing. Notably, specific taxa, (C. aerofaciens and Erysipelotrichaceae_Cc115), showed significant unexplained increase.

CONCLUSION: Long-term-stool-storage enhances FMT accessibility without compromising its success, despite taxonomic changes after 24 months.}, } @article {pmid39672439, year = {2024}, author = {Chen, P and Chen, F and Hou, T and Hu, X and Xia, C and Zhang, J and Shen, S and Li, C and Li, K}, title = {Administration time modify the anxiolytic and antidepressant effects of inulin via gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {288}, number = {}, pages = {138698}, doi = {10.1016/j.ijbiomac.2024.138698}, pmid = {39672439}, issn = {1879-0003}, abstract = {An imbalance in the microbiota-gut-brain axis exerts an essential effect on the pathophysiology of depressive and anxiety disorders. Our previous research revealed that the timing of inulin administration altered its effects on chronic unpredictable mild stress (CUMS)-induced anxiety and depression. However, it is still unclear if the gut-brain axis is primarily responsible for these effects. In this study, fecal microbiota transplantation (FMT) confirmed that inulin administration at different times alleviated CUMS-induced anxiety- and depression-like behaviors via the gut-brain axis. The time of administration seemed to modify the anxiolytic and antidepressant effects of inulin, and inulin intervention in the evening was more pronounced in inhibiting the inflammatory responses than that of morning inulin intervention. Serum metabolomics analysis showed that the main differential metabolites, including fenofibric acid, 4'-Hydroxyfenoprofen glucuronide and 5-(4-Hydroxybenzyl)thiazolidine-2,4-dione may be vital for the anxiolytic and antidepressant effects of different inulin treatment times. Our results suggested that inulin administration in the evening was more effective in alleviating the inflammatory responses and improving amino acids metabolism. This study provides a new potential link between the microbiota-gut-brain axis and chrono-nutrition, demonstrating that a more appropriate administration time results in a better intervention effect.}, } @article {pmid39672393, year = {2024}, author = {He, P and He, H and Su, C and Liu, Y and Wang, J and Wu, Y and Wang, B and Wang, S and Zhao, J}, title = {Amomum villosum Lour. alleviates pre-eclampsia by inducing enrichment of Bifidobacterium bifidum through vanillic acid to inhibit placental ferroptosis.}, journal = {Journal of ethnopharmacology}, volume = {}, number = {}, pages = {119217}, doi = {10.1016/j.jep.2024.119217}, pmid = {39672393}, issn = {1872-7573}, abstract = {Amomum villosum Lour. (AVL), a traditional Chinese medicine, is widely used to pregnancy-related vomiting and prevent miscarriage. Pre-eclampsia (PE) is a severe pregnancy syndrome. Recent studies have demonstrated interactions between PE and the digestive system. However, it is uncertain that AVL against PE was associated with the gut.

AIM OF THE STUDY: The current research examined the curative impact of AVL on PE and underly mechanisms based on the gut-placenta axis.

MATERIALS AND METHODS: A water decoction of AVL (WOA) was extracted in boiling water, and then the decoction was converted into dried particles by freeze drying. An NG-nitro-L-arginine methyl ester (L-NAME)-induced PE mouse model was established and the preventative activity of WOA was evaluated. Furthermore, the gut microbial composition and structure were analyzed using 16S rRNA gene sequencing. Fecal microbiota transplantation (FMT) experiment was applied to confirm the efficacy of gut microbiota remodeled by WOA.

RESULTS: WOA presented protective efficacy against PE. Notably, WOA induced a significant decrease in maternal hypertension and urine protein levels and promoted fetal intrauterine growth in a dose-dependent manner, thereby improving adverse pregnancy outcomes. Moreover, WOA modulated the angiogenic imbalance by decreasing the ratio between sFlt-1 (soluble fms-like tyrosine kinase 1) and PlGF (placental growth factor) to repair placental injury and inhibited placental ferroptosis by increasing the protein levels of FPN1, FTH1, xCT, and GPX4. Tight junction proteins (ZO-1, Occludin, Claudin1) in the placenta and colon were significantly upregulated by WOA, leading to enhanced placental and gut barriers. WOA rescued intestinal dysbiosis by enriching Bifidobacterium and Akkermansia. Fecal microbiota transplantation (FMT) experiments revealed that the protection of WOA on placenta and gut were dependent on the gut microbial composition. Furthermore, supplementation with both Bifidobacterium bifidum (B. bifidum) and vanillic acid (VA, the major component of WOA) ameliorated PE symptoms. Intriguingly, results from both in vivo and in vitro analyses indicated that the B. bifidum population was enriched by VA.

CONCLUSIONS: This research is the first to demonstrate that WOA prevents PE by enriching Bifidobacterium bifidum, strengthening the gut-placenta barrier, and inhibiting placental ferroptosis. Our findings provide compelling evidence for the vital involvement of the gut-placental axis in the protection of AVL on PE, presenting a novel target for the clinic.}, } @article {pmid39671402, year = {2024}, author = {, }, title = {Retraction: Fecal microbiota transplantation for treatment of recurrent C. difficile infection: An updated randomized controlled trial meta-analysis.}, journal = {PloS one}, volume = {19}, number = {12}, pages = {e0316040}, pmid = {39671402}, issn = {1932-6203}, } @article {pmid39670752, year = {2024}, author = {Peterson, D and Weidenmaier, C and Timberlake, S and Gura Sadovsky, R}, title = {Depletion of key gut bacteria predicts disrupted bile acid metabolism in inflammatory bowel disease.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0199924}, doi = {10.1128/spectrum.01999-24}, pmid = {39670752}, issn = {2165-0497}, abstract = {The gut microbiome plays a key role in bile acid (BA) metabolism, where a diversity of metabolic products contribute to human health and disease. In particular, Inflammatory Bowel Disease (IBD) is characterized by a low concentration of secondary bile acids (SBAs), whose transformation from primary bile acids (PBAs) is an essential function performed solely by gut bacteria. BA-transformation activity mediated by the bile acid inducible (bai) operon has been functionally characterized in the genus Clostridium, and homologous bai gene sequences have been found in metagenome-assembled genomes (MAGs) belonging to other taxa in the human gut, but it is unclear which species of bai-carrying bacteria perform physiologically significant amounts of bile acid transformation in healthy and sick individuals. Here, we analyzed hundreds of stool samples with paired metagenomic and metabolomic data from IBD patients and controls and found that the abundance of the bai operon in metagenomic samples was highly predictive of that sample's high- or low-SBA metabolic state. We further found that bai genes from the Clostridium species best characterized as BA transformers were more prevalent in IBD patients than in non-IBD controls, while bai genes from uncharacterized taxa known only from MAGs were much more physiologically relevant in non-IBD samples. These un-isolated clades of BA-transforming bacteria merit further research; as beyond their prevalence in the human population, we found some cases in which they engrafted in IBD patients who had undergone fecal microbiota transplantation and experienced a clinical response.IMPORTANCEIn this paper, we identify specific bacteria that perform an important metabolic function in the human gut and demonstrate that in the guts of a large subset of patients with IBD, these bacteria are missing and the function is defective. This is a rare example where the correlation between the absence of specific bacteria and the dysfunction of metabolism is directly observed, not in mice nor in the lab, but in physiologic microbial communities in the human gut. Our results point to a path for studying how a small but important set of bacteria is affected by conditions in the IBD gut and perhaps to the development of interventions to mitigate the loss of these bacteria in IBD.}, } @article {pmid39669573, year = {2024}, author = {Yan, J and Yang, L and Ren, Q and Zhu, C and Du, H and Wang, Z and Qi, Y and Xian, X and Chen, D}, title = {Gut microbiota as a biomarker and modulator of anti-tumor immunotherapy outcomes.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1471273}, pmid = {39669573}, issn = {1664-3224}, mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; *Neoplasms/therapy/immunology ; *Immunotherapy/methods ; *Immune Checkpoint Inhibitors/therapeutic use ; Animals ; Biomarkers, Tumor ; Probiotics/therapeutic use ; Treatment Outcome ; Fecal Microbiota Transplantation ; Prebiotics/administration & dosage ; }, abstract = {Although immune-checkpoint inhibitors (ICIs) have significantly improved cancer treatment, their effectiveness is limited by primary or acquired resistance in many patients. The gut microbiota, through its production of metabolites and regulation of immune cell functions, plays a vital role in maintaining immune balance and influencing the response to cancer immunotherapies. This review highlights evidence linking specific gut microbial characteristics to increased therapeutic efficacy in a variety of cancers, such as gastrointestinal cancers, melanoma, lung cancer, urinary system cancers, and reproductive system cancers, suggesting the gut microbiota's potential as a predictive biomarker for ICI responsiveness. It also explores the possibility of enhancing ICI effectiveness through fecal microbiota transplantation, probiotics, prebiotics, synbiotics, postbiotics, and dietary modifications. Moreover, the review underscores the need for extensive randomized controlled trials to confirm the gut microbiota's predictive value and to establish guidelines for microbiota-targeted interventions in immunotherapy. In summary, the article suggests that a balanced gut microbiota is key to maximizing immunotherapy benefits and calls for further research to optimize microbiota modulation strategies for cancer treatment. It advocates for a deeper comprehension of the complex interactions between gut microbiota, host immunity, and cancer therapy, aiming for more personalized and effective treatment options.}, } @article {pmid39668679, year = {2024}, author = {Vitarelli, A and Minafra, P and Vulpi, M and Piana, A and Torre, G and Carbonara, U and Divenuto, L and Papapicco, G and Chiaradia, F and Alba, S and Lucarelli, G and Battaglia, M and Ditonno, P}, title = {A new approach to repair recurrent vescicourethral anastomotic strictures after radical prostatectomy: The use of prerectal access.}, journal = {Urologia}, volume = {}, number = {}, pages = {3915603241300877}, doi = {10.1177/03915603241300877}, pmid = {39668679}, issn = {1724-6075}, abstract = {BACKGROUND: Vesicourethral anastomosis stenosis (VUAS) is a well-known complication of prostate cancer treatments, observed in up to 26% of the cases after radical prostatectomy. Conservative management, with single or even repeated transurethral dilation or endoscopic incision of the stenosis, is successful in many cases, but up to 9% of patients are destined to fail after endoscopic treatment. In these cases, a revision of the vesicourethral anastomosis is necessary and can be realized with different surgical approaches. We aim to describe the technique and the outcomes of a new prerectal approach for VUAS repair.

METHODS: Twelve patients with recalcitrant VUAS following radical prostatectomy were enrolled between May 2014 and September 2018 for prerectal transperineal re-anastomosis. The evaluated outcomes were: the rate of successful anatomical repair at 3 months after surgery and at the last follow-up, postoperative incontinence and complications rate, and the need for further treatments.

RESULTS: No major intraoperative complications occurred. After a median follow-up of 46 months (IQR 36-55), 10 patients (83.3%) achieved a good anatomical repair even if one man required an endoscopic urethrotomy, while two patients (16.67%) with a history of pelvic radiotherapy developed a surgical site infection that required toilette and external urinary diversion. Among the others, nine (75%) developed severe stress urinary incontinence, with resolution of their condition. No patient reported significant postoperative pain or fecal incontinence.

CONCLUSIONS: The prerectal approach to VUAS repair allows direct access to the posterior urethra and the anastomosis, providing a better mobilization of the bladder neck for tension-free anastomosis. However, patients with a history of pelvic radiotherapy have a higher risk of complications. Postoperative incontinence is very common, but urinary continence could be restored with subsequent artificial urinary sphincter placement.}, } @article {pmid39667939, year = {2024}, author = {Dang, H and Feng, P and Zhang, S and Peng, L and Xing, S and Li, Y and Wen, X and Zhou, L and Goswami, S and Xiao, M and Barker, N and Sansonetti, P and Kundu, P}, title = {Maternal gut microbiota influence stem cell function in offspring.}, journal = {Cell stem cell}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.stem.2024.10.003}, pmid = {39667939}, issn = {1875-9777}, abstract = {The maternal microbiome influences child health. However, its impact on a given offspring's stem cells, which regulate development, remains poorly understood. To investigate the role of the maternal microbiome in conditioning the offspring's stem cells, we manipulated maternal microbiota using Akkermansia muciniphila. Different maternal microbiomes had distinct effects on proliferation and differentiation of neuronal and intestinal stem cells in the offspring, influencing their developmental trajectory, physiology, and long-term health. Transplantation of altered maternal microbiota into germ-free mice transmitted these stem cell phenotypes to the recipients' offspring. The progeny of germ-free mice selectively colonized with Akkermansia did not display these stem cell traits, emphasizing the importance of microbiome diversity. Metabolically more active maternal microbiomes enriched the levels of circulating short-chain fatty acids (SCFAs) and amino acids, leaving distinct transcriptomic imprints on the mTOR pathway of offsprings' stem cells. Blocking mTOR signaling during pregnancy eliminated the maternal-microbiome-mediated effects on stem cells. These results suggest a fundamental role of the maternal microbiome in programming offsprings' stem cells and represent a promising target for interventions.}, } @article {pmid39667762, year = {2024}, author = {Zhang, QW and Yang, MJ and Liao, CY and Taha, R and Li, QY and Abdelmotalab, MI and Zhao, SY and Xu, Y and Jiang, ZZ and Chu, CH and Huang, X and Jiao, CH and Sun, LX}, title = {Atractylodes macrocephala Koidz polysaccharide ameliorates DSS-induced colitis in mice by regulating the gut microbiota and tryptophan metabolism.}, journal = {British journal of pharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1111/bph.17409}, pmid = {39667762}, issn = {1476-5381}, support = {82074115//National Natural Science Foundation of China/ ; 82174072//National Natural Science Foundation of China/ ; JSPH-MB-2022-2 supporting//Clinical Capability Enhancement Project Medical/ ; JSPH-MB-2022-2//Clinical Capability Enhancement Project/ ; }, abstract = {BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease, and the range of current clinical treatments is not ideal. We previously found that polysaccharide of Atractylodes macrocephala Koidz (PAMK) is beneficial in DSS-induced colitis, and we aimed to investigate the underlying mechanisms in this study.

EXPERIMENTAL APPROACH: PAMK was used to treat DSS-induced colitis in mice, 16S rRNA sequencing analysis was used to detect changes in the intestinal microbiota, targeted metabolomics analysis was used to determine the content of tryptophan-metabolizing bacteria, and western blotting was used to determine aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) levels. Furthermore, antibiotic-mediated depletion of gut microbiota and faecal microbiota transplantation were performed to assess the role of the gut microbiota in PAMK alleviation of colitis.

KEY RESULTS: PAMK treatment relieved intestinal microbiota dysbiosis in mice with colitis, contributed to the proliferation of tryptophan-metabolizing bacteria, and increased the levels of tryptophan metabolites, resulting in a significant increase in the nuclear translocation of PXR and expression of PXR and its target genes, but not AhR. The gut microbiota is important in PAMK treatment of colitis, including in the alleviation of symptoms, inhibition of inflammation, maintenance of the integrity of the intestinal barrier, and the regulation of the Th17/Treg cell balance.

CONCLUSION AND IMPLICATIONS: Based on our findings, we elucidate a novel mechanism by which PAMK alleviates DSS-induced colitis and thus provides evidence to support the potential development of PAMK as a new clinical drug against UC.}, } @article {pmid39667450, year = {2024}, author = {Fu, Q and Yang, Y and Tian, Q and Zhu, Y and Xu, H and Wang, J and Huang, Q}, title = {Exploring the mechanism of Paotianxiong polysaccharide in the treatment of chronic kidney disease combining metabolomics and microbiomics technologies.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {138629}, doi = {10.1016/j.ijbiomac.2024.138629}, pmid = {39667450}, issn = {1879-0003}, abstract = {A close relationship between the pathogenesis of chronic kidney disease (CKD) and abnormalities in the gut-kidney axis. Paotianxiong polysaccharides (PTXP) that have demonstrated therapeutic effects on CKD. However, the specific mechanism by which PTXP ameliorates CKD through the gut-kidney axis remains to be explored. In this study, the microbiomes and metabolomics were combined to investigate the impact of PTXP on intestinal flora structure and metabolism, further unveiling the relationship through correlation analysis. The results showed that PTXP intervention significantly modulated renal function abnormalities in CKD rats and significantly modulates gut microbial disorders, evidenced by an increased abundance of Lactobacillus murinus, Bacteroides fragilis, and a decreased abundance of Bifidobacterium pseudolongum. Furthermore, PTXP reversed the changes in intestinal metabolites, such as linoleic acid and docosahexaenoic acid, induced by CKD and identified unsaturated fatty acid metabolism as a key metabolic pathway. Correlation analyses also revealed associations among gut microorganisms, metabolites, and renal function indexes, confirming that PTXP alleviated CKD through the gut-kidney axis. Moreover, the above conclusions were verified by fecal bacteria transplantation experiments. These findings provide insights into the mechanism of PTXP for the treatment of CKD and provide new targets for the treatment of CKD.}, } @article {pmid39666007, year = {2025}, author = {Shang, J and Del Valle, DM and Britton, GJ and Mead, KR and Rajpal, U and Chen-Liaw, A and Mogno, I and Li, Z and Menon, R and Gonzalez-Kozlova, E and Elkrief, A and Peled, JU and Gonsalves, TR and Shah, NJ and Postow, M and Colombel, JF and Gnjatic, S and Faleck, DM and Faith, JJ}, title = {Baseline colitogenicity and acute perturbations of gut microbiota in immunotherapy-related colitis.}, journal = {The Journal of experimental medicine}, volume = {222}, number = {1}, pages = {}, pmid = {39666007}, issn = {1540-9538}, support = {U24 CA224319/CA/NCI NIH HHS/United States ; U01 DK124165/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; F30 CA261144/CA/NCI NIH HHS/United States ; //Memorial Sloan-Kettering Cancer Center/ ; K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K08HL143189/NH/NIH HHS/United States ; }, mesh = {*Gastrointestinal Microbiome/immunology/drug effects ; Animals ; Humans ; *Colitis/microbiology/immunology/chemically induced ; Mice ; *Immunotherapy/adverse effects/methods ; Female ; Male ; Immune Checkpoint Inhibitors/adverse effects/pharmacology ; Mice, Inbred C57BL ; Middle Aged ; Aged ; Feces/microbiology ; Neoplasms/immunology/microbiology/therapy/drug therapy ; }, abstract = {Immunotherapy-related colitis (irC) frequently emerges as an immune-related adverse event during immune checkpoint inhibitor therapy and is presumably influenced by the gut microbiota. We longitudinally studied microbiomes from 38 ICI-treated cancer patients. We compared 13 ICI-treated subjects who developed irC against 25 ICI-treated subjects who remained irC-free, along with a validation cohort. Leveraging a preclinical mouse model, predisease stools from irC subjects induced greater colitigenicity upon transfer to mice. The microbiota during the first 10 days of irC closely resembled inflammatory bowel disease microbiomes, with reduced diversity, increased Proteobacteria and Veillonella, and decreased Faecalibacterium, which normalized before irC remission. These findings highlight the irC gut microbiota as functionally distinct but phylogenetically similar to non-irC and healthy microbiomes, with the exception of an acute, transient disruption early in irC. We underscore the significance of longitudinal microbiome profiling in developing clinical avenues to detect, monitor, and mitigate irC in ICI therapy cancer patients.}, } @article {pmid39664442, year = {2024}, author = {Chen, L and Zhang, K and Liu, J and Li, X and Liu, Y and Ma, H and Yang, J and Li, J and Chen, L and Hsu, C and Zeng, J and Xie, X and Wang, Q}, title = {The role of the microbiota-gut-brain axis in methamphetamine-induced neurotoxicity: Disruption of microbial composition and short-chain fatty acid metabolism.}, journal = {Acta pharmaceutica Sinica. B}, volume = {14}, number = {11}, pages = {4832-4857}, pmid = {39664442}, issn = {2211-3835}, abstract = {Methamphetamine (METH) abuse is associated with significant neurotoxicity, high addiction potential, and behavioral abnormalities. Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders. However, the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored. In this study, we employed fecal microbiota transplantation (FMT) and antibiotic (Abx) intervention to manipulate the gut microbiota in mice administered METH. Furthermore, we supplemented METH-treated mice with short-chain fatty acids (SCFAs) and pioglitazone (Pio) to determine the protective effects on gut microbiota metabolism. Finally, we assessed the underlying mechanisms of the gut-brain neural circuit in vagotomized mice. Our data provide compelling evidence that modulation of the gut microbiome through FMT or microbiome knockdown by Abx plays a crucial role in METH-induced neurotoxicity, behavioral disorders, gut microbiota disturbances, and intestinal barrier impairment. Furthermore, our findings highlight a novel prevention strategy for mitigating the risks to both the nervous and intestinal systems caused by METH, which involves supplementation with SCFAs or Pio.}, } @article {pmid39664063, year = {2024}, author = {Li, L and Cai, F and Guo, C and Liu, Z and Qin, J and Huang, J}, title = {Gut microbiome and NAFLD: impact and therapeutic potential.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1500453}, pmid = {39664063}, issn = {1664-302X}, abstract = {Non-Alcoholic Fatty Liver Disease (NAFLD) affects approximately 32.4% of the global population and poses a significant health concern. Emerging evidence underscores the pivotal role of the gut microbiota-including bacteria, viruses, fungi, and parasites-in the development and progression of NAFLD. Dysbiosis among gut bacteria alters key biological pathways that contribute to liver fat accumulation and inflammation. The gut virome, comprising bacteriophages and eukaryotic viruses, significantly shapes microbial community dynamics and impacts host metabolism through complex interactions. Similarly, gut fungi maintain a symbiotic relationship with bacteria; the relationship between gut fungi and bacteria is crucial for overall host health, with certain fungal species such as Candida in NAFLD patients showing detrimental associations with metabolic markers and liver function. Additionally, the "hygiene hypothesis" suggests that reduced exposure to gut parasites may affect immune regulation and metabolic processes, potentially influencing conditions like obesity and insulin resistance. This review synthesizes current knowledge on the intricate interactions within the gut microbiota and their associations with NAFLD. We highlight the therapeutic potential of targeting these microbial communities through interventions such as probiotics, prebiotics, and fecal microbiota transplantation. Addressing the complexities of NAFLD requires comprehensive strategies that consider the multifaceted roles of gut microorganisms in disease pathology.}, } @article {pmid39664050, year = {2024}, author = {Alhamlan, FS and Albadawi, IA and Al-Qahtani, AA and Awartani, KA and Obeid, DA and Tulbah, AM}, title = {Cervicovaginal and gastrointestinal microbiomes in gynecological cancers and their roles in therapeutic intervention.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1489942}, pmid = {39664050}, issn = {1664-302X}, abstract = {Cancer remains a significant global health concern, and understanding factors that regulate cancer development is important. The microbiome, with its potential role in cancer development, progression, and treatment, has garnered increasing attention in recent years. The cervicovaginal and gastrointestinal microbiomes in females constitute complex biological ecosystems. Although the gut microbiome has been extensively studied, little is known about the cervicovaginal microbiome. The microbiome plays a crucial role in maintaining local microenvironments and tissue homeostasis, but dysbiosis can disrupt this fine balance and contribute to pathological ramifications leading to cancer. This review explores the current understanding of the microbiome's correlation with gynecological cancers and highlights the potential of microbiome-based interventions to improve outcomes in these cancers. In addition, this review underscores the gaps and limitations in the literature, such as findings in specific ethnicities compared with understudied ethnicities. In addition, discrepancies in molecular techniques and terminology (microbiome vs. microbiota) used in the literature are addressed. Emerging evidence linking gynecological cancers and dysbiosis underscores microbiota as a potential target for cancer prevention and therapy. Manipulating the microbiome, such as through the use of probiotics, prebiotics, antibiotics, or vaginal and fecal transplantation, has demonstrated benefits in the treatment of chronic and inflammatory conditions. Further translational research in this field is needed to integrate the benefits of beneficial microorganisms in the fight against gynecological cancers.}, } @article {pmid39662821, year = {2024}, author = {Groenewegen, B and van Lingen, E and Kovynev, A and van den Berg, AJ and Berssenbrugge, EKL and Sanders, IMJG and van Prehn, J and van Nood, E and Goorhuis, A and Kuijper, EJ and Smits, WK and Wiese, M and Keller, JJ and Ducarmon, QR and Terveer, EM and , }, title = {The presence of Clostridioides difficile in faeces before and after faecal microbiota transplantation and its relation with recurrent C. difficile infection and the gut microbiota in a Dutch cohort.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cmi.2024.12.003}, pmid = {39662821}, issn = {1469-0691}, abstract = {OBJECTIVES: To study the presence of Clostridioides difficile in faeces of patients with recurrent C. difficile infection (rCDI) before and after faecal microbiota transplantation (FMT) and to identify risk factors for faecal C. difficile and CDI recurrence.

METHODS: N=83 faecal sample triads (pre-FMT (∼one day), post-FMT (∼three weeks), and a corresponding FMT donor sample), and n=22 long-term (∼1-3 years) follow-up faecal samples (LTFU) were collected from FMT-treated patients. The presence of C. difficile in faeces was assessed by enrichment broth culture and PCR (tcdB gene) and associated with patient characteristics, FMT outcome, duration of pre-FMT vancomycin, FMT donor, post-FMT antibiotic use, and faecal microbiota composition (shotgun metagenomics).

RESULTS: The FMT cure rate for rCDI was 92.8% (77/83), with six early CDI recurrences (
CONCLUSIONS: While eradication of C. difficile is not required for clinical cure of rCDI by FMT, it is associated with reduced prevalence of early CDI recurrence, as are the full completion of pre-FMT vancomycin (at least 10 days) and avoiding post-FMT antibiotics.}, } @article {pmid39659943, year = {2024}, author = {Zhao, W and Chen, Y and Xiao, J and Tang, Z and Wang, L and Ren, Y and Chen, Y}, title = {Updated outcomes and exploratory analysis of RENMIN-215: tislelizumab plus fruquintinib and fecal microbiota transplantation in refractory microsatellite stable metastatic colorectal cancer.}, journal = {American journal of cancer research}, volume = {14}, number = {11}, pages = {5351-5364}, pmid = {39659943}, issn = {2156-6976}, abstract = {Primary analysis of the open-label, single-arm, phase II RENMIN-215 trial (primary data cutoff date: July 10, 2023) showed promising efficacy and tolerable safety with tislelizumab plus fruquintinib and fecal microbiota transplantation (FMT) in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Here, we reported updated survival and safety results with a median follow-up of 34.0 months (data cut-off May 20, 2024), as well as patient-reported outcomes and laboratory analysis. Twenty patients with MSS mCRC resistant or refractory to at least second-line therapy were enrolled and received tislelizumab plus fruquintinib and FMT. The primary endpoint was progression-free survival. Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate, safety, health-related quality of life questionnaire and exploratory laboratory tests. In addition, 94 mCRC patients who received third-line or above immunotherapy in real world were screened for propensity score matching (PSM) analysis to compare efficacy. Our results showed that the median OS was 13.7 months (95% CI, 9.3-17.7), and the ORR was 20.0% (95% CI, 5.7-43.7). After PSM, the median OS benefit of the study regimen remained statistically significant (HR = 0.26; 95% CI, 0.07-0.95; P = 0.042). Patients with primary tumor surgery had better clinical outcomes. No new safety concerns were detected. Seven (35.0%) patients had one or more grade 3 treatment-related adverse events. The majority of patients had improved or stable global health status (GHS). Median time to deterioration for GHS was 7.7 months. Peripheral blood lymphocyte analysis showed that increased gamma-delta 2 T cells were positively associated with improved response and survival. To conclude, the updated results provide further evidence of sustained antitumor activity of tislelizumab plus fruquintinib and FMT in heavily pretreated MSS mCRC patients with a consistent safety profile.}, } @article {pmid39659426, year = {2024}, author = {Abildinova, GZ and Benberin, VV and Vochshenkova, TA and Afshar, A and Mussin, NM and Kaliyev, AA and Zhussupova, Z and Tamadon, A}, title = {The gut-brain-metabolic axis: exploring the role of microbiota in insulin resistance and cognitive function.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1463958}, pmid = {39659426}, issn = {1664-302X}, abstract = {The gut-brain-metabolic axis has emerged as a critical area of research, highlighting the intricate connections between the gut microbiome, metabolic processes, and cognitive function. This review article delves into the complex interplay between these interconnected systems, exploring their role in the development of insulin resistance and cognitive decline. The article emphasizes the pivotal influence of the gut microbiota on central nervous system (CNS) function, demonstrating how microbial colonization can program the hypothalamic-pituitary-adrenal (HPA) axis for stress response in mice. It further elucidates the mechanisms by which gut microbial carbohydrate metabolism contributes to insulin resistance, a key factor in the pathogenesis of metabolic disorders and cognitive impairment. Notably, the review highlights the therapeutic potential of targeting the gut-brain-metabolic axis through various interventions, such as dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation (FMT). These approaches have shown promising results in improving insulin sensitivity and cognitive function in both animal models and human studies. The article also emphasizes the need for further research to elucidate the specific microbial species and metabolites involved in modulating the gut-brain axis, as well as the long-term effects and safety of these therapeutic interventions. Advances in metagenomics, metabolomics, and bioinformatics are expected to provide deeper insights into the complex interactions within the gut microbiota and their impact on host health. Overall, this comprehensive review underscores the significance of the gut-brain-metabolic axis in the pathogenesis and treatment of metabolic and cognitive disorders, offering a promising avenue for the development of novel therapeutic strategies targeting this intricate system.}, } @article {pmid39658705, year = {2024}, author = {Wang, Z and Wang, Z and Lu, T and Yuan, G and Chen, W and Jin, J and Jiang, X and Yan, W and Yuan, K and Zou, G and Bao, Y and Shi, J and Liu, X and Wei, H and Han, Y and Lu, L}, title = {Gut microbiota regulate insomnia-like behaviors via gut-brain metabolic axis.}, journal = {Molecular psychiatry}, volume = {}, number = {}, pages = {}, pmid = {39658705}, issn = {1476-5578}, support = {82288101//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Sleep interacts reciprocally with the gut microbiota. However, mechanisms of the gut microbe-brain metabolic axis that are responsible for sleep behavior have remained largely unknown. Here, we showed that the absence of the gut microbiota can alter sleep behavior. Sleep deprivation reduced butyrate levels in fecal content and the hypothalamus in specific pathogen-free mice but not in germ-free mice. The microbial metabolite butyrate can promote sleep by modulating orexin neuronal activity in the lateral hypothalamic area in mice. Insomnia patients had lower serum butyrate levels and a deficiency in butyrate-producing species within the gut microbiota. Transplantation of the gut microbiota from insomnia patients to germ-free mice conferred insomnia-like behaviors, accompanied by a decrease in serum butyrate levels. The oral administration of butyrate rescued sleep disturbances in recipient mice. Overall, these findings reveal the causal role of microbial metabolic pathways in modulating insomnia-like behaviors, suggesting potential therapeutic strategies for treating sleep disorders.}, } @article {pmid39658176, year = {2025}, author = {Guo, B and Zhang, W and Zhang, J and Zou, J and Dong, N and Liu, B}, title = {Euglena gracilis polysaccharide modulated gut dysbiosis of obese individuals via acetic acid in an in vitro fermentation model.}, journal = {Food research international (Ottawa, Ont.)}, volume = {199}, number = {}, pages = {115385}, doi = {10.1016/j.foodres.2024.115385}, pmid = {39658176}, issn = {1873-7145}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Dysbiosis ; *Fermentation ; *Acetic Acid/metabolism ; Humans ; *Obesity/metabolism/microbiology ; *Polysaccharides/pharmacology/metabolism ; *Euglena gracilis/metabolism ; Prebiotics ; Male ; Feces/microbiology ; Adult ; Bacteria/metabolism/classification/drug effects ; Lipid Metabolism/drug effects ; Female ; }, abstract = {Gut dysbiosis is a characteristic feature of obesity and targeting gut microbiota presents a promising approach to attenuate obesity. Euglena gracilis polysaccharide (EGP) has emerged as a potential prebiotic capable of promoting health-beneficial bacteria. However, its effects on the gut dysbiosis of obese individuals remain unclear. This study investigated the impacts of EGP on gut microbiota from both non-obese and obese individuals using an in vitro fermentation model. Results showed that EGP significantly altered the gut microbiota composition and metabolism. Specifically, EGP improved the relative abundance of Paeniclostridium, Clostridium_sensu_stricto_1 and Paraclostridium of the non-obese individuals and Providencia, Enterococcus and Bacteroides of the obese individuals. Metabolomics results showed EGP significantly altered the lipid metabolism especially in the obese group with enriched bile secretion and cholesterol metabolism pathways. Noting that acetic acid was significantly increased in both groups, these acetic acid favorable microbiota from non-obese individuals was collected with acetic acid supplementation. Transplantation of these acetic acid-induced microbiota (AAiM) notably improved the richness and diversity of fecal microbiota of the obese individuals, enhancing the growth of probiotics like Bacteroides and Bifidobacterium. Consequently, AAiM significantly restructured macronutrients (including amino acids, carbohydrates and lipids) metabolism of the gut microbiota from obese individuals. Altogether, this study underscores the potential of EGP and acetic acid favorable microbiota in manipulating obesity-associated gut dysbiosis via acetic acid production.}, } @article {pmid39656490, year = {2024}, author = {Balakrishnan, R and Kang, SI and Lee, JY and Rho, YK and Kim, BK and Choi, DK}, title = {Gut Microbiota-Immune System Interactions in Health and Neurodegenerative Diseases: Insights into Molecular Mechanisms and Therapeutic Applications.}, journal = {Aging and disease}, volume = {}, number = {}, pages = {}, doi = {10.14336/AD.2024.1362}, pmid = {39656490}, issn = {2152-5250}, abstract = {The human body contains approximately 100 trillion microorganisms, predominantly within the gastrointestinal tract, collectively called the gut microbiota. Investigations have revealed the bidirectional communication between the gut microbiota and the brain, characterized as the "microbiota-gut-brain axis." This axis represents an important regulator of brain development and function, immune system development, and nutrient metabolism, making it a target for efforts to alleviate the development and progression of neurodegenerative diseases (NDDs). Despite extensive biomedical and clinical research, our understanding of the causes, optimal treatment, and progression of NDDs remains limited. This paper aims to summarize the available knowledge on the role played by gut microbiota and how it is connected to the progression of neurodegenerative conditions; in particular, the relationship between the microbiota and gut-brain communications and the gut microbiota and neuro-immune conditions is reviewed. We discuss how and why the gut immune system communicates with the brain and how this communication impacts neurodegeneration. Next, we examine the alterations in the gut microbiota, immune response, and brain changes associated with gut dysbiosis. Finally, we highlight the preclinical and clinical evidence for probiotics, prebiotics, fecal microbiota transplantation, dietary supplements, natural drugs, and exercise intervention as potential therapeutic approaches that could lead to a new treatment paradigm for NDDs.}, } @article {pmid39653685, year = {2024}, author = {Li, X and Zheng, P and Zou, Y and Guan, L and Li, N and Liu, J and Lu, N and Zhu, Y and He, C}, title = {Dietary inulin ameliorates obesity-induced severe acute pancreatitis via gut-pancreas axis.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2436949}, pmid = {39653685}, issn = {1949-0984}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Obesity/metabolism ; Mice ; *Inulin/pharmacology/administration & dosage ; *Diet, High-Fat/adverse effects ; *Mice, Inbred C57BL ; Male ; *Pancreas/pathology/metabolism/drug effects ; *Pancreatitis/metabolism ; Dysbiosis/microbiology ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Bacteria/classification/isolation & purification/metabolism/genetics ; }, abstract = {Obesity is a definitive factor of severity and mortality of acute pancreatitis (AP), and gut microbiota dysbiosis is involved in its pathogenesis. However, the effect of gut microbiota modulation by dietary components on high fat diet (HFD)-induced severe AP remains unclear. Here, we found that the inulin, a soluble dietary fiber, mitigated pancreatic injury and systematic inflammation in mice fed HFD, which was dependent on gut microbiota as this protective effect was attenuated in germ-free mice. Inulin treatment suppressed the overgrowth of pathogenic bacteria Escherichia Shigella, Enterococcus, Klebsiella, while increased the abundance of probiotics Akkermansia. Fecal microbiota transplantation from inulin-treated mice to recipient mice reduced pancreatic damage and remodeled intestinal homeostasis. Additionally, inulin increased fecal short chain fatty acids (SCFAs), strengthened gut barrier and restored Paneth cells. The beneficial effect of inulin on improving pancreatic damage and leaky gut was diminished after the suppression of SCFAs. Notably, SCFAs administration, especially butyrate, to HFD mice blocked pancreatic and intestinal injury with the inhibition of histone deacetylase 3 (HDAC3), and pharmacological HDAC3 inhibition mimicked the ameliorative effect of SCFAs. Mechanically, butyrate modulated macrophage M1/M2 polarization balance by suppressing HDAC3 and subsequent acetylation of histone H3K27. Collectively, our data offer new insights into the gut microbiota-pancreas axis that may be leveraged to augment the potential supplementation of prebiotic inulin in the management of obesity associated severe AP.}, } @article {pmid39653155, year = {2024}, author = {Zhao, Y and Sun, S and Liu, J and Zheng, M and Liu, M and Liu, J and Liu, H}, title = {Investigation of the protective mechanism of paeoniflorin against hyperlipidemia by an integrated metabolomics and gut microbiota strategy.}, journal = {The Journal of nutritional biochemistry}, volume = {}, number = {}, pages = {109831}, doi = {10.1016/j.jnutbio.2024.109831}, pmid = {39653155}, issn = {1873-4847}, abstract = {The prevalence of hyperlipidemia is gradually increasing globally, posing a serious threat to public health. Previous studies have shown that paeoniflorin (PF) effectively improved abnormal lipid metabolism in atherosclerotic mice. However, the anti-hyperlipidemia effect and potential mechanism of paeoniflorin remain unclear. The gut microbiota (GM) is closely related to hyperlipidemia. This study was aimed to investigate effects of PF on improving the health of high-fat diet (HFD)-induced hyperlipidemic mice by modulating GM. A hyperlipidemic mouse model was established using an HFD, and the hypolipidemic effect of PF was detected in vivo. Besides16S ribosomal RNA sequencing and SCFAs metabolic analysis were performed to explore the lipid-lowering mechanism of PF. Importantly, fecal microbiota transplantation (FMT) experiments were conducted to verify the lipid-lowering mechanism of PF. The results showed that PF significantly inhibited the development of hyperlipidemia, reduced serum lipid and inflammatory cytokine levels, and improved liver steatosis. In addition, 16S rRNA sequencing revealed that PF treatment significantly increased the relative abundance of Lactobacillus, Coprococcus, Blautia, Roseburia, and Bacteroides while reducing the relative abundance of Prevotella. Meanwhile, the results of targeted metabolomics indicate that PF therapy can effectively restore butyric acid and propionic acid levels in the intestine. The FMT experiments further demonstrated that PF improved hyperlipidemia by regulating GM and its metabolites. The above results provide a valuable theoretical basis for the development and application of PF as a functional food for hyperlipidemia.}, } @article {pmid39652283, year = {2024}, author = {Lou, L and Zhou, L and Wang, Y}, title = {Gut Microbiota: A Modulator and Therapeutic Target for Chronic Pain.}, journal = {Molecular neurobiology}, volume = {}, number = {}, pages = {}, pmid = {39652283}, issn = {1559-1182}, abstract = {Chronic pain is a prevalent condition, impacting nearly one-fifth of the global population. Despite the availability of various clinical treatments, each comes with inherent limitations, and few offer a complete cure, resulting in a significant social and economic burden. Therefore, it is important to determine the pathogenesis and causes of chronic pain. Numerous studies have shown a close link between the intestinal microflora and chronic pain. The gut microbiota can exert their effects on chronic pain through both central and peripheral mechanisms and is able to communicate with the brain through its own components or metabolites. They also can regulate chronic pain by affecting pro- and anti-inflammatory cells. This review is aimed at reviewing the connection between gut flora and different types of chronic pain, including visceral pain, neuropathic pain, inflammatory pain, musculoskeletal pain, migraine, and chronic cancer pain; exploring the central and peripheral mechanisms of the influence of gut flora on chronic pain; and attempting to provide novel treatment options for chronic pain, that is, the gut microbiota can be regulated by probiotics, fecal microbial transplantation, and natural products to treat chronic pain. By examining the intricate relationship between gut flora and chronic pain, the review sought to pave the way for new treatment strategies that target the gut microbiota, offering hope for more effective pain management.}, } @article {pmid39651062, year = {2024}, author = {Kaundal, S and Patil, AN and Ks, L and Sharma, V and Arora, A and Singh, C and Jandial, A and Jain, A and Prakash, G and Khadwal, A and Malhotra, P and Lad, DP}, title = {A role for diet and gut microbiota metabolites in autologous hematopoietic cell transplant recipients.}, journal = {Blood cell therapy}, volume = {7}, number = {4}, pages = {101-105}, pmid = {39651062}, issn = {2432-7026}, abstract = {INTRODUCTION: The gut microbiome has an established role in allogeneic hematopoietic cell transplantation (allo-HCT), but not in an auto-HCT setting. We have hypothesized that fecal short-chain fatty acids (SCFA) and urinary 3-indoxyl sulfate (3-IS), which are metabolites derived from the action of the gut microbiome on dietary fiber, play a role in auto-HCT outcomes.

METHODS: This was a single-center prospective study involving auto-HCT recipients. Baseline patient and disease details, diet diaries, and antibiotic exposure were recorded in consenting patients. Serial (pre-HCT, week two, and week four post-HCT) SCFA and urine 3-IS levels were measured using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). HCT outcomes were correlated with these metabolites.

RESULTS: Thirty patients (myeloma, n=13; lymphoma, n=17) were analyzed. The levels of urinary 3-IS, fecal acetate, propionate, and butyrate were found to be decreased at week two and were recovered by week four post-HCT. Those with low median nadir fecal butyrate levels at week two also had significantly lower pre-HCT and week four butyrate levels. Recipients with low butyrate levels had more grade ≥2 mucositis (80% vs. 33%, p=0.01) and low fiber intake (10.4 g vs. 13.6 g, p=0.04). They also had more carbapenem exposure (93% vs. 47%, p=0.005) and prolonged antibiotics (11 days vs. 8 days, p=0.008). There were no differences in the time to neutrophil or platelet engraftment, mortality, or disease response.

CONCLUSION: Low pre-HCT fecal butyrate levels tend to persist post-HCT and they are associated with mucositis, dietary fiber intake, and antibiotic exposure. The gut microbiome and its modulation may play a role in auto-HCT settings.}, } @article {pmid39651029, year = {2024}, author = {Suresh, SB and Malireddi, A and Abera, M and Noor, K and Ansar, M and Boddeti, S and Nath, TS}, title = {Gut Microbiome and Its Role in Parkinson's Disease.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73150}, pmid = {39651029}, issn = {2168-8184}, abstract = {Parkinson's disease (PD) afflicted more than 8.5 million people globally in 2019, as the prevalence of the condition more than doubled during the preceding 25 years. Both non-motor symptoms, such as mood disorders and cognitive impairment, and motor symptoms, such as tremors and rigidity, are indicative of this progressive neurodegenerative disease. Recent data indicates a significant role for the gut microbiome in PD pathogenesis and progression, emphasizing the microbiota-gut-brain axis. In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement, this systematic review summarizes our current knowledge about the function of the gut microbiome in PD, highlighting recurrent microbial alterations and assessing microbiome-based treatment strategies. The review revealed several consistent patterns in the gut microbiota of PD patients, including reduced microbial diversity and specific taxonomic alterations, including a drop in Firmicutes abundance and an increase in Proteobacteria abundance. Functional changes in the gut microbiome, such as altered short-chain fatty acid (SCFA) production and tryptophan metabolism, were also noted. These microbial changes were observed even in early-stage and drug-naïve PD patients, suggesting they are not merely a consequence of disease progression or medication use. The review highlighted potential mechanisms linking gut microbiome alterations to PD, including increased intestinal permeability, neuroinflammation, and modulation of alpha-synuclein aggregation. Probiotics, prebiotics, and fecal microbiota transplantation are a few interventions that try to modify the gut microbiome and might be possible to halt the advancement of PD and enhance patients' quality of life with the condition. Future research should focus on establishing causality through large-scale longitudinal studies, standardizing microbiome analysis methods, and exploring personalized microbiome-based therapies.}, } @article {pmid39650985, year = {2024}, author = {Ina, EA and Ziton, S and Dourvetakis, K and Corallo, JP}, title = {Loop Ileostomy With Colonic Lavage: Case Report of an Alternative to Total Colectomy in the Setting of Fulminant Clostridium difficile Colitis.}, journal = {Cureus}, volume = {16}, number = {11}, pages = {e73141}, pmid = {39650985}, issn = {2168-8184}, abstract = {Fulminant Clostridium difficile colitis is a severe and potentially life-threatening form of Clostridium difficile-associated bacterial disease leading to inflammation and damage to the colon. Complications such as toxic megacolon, sepsis, and multi-organ failure commonly occur in individuals with compromised immune systems and recent antibiotic use. Management of Clostridium difficile colitis involves optimization of fluid and electrolyte balance, and elimination of bacteria commonly by administering vancomycin or fidaxomicin. In cases where pharmacological management has been ineffective, fecal microbiota transplantation and surgical intervention demonstrated success. Historically, surgical intervention has involved a total abdominal colectomy with end ileostomy; however, other surgical options have shown increasing benefits with preservation of the colon. This case report aims to provide an example of an alternative management strategy for fulminant Clostridium difficile infections, via the use of a loop ileostomy and colonic lavage. The combination of loop ileostomy and colonic lavage promotes bowel rest, removes toxins, and promotes healing while decreasing inflammation. As with all management modalities, it is essential to recognize the associated complications. The potential benefits should be carefully weighed against the risks on a case-by-case basis with the help of a multidisciplinary team as illustrated through this case report. Overall, early recognition and treatment of fulminant Clostridium difficile colitis using loop ileostomy and colonic lavage prevents further disease progression and improves patient outcomes.}, } @article {pmid39649613, year = {2024}, author = {Moreau, GB and Young, M and Behm, B and Tanyüksel, M and Ramakrishnan, G and Petri, WA}, title = {FMT Restores Colonic Protein Biosynthesis and Cell Proliferation in Patients with Recurrent Clostridioides difficile Disease.}, journal = {medRxiv : the preprint server for health sciences}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.28.24318101}, pmid = {39649613}, abstract = {Recurrent C. difficile infection (CDI) is a major health threat with significant mortality and financial costs. Fecal Microbiota Transplantation (FMT) is an effective therapy, however the mechanisms by which it acts, particularly on the host, are poorly understood. Here we enrolled a prospective cohort of human patients with recurrent CDI (n=16) undergoing FMT therapy. Colonic biopsies were collected and bulk RNA sequencing was performed to compare changes in host gene expression pre- and two months post-FMT. Transcriptional profiles were significantly altered after FMT therapy, with many differentially expressed genes (∼15% of annotated genes detected). Enrichment analysis determined that these changes were reflective of increased protein production post-FMT, with enrichment of pathways such as Ribosome Biogenesis, Protein Processing, and signaling pathways (Myc, mTORc1, E2F) associated with cell proliferation and protein biosynthesis. Histology of H&E-stained biopsies identified a significant increase in colonic crypt length post-FMT, suggesting that this treatment promotes cell proliferation. Crypt length was significantly correlated with enriched Myc and mTOR signaling pathways as well as genes associated with polyamine biosynthesis, providing a potential mechanism through which this may occur. Finally, signaling pathways upstream of Myc and mTOR, notably IL-33 Signaling and EGFR ligands, were significantly upregulated, suggesting that FMT may utilize these signals to promote cell proliferation and restoration of the intestine.}, } @article {pmid39647752, year = {2024}, author = {Li, K and Ran, X and Han, J and Ding, H and Wang, X and Li, Y and Guo, W and Li, X and Guo, W and Fu, S and Bi, J}, title = {Astragalus polysaccharide alleviates mastitis disrupted by Staphylococcus aureus infection by regulating gut microbiota and SCFAs metabolism.}, journal = {International journal of biological macromolecules}, volume = {286}, number = {}, pages = {138422}, doi = {10.1016/j.ijbiomac.2024.138422}, pmid = {39647752}, issn = {1879-0003}, abstract = {Polysaccharides, key bioactive compounds derived from Chinese herbs, are increasingly recognized for their therapeutic potential in modulating gut microbiota to treat various diseases. However, their efficacy in alleviating mammary inflammation and oxidative stress and protecting the blood-milk barrier (BMB) compromised by Staphylococcus aureus (S. au) infection remains uncertain. As evidence for the gut-mammary axis grows, identifying natural prebiotic components that affect this axis is crucial. This study reveals that Astragalus polysaccharide (APS), the primary active constituent of Astragalus, effectively mitigates S. au infection in murine mammary glands, suppresses inflammatory responses, reduces oxidative stress, and restores BMB integrity. The involvement of APS in modulating gut microbiota was substantiated through gut microbial depletion experiments and fecal microbiota transplantation (FMT). Notably, APS uniquely enriched Ruminococcus bromii (R. bromii) in the gut, facilitating the metabolism of short-chain fatty acids (SCFAs), particularly acetate and butyrate, which are pivotal to APS's protective effects. Collectively, these results propose a novel therapeutic approach for the treatment and prevention of S. au-induced mastitis, leveraging APS and R. bromii as prebiotics and probiotics, respectively.}, } @article {pmid39647571, year = {2024}, author = {Sharma, A and Kapur, S and Kancharla, P and Yang, T}, title = {Sex Differences in Gut Microbiota, Hypertension, and Cardiovascular Risk.}, journal = {European journal of pharmacology}, volume = {}, number = {}, pages = {177183}, doi = {10.1016/j.ejphar.2024.177183}, pmid = {39647571}, issn = {1879-0712}, abstract = {The intricate ecosystem of the gut microbiome exhibits sex-specific differences, influencing the susceptibility to cardiovascular diseases (CVD). Imbalance within the gut microbiome compromises the gut barrier, activates inflammatory pathways, and alters the production of metabolites, all of which initiate chronic diseases including CVD. In particular, the interplay between lifestyle choices, hormonal changes, and metabolic byproducts uniquely affects sex-specific gut microbiomes, potentially shaping the risk profiles for hypertension and CVD differently in men and women. Understanding the gut microbiome's role in CVD risk offers informative reasoning behind the importance of developing tailored preventative strategies based on sex-specific differences in CVD risk. Furthermore, insight into the differential impact of social determinants and biological factors on CVD susceptibility emphasizes the necessity for more nuanced approaches. This review also outlines specific dietary interventions that may enhance gut microbiome health, offering a glimpse into potential therapeutic avenues for reducing CVD risk that require greater awareness. Imbalance in natural gut microbiomes may explain etiologies of chronic diseases; we advocate for future application to alter the gut microbiome as possible treatment of the aforementioned diseases. This review mentions the idea of altering the gut microbiome through interventions such as fecal microbiota transplantation (FMT), a major application of microbiome-based therapy that is first-line for Clostridium difficile infections and patient-specific probiotics highlights more innovative approaches to hypertension and CVD prevention. Through increased analysis of gut microbiota compositions along with patient-centric probiotics and microbiome transfers, this review advocates for future preventative strategies for hypertension.}, } @article {pmid39647535, year = {2024}, author = {Casañas-Martínez, M and Barbero-Herranz, R and Alegre-González, D and Mosquera-Lozano, JD and Campo, RD and , }, title = {Fecal Microbiota Transplantation in a Long-Standing Auto-Brewery Syndrome with Complex Symptomatology.}, journal = {Journal of hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhep.2024.12.005}, pmid = {39647535}, issn = {1600-0641}, } @article {pmid39645284, year = {2024}, author = {Dean, NJ and d'Arienzo, PD and Ibraheim, H and Lee, KA and Olsson-Brown, AC and Pinato, DJ and Powell, N}, title = {The role of the gut microbiome in regulating the response to immune checkpoint inhibitor therapy.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101944}, doi = {10.1016/j.bpg.2024.101944}, pmid = {39645284}, issn = {1532-1916}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects/physiology ; *Immune Checkpoint Inhibitors/therapeutic use/pharmacology ; *Neoplasms/drug therapy/microbiology/immunology ; Immunotherapy/methods ; Treatment Outcome ; Anti-Bacterial Agents/therapeutic use/pharmacology ; }, abstract = {Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet the proportion of patients who achieve long-term disease control remain suboptimal. Over the past decade, the gut microbiome has been shown to influence immune-mediated tumour suppression as well as responses to ICI therapies. Compositional differences in gut microbiome may account for the differences in outcomes from immune checkpoint blockade. Identifying microbiota species associated with favourable/unfavourable outcomes and modelling their dynamics throughout the course of ICI treatment could help develop predictive biomarkers of immunotherapy response, and manipulating the gut microbiome represent a novel approach to enhancing ICI effectiveness. Clinically, this raises the prospect of using gut microbiome-based therapies to overcome primary resistance to ICIs, mitigate the effects of microbiome-altering drugs such as antibiotics or proton pump inhibitors, and improve overall survival in patients across numerous different cancer types.}, } @article {pmid39645282, year = {2024}, author = {Józefczuk, P and Biliński, J and Minkowska, A and Łaguna, P}, title = {Gut microbiome in children undergoing hematopoietic stem cell transplantation.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101955}, doi = {10.1016/j.bpg.2024.101955}, pmid = {39645282}, issn = {1532-1916}, mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Gastrointestinal Microbiome/physiology ; Child ; Animals ; }, abstract = {Hematopoietic stem cell transplantation (HSCT) is used in children as a treatment for various cancers, e.g. acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), or other diseases, e.g. severe congenital immunodeficiency, metabolic disorders, hence the patient population is quite diverse. There is an increasing interest on the role of the microbiome in peri-transplant period. In this review, concepts of HSCT with the focus on the importance of microbiome composition, its changes during treatment and possible microbiota oriented interventions will be discussed. This paper analyzes data in pediatric population, but in view of interesting results and absence of analogous data for pediatric patients, it also looks at studies performed on adult population and pre-clinical trials on animals discussing possible translation to children.}, } @article {pmid39645278, year = {2024}, author = {Garcia-Mateo, S and Rondinella, D and Ponziani, FR and Miele, L and Gasbarrini, A and Cammarota, G and Lanas, Á and Gomollón, F}, title = {Gut microbiome and metabolic dysfunction-associated steatotic liver disease: Pathogenic role and potential for therapeutics.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {72}, number = {}, pages = {101924}, doi = {10.1016/j.bpg.2024.101924}, pmid = {39645278}, issn = {1532-1916}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; *Prebiotics/administration & dosage ; Non-alcoholic Fatty Liver Disease/microbiology/therapy/metabolism ; Dysbiosis ; Diet, Mediterranean ; }, abstract = {Gut microbiota plays key functions in the human body, and its alteration is associated with several human disorders. Moreover, its manipulation is being investigated as a potential therapeutic strategy. In this narrative review we will dissect the involvement of the gut microbiota and of the gut-liver axis on metabolic dysfunction-associated steatotic liver disease (MASLD). Additionally, we will review the effects of lifestyle interventions commonly used for MASLD (i.e. Mediterranean diet and physical exercise) on gut microbiome, to understand if their beneficial effect can be microbially mediated. Finally, we will discuss the role and the available evidence of therapeutic microbiome modulators, including prebiotics, probiotics, symbiotics, and fecal microbiota transplantation (FMT), in the management of MASLD.}, } @article {pmid39643421, year = {2025}, author = {Zhang, S and Zhou, R and Xie, X and Xiong, S and Li, L and Li, Y}, title = {Polysaccharides from Lycium barbarum, yam, and sunflower ameliorate colitis in a structure and intrinsic flora-dependent manner.}, journal = {Carbohydrate polymers}, volume = {349}, number = {Pt A}, pages = {122905}, doi = {10.1016/j.carbpol.2024.122905}, pmid = {39643421}, issn = {1879-1344}, mesh = {Animals ; *Dioscorea/chemistry ; Mice ; *Mice, Inbred C57BL ; *Gastrointestinal Microbiome/drug effects ; *Colitis/drug therapy/chemically induced ; *Helianthus/chemistry ; Female ; *Polysaccharides/pharmacology/chemistry ; Lycium/chemistry ; Mice, Inbred ICR ; Disease Models, Animal ; Cytokines/metabolism ; Drugs, Chinese Herbal/pharmacology/chemistry ; }, abstract = {Polysaccharides have been suggested to ameliorate metabolic diseases. However, their differential colitis-mitigating effects in mouse models with different colony structures remain poorly understood. Therefore, this study investigated the effects of polysaccharides from Lycium barbarum (LBP), sunflower (SP), and yam (YP) on colitis in C57BL/6 J (B6) mice born via vaginal delivery (VD) and in both caesarean section (CS)- and VD-born Institute of Cancer Research (ICR) mice. LBP was mainly composed of glucose (30.2 %), galactose (27.5 %), and arabinose (26.9 %). The main components of SP and YP were galacturonic acid (75.8 %) and glucose (98.1 %), respectively. Interestingly, LBP effectively alleviated body weight loss, reduced inflammatory cytokine levels, and restored intestinal barrier function in all three mouse models. Moreover, LBP decreased the abundance of norank_f__norank_o__Clostridia_UCG-014, Coriobacteriaceae_UCG-002, and norank_f_Eubacterium_coprostanoligenes_group in B6 mice, and the abundance of these genera positively correlated with pro-inflammatory cytokine levels. LBP increased the abundance of Lactobacillus, which was positively correlated with the levels of the protective factor, IL-10, in CS-born ICR mice. Collectively, our study suggests the potential application of LBP in the treatment of ulcerative colitis. We also provide an alternative method for restoring intestinal homeostasis in CS-born offspring.}, } @article {pmid39643403, year = {2025}, author = {Zhang, Y and Ji, W and Qin, H and Chen, Z and Zhou, Y and Zhou, Z and Wang, J and Wang, K}, title = {Astragalus polysaccharides alleviate DSS-induced ulcerative colitis in mice by restoring SCFA production and regulating Th17/Treg cell homeostasis in a microbiota-dependent manner.}, journal = {Carbohydrate polymers}, volume = {349}, number = {Pt A}, pages = {122829}, doi = {10.1016/j.carbpol.2024.122829}, pmid = {39643403}, issn = {1879-1344}, mesh = {Animals ; *Colitis, Ulcerative/drug therapy/chemically induced/immunology ; *Th17 Cells/drug effects/immunology ; Mice ; *Gastrointestinal Microbiome/drug effects ; *Dextran Sulfate ; *Polysaccharides/pharmacology/chemistry ; *T-Lymphocytes, Regulatory/drug effects/immunology/metabolism ; *Mice, Inbred C57BL ; Homeostasis/drug effects ; Fatty Acids, Volatile/metabolism ; Male ; Astragalus Plant/chemistry ; Astragalus propinquus/chemistry ; Fecal Microbiota Transplantation ; }, abstract = {Natural polysaccharides from Astragalus membranaceus have been shown to relieve ulcerative colitis (UC). However, the mechanism and causal relationship between the gut microbiota and Astragalus polysaccharides (APS) treatment of UC are unclear. The results of the present study showed that APS ameliorated colonic injury and the disruption of the gut microbiota and restored intestinal immune homeostasis in mice with DSS-induced colitis. Meanwhile, we found that APS treatment was ineffective in antibiotic-treated colitis mice but was effective when FMT (Fecal microbiota transplantation) was performed on UC mice using APS-treated mice as donors. APS increased the proportion of relevant microbiota that produce SCFAs and both direct administration of APS and administration of APS-adjusted gut microbiota significantly promoted the production of SCFAs in colitis mice. We demonstrated that APS dually inhibited NF-κB activation via the TLR4 and HDAC3 pathways and improved the balance in Th17/Treg cells in UC mice. In conclusion, our study revealed that APS is a promising prebiotic agent for the maintenance of intestinal health and demonstrated that APS may ameliorate colitis in a gut microbiota-dependent manner.}, } @article {pmid39640634, year = {2024}, author = {Nezhadi, J and Fadaee, M and Ahmadi, S and Kafil, HS}, title = {Microbiota transplantation.}, journal = {Heliyon}, volume = {10}, number = {20}, pages = {e39047}, pmid = {39640634}, issn = {2405-8440}, abstract = {Microbiota refers to a collection of living microorganisms, including bacteria, yeasts, and viruses, that coexist in various sites of the human body. Microbiota can perform multiple functions in the body, which have an essential effect on human health and homeostasis. For example, the microbiota can digest polysaccharides, produce vitamins, modulate the immune system, and protect the body against pathogens. Various factors can occasionally alter the microbiota population in the human body, a condition known as dysbiosis. Dysbiosis can disrupt the homeostasis of a person's body and cause disease. Recent years have witnessed efforts to restore the microbiota population of an individual's body to its original state and eradicate dysbiosis through microbiota transplantation. The noteworthy point is that different methods such as fecal microbiota transplantation, vaginal microbiota transplantation (VMT), skin microbiota transplantation (SMT), oral microbiota transplantation (OMT), washed microbiota transplantation (WMT), and sinonasal microbiota transplantation (SiMT) are used for microbiota transplantation (MT). According to the results of studies and the usefulness of MT in improving a person's health, the purpose of this study is to investigate different methods of MT to eliminate dysbiosis.}, } @article {pmid39640340, year = {2024}, author = {Ma, BDY and Chan, TYH and Lo, BWY}, title = {Unveiling the hidden culprit: How the brain-gut axis fuels neuroinflammation in ischemic stroke.}, journal = {Surgical neurology international}, volume = {15}, number = {}, pages = {394}, pmid = {39640340}, issn = {2229-5097}, abstract = {BACKGROUND: The brain-gut axis represents a bidirectional communication network between the gut microbiome and the central nervous system that plays an important role in homeostasis. Compelling evidence now confirms that ischemic stroke disrupts this delicate balance by inducing gut dysbiosis.

METHODS: A comprehensive literature search was performed in PubMed, Web of Science, and Google Scholar for articles published between January 2000 and January 2023 using relevant keywords. Studies were limited to English and included original studies, literature, and systematic reviewers from peer-reviewed journals which discussed gut microbiota composition in models/subjects with ischemic stroke or assessed stroke impact on gut microbiota. Comments, meeting abstracts, and case reports were excluded. From the 80 relevant articles, we summarized key findings related to gut microbiota changes after stroke and their association with stroke outcomes.

RESULTS: Emerging preclinical evidence underscores the pivotal role of the gut microbiome in glial cell development and function. Germ-free models exhibit compromised microglial activation and impaired cellular debris clearance, exacerbating tissue damage following ischemic stroke. Targeted interventions, including prebiotics, probiotics, and fecal microbiota transplantation, have demonstrated efficacy in rescuing glial phenotypes in preclinical stroke models. Beyond its local effects, the gut microbiome significantly influences systemic immunity. Ischemic stroke polarizes pro-inflammatory phenotypes of neutrophils and T cells, amplifying neurovascular inflammation. Microbiota manipulation modulates leukocyte trafficking and metabolic signaling, offering potential avenues to mitigate infarct pathology.

CONCLUSION: Our review demonstrates that in preclinical stroke models, modulating the lipopolysaccharide, short-chain fatty acid, and trimethylamine N-oxide pathways through the gut-brain axis reduces infarct sizes and edema and improves functional recovery after ischemic stroke. Further exploration of this important axis may unveil additional adjunctive stroke therapies by elucidating the complex interplay between the microbiome and the brain. Rigorously controlled clinical studies are now warranted to translate these promising preclinical findings and investigate whether manipulating the microbiome-brain relationship can help improve outcomes for stroke patients. Overall, continued research on the gut-brain axis holds exciting possibilities for developing novel treatment strategies that may enhance recovery after stroke.}, } @article {pmid39640265, year = {2024}, author = {Wang, H and Deng, F and Luo, M and Wang, X}, title = {Case report: Fecal microbiota transplant for Clostridium difficile infection in a pregnant patient with acute severe ulcerative colitis.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1417003}, pmid = {39640265}, issn = {1664-3224}, mesh = {Humans ; Female ; *Fecal Microbiota Transplantation ; Pregnancy ; *Colitis, Ulcerative/therapy/immunology/microbiology ; Adult ; *Clostridium Infections/therapy/immunology ; Clostridioides difficile ; Gastrointestinal Microbiome ; Pregnancy Complications, Infectious/therapy/microbiology ; Treatment Outcome ; Acute Disease ; Severity of Illness Index ; }, abstract = {Ulcerative colitis (UC) is a chronic colonic mucosal inflammation characterized by reduced gut microbial diversity. Patients with UC at pregnancy are prone to suffer from severe disease progression due to the changes of hormone and immune regulation. Fecal microbiota transplant (FMT) is a promising therapy for UC and recurrent Clostridium difficile infection (CDI). However, acute severe ulcerative colitis (ASUC) treatment especially in patients at pregnancy is clinically challenging. Herein, we report a 34-year-old pregnant woman who manifested with numerous bloody stools and markedly elevated serological inflammatory indicators and was diagnosed with ASUC and concurrent CDI. The use of intravenous injection steroids and anti-TNF-α therapy failed to improve her condition. Frozen encapsulated FMT therapy was finally performed to this patient with clearly improved symptoms and indications of safe delivery without UC flares or complications, and markedly increased diversity of the gut microbiota was also shown in this patient after FMT. This report firstly describes FMT as a safe salvage therapy for a pregnant patient with CDI and ASUC refractory to intravenous steroids and anti-TNF therapy.}, } @article {pmid39638178, year = {2024}, author = {Gong, JZ and Huang, JJ and Pan, M and Jin, QW and Fan, YM and Shi, WQ and Huang, SY}, title = {Cathepsin L of Fasciola hepatica meliorates colitis by altering the gut microbiome and inflammatory macrophages.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {138270}, doi = {10.1016/j.ijbiomac.2024.138270}, pmid = {39638178}, issn = {1879-0003}, abstract = {Helminths can relieve the development of autoimmune diseases and inflammatory diseases, by inducing anti-inflammatory innate immune responses. Here, we report that CL7, a Cathepsin L protein secreted by Fasciola hepatica, inhibited the activation of the NF-κB and MAPK signaling resulting in reduced secretion of inflammatory mediators in macrophages. Furthermore，we found that CL7 could prevent dextran sulfate sodium (DSS) induced ulcerative colitis (UC). CL7 and ESP administration restored DSS-induced body weight loss, colon shortening, and injury, significantly decreased the disease activity index (DAI) and alleviated colonic epithelial injury. CL7 noticeably suppressed the DSS-triggered M1 polarization upregulation and inhibited IL-17 and other inflammatory mediator production in UC mice. Additionally, CL7 ameliorated DSS-induced microbiota dysbiosis. Results of Antibiotic treatment (ABX) and fecal microbial transplants (FMT) suggested that the gut microbiota played an important role in CL7 treating UC. These findings propose that CL7 could be a promising strategy for UC therapy.}, } @article {pmid39635024, year = {2024}, author = {Skladany, L and Kubanek, N and Adamcova Selcanova, S and Zilincanova, D and Havaj, D and Sulejova, K and Soltys, K and Messingerova, L and Lichvar, M and Laffers, L and Zilincan, M and Honsova, E and Liptak, P and Banovcin, P and Bures, J and Koller, T and Golubnitschaja, O and Arab, JP}, title = {3PM-guided innovation in treatments of severe alcohol-associated hepatitis utilizing fecal microbiota transplantation.}, journal = {The EPMA journal}, volume = {15}, number = {4}, pages = {677-692}, pmid = {39635024}, issn = {1878-5077}, abstract = {RATIONALE: Severe alcohol-associated hepatitis (SAH) is the most critical, acute, inflammatory phenotype within the alcohol-associated liver disease (ALD) spectrum, characterized by high 30- and 90-day mortality. Since several decades, corticosteroids (CS) are the only approved pharmacotherapy offering highly limited survival benefits. Contextually, there is an evident demand for 3PM innovation in the area meeting patients' needs and improving individual outcomes. Fecal microbiota transplantation (FMT) has emerged as one of the new potential therapeutic options. In this study, we aimed to address the crucial 3PM domains in order to assess (i) the impact of FMT on mortality in SAH patients beyond CS, (ii) to identify factors associated with the outcome to be improved (iii) the prediction of futility, (iv) prevention of suboptimal individual outcomes linked to increased mortality, and (v) personalized allocation of therapy.

METHODS: We conducted a prospective study (NCT04758806) in adult patients with SAH who were non-responders (NR) to or non-eligible (NE) for CS between January 2018 and August 2022. The intervention consisted of five 100 ml of FMT, prepared from 30 g stool from an unrelated healthy donor and frozen at - 80 °C, administered daily to the upper gastrointestinal (GI) tract. We evaluated the impact of FMT on 30- and 90-day mortality which we compared to the control group selected by the propensity score matching and treated by the standard of care; the control group was derived from the RH7 registry of patients hospitalized at the liver unit (NCT04767945). We have also scrutinized the FMT outcome against established and potential prognostic factors for SAH - such as the model for end-stage liver disease (MELD), Maddrey Discriminant Function (MDF), acute-on-chronic liver failure (ACLF), Liver Frailty Index (LFI), hepatic venous-portal pressure gradient (HVPG) and Alcoholic Hepatitis Histologic Score (AHHS) - to see if the 3PM method assigns them a new dimension in predicting response to therapy, prevention of suboptimal individual outcomes, and personalized patient management.

RESULTS: We enrolled 44 patients with SAH (NR or NE) on an intention-to-treat basis; we analyzed 33 patients per protocol for associated factors (after an additional 11 being excluded for receiving less than 5 doses of FMT), and 31 patients by propensity score matching for corresponding individual outcomes, respectively. The mean age was 49.6 years, 11 patients (33.3%) were females. The median MELD score was 29, and ACLF of any degree had 27 patients (81.8%). FMT improved 30-day mortality (p = 0.0204) and non-significantly improved 90-day mortality (p = 0.4386). Univariate analysis identified MELD ≥ 30, MDF ≥ 90, and ACLF grade > 1 as significant predictors of 30-day mortality, (p = 0.031; p = 0.014; p = 0.034). Survival was not associated with baseline LFI, HVPG, or AHHS.

In the most difficult-to-treat sub-cohort of patients with SAH (i.e., NR/NE), FMT improved 30-day mortality. Factors associated with benefit included MELD ≤ 30, MDF ≤ 90, and ACLF < 2. These results support the potential of gut microbiome as a therapeutic target in the context of 3PM research and vice versa - to use 3PM methodology as the expedient unifying template for microbiome research. The results allow for immediate impact on the innovative concepts of (i) personalized phenotyping and stratification of the disease for the clinical research and practice, (ii) multilevel predictive diagnosis related to personalized/precise treatment allocation including evidence-based (ii) prevention of futile and sub-optimally effective therapy, as well as (iii) targeted prevention of poor individual outcomes in patients with SAH. Moreover, our results add to the existing evidence with the potential to generate new research along the SAH's pathogenetic pathways such as diverse individual susceptibility to alcohol toxicity, host-specific mitochondrial function and systemic inflammation, and the role of gut dysbiosis thereof.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00381-5.}, } @article {pmid39633321, year = {2024}, author = {Farias, RM and Jiang, Y and Levy, EJ and Hwang, C and Wang, J and Burton, EM and Cohen, L and Ajami, N and Wargo, JA and Daniel, CR and McQuade, JL}, title = {Diet and Immune Effects Trial (DIET)- a randomized, double-blinded dietary intervention study in patients with melanoma receiving immunotherapy.}, journal = {BMC cancer}, volume = {24}, number = {1}, pages = {1493}, pmid = {39633321}, issn = {1471-2407}, support = {R25 CA203650/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Melanoma/therapy/immunology/diet therapy ; Double-Blind Method ; *Gastrointestinal Microbiome/immunology ; Female ; Male ; Immunotherapy/methods ; Dietary Fiber/administration & dosage ; Adult ; Middle Aged ; Immune Checkpoint Inhibitors/therapeutic use ; Quality of Life ; Aged ; Diet ; Skin Neoplasms/diet therapy/immunology/therapy ; }, abstract = {BACKGROUND: Gut microbiome modulation is a promising strategy for enhancing the response to immune checkpoint blockade (ICB). Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB-naïve and refractory melanoma patients; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota, and we have previously shown that (a) habitual high dietary fiber intake is associated with an improved response to ICB and (b) fiber manipulation in mice impacts antitumor immunity. We recently demonstrated the feasibility of a controlled high-fiber dietary intervention (HFDI) conducted in melanoma survivors with excellent compliance and tolerance. Building on this, we are now conducting a phase II randomized trial of HFDI versus a healthy control diet in melanoma patients receiving ICB.

METHODS: This is a randomized, double-blind, fully controlled feeding study that will enroll 45 melanoma patients starting standard-of-care (SOC) ICB in three settings: adjuvant, neoadjuvant, and unresectable. Patients are randomized 2:1 to the HFDI (target fiber 50 g/day from whole foods) or healthy control diet (target fiber 20 g/day) stratified by BMI and cohort. All meals are prepared by the MD Anderson Bionutrition Core and are isocaloric and macronutrient-controlled. The intervention includes a 1-week equilibration period and then up to 11 weeks of diet intervention. Longitudinal blood, stool and tumor tissue (if available) are collected throughout the trial and at 12 weeks post intervention.

DISCUSSION: This DIET study is the first fully controlled feeding study among cancer patients who are actively receiving immunotherapy. The goal of the current study is to establish the effects of dietary intervention on the structure and function of the gut microbiome in patients with melanoma treated with SOC immunotherapies. The secondary endpoints include changes in systemic and tumor immunity, changes in the metabolic profile, quality of life, symptoms, disease response and immunotherapy toxicity.

TRIAL REGISTRATION: This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov, under the identifier NCT04645680. First posted 2020-11-27; last verified 2024-06.}, } @article {pmid39633000, year = {2024}, author = {Yang, D and Fu, S and Shi, Y}, title = {Gut microbiota modulation: a novel mechanism in arb-mediated hypertension treatment.}, journal = {Hypertension research : official journal of the Japanese Society of Hypertension}, volume = {}, number = {}, pages = {}, pmid = {39633000}, issn = {1348-4214}, } @article {pmid39631325, year = {2024}, author = {Zhang, Y and Liu, Q and Xie, H and Zhang, W and Lin, X and Zhang, H and Yu, H and Ma, Y and Zhang, C and Geng, H and Shi, N and Cui, L and Li, B and Li, YF}, title = {Fecal microbiota transplantation as an effective way in treating methylmercury-poisoned rats.}, journal = {The Science of the total environment}, volume = {957}, number = {}, pages = {177850}, doi = {10.1016/j.scitotenv.2024.177850}, pmid = {39631325}, issn = {1879-1026}, abstract = {Methylmercury (MeHg) can cause devastating neurotoxicity in animals and human beings. Gut microbiota dysbiosis has been found in MeHg-poisoned animals. Fecal microbiota transplantation (FMT) has been shown to improve clinical outcomes in a variety of diseases such as epilepsy, amyotrophic lateral sclerosis (ALS) and autism. The aim of this study was to investigate the effects of FMT on MeHg-poisoned rats. FMT treatment was applied to MeHg-poisoned rats for 14 days. The neurobehavior, weight changes, dopamine (DA), the total Hg and MeHg level were evaluated. Besides, the gut microbiota and metabolites change in feces were also checked. It was found that FMT helped weight gain, alleviated the neurological disorders, enhanced fecal mercury excretion and MeHg demethylation, reconstructed gut microbiome and promoted the production of gut-brain axis related-metabolites in MeHg-poisoned rats. This study elaborates on the therapeutic efficacy of FMT in treating of MeHg-poisoned rats, which sheds lights on the treatment of neurological diseases like Minamata Disease and even Parkinson's Disease.}, } @article {pmid39630000, year = {2024}, author = {Barbosa, IG and Miranda, AS and Berk, M and Teixeira, AL}, title = {The involvement of the microbiota-gut-brain axis in the pathophysiology of mood disorders and therapeutic implications.}, journal = {Expert review of neurotherapeutics}, volume = {}, number = {}, pages = {}, doi = {10.1080/14737175.2024.2438646}, pmid = {39630000}, issn = {1744-8360}, abstract = {INTRODUCTION: There is a growing body of evidence implicating gut-brain axis dysfunction in the pathophysiology of mood disorders. Accordingly, gut microbiota has become a promising target for the development of biomarkers and novel therapeutics for bipolar and depressive disorders.

AREAS COVERED: We describe the observed changes in the gut microbiota of patients with mood disorders and discuss the available studies assessing microbiota-based strategies for their treatment.

EXPERT OPINION: Microbiota-targeted interventions, such as symbiotics, prebiotics, paraprobiotics, and fecal microbiota transplants seem to attenuate the severity of depressive symptoms. The available results must be seen as preliminary and need to be replicated and/or confirmed in larger and independent studies, also considering the pathophysiological and clinical heterogeneity of mood disorders.}, } @article {pmid39629909, year = {2024}, author = {Sin, HCL and Haifer, C}, title = {Faecal transplantation: the good, the bad and the ugly.}, journal = {Internal medicine journal}, volume = {}, number = {}, pages = {}, doi = {10.1111/imj.16559}, pmid = {39629909}, issn = {1445-5994}, abstract = {There continues to be significant interest from both clinicians and patients in using faecal transplantation, as the integral role of the gut microbiome is increasingly recognised in various disease conditions, both within and beyond the gut. This Clinical Perspectives article provides an overview of existing literature, factors limiting the use of faecal microbial transplantation in clinical practice and exciting new advancements on the horizon.}, } @article {pmid39628464, year = {2024}, author = {Hu, X and Wu, Q and Huang, L and Xu, J and He, X and Wu, L}, title = {Clinical efficacy of washed microbiota transplantation on metabolic syndrome and metabolic profile of donor outer membrane vesicles.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1465499}, pmid = {39628464}, issn = {2296-861X}, abstract = {OBJECT: To clarify the clinical efficacy of washed microbiota transplantation (WMT) for metabolic syndrome (MetS), and explore the differences in the metabolic profile of bacterial outer membrane vesicles (OMVs) in donor fecal bacteria suspension received by MetS patients with good and poor outcomes, and to construct a predictive model for the efficacy of WMT for MetS using differential metabolites.

METHODS: Medical data 65 MetS patients who had completed at least 2 courses of WMT from 2017.05 to 2023.07 were collected. Fecal bacteria suspension of WMT donors were collected, and the clinical data of MetS patients treated with WMT during this period were collected as well. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared. OMVs were isolated from donor fecal bacteria suspension and off-target metabolomic sequencing was performed by Liquid Chromatograph Mass Spectrometer (LC-MS).

RESULTS: Compared with baseline, Body mass index (BMI), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) of MetS patients showed significant decreases after the 1st (short-term) and 2nd (medium-term) courses, and fasting blood glucose (FBG) also showed significant decreases after the 1st session. There was a significant difference between the Marked Response OMVs and the Moderate Response OMVs. It was showed that 960 metabolites were significantly up-regulated in Marked Response OMVs and 439 metabolites that were significantly down-regulated. The ROC model suggested that 9-carboxymethoxymethylguanine, AUC = 0.8127, 95% CI [0.6885, 0.9369], was the most potent metabolite predicting the most available metabolite for efficacy.

CONCLUSION: WMT had significant short-term and medium-term clinical efficacy in MetS. There were differences in the structure of metabolites between Marked Response OMVs and Moderate Response OMVs. The level of 9-Carboxy methoxy methylguanine in Marked Response OMVs can be a good predictor of the efficacy of WMT in the treatment of MetS.}, } @article {pmid39624719, year = {2024}, author = {Xiang, A and Chang, Y and Shi, L and Zhou, X}, title = {Mapping the relationship between alcohol use disorder and gut microbiota: a 20-year bibliometric study.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1457969}, pmid = {39624719}, issn = {1664-302X}, abstract = {BACKGROUND: Alcohol use disorder (AUD) is a psychiatric disorder that is widespread worldwide. Alcohol use is a significant contributor to the global burden of death, disability and disease. Modulation of the gut microbiota is a promising approach to improve the efficacy and minimize the adverse effects of colorectal cancer treatment. The relationship between the presence of microbes and AUD has been widely validated. However, few studies have examined this relationship using bibliometric methods. Therefore, this study analyzes the research hotspots and trends in human gut microbiology and AUD over the last two decades from a bibliometric perspective. This study aims at provide new directions for basic and clinical research in this field.

OBJECTIVE: A comprehensive discussion of the relationship between the current state of research and trends in AUD and intestinal flora.

METHODS: We collected publications from the Web of Science Core Collection database from 2003 to 2023 according to established inclusion criteria. We analyzed countries, institutions, authors, and research contributions using CiteSpace, VOSviewer, and Scimago Graphics to visualize research trends in the field.

RESULTS: A total of 2,102 publications were obtained, with a rapid increase in the number of publications since 2016. The United States and China are major contributors to the field and have established a network of partners in several countries. Five hundred ninety-five academic journals published articles on the topic. The author with the highest number of publications is Prof. Bernd Schnabl of the Department of Gastroenterology at the University of California, San Diego. In addition to "gut flora" and "AUD," high frequency words in the keyword co-occurrence network analysis included alcoholic liver disease, tryptophan metabolism, enterohepatic axis, and fecal microbial transplantation.

CONCLUSION: The results of this study provide a bibliometric analysis and visualization of key research areas in the gut microbiota and AUD over the past 20 years. The results suggest that the role of the gut microbiota in AUD and its potential mechanisms, especially therapeutic targets, should be closely monitored and could become a hot topic in the field.}, } @article {pmid39621384, year = {2024}, author = {Hoeg, A and Kuchma, N and Krane, A and Graiziger, C and Thomas, J and Kelly, CR and Khoruts, A}, title = {Oral Capsule FMT Combined With Bezlotoxumab Is a Successful Rescue Protocol Following Failure of FMT Alone in the Treatment of Recurrent C. difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000002108}, pmid = {39621384}, issn = {1539-2031}, abstract = {GOALS: Evaluate the benefit of adding bezlotoxumab to repeat fecal microbiota transplantation (FMT) in patients with recurrent Clostridioides difficile infections after the failure of FMT alone.

BACKGROUND: The initial failure of FMT in breaking the cycle of recurrent Clostridium difficile(C. difficile) infections is associated with a greater risk of subsequent failure. Our previous analysis showed that FMT failure is associated with delayed repair of fecal microbiota at 1 week after administration. We hypothesized that increasing the symptom-free interval by adding bezlotoxumab would improve the outcomes of a second FMT.

STUDY: A new rescue protocol that combines FMT with bezlotoxumab for patients who previously failed FMT alone was implemented in 2 academic medical centers. The clinical outcomes of a new protocol were captured in a prospective registry. The results were compared in a retrospective analysis of clinical outcomes of prior experience with repeat FMT by itself. All FMT preparations were standardized for dose. Bezlotoxumab administration was synchronized temporally with the second FMT to maximize its duration of action.

RESULTS: Our historical cure rate of second FMT in treatment of recurrent C. difficile infection was 48% (15/31 patients). Addition of bezlotoxumab to the second FMT resulted in a cure rate of 89% (24/27 patients).

CONCLUSIONS: Addition of bezlotoxumab markedly improved the cure rate of the second FMT following initial FMT failure. The rationale for the protocol design highlights the importance of understanding the pharmacokinetics of both bezlotoxumab and FMT. Similar principles may apply to other live biotherapeutic products that are becoming available for prevention of C. difficile infection recurrence.}, } @article {pmid39619696, year = {2024}, author = {Kang, P and Bae, GS and Jeon, E and Choi, J and Hwang, EH and Kim, G and Baek, SH and Shim, K and An, YJ and Lim, KS and Kim, Y and Oh, T and Hong, JJ and Lee, WK and Kim, SH and Koo, BS}, title = {Comprehensive effects of fecal microbiota transplantation on cynomolgus macaques across various fecal conditions.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1458923}, pmid = {39619696}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) and probiotics therapies represent key clinical options, yet their complex effects on the host are not fully understood. We evaluated the comprehensive effects of FMT using diarrheal or normal feces, as well as probiotic therapies, on multiple anatomical sites in healthy cynomolgus macaques through colonoscopy and surgery. Our research revealed that FMT led to a partial microbiome transplantation without exhibiting the donor's fecal clinical characteristics. Notably, FMT increased insulin and C-peptide levels in each animal according time series, regardless of fecal conditions. Immunologically, a reduction in neutrophil-to-lymphocyte ratio were exclusively observed in femoral veins of FMT group. In blood chemistry analyses, reductions in aspartate aminotransferase, blood urea nitrogen, and creatinine were observed in the femoral veins, while elevated levels of alanine aminotransferase and calcium were exclusively detected in the portal veins. These changes were not observed in the probiotic group. Also, short chain fatty acids were significantly higher increase in portal veins rather than femoral veins. Transcriptome analysis of liver tissues showed that metabolic pathways were primarily affected by both FMT and probiotics therapies. In summary, FMT therapy significantly influenced metabolic, immunologic and transcriptomic responses in normal macaque models, regardless of fecal conditions. Also, these macaque models, which utilize surgery and colonoscopy, serve as a human-like preclinical platform for evaluating long-term effects and anatomically specific responses to gut-targeted interventions, without the need for animal sacrifice.}, } @article {pmid39619695, year = {2024}, author = {Han, X and Zhang, BW and Zeng, W and Ma, ML and Wang, KX and Yuan, BJ and Xu, DQ and Geng, JX and Fan, CY and Gao, ZK and Arshad, M and Gao, S and Zhao, L and Liu, SL and Mu, XQ}, title = {Suppressed oncogenic molecules involved in the treatment of colorectal cancer by fecal microbiota transplantation.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1451303}, pmid = {39619695}, issn = {1664-302X}, abstract = {Dysbiosis of the intestinal microbiota is prevalent among patients with colorectal cancer (CRC). This study aims to explore the anticancer roles of the fecal microbiota in inhibiting the progression of colorectal cancer and possible mechanisms. The intestinal microbial dysbiosis in CRC mice was significantly ameliorated by fecal microbiota transplantation (FMT), as indicated by the restored ACE index and Shannon index. The diameter and number of cancerous foci were significantly decreased in CRC mice treated with FMT, along with the restoration of the intestinal mucosal structure and the lessening of the gland arrangement disorder. Key factors in oxidative stress (TXN1, TXNRD1, and HIF-1α); cell cycle regulators (IGF-1, BIRC5, CDK8, HDAC2, EGFR, and CTSL); and a critical transcription factor of the innate immune signal pathway (IRF5) were among the repressed oncogenic targets engaged in the FMT treatment of CRC. Correlation analysis revealed that their expressions were positively correlated with uncultured_bacterium_o_Mollicutes_RF39, Rikenellaceae_RC9_gut_group, and negatively correlated with Bacillus, Marvinbryantia, Roseburia, Angelakisella, Enterorhabdus, Bacteroides, Muribaculum, and genera of uncultured_bacterium_f_Eggerthellaceae, uncultured_bacterium_f_Xanthobacteraceae, Prevotellaceae_UCG-001, uncultured_bacterium_f_Erysipelotrichaceae, uncul-tured_bacterium_f_Lachnospiraceae, uncultured_bacterium_f_Ruminococcaceae, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-005, and uncultured_bacterium_f_Peptococcaceae. This study provides more evidence for the application of FMT in the clinical treatment of CRC.}, } @article {pmid39619660, year = {2024}, author = {Xi, M and Ruan, Q and Zhong, S and Li, J and Qi, W and Xie, C and Wang, X and Abuduxiku, N and Ni, J}, title = {Periodontal bacteria influence systemic diseases through the gut microbiota.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1478362}, pmid = {39619660}, issn = {2235-2988}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology ; Diabetes Mellitus/microbiology ; Alzheimer Disease/microbiology ; Bacteria/classification/genetics/pathogenicity ; Cardiovascular Diseases/microbiology ; Mouth/microbiology ; Animals ; }, abstract = {Many systemic diseases, including Alzheimer disease (AD), diabetes mellitus (DM) and cardiovascular disease, are associated with microbiota dysbiosis. The oral and intestinal microbiota are directly connected anatomically, and communicate with each other through the oral-gut microbiome axis to establish and maintain host microbial homeostasis. In addition to directly, periodontal bacteria may also be indirectly involved in the regulation of systemic health and disease through the disturbed gut. This paper provides evidence for the role of periodontal bacteria in systemic diseases via the oral-gut axis and the far-reaching implications of maintaining periodontal health in reducing the risk of many intestinal and parenteral diseases. This may provide insight into the underlying pathogenesis of many systemic diseases and the search for new preventive and therapeutic strategies.}, } @article {pmid39617896, year = {2024}, author = {Feng, R and Zhu, Q and Wang, A and Wang, H and Wang, J and Chen, P and Zhang, R and Liang, D and Teng, J and Ma, M and Ding, X and Wang, X}, title = {Effect of fecal microbiota transplantation on patients with sporadic amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled trial.}, journal = {BMC medicine}, volume = {22}, number = {1}, pages = {566}, pmid = {39617896}, issn = {1741-7015}, mesh = {Humans ; *Amyotrophic Lateral Sclerosis/therapy ; *Fecal Microbiota Transplantation/methods ; Double-Blind Method ; Female ; Male ; Middle Aged ; Aged ; Gastrointestinal Microbiome/physiology ; Treatment Outcome ; Quality of Life ; Adult ; }, abstract = {BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder marked by the progressive loss of motor neurons. Recent insights into ALS pathogenesis underscore the pivotal role of the gut microbiome, prompting an investigation into the potential therapeutic impact of fecal microbiota transplantation (FMT) on sporadic ALS patients.

METHODS: Conducted as a double-blind, placebo-controlled, parallel-group, randomized clinical trial, the study enrolled 27 participants from October 2022 to April 2023. The participants were followed up for 6 months from February 2023 to October 2023, during in-person visits at baseline, week 15, week 23, and week 35. The participants, evenly randomized, received either healthy donor FMT (FMT, n = 14) or a mixture of 0.9% saline and food coloring (E150c) as sham transplantation (placebo, n = 13). The primary outcome measured the change in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score from baseline to week 35. Secondary outcomes included changes in gastrointestinal and respiratory functions, muscle strength, autonomic function, cognition, quality of life, intestinal microbiome composition, and plasm neurofilament light chain protein (NFL). Efficacy and safety outcomes were assessed in the intention-to-treat population.

RESULTS: A total of 27 randomized patients (47% women; mean age, 67.2 years), 24 participants completed the entire study. Notably, ALSFRS-R score changes exhibited no significant differences between FMT (6.1 [SD, 3.11]) and placebo (6.41[SD, 2.73]) groups from baseline to week 35. Secondary efficacy outcomes, encompassing respiratory function, muscle strength, autonomic function, cognition, quality of life, and plasm NFL, showed no significant differences. Nevertheless, the FMT group exhibited improvements in constipation, depression, and anxiety symptoms. FMT induced a shift in gut microbiome community composition, marked by increased abundance of Bifidobacterium, which persisted until week 15 (95% CI, 0.04 to 0.28; p = 0.01). Gastrointestinal adverse events were the primary manifestations of FMT-related side effects.

CONCLUSIONS: In this clinical trial involving 27 sporadic ALS patients, FMT did not significantly slow the decline in ALSFRS-R score. Larger multicenter trials are needed to confirm the efficacy of FMT in sporadic ALS patients and to explore the underlying biological mechanisms.

TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR 2200064504.}, } @article {pmid39471905, year = {2025}, author = {Salia, S and Burke, FF and Hinks, ME and Randell, AM and Matheson, MA and Walling, SG and Swift-Gallant, A}, title = {Gut microbiota transfer from the preclinical maternal immune activation model of autism is sufficient to induce sex-specific alterations in immune response and behavioural outcomes.}, journal = {Brain, behavior, and immunity}, volume = {123}, number = {}, pages = {813-823}, doi = {10.1016/j.bbi.2024.10.030}, pmid = {39471905}, issn = {1090-2139}, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; Female ; Male ; Mice ; *Disease Models, Animal ; *Mice, Inbred C57BL ; *Autism Spectrum Disorder/immunology/microbiology ; *Behavior, Animal/physiology ; Pregnancy ; Fecal Microbiota Transplantation ; Autistic Disorder/immunology/microbiology ; Sex Characteristics ; Social Behavior ; Sex Factors ; Anxiety/immunology/microbiology ; Cytokines/metabolism ; }, abstract = {The gut microbiome plays a vital role in health and disease, including neurodevelopmental disorders like autism spectrum disorder (ASD). ASD affects 4:1 males-to-females, and sex differences are apparent in gut microbiota composition among ASD individuals and in animal models of this condition, such as the maternal immune activation (MIA) mouse model. However, few studies have included sex as a biological variable when assessing the role of gut microbiota in mediating ASD symptoms. Using the MIA model of ASD, we assessed whether gut microbiota contributes to the sex differences in the presentation of ASD-like behaviors. Gut microbiota transplantation from MIA or vehicle/control male and female mice into healthy, otherwise unmanipulated, 4-week-old C57Bl/6 mice was performed for 6 treatments over 12 days. Colonization with male, but not female, MIA microbiota was sufficient to reduce sociability, decrease microbiota diversity and increase neuroinflammation with more pronounced deficits in male recipients. Colonization with both male and female donor microbiota altered juvenile ultrasonic vocalizations and anxiety-like behavior in recipients of both sexes, and there was an accompanied change in the gut microbiota and serum cytokine IL-4 and IL-7 levels of all recipients of MIA gut microbiota. In addition to the increases in gut microbes associated with pathological states, the female donor microbiota profile also had increases in gut microbes with known neural protective effects (e.g., Lactobacillus and Rikenella). These results suggest that gut reactivity to environmental insults, such as in the MIA model, may play a role in shaping the sex disparity in ASD development.}, } @article {pmid39617011, year = {2024}, author = {Berzack, S and Galor, A}, title = {Microbiome-based therapeutics for ocular diseases.}, journal = {Clinical & experimental optometry}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/08164622.2024.2422479}, pmid = {39617011}, issn = {1444-0938}, abstract = {The relationship between the gut microbiome and ocular health has garnered increasing attention within the scientific community. Recent research has focused on the gut-eye axis, examining whether imbalances within the gut microbiome can influence the development, progression and severity of ocular diseases, including dry eye disease, uveitis, and glaucoma. Dysbiosis within the gut microbiome is linked to immune dysregulation, chronic inflammation, and epithelial barrier dysfunction, all of which contribute to ocular pathology. This review synthesises current evidence on these associations, exploring how gut microbiome alterations drive disease mechanisms. Furthermore, it examines the therapeutic potential of microbiome-targeted interventions, including antibiotics, prebiotics, probiotics, and faecal microbiota transplantation, all of which aim to restore microbial balance and modulate immune responses. As the prevalence of these conditions continues to rise, a deeper understanding of the gut-eye axis may facilitate the development of novel, targeted therapies to address unmet needs in the management of ocular diseases.}, } @article {pmid39614243, year = {2024}, author = {Gan, G and Zhang, R and Zeng, Y and Lu, B and Luo, Y and Chen, S and Lei, H and Cai, Z and Huang, X}, title = {Fecal microbiota transplantation validates the importance of gut microbiota in an ApoE[-/-] mouse model of chronic apical periodontitis-induced atherosclerosis.}, journal = {BMC oral health}, volume = {24}, number = {1}, pages = {1455}, pmid = {39614243}, issn = {1472-6831}, support = {2022QNA073//Fujian Provincial Health Technology Project/ ; 2022GGA042//Fujian Provincial Health Technology Project/ ; 2023J01709//Fujian Province Natural Science Founding of China/ ; 81970926//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Atherosclerosis/microbiology/etiology ; *Gastrointestinal Microbiome ; Mice ; *Fecal Microbiota Transplantation ; *Periapical Periodontitis/microbiology/metabolism ; *Disease Models, Animal ; *Methylamines/blood/metabolism ; Apolipoproteins E ; Male ; Mice, Inbred C57BL ; Oxygenases/metabolism ; }, abstract = {BACKGROUND: Chronic apical periodontitis (CAP) has been linked to the development of atherosclerosis, although the underlying mechanisms remain unclear. This study aimed to investigate the role of gut microbiota disruption in CAP-induced atherosclerosis development, focusing on trimethylamine N-oxide (TMAO)-related metabolites.

METHODS: The study utilized fecal microbiota transplantation (FMT) to transfer gut microbiota from mice with CAP to healthy mice. Atherosclerosis development was assessed by analyzing lesions in the aortic arch and aortic root. Serum lipid and inflammatory factor levels were measured. Composition and diversity of gut microbiota were analyzed using targeted metabolomics, with a focus on the ratio of Firmicutes to Bacteroidetes. The expression of hepatic flavin-containing monooxygenase 3 (FMO3) and serum TMAO levels were also evaluated.

RESULTS: Mice receiving gut microbiota from CAP mice showed increased atherosclerotic lesions compared to controls, without significant differences in serum lipid or inflammatory factor levels. Alterations in gut microbiota composition were observed, characterized by an increase in the Firmicutes to Bacteroidetes ratio. Peptostreptococcaceae abundance positively correlated with atherosclerosis severity, while Odoribacteraceae showed a negative correlation. No significant differences were found in hepatic FMO3 expression or serum TMAO levels.

CONCLUSIONS: The study confirms the role of gut microbiota disruption in CAP-mediated atherosclerosis development, independent of serum lipid or TMAO levels. Alterations in gut microbiota composition, particularly increased Firmicutes to Bacteroidetes ratio and specific bacterial families, were associated with atherosclerosis severity. These findings highlight the intricate interplay between gut microbiota and cardiovascular health in the context of CAP.}, } @article {pmid39612216, year = {2024}, author = {Wang, T and Luo, Y and Kong, X and Fang, L and Zhu, L and Yu, B and Zheng, P and Huang, Z and Mao, X and Jie, Y and Luo, J and Yan, H and He, J}, title = {Multiomics comparative analysis of feces AMRGs of Duroc pigs and Tibetan and the effect of fecal microbiota transplantation on AMRGs upon antibiotic exposure.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0198324}, doi = {10.1128/spectrum.01983-24}, pmid = {39612216}, issn = {2165-0497}, abstract = {UNLABELLED: Fecal matter is recognized as both a reservoir and a transmission source for various antimicrobial resistance genes (AMRGs). However, the transcriptional activity of AMRGs in swine feces is not well understood. In addition, the effect of fecal microbiota transplantation (FMT) on the excretion of AMRGs has rarely been reported. Our study explored the diversity, abundance, transcriptional activity, and bacterial hosts of AMRGs in Tibetan and Duroc pig feces using metagenomic and metatranscriptomic sequencing technologies. We discovered a significantly higher genomic abundance of AMRGs in the feces of Duroc pigs compared to Tibetan pigs (P < 0.001), although the transcript levels did not show a significant difference. The results showed that the core composition of AMRGs in pig feces varied considerably, with the most transcriptionally active AMRGs being oqxB, tetQ, Bla1, dfrA1, and amrB. Furthermore, the Firmicutes phylum is the main host of AMRGs. By transplanting fecal flora from Tibetan and Duroc pigs into the intestines of Duroc Landrace Yorkshire (DLY) piglets after acute antibiotic exposure, we found that only Tibetan pig fecal flora significantly reduced AMRGs in the feces of DLY piglets (P < 0.05). The effectiveness of Tibetan pig fecal microorganisms in removing AMRGs from DLY pig feces was mainly influenced by microbial communities, especially the Bacteroidota phylum. These findings offer valuable insights for the prevention and control of AMRG pollution.

IMPORTANCE: To the best of our knowledge, this study represents the first comprehensive analysis of antimicrobial resistance gene (AMRGs) expression in the fecal microbiota of Tibetan and Duroc pigs, employing an integrated metagenomic and metatranscriptomic approach. Our findings indicate a higher risk of AMRGs transmission in the feces of Duroc pigs compared to Tibetan pigs. Given the escalating antimicrobial resistance crisis, novel therapeutic interventions are imperative to mitigate gut colonization by pathogens and AMRGs. In this regard, we investigated the impact of fecal microbiota from Tibetan and Duroc pig sources on AMRGs excretion in Duroc Landrace Yorkshire (DLY) piglets' feces following acute antibiotic exposure. Remarkably, only fecal microbiota sourced from Tibetan pigs exhibited a reduction in AMRGs excretion in DLY piglets' feces. This underscores the significance of evaluating the presence of AMRGs within donor fecal microbiota for effective AMRGs decolonization strategies.}, } @article {pmid39608831, year = {2024}, author = {Tang, JMF and Habib, F and Rahmdil, M and Apostolou, N}, title = {Autologous faecal microbiota transplantation via double barrel stoma to treat chronic diversion colitis.}, journal = {BMJ case reports}, volume = {17}, number = {11}, pages = {}, doi = {10.1136/bcr-2024-262806}, pmid = {39608831}, issn = {1757-790X}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; *Colitis/therapy/microbiology/surgery ; *Ileostomy ; Male ; Transplantation, Autologous ; Middle Aged ; Treatment Outcome ; Chronic Disease ; Female ; }, abstract = {Diversion colitis is a common phenomenon affecting patients after defunctioning ileostomy. We present a complex case of diversion colitis where the patient was deemed unsuitable for restorative surgery due to multiple areas of stricturing in a long defunctioned colonic segment. Despite initial treatments with rectally administered topical mesalazine, butyrate enemas and topical steroid therapy, the patient remained symptomatic with rectal bleeding and mucus discharge. Furthermore, the appearance of colitis could be appreciated on endoscopy and radiological investigations with changes in histology consistent with moderate-severe diversion colitis. This article describes our experience in the use of autologous faecal transplant administered via the efferent loop of a double-barrel ileostomy to successfully treat diversion colitis refractory to standard topical therapy.}, } @article {pmid39607612, year = {2024}, author = {Qasem, HH and El-Sayed, WM}, title = {The bacterial microbiome and cancer: development, diagnosis, treatment, and future directions.}, journal = {Clinical and experimental medicine}, volume = {25}, number = {1}, pages = {12}, pmid = {39607612}, issn = {1591-9528}, mesh = {Humans ; *Neoplasms/therapy/microbiology/diagnosis ; *Dysbiosis ; *Microbiota ; Bacteria/classification/genetics ; Probiotics/therapeutic use ; }, abstract = {The term "microbiome" refers to the collection of bacterial species that reside in the human body's tissues. Sometimes, it is used to refer to all microbial entities (bacteria, viruses, fungi, and others) which colonize the human body. It is now generally acknowledged that the microbiome plays a critical role in the host's physiological processes and general well-being. Changes in the structure and/or function of the microbiome (dysbiosis) are linked to the development of many diseases including cancer. The claim that because of their negatively charged membrane, cancer cells are more vulnerable to some bacteria than normal cells and that is how the link between these bacteria and cancer evolved has been refuted. Furthermore, the relationship between the microbiome and cancer is more evident in the emerging field of cancer immunotherapy. In this narrative review, we detailed the correlation between the presence/absence of specific bacterial species and the development, diagnosis, prognosis, and treatment of some types of cancer including colorectal, lung, breast, and prostate cancer. In addition, we discussed the mechanisms of microbiome-cancer interactions including genotoxin production, the role of free radicals, modification of signaling pathways in host cells, immune modulation, and modulation of drug metabolism by microbiome. Future directions and clinical application of microbiome in the early detection, prognosis, and treatment of cancer emphasizing on the role of fecal transplantation, probiotics, prebiotics, and microbiome biomarkers were also considered.}, } @article {pmid39606629, year = {2024}, author = {Zhang, Z and Yang, M and Zhou, T and Chen, Y and Zhou, X and Long, K}, title = {Emerging trends and hotspots in intestinal microbiota research in sepsis: bibliometric analysis.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1510463}, pmid = {39606629}, issn = {2296-858X}, abstract = {BACKGROUND: The association between the gut microbiota and sepsis has garnered attention in the field of intestinal research in sepsis. This study utilizes bibliometric methods to visualize and analyze the literature on gut microbiota research in sepsis from 2011 to 2024, providing a scientific foundation for research directions and key issues in this domain.

METHODS: Original articles and reviews of gut microbiota research in sepsis, which published in English between 2011 and 2024, were obtained from the Web of Science Core Collection on June 21, 2024. Python, VOSviewer, and CiteSpace software were used for the visual analysis of the retrieved data.

RESULTS: A total of 1,031 articles were analyzed, originating from 72 countries or regions, 1,614 research institutions, and 6,541 authors. The articles were published in 434 different journals, covering 89 different research fields. The number of publications and citations in this research area showed a significant growth trend from 2011 to 2024, with China, the United States, and the United Kingdom being the main research forces. Asada Leelahavanichkul from Thailand was identified as the most prolific author, making him the most authoritative expert in this field. "Nutrients" had the highest number of publications, while "Frontiers in Cellular and Infection Microbiology," "Frontiers in Immunology" and "the International Journal of Molecular Sciences" have shown increasing attention to this field in the past 2 years. Author keywords appearing more than 100 times included "gut microbiota (GM)," "sepsis" and "microbiota." Finally, this study identified "lipopolysaccharides (LPS)," "short-chain fatty acids (SCFAs)," "probiotics," "fecal microbiota transplantation (FMT)" and "gut-liver axis" as the research hotspots and potential frontier directions in this field.

CONCLUSION: This bibliometric study summarizes current important perspectives and offers comprehensive guidance between sepsis and intestinal microbiota, which may help researchers choose the most appropriate research directions.}, } @article {pmid39605286, year = {2024}, author = {Yerushalmy-Feler, A and Spencer, EA and Dolinger, MT and Suskind, DL and Mitrova, K and Hradsky, O and Conrad, MA and Kelsen, JR and Uhlig, HH and Tzivinikos, C and Ancona, S and Wlazlo, M and Hackl, L and Shouval, DS and Bramuzzo, M and Urlep, D and Olbjorn, C and D'Arcangelo, G and Pujol-Muncunill, G and Yogev, D and Kang, B and Gasparetto, M and Rungø, C and Kolho, KL and Hojsak, I and Norsa, L and Rinawi, F and Sansotta, N and Magen Rimon, R and Granot, M and Scarallo, L and Trindade, E and Velasco Rodríguez-Belvís, M and Turner, D and Cohen, S}, title = {Upadacitinib for Induction of Remission in Pediatric Ulcerative Colitis: An International Multi‑center Study.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjae182}, pmid = {39605286}, issn = {1876-4479}, abstract = {BACKGROUND AND AIMS: Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U.

METHODS: In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical and laboratory data as well as adverse events (AEs) were recorded at week 8 post induction.

RESULTS: One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. AEs were recorded in 37 children, including one serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n=13), acne (n=12), and infections (n=10, five of whom with herpes viruses).

CONCLUSION: Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.}, } @article {pmid39605077, year = {2024}, author = {Zou, P and Bi, Y and Tong, Z and Wu, T and Li, Q and Wang, K and Fan, Y and Zhao, D and Wang, X and Shao, H and Huang, H and Ma, S and Qian, Y and Zhang, G and Liu, X and Jin, Q and Ru, Q and Qian, Z and Sun, W and Chen, Q and You, L and Wang, F and Zhang, X and Qiu, Z and Lin, Q and Lv, J and Zhang, Y and Geng, J and Mao, R and Liu, J and Zheng, Y and Ding, F and Wang, H and Gao, H}, title = {Comparisons of efficacy and safety of 400 or 800 ml bacterial count fecal microbiota transplantation in the treatment of recurrent hepatic encephalopathy: a multicenter prospective randomized controlled trial in China.}, journal = {Trials}, volume = {25}, number = {1}, pages = {799}, pmid = {39605077}, issn = {1745-6215}, mesh = {Humans ; *Hepatic Encephalopathy/therapy/microbiology ; Prospective Studies ; *Fecal Microbiota Transplantation/adverse effects ; China ; *Quality of Life ; Treatment Outcome ; *Recurrence ; Multicenter Studies as Topic ; Male ; Bacterial Load ; Randomized Controlled Trials as Topic ; Middle Aged ; Adult ; Female ; }, abstract = {BACKGROUND: Hepatic encephalopathy (HE) represents a critical complications of end-stage liver disease, serving as an independent predictor of mortality among patients with cirrhosis. Despite effective treatment with rifaximin, some patients with HE still progress to recurrent episodes, posing a significant therapeutic challenge. Recurrent HE is defined as experiencing two or more episodes within a 6-month period. Previous research has suggested that FMT may emerge as a promising treatment for recurrent HE. However, there remains a critical need to explore the optimal dosage. This trial aims to abscess the efficacy and safety of two FMT dosages: 800 ml or 400 ml total bacterial count, including mortality and quality of life.

METHODS: This multicenter, prospective, randomized controlled trial will enroll 100 eligible patients from 31 hospitals in China. Participants will be randomly assigned in a 1:1 ratio to either the high-dose group (800 ml total bacterial count) or the low-dose group (400 ml total bacterial count). The primary objective is to assess the efficacy and safety of both dosages on outcomes at 24 and 48 weeks, including mortality and quality of life.

DISCUSSION: If either or both dosages of FMT demonstrate safe and effective treatment of recurrent HE, leading to improve quality of life and survival at 24 and 48 weeks, this trial would address a significant gap in the management of recurrent HE, carrying innovative and clinically significant implications.

TRIAL REGISTRATION: NCT05669651 on ClinicalTrials.gov. Registered on 29 December 2022. CHiCTR2200067135 on China Registered Clinical Trial Registration Center. Registered on 27 December 2022.}, } @article {pmid39269772, year = {2024}, author = {Rahal, Z and Liu, Y and Peng, F and Yang, S and Jamal, MA and Sharma, M and Moreno, H and Damania, AV and Wong, MC and Ross, MC and Sinjab, A and Zhou, T and Chen, M and Tarifa Reischle, I and Feng, J and Chukwuocha, C and Tang, E and Abaya, C and Lim, JK and Leung, CH and Lin, HY and Deboever, N and Lee, JJ and Sepesi, B and Gibbons, DL and Wargo, JA and Fujimoto, J and Wang, L and Petrosino, JF and Ajami, NJ and Jenq, RR and Moghaddam, SJ and Cascone, T and Hoffman, K and Kadara, H}, title = {Inflammation Mediated by Gut Microbiome Alterations Promotes Lung Cancer Development and an Immunosuppressed Tumor Microenvironment.}, journal = {Cancer immunology research}, volume = {12}, number = {12}, pages = {1736-1752}, doi = {10.1158/2326-6066.CIR-24-0469}, pmid = {39269772}, issn = {2326-6074}, support = {R01 CA205608/CA/NCI NIH HHS/United States ; R01 CA248731/CA/NCI NIH HHS/United States ; R01CA248731//National Cancer Institute (NCI)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/immunology ; *Tumor Microenvironment/immunology ; *Lung Neoplasms/immunology/microbiology/pathology ; Mice ; Humans ; *Inflammation/immunology ; Adenocarcinoma of Lung/immunology/microbiology/pathology ; Lipocalin-2/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Mice, Knockout ; }, abstract = {Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely coupled with tobacco-associated lung adenocarcinoma in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice exacerbates protumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on lung adenocarcinoma development remains poorly understood. In this study, we investigated the role of gut microbiome changes in lung adenocarcinoma development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of proinflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagated systemically, exerting immunosuppression within the tumor microenvironment, augmenting tumor growth through an IL6-dependent mechanism and dampening response to immunotherapy. Corroborating our preclinical findings, we found that patients with lung adenocarcinoma with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in lung adenocarcinoma and present new potential targets for interception and therapy.}, } @article {pmid39604726, year = {2024}, author = {Chen-Liaw, A and Aggarwala, V and Mogno, I and Haifer, C and Li, Z and Eggers, J and Helmus, D and Hart, A and Wehkamp, J and Lamousé-Smith, ESN and Kerby, RL and Rey, FE and Colombel, JF and Kamm, MA and Olle, B and Norman, JM and Menon, R and Watson, AR and Crossett, E and Terveer, EM and Keller, JJ and Borody, TJ and Grinspan, A and Paramsothy, S and Kaakoush, NO and Dubinsky, MC and Faith, JJ}, title = {Gut microbiota strain richness is species specific and affects engraftment.}, journal = {Nature}, volume = {}, number = {}, pages = {}, pmid = {39604726}, issn = {1476-4687}, abstract = {Despite the fundamental role of bacterial strain variation in gut microbiota function[1-6], the number of unique strains of a species that can stably colonize the human intestine is still unknown for almost all species. Here we determine the strain richness (SR) of common gut species using thousands of sequenced bacterial isolates with paired metagenomes. We show that SR varies across species, is transferable by faecal microbiota transplantation, and is uniquely low in the gut compared with soil and lake environments. Active therapeutic administration of supraphysiologic numbers of strains per species increases recipient SR, which then converges back to the population average after dosing is ceased. Stratifying engraftment outcomes by high or low SR shows that SR predicts microbial addition or replacement in faecal transplants. Together, these results indicate that properties of the gut ecosystem govern the number of strains of each species colonizing the gut and thereby influence strain addition and replacement in faecal microbiota transplantation and defined live biotherapeutic products.}, } @article {pmid39604623, year = {2024}, author = {Procházková, N and Laursen, MF and La Barbera, G and Tsekitsidi, E and Jørgensen, MS and Rasmussen, MA and Raes, J and Licht, TR and Dragsted, LO and Roager, HM}, title = {Gut physiology and environment explain variations in human gut microbiome composition and metabolism.}, journal = {Nature microbiology}, volume = {9}, number = {12}, pages = {3210-3225}, pmid = {39604623}, issn = {2058-5276}, support = {NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NNF19OC0056246//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Feces/microbiology ; Adult ; Hydrogen-Ion Concentration ; Male ; Female ; Bacteria/classification/metabolism/genetics/isolation & purification ; Gastrointestinal Transit/physiology ; Young Adult ; Middle Aged ; Diet ; Fermentation ; Gastrointestinal Tract/microbiology/metabolism ; Methane/metabolism ; Healthy Volunteers ; }, abstract = {The human gut microbiome is highly personal. However, the contribution of gut physiology and environment to variations in the gut microbiome remains understudied. Here we performed an observational trial using multi-omics to profile microbiome composition and metabolism in 61 healthy adults for 9 consecutive days. We assessed day-to-day changes in gut environmental factors and measured whole-gut and segmental intestinal transit time and pH using a wireless motility capsule in a subset of 50 individuals. We observed substantial daily fluctuations, with intra-individual variations in gut microbiome and metabolism associated with changes in stool moisture and faecal pH, and inter-individual variations accounted for by whole-gut and segmental transit times and pH. Metabolites derived from microbial carbohydrate fermentation correlated negatively with the gut passage time and pH, while proteolytic metabolites and breath methane showed a positive correlation. Finally, we identified associations between segmental transit time/pH and coffee-, diet-, host- and microbial-derived metabolites. Our work suggests that gut physiology and environment are key to understanding the individuality of the human gut microbial composition and metabolism.}, } @article {pmid39604327, year = {2024}, author = {Saeed, H and Díaz, LA and Gil-Gómez, A and Burton, J and Bajaj, J and Romero-Gomez, M and Arrese, M and Arab, JP and Khan, MQ}, title = {Microbiome-Centered Therapies for the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Clinical and molecular hepatology}, volume = {}, number = {}, pages = {}, doi = {10.3350/cmh.2024.0811}, pmid = {39604327}, issn = {2287-285X}, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant global health issue, affecting over 30% of the population worldwide due to the rising prevalence of metabolic risk factors such as obesity and type 2 diabetes mellitus (T2DM). This spectrum of liver disease ranges from isolated steatosis to more severe forms such as steatohepatitis, fibrosis, and cirrhosis. Recent studies highlight the role of gut microbiota in MASLD pathogenesis, showing that dysbiosis significantly impacts metabolic health and the progression of liver disease. This review critically evaluates current microbiome-centered therapies in MASLD management, including prebiotics, probiotics, synbiotics, fecal microbiota transplantation (FMT), and emerging therapies such as engineered bacteria and bacteriophage therapy. We explore the scientific rationale, clinical evidence, and potential mechanisms by which these interventions influence MASLD. The gut-liver axis is crucial in MASLD, with notable changes in microbiome composition linked to disease progression. For instance, specific microbial profiles and reduced alpha diversity are associated with MASLD severity. Therapeutic strategies targeting the microbiome could modulate disease progression by improving gut permeability, reducing endotoxin-producing bacteria, and altering bile acid metabolism. Although promising, these therapies require further research to fully understand their mechanisms and optimize their efficacy. This review integrates findings from clinical trials and experimental studies, providing a comprehensive overview of microbiome-centered therapies' potential in managing MASLD. Future research should focus on personalized strategies, utilizing microbiome features, blood metabolites, and customized dietary interventions to enhance the effectiveness of these therapies.}, } @article {pmid39603188, year = {2024}, author = {Xie, C and Liang, Q and Cheng, J and Yuan, Y and Xie, L and Ji, J}, title = {Transplantation of fecal microbiota from low to high residual feed intake chickens: Impacts on RFI, microbial community and metabolites profiles.}, journal = {Poultry science}, volume = {104}, number = {1}, pages = {104567}, doi = {10.1016/j.psj.2024.104567}, pmid = {39603188}, issn = {1525-3171}, abstract = {Improving feed efficiency is vital to bolster profitability and sustainability in poultry production. Although several studies have established links between gut microbiota and feed efficiency, the direct effects remain unclear. In this study, two distinct lines of Huiyang bearded chickens, exhibiting significant differences in residual feed intake (RFI), were developed after 15 generations of selective breeding. Fecal microbiota transplantation (FMT) from low RFI (LRFI) chickens to high RFI (HRFI) chickens resulted in a reduction trend in RFI, decreasing from 5.65 to 4.49 in the HRFI recipient chickens (HFMT). Microbiota composition and functional profiles in LRFI and HFMT chickens formed a distinct cluster compared to HRFI chickens. Using 16S rDNA sequencing and RandomForest analysis, Slackia, Peptococcus, Blautia, and Dorea were identified as key microbial markers associated with feed efficiency. Additionally, untargeted metabolomics identified common differential metabolites between HFMT and LRFI vs. HRFI groups. Correlation analysis showed significant correlations between these microbial markers and differential metabolites. These findings provide a foundation for microbiome-based strategies to improve feed efficiency in poultry.}, } @article {pmid39600755, year = {2024}, author = {Castro-Vidal, ZA and Mathew, F and Ibrahim, AA and Shubhangi, F and Cherian, RR and Choi, HK and Begum, A and Ravula, HK and Giri, H}, title = {The Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Various Neurocognitive Disorders.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72451}, pmid = {39600755}, issn = {2168-8184}, abstract = {This review explores the critical role of the human microbiome in neurological and neurodegenerative disorders, focusing on gut-brain axis dysfunction caused by dysbiosis, an imbalance in gut bacteria. Dysbiosis has been linked to diseases such as Alzheimer's disease, Parkinson's disease (PD), multiple sclerosis (MS), and stroke. The gut microbiome influences the central nervous system (CNS) through signaling molecules, including short-chain fatty acids, neurotransmitters, and metabolites, impacting brain health and disease progression. Emerging therapies, such as fecal microbiota transplantation (FMT), have shown promise in restoring microbial balance and alleviating neurological symptoms, especially in Alzheimer's and PD. Additionally, nutritional interventions such as probiotics, prebiotics, and specialized diets are being investigated for their ability to modify gut microbiota and improve patient outcomes. This review highlights the therapeutic potential of gut microbiota modulation but emphasizes the need for further clinical trials to establish the safety and efficacy of these interventions in neurological and mental health disorders.}, } @article {pmid39600698, year = {2024}, author = {Liu, X and Li, B and Liang, L and Han, J and Mai, S and Liu, L}, title = {From microbes to medicine: harnessing the power of the microbiome in esophageal cancer.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1450927}, pmid = {39600698}, issn = {1664-3224}, mesh = {Humans ; *Esophageal Neoplasms/therapy/microbiology/immunology ; *Dysbiosis/therapy/microbiology ; *Gastrointestinal Microbiome/immunology ; Animals ; Probiotics/therapeutic use ; Microbiota/immunology ; }, abstract = {Esophageal cancer (EC) is a malignancy with a high incidence and poor prognosis, significantly influenced by dysbiosis in the esophageal, oral, and gut microbiota. This review provides an overview of the roles of microbiota dysbiosis in EC pathogenesis, emphasizing their impact on tumor progression, drug efficacy, biomarker discovery, and therapeutic interventions. Lifestyle factors like smoking, alcohol consumption, and betel nut use are major contributors to dysbiosis and EC development. Recent studies utilizing advanced sequencing have revealed complex interactions between microbiota dysbiosis and EC, with oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promoting inflammation and suppressing immune responses, thereby driving carcinogenesis. Altered esophageal microbiota, characterized by reduced beneficial bacteria and increased pathogenic species, further exacerbate local inflammation and tumor growth. Gut microbiota dysbiosis also affects systemic immunity, influencing chemotherapy and immunotherapy efficacy, with certain bacteria enhancing or inhibiting treatment responses. Microbiota composition shows potential as a non-invasive biomarker for early detection, prognosis, and personalized therapy. Novel therapeutic strategies targeting the microbiota-such as probiotics, dietary modifications, and fecal microbiota transplantation-offer promising avenues to restore balance and improve treatment efficacy, potentially enhancing patient outcomes. Integrating microbiome-focused strategies into current therapeutic frameworks could improve EC management, reduce adverse effects, and enhance patient survival. These findings highlight the need for further research into microbiota-tumor interactions and microbial interventions to transform EC treatment and prevention, particularly in cases of late-stage diagnosis and poor treatment response.}, } @article {pmid39600557, year = {2024}, author = {Wohl, P and Krausova, A and Wohl, P and Fabian, O and Bajer, L and Brezina, J and Drastich, P and Hlavaty, M and Novotna, P and Kahle, M and Spicak, J and Gregor, M}, title = {Limited validity of Mayo endoscopic subscore in ulcerative colitis with concomitant primary sclerosing cholangitis.}, journal = {World journal of gastrointestinal endoscopy}, volume = {16}, number = {11}, pages = {607-616}, pmid = {39600557}, issn = {1948-5190}, abstract = {BACKGROUND: Ulcerative colitis (UC) with concomitant primary sclerosing cholangitis (PSC) represents a distinct disease entity (PSC-UC). Mayo endoscopic subscore (MES) is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear.

AIM: To assess the accuracy of MES in UC and PSC-UC patients, we performed histological scoring using Nancy histological index (NHI).

METHODS: MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy. NHI and inflammation were evaluated in biopsies from the cecum, rectum, and terminal ileum. In addition, perinuclear anti-neutrophil cytoplasmic antibodies, fecal calprotectin, body mass index, and other relevant clinical characteristics were collected.

RESULTS: The median MES and NHI were similar for UC patients (MES grade 2 and NHI grade 2 in the rectum) but were different for PSC-UC patients (MES grade 0 and NHI grade 2 in the cecum). There was a correlation between MES and NHI for UC patients (Spearman's r = 0.40, P = 0.029) but not for PSC-UC patients. Histopathological examination revealed persistent microscopic inflammation in 88% of PSC-UC patients with MES grade 0 (46% of all PSC-UC patients). Moreover, MES overestimated the severity of active inflammation in an additional 11% of PSC-UC patients.

CONCLUSION: MES insufficiently identifies microscopic inflammation in PSC-UC. This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.}, } @article {pmid39599742, year = {2024}, author = {Al-Habsi, N and Al-Khalili, M and Haque, SA and Elias, M and Olqi, NA and Al Uraimi, T}, title = {Health Benefits of Prebiotics, Probiotics, Synbiotics, and Postbiotics.}, journal = {Nutrients}, volume = {16}, number = {22}, pages = {}, pmid = {39599742}, issn = {2072-6643}, support = {(SR/AGR/Food/23/01)//His Majesty Trust Funds/ ; }, mesh = {Humans ; *Prebiotics/administration & dosage ; *Probiotics/administration & dosage ; *Synbiotics/administration & dosage ; *Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; Functional Food ; }, abstract = {The trillions of microbes that constitute the human gut microbiome play a crucial role in digestive health, immune response regulation, and psychological wellness. Maintaining gut microbiota is essential as metabolic diseases are associated with it. Functional food ingredients potentially improving gut health include prebiotics, probiotics, synbiotics, and postbiotics (PPSPs). While probiotics are living bacteria that provide health advantages when ingested sufficiently, prebiotics are non-digestible carbohydrates that support good gut bacteria. Synbiotics work together to improve immunity and intestinal health by combining probiotics and prebiotics. Postbiotics have also demonstrated numerous health advantages, such as bioactive molecules created during probiotic fermentation. According to a recent study, PPSPs can regulate the synthesis of metabolites, improve the integrity of the intestinal barrier, and change the gut microbiota composition to control metabolic illnesses. Additionally, the use of fecal microbiota transplantation (FMT) highlights the potential for restoring gut health through microbiota modulation, reinforcing the benefits of PPSPs in enhancing overall well-being. Research has shown that PPSPs provide several health benefits, such as improved immunological function, alleviation of symptoms associated with irritable bowel disease (IBD), decreased severity of allergies, and antibacterial and anti-inflammatory effects. Despite encouraging results, many unanswered questions remain about the scope of PPSPs' health advantages. Extensive research is required to fully realize the potential of these functional food components in enhancing human health and well-being. Effective therapeutic and prophylactic measures require further investigation into the roles of PPSPs, specifically their immune-system-modulating, cholesterol-lowering, antioxidant, and anti-inflammatory characteristics.}, } @article {pmid39598283, year = {2024}, author = {Mederle, AL and Dima, M and Stoicescu, ER and Căpăstraru, BF and Levai, CM and Hațegan, OA and Maghiari, AL}, title = {Impact of Gut Microbiome Interventions on Glucose and Lipid Metabolism in Metabolic Diseases: A Systematic Review and Meta-Analysis.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {11}, pages = {}, pmid = {39598283}, issn = {2075-1729}, abstract = {BACKGROUND: The gut microbiome is increasingly recognized as a key player in metabolic health, influencing glucose and lipid metabolism through various mechanisms. However, the efficacy of gut microbiota-targeted interventions, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and diet-based treatments, remains unclear for specific metabolic outcomes. In this study, the aim was to evaluate the impact of these interventions on the glucose and lipid parameters in individuals with metabolic diseases such as diabetes mellitus (DM), obesity, and metabolic syndrome.

METHODS: This systematic review and meta-analysis included 41 randomized controlled trials that investigated the effects of gut microbiota-targeted treatments on metabolic parameters such as fasting glucose, glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. A comprehensive search was conducted using databases like PubMed, Google Scholar, and Scopus, focusing on interventions targeting the gut microbiota. A meta-analysis was performed using random-effects models, with effect sizes calculated for each outcome. Risk of bias was assessed using the Cochrane Risk of Bias tool.

RESULTS: Gut microbiota-targeted interventions significantly reduced fasting glucose, HbA1c, HOMA-IR, total cholesterol, LDL-C, and triglycerides, with moderate heterogeneity observed across studies. The interventions also led to modest increases in HDL-C levels. Probiotic and synbiotic interventions showed the most consistent benefits in improving both glucose and lipid profiles, while FMT yielded mixed results. Short-term interventions showed rapid microbial shifts but less pronounced metabolic improvements, whereas longer-term interventions had more substantial metabolic benefits.

CONCLUSIONS: In this study, it is demonstrated that gut microbiota-targeted interventions can improve key metabolic outcomes, offering a potential therapeutic strategy for managing metabolic diseases. However, the effectiveness of these interventions varies depending on the type, duration, and population characteristics, highlighting the need for further long-term studies to assess the sustained effects of microbiota modulation on metabolic health.}, } @article {pmid39597729, year = {2024}, author = {Alexandrescu, L and Suceveanu, AP and Stanigut, AM and Tofolean, DE and Axelerad, AD and Iordache, IE and Herlo, A and Nelson Twakor, A and Nicoara, AD and Tocia, C and Dumitru, A and Dumitru, E and Condur, LM and Aftenie, CF and Tofolean, IT}, title = {Intestinal Insights: The Gut Microbiome's Role in Atherosclerotic Disease: A Narrative Review.}, journal = {Microorganisms}, volume = {12}, number = {11}, pages = {}, pmid = {39597729}, issn = {2076-2607}, abstract = {Recent advances have highlighted the gut microbiota as a significant contributor to the development and progression of atherosclerosis, which is an inflammatory cardiovascular disease (CVD) characterized by plaque buildup within arterial walls. The gut microbiota, consisting of a diverse collection of microorganisms, impacts the host's metabolism, immune responses, and lipid processing, all of which contribute to atherosclerosis. This review explores the complex mechanisms through which gut dysbiosis promotes atherogenesis. We emphasize the potential of integrating microbiota modulation with traditional cardiovascular care, offering a holistic approach to managing atherosclerosis. Important pathways involve the translocation of inflammatory microbial components, modulation of lipid metabolism through metabolites such as trimethylamine-N-oxide (TMAO), and the production of short-chain fatty acids (SCFAs) that influence vascular health. Studies reveal distinct microbial profiles in atherosclerosis patients, with increased pathogenic bacteria (Megamonas, Veillonella, Streptococcus) and reduced anti-inflammatory genera (Bifidobacterium, Roseburia), highlighting the potential of these profiles as biomarkers and therapeutic targets. Probiotics are live microorganisms that have health benefits on the host. Prebiotics are non-digestible dietary fibers that stimulate the growth and activity of beneficial gut bacteria. Interventions targeting microbiota, such as probiotics, prebiotics, dietary modifications, and faecal microbiota transplantation (FMT), present effective approaches for restoring microbial equilibrium and justifying cardiovascular risk. Future research should focus on longitudinal, multi-omics studies to clarify causal links and refine therapeutic applications.}, } @article {pmid39597606, year = {2024}, author = {Qiao, Y and Feng, Q and Wang, Q and Zhao, Q and Zhu, S and Zhao, F and Wang, Z and Zhang, R and Wang, J and Yu, Y and Han, H and Dong, H}, title = {Alteration in the Gut Microbiota of Chickens Resistant to Eimeria tenella Infection.}, journal = {Microorganisms}, volume = {12}, number = {11}, pages = {}, pmid = {39597606}, issn = {2076-2607}, support = {Grant No. 2023YFD18024//National Key Research and Development Program of China/ ; XZ202401ZY0052//Key Research and Development of Science and Technology Plan in Tibet Autonomous Region/ ; Grant No. 32373038//National Natural Science Foundation of China/ ; NPRC-2019-194-30//National Parasitic Resources Center/ ; }, abstract = {Avian coccidiosis, caused by several species of Eimeria, is a widespread and economically important poultry disease that inflicts severe losses in the poultry industry. Understanding the interplay between Eimeria and gut microbiota is critical for controlling coccidiosis and developing innovative treatments to ensure good poultry health. In the present study, chickens were immunized six times with a low dose of Eimeria tenella, resulting in complete immunity against Eimeria infection. The results of fecal microbiota transplantation showed that the gut microbiota of immunized chickens induced a certain degree of resistance to coccidial infection. To investigate the types of intestinal microbiota involved in the development of resistance to Eimeria, the intestinal contents and fecal samples from both immunized and unimmunized groups were collected for 16S rRNA gene sequencing. The results showed that, at the genus level, the abundance of the Eubacterium coprostanoligenes group, Erysipelatoclostridium, Shuttleworthia, and Colidextribacter was significantly increased in the intestinal content of immunized chickens, whereas the abundance of Eisenbergiella was significantly decreased. In fecal samples, the abundance of Clostridiaceae and Muribaculaceae significantly increased, whereas that of Bacillales significantly decreased. These findings will help to elucidate the interactions between E. tenella and the gut microbiota of chickens, providing a basis for isolating E. tenella-resistant strains from the gut microbiome and developing new vaccines against coccidiosis.}, } @article {pmid39597084, year = {2024}, author = {Ko, Y and Alaedin, S and Fernando, D and Zhou, J and Ho, V}, title = {A Review of Fecal Microbiota Transplantation in Children-Exploring Its Role in the Treatment of Inflammatory Bowel Diseases.}, journal = {Medicina (Kaunas, Lithuania)}, volume = {60}, number = {11}, pages = {}, pmid = {39597084}, issn = {1648-9144}, mesh = {Humans ; *Fecal Microbiota Transplantation/methods ; Child ; *Inflammatory Bowel Diseases/therapy/microbiology ; Gastrointestinal Microbiome ; Treatment Outcome ; }, abstract = {Background and Objectives: There is an increasing use of fecal matter transplantation (FMT) worldwide as research into the impact of the gut microbiome in various disease states is growing. FMT is the transfer of stool from a healthy human donor to a patient for the purpose of restoring intestinal dysbiosis. This review will assess the efficacy and safety of FMT in the treatment of pediatric inflammatory bowel diseases (IBDs) and explore the future directions of the use of FMT in children. Materials and Methods: A systematic review was performed where a literature search of publications published prior to 15 September 2023 was performed. Efficacy outcomes and safety data as well as microbiome analysis were reviewed from the studies where applicable. Results: Nine studies on UC and two studies on CD satisfied eligibility criteria and individually analysed. Most of the studies provided microbiome analyses. Conclusions: FMT is a safe treatment for paediatric IBD, and is shown to be effective in inducing clinical response by some studies. However the lack of randomized controlled trials limited the results of our study.}, } @article {pmid39596154, year = {2024}, author = {Sevcikova, A and Martiniakova, M and Omelka, R and Stevurkova, V and Ciernikova, S}, title = {The Link Between the Gut Microbiome and Bone Metastasis.}, journal = {International journal of molecular sciences}, volume = {25}, number = {22}, pages = {}, pmid = {39596154}, issn = {1422-0067}, support = {2/0069/22//Scientific Grant Agency of the Ministry of Education, Research, Development, and Youth of the Slovak Republic and Slovak Academy of Sciences (VEGA)/ ; 1/0071/24//Scientific Grant Agency of the Ministry of Education, Research, Development, and Youth of the Slovak Republic and Slovak Academy of Sciences/ ; KEGA 034UKF-4/2022//Ministry of Education, Research, Development, and Youth of the Slovak Republic/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Bone Neoplasms/secondary/microbiology ; Animals ; Dysbiosis/microbiology ; Probiotics ; }, abstract = {The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host's immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors and extensive blood flow, especially affecting patients with thyroid, prostate, breast, lung, and kidney cancers, where bone metastases severely reduce the quality of life. While the involvement of the gut microbiome in bone metastasis formation is still being explored, proposed mechanisms suggest that intestinal dysbiosis may alter the bone microenvironment via the gut-immune-bone axis, fostering a premetastatic niche and immunosuppressive milieu suitable for cancer cell colonization. Disruption in the delicate balance of bone modeling and remodeling may further create a favorable environment for metastatic growth. This review focuses on the link between beneficial or dysbiotic microbiome composition and bone homeostasis, as well as the role of the microbiome in bone metastasis development. It also provides an overview of clinical trials evaluating the impact of gut microbial community structure on bone parameters across various conditions or health-related issues. Dietary interventions and microbiota modulation via probiotics, prebiotics, and fecal microbiota transplantation help support bone health and might offer promising strategies for addressing bone-related complications in cancer.}, } @article {pmid39595097, year = {2024}, author = {López-Tenorio, II and Aguilar-Villegas, ÓR and Espinoza-Palacios, Y and Segura-Real, L and Peña-Aparicio, B and Amedei, A and Aguirre-García, MM}, title = {Primary Prevention Strategy for Non-Communicable Diseases (NCDs) and Their Risk Factors: The Role of Intestinal Microbiota.}, journal = {Biomedicines}, volume = {12}, number = {11}, pages = {}, pmid = {39595097}, issn = {2227-9059}, support = {CF 2023-2024 -734//Consejo Nacional de Humanidades, Ciencias y Tecnologías/ ; IN21222//Universidad Nacional Autónoma de México/ ; }, abstract = {Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide. These conditions have numerous health consequences and significantly impact patients' lifestyles. Effective long-term treatment is essential since NCDs are irreversible. Therefore, primary healthcare must be both exclusive and of the highest quality, ensuring comprehensive care. The primary goal should be to improve quality of life with a focus on patients, families, and communities, as most of these diseases can be prevented and controlled, although not cured. Several factors have been linked to individual health, including social, cultural, and economic aspects, lifestyle, and certain environmental factors, including work, that can have positive or negative effects. More of these variables may contribute to the onset of NCDs, which are defined by their chronic nature, propensity for prolongation, and generally slow rate of progression. Examples of NCDs include hypertension, type 2 diabetes (T2D), dyslipidemia, and fatty liver disease linked to metabolic dysfunction. The onset of these diseases has been associated with an imbalance in certain microbial niches, such as the gut, which hosts billions of microorganisms performing multiple metabolic functions, such as the production of metabolites like bile acids (BAs), short-chain fatty acids (SCFAs), and trimethylamine N-oxide (TMAO). Therefore, lifestyle changes and personal habits can significantly impact the gut microbiota (GM), potentially preventing chronic diseases associated with metabolism. NCDs are highly prevalent worldwide, prompting increased attention to strategies for modifying the intestinal microbiota (IM). Approaches such as probiotics, prebiotics, synbiotics, and fecal transplantation (FMT) have demonstrated improvements in the quality of life for individuals with these conditions. Additionally, lifestyle changes and the adoption of healthy habits can significantly impact IM and may help prevent chronic diseases related to metabolism. Therefore, the main aim of this review is to analyze and understand the importance of microbiota intervention in the prevention of non-communicable diseases. R3:A1.}, } @article {pmid39594528, year = {2024}, author = {Scarpellini, E and Scarcella, M and Tack, JF and Scarlata, GGM and Zanetti, M and Abenavoli, L}, title = {Gut Microbiota and Metabolic Dysfunction-Associated Steatotic Liver Disease.}, journal = {Antioxidants (Basel, Switzerland)}, volume = {13}, number = {11}, pages = {}, doi = {10.3390/antiox13111386}, pmid = {39594528}, issn = {2076-3921}, abstract = {Background: The gut microbiota constitutes a complex microorganism community that harbors bacteria, viruses, fungi, protozoa, and archaea. The human gut bacterial microbiota has been extensively proven to participate in human metabolism, immunity, and nutrient absorption. Its imbalance, namely "dysbiosis", has been linked to disordered metabolism. Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the features of deranged human metabolism and is the leading cause of liver cirrhosis and hepatocellular carcinoma. Thus, there is a pathophysiological link between gut dysbiosis and MASLD. Aims and Methods: We aimed to review the literature data on the composition of the human bacterial gut microbiota and its dysbiosis in MASLD and describe the concept of the "gut-liver axis". Moreover, we reviewed the approaches for gut microbiota modulation in MASLD treatment. Results: There is consolidated evidence of particular gut dysbiosis associated with MASLD and its stages. The model explaining the relationship between gut microbiota and the liver has a bidirectional organization, explaining the physiopathology of MASLD. Oxidative stress is one of the keystones in the pathophysiology of MASLD and fibrosis generation. There is promising and consolidated evidence for the efficacy of pre- and probiotics in reversing gut dysbiosis in MASLD patients, with therapeutic effects. Few yet encouraging data on fecal microbiota transplantation (FMT) in MASLD are available in the literature. Conclusions: The gut dysbiosis characteristic of MASLD is a key target in its reversal and treatment via diet, pre/probiotics, and FMT treatment. Oxidative stress modulation remains a promising target for MASLD treatment, prevention, and reversal.}, } @article {pmid39593402, year = {2024}, author = {Tian, B and Pan, Y and Zhang, X and Wu, Y and Luo, X and Yang, K}, title = {Etiolated-green tea attenuates colonic barrier dysfunction and inflammation in high-fat diet-induced mice by modulating gut microbiota.}, journal = {Food research international (Ottawa, Ont.)}, volume = {197}, number = {Pt 1}, pages = {115192}, doi = {10.1016/j.foodres.2024.115192}, pmid = {39593402}, issn = {1873-7145}, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Diet, High-Fat/adverse effects ; *Tea/chemistry ; Mice ; Male ; *Colon/microbiology/metabolism/drug effects ; *Mice, Inbred C57BL ; *Inflammation ; Fatty Acids, Volatile/metabolism ; Dysbiosis ; Obesity/metabolism ; NF-kappa B/metabolism ; Intestinal Mucosa/metabolism/drug effects ; Fecal Microbiota Transplantation ; Toll-Like Receptor 4/metabolism ; Signal Transduction/drug effects ; Receptors, G-Protein-Coupled/metabolism ; Tight Junctions/drug effects/metabolism ; }, abstract = {Colonic barrier dysfunction and inflammation arising from dysbiosis gut microbiota (GM) are strongly associated with a high-fat diet (HFD). Yellow leaf green tea (YLGT), a novel variety of etiolated-green tea, improving the intestinal barrier and inflammation is related to the regulation of GM disorders. To explore the ameliorative mechanism of YLGT, mice were fed an HFD with or without YLGT at doses of 150, 300, and 450 mg kg[-1] for 12 weeks. YLGT rectified the GM imbalance, enriched short-chain fatty acid (SCFA)-producing bacteria and gut SCFA contents, activated G protein-coupled receptors, inhibited TLR4/NF-κB signaling pathway, strengthened the tight junction, and repaired the damaged intestinal barrier. The fecal microbiota transplantation experiment further confirmed that the GM was a key element in the anti-obesity and anti-intestinal inflammation effect of YLGT. YLGT has great promise in attenuating obesity-induced intestinal dysfunction. This research provides novel insights into the new mechanism of YLGT on HFD-induced obesity.}, } @article {pmid39592752, year = {2024}, author = {Chatthanathon, P and Leelahavanichkul, A and Cheibchalard, T and Wilantho, A and Hirankarn, N and Somboonna, N}, title = {Author Correction: Comparative time-series analyses of gut microbiome profiles in genetically and chemically induced lupus-prone mice and the impacts of fecal transplantation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {29391}, doi = {10.1038/s41598-024-79960-5}, pmid = {39592752}, issn = {2045-2322}, } @article {pmid39592644, year = {2024}, author = {Hunthai, S and Usawachintachit, M and Taweevisit, M and Srisa-Art, M and Anegkamol, W and Tosukhowong, P and Rattanachaisit, P and Chuaypen, N and Dissayabutra, T}, title = {Publisher Correction: Unraveling the role of gut microbiota by fecal microbiota transplantation in rat model of kidney stone disease.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {29360}, doi = {10.1038/s41598-024-78864-8}, pmid = {39592644}, issn = {2045-2322}, } @article {pmid39592438, year = {2024}, author = {Zhang, S and Wen, H and Chen, Y and Ning, J and Hu, D and Dong, Y and Yao, C and Yuan, B and Yang, S}, title = {Crosstalk between gut microbiota and tumor: tumors could cause gut dysbiosis and metabolic imbalance.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13763}, pmid = {39592438}, issn = {1878-0261}, support = {82303747//National Natural Science Foundation of China/ ; 2020GXLH-Y-010//Key Research and Development Projects of Shaanxi Province/ ; 2022JM-509//Natural Science Basic Research Program of Shaanxi Province/ ; }, abstract = {Gut microbiota has a proven link with the development and treatment of cancer. However, the causality between gut microbiota and cancer development is still unknown and deserves exploration. In this study, we aimed to explore the alterations in gut microbiota in murine tumor models and the crosstalk between the tumor and the gut microbiota. The subcutaneous and intravenous murine tumor models using both the colorectal cancer cell line MC38 and lung cancer cell line LLC were constructed. Then fecal samples before and after tumor inoculation were collected for whole metagenomics sequencing. Both subcutaneous and metastatic tumors markedly elevated the α-diversity of the gut microbiota. Relative abundance of Ligilactobacillus and Lactobacillus was reduced after subcutaneously inoculating tumor cells, whereas Bacteroides and Duncaniella were reduced in metastatic tumors, regardless of tumor type. At the species level, Lachnospiraceae bacterium was enriched after both subcutaneous and intravenous tumors inoculation, whereas levels of Muribaculaceae bacterium Isolate-110 (HZI), Ligilactobacillus murinus and Bacteroides acidifaciens reduced. Metabolic function analysis showed that the reductive pentose phosphate cycle, urea cycle, ketone body biosynthesis, ectoine biosynthesis, C4-dicarboxylic acid cycle, isoleucine biosynthesis, inosine 5'-monophosphate (IMP), and uridine 5'-monophosphate (UMP) biosynthesis were elevated after tumor inoculation, whereas the cofactor and vitamin biosynthesis were deficient. Principal coordinates analysis (PCoA) showed that subcutaneous and metastatic tumors partially shared the same effect patterns on gut microbiota. Furthermore, fecal microbiota transplantation revealed that this altered microbiota could influence tumor growth. Taken together, this study demonstrated that both colorectal cancer (MC38) and non-colorectal cancer (LLC) can cause gut dysbiosis and metabolic imbalance, regardless of tumor type and process of tumor inoculation, and this dysbiosis influenced the tumor growth. This research gives novel insights into the crosstalk between tumors and the gut microbiota.}, } @article {pmid39591377, year = {2024}, author = {Tafader, A and Bajaj, JS}, title = {Present and future of fecal microbiome transplantation in cirrhosis.}, journal = {Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society}, volume = {}, number = {}, pages = {}, doi = {10.1097/LVT.0000000000000542}, pmid = {39591377}, issn = {1527-6473}, abstract = {Over the last few decades, there have been tremendous advances in our understanding of the role of the gut microbiome in cirrhosis and the clinical sequelae that follows. Progressive dysbiosis and immune dysregulation occurs in patients with cirrhosis. In fact, alterations in the gut microbiome occur long before a diagnosis of cirrhosis is made. Understandably, our attention has recently been diverted towards potential modulators of the gut microbiome and the gut-liver axis as targets for treatment. The goal of this review is to highlight the utility of manipulating the gut microbiome with a focus on fecal microbiome transplantation (FMT) in patients with cirrhosis. In addition, we will provide an overview of disease-specific microbial alterations and the resultant impact this has on cirrhosis-related complications.}, } @article {pmid39590350, year = {2024}, author = {Chen, Z and Liao, Y and Chai, S and Yang, Y and Ga, Q and Ge, R and Wang, S and Liu, S}, title = {Modification of Intestinal Flora Can Improve Host Metabolism and Alleviate the Damage Caused by Chronic Hypoxia.}, journal = {Current issues in molecular biology}, volume = {46}, number = {11}, pages = {12733-12745}, pmid = {39590350}, issn = {1467-3045}, support = {[2130122.1779.36]//Qinghai Province Cattle Industry Science and Technology Innovation Platform under Grant/ ; }, abstract = {Prolonged exposure to hypoxic conditions can lead to reduced appetite, stunted growth, systemic inflammation, and pulmonary hypertension. Previous studies have indicated a correlation between gut dysbiosis and the development of hypoxia-related hazards. We designed an experiment to investigate the effect of microbiota on mitigating hypoxic damage. Gut microbiota from high-altitude-adapted species (Ochotona curzoniae) were transplanted into Sprague Dawley (SD) rats, which were then housed in a simulated 6000 m altitude environment for 30 days. After the experiment, we conducted analyses on average daily weight gain (ADG), feed conversion ratio (FCR), mean pulmonary artery pressure (mPAP), gut flora, and fecal metabolism. The results demonstrated that the ADG in the transplantation group (2.98 ± 0.17 g) was significantly higher than in the control groups (2.68 ± 0.19 g and 2.26 ± 0.13 g) (p < 0.05). The FCR was reduced in the transplantation group (6.30 ± 0.33 g) compared to the control groups (8.20 ± 1.15 g and 8.83 ± 0.45 g) (p < 0.05). The mPAP was decreased in the transplantation group (38.1 ± 1.13 mmHg) compared to the control groups (43.4 ± 1.30 mmHg and 43.5 ± 1.22 mmHg) (p < 0.05). Multi-omics analysis revealed that Lachnospiraceae, Desulfovibrionaceae, and specific amino acid metabolic pathways play crucial roles in hypoxia and are associated with both inflammation and nutritional metabolism. This study proposes a novel approach to the treatment of hypoxic pulmonary hypertension and holds potential significance for improving high-altitude developmental potential.}, } @article {pmid39589553, year = {2025}, author = {Kellogg, TD and Ceglia, S and Mortzfeld, BM and Tanna, TM and Zeamer, AL and Mancini, MR and Foley, SE and Ward, DV and Bhattarai, SK and McCormick, BA and Reboldi, A and Bucci, V}, title = {Succinate-producing microbiota drives tuft cell hyperplasia to protect against Clostridioides difficile.}, journal = {The Journal of experimental medicine}, volume = {222}, number = {1}, pages = {}, doi = {10.1084/jem.20232055}, pmid = {39589553}, issn = {1540-9538}, support = {PRMP W81XWH2020013//Congressionally Directed Medical Research Programs/ ; /GATES/Bill & Melinda Gates Foundation/United States ; U01AI172987/NH/NIH HHS/United States ; //Kenneth Rainin Foundation/ ; //American Association of Immunologists/ ; //Charles A. King Trust/ ; }, mesh = {Animals ; *Clostridioides difficile ; Mice ; *Succinic Acid/metabolism ; *Hyperplasia ; *Gastrointestinal Microbiome ; *Clostridium Infections/microbiology/metabolism ; Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Anti-Bacterial Agents/pharmacology ; Colon/microbiology/pathology/metabolism ; Mice, Knockout ; Cytokines/metabolism ; Tuft Cells ; }, abstract = {The role of microbes and their metabolites in modulating tuft cell (TC) dynamics in the large intestine and the relevance of this pathway to infections is unknown. Here, we uncover that microbiome-driven colonic TC hyperplasia protects against Clostridioides difficile infection. Using selective antibiotics, we demonstrate increased type 2 cytokines and TC hyperplasia in the colon but not in the ileum. We demonstrate the causal role of the microbiome in modulating this phenotype using fecal matter transplantation and administration of consortia of succinate-producing bacteria. Administration of succinate production-deficient microbes shows a reduced response in a Pou2f3-dependent manner despite similar intestinal colonization. Finally, antibiotic-treated mice prophylactically administered with succinate-producing bacteria show increased protection against C. difficile-induced morbidity and mortality. This effect is nullified in Pou2f3-/- mice, confirming that the protection occurs via the TC pathway. We propose that activation of TCs by the microbiota in the colon is a mechanism evolved by the host to counterbalance microbiome-derived cues that facilitate invasion by pathogens.}, } @article {pmid39589476, year = {2024}, author = {Ma, G and Chen, Z and Li, Z and Xiao, X}, title = {Unveiling the neonatal gut microbiota: exploring the influence of delivery mode on early microbial colonization and intervention strategies.}, journal = {Archives of gynecology and obstetrics}, volume = {}, number = {}, pages = {}, pmid = {39589476}, issn = {1432-0711}, support = {No. 81771664//National Natural Science Foundation of China/ ; }, abstract = {Recent research has emphasized the critical importance of establishing the neonatal gut microbiota for overall health and immune system development, prompting deeper studies about the early formation of neonatal gut microbiota and its influencing factors. Various factors, including maternal and environmental factors, affect the early formation of neonatal gut microbiota, in which delivery mode has been considered as one of the most crucial influencing factors. In recent years, the increasing trend of cesarean section during childbirth has become a serious challenge for global public health. This review thoroughly analyzes the effects of vaginal delivery and cesarean section on the establishment of neonatal gut microbiota and the potential long-term impacts. In addition, we analyze and discuss interventions such as probiotics, prebiotics, vaginal seeding, fecal microbiota transplantation, and breastfeeding to address the colonization defects of the neonatal gut microbiota caused by cesarean section, aiming to provide theoretical basis for the prevention and treatment of colonization defects and related diseases in infants caused by cesarean section in clinical practice and to provide a theoretical foundation for optimizing the development of neonatal gut microbiota.}, } @article {pmid39589434, year = {2024}, author = {Liu, L and Zhu, JW and Wu, JL and Li, MZ and Lu, ML and Yu, Y and Pan, L}, title = {Insomnia and intestinal microbiota: a narrative review.}, journal = {Sleep & breathing = Schlaf & Atmung}, volume = {29}, number = {1}, pages = {10}, pmid = {39589434}, issn = {1522-1709}, support = {No. ZR2021MH360//Natural Science Foundation of Shandong Province/ ; No. 82370092//National Natural Science Foundation of China/ ; No. 2023SHFZ033//Science and Technology Innovation Project of Binzhou Social Development/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; *Sleep Initiation and Maintenance Disorders/therapy/physiopathology/microbiology ; Fecal Microbiota Transplantation ; Brain-Gut Axis/physiology ; Probiotics/therapeutic use ; }, abstract = {PURPOSE: The intestinal microbiota and insomnia interact through the microbiota-gut-brain axis. The purpose of this review is to summarize and analyze the changes of intestinal microbiota in insomnia, the interaction mechanisms between intestinal microbiota and insomnia and the treatment methods based on the role of microbiota regulation in insomnia, in order to reveal the feasibility of artificial intervention of intestinal microbiota to improve insomnia.

METHODS: Pubmed/ Embase were searched through March 2024 to explore the relevant studies, which included the gut microbiota characteristics of insomnia patients, the mechanisms of interaction between insomnia and gut microbiota, and the relationship between gut microbiota and insomnia treatment.

RESULTS: Numerous studies implicated insomnia could induce intestinal microbiota disorder by activating the immune response, the hypothalamic-pituitary-adrenal axis, the neuroendocrine system, and affecting bacterial metabolites, resulting in intestinal ecological imbalance, intestinal barrier destruction and increased permeability. The intestinal microbiota exerted an influence on the central nervous system through its interactions with intestinal neurons, releasing neurotransmitters and inflammatory factors, which in turn, can exacerbate symptoms of insomnia. Artificial interventions of gut microbiota included probiotics, traditional Chinese medicine, fecal microbiota transplantation, diet and exercise, whose main pathway of action is to improve sleep by affecting the release of neurotransmitters and gut microbial metabolites.

CONCLUSION: There is an interaction between insomnia and gut microbiota, and it is feasible to diagnose and treat insomnia by focusing on changes in the gut microbiota of patients with insomnia. Large cross-sectional studies and fecal transplant microbiota studies are still needed in the future to validate its safety and efficacy.}, } @article {pmid39588934, year = {2024}, author = {Gil-Gómez, A and Muñoz-Hernández, R and Martínez, F and Jiménez, F and Romero-Gómez, M}, title = {Hepatic encephalopathy: experimental drugs in development and therapeutic potential.}, journal = {Expert opinion on investigational drugs}, volume = {}, number = {}, pages = {1-12}, doi = {10.1080/13543784.2024.2434053}, pmid = {39588934}, issn = {1744-7658}, abstract = {INTRODUCTION: Hepatic encephalopathy (HE) presents a complex pathophysiology, creating multiple potential treatment avenues. This review covers current and emerging treatments for HE.

AREAS COVERED: Standard therapies, including non-absorbable disaccharides and rifaximin, are widely used but show inconsistent efficacy. Alternatives such as polyethylene glycol and L-ornithine L-aspartate have been effective in certain cases. Advancements in understanding HE reveal a growing need for personalized treatments. Novel approaches targeting immune modulation and neuroinflammation are under investigation, though clinical translation is slow. Nutritional interventions and fecal microbiota transplantation show potential but lack robust evidence. Innovative therapies like gene and cell therapies, as well as extracellular vesicles from mesenchymal stem cells, present promising avenues for liver disease treatment, potentially benefiting HE.

EXPERT OPINION: A key challenge in HE research is the design of randomized clinical trials, which often suffer from small sample sizes, heterogeneity in patient population, and inconsistent blinding. Additionally, the multifactorial nature of HE, together with a high spontaneous response rate, complicates efforts to isolate treatment effects. Despite current limitations, ongoing research and technological advances hold promise for more effective and individualized HE treatments in the future.}, } @article {pmid39588716, year = {2024}, author = {Tiwari, A and Ika Krisnawati, D and Susilowati, E and Mutalik, C and Kuo, TR}, title = {Next-Generation Probiotics and Chronic Diseases: A Review of Current Research and Future Directions.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c08702}, pmid = {39588716}, issn = {1520-5118}, abstract = {The burgeoning field of microbiome research has profoundly reshaped our comprehension of human health, particularly highlighting the potential of probiotics and fecal microbiota transplantation (FMT) as therapeutic interventions. While the benefits of traditional probiotics are well-recognized, the efficacy and mechanisms remain ambiguous, and FMT's long-term effects are still being investigated. Recent advancements in high-throughput sequencing have identified gut microbes with significant health benefits, paving the way for next-generation probiotics (NGPs). These NGPs, engineered through synthetic biology and bioinformatics, are designed to address specific disease states with enhanced stability and viability. This review synthesizes current research on NGP stability, challenges in delivery, and their applications in preventing and treating chronic diseases such as diabetes, obesity, and cardiovascular diseases. We explore the physiological characteristics, safety profiles, and mechanisms of action of various NGP strains while also addressing the challenges and opportunities presented by their integration into clinical practice. The potential of NGPs to revolutionize microbiome-based therapies and improve clinical outcomes is immense, underscoring the need for further research to optimize their efficacy and ensure their safety.}, } @article {pmid39588509, year = {2024}, author = {Zhang, A and Chen, S and Zhu, Y and Wu, M and Lu, B and Zhou, X and Zhu, Y and Xu, X and Liu, H and Zhu, F and Lin, R}, title = {Intestinal microbiome changes and mechanisms of maintenance hemodialysis patients with constipation.}, journal = {Frontiers in cellular and infection microbiology}, volume = {14}, number = {}, pages = {1495364}, pmid = {39588509}, issn = {2235-2988}, mesh = {Humans ; *Constipation/microbiology ; *Gastrointestinal Microbiome ; *Renal Dialysis ; *Feces/microbiology ; Male ; *RNA, Ribosomal, 16S/genetics ; Middle Aged ; Female ; *Bacteria/classification/isolation & purification/genetics ; Aged ; Adult ; }, abstract = {BACKGROUND: Constipation is a common symptom in maintenance hemodialysis patients and greatly affects the quality of survival of hemodialysis patients. Fecal microbiota transplantation and probiotics are feasible treatments for functional constipation, but there is still a gap in the research on the characteristics of gut flora in patients with maintenance hemodialysis combined with constipation. The aim of this study is to clarify the characteristics of the intestinal flora and its changes in maintenance hemodialysis patients with constipation.

METHODS: Fecal samples were collected from 45 participants, containing 15 in the maintenance hemodialysis constipation group,15 in the maintenance hemodialysis non-constipation group and 15 in the healthy control group. These samples were analyzed using 16S rRNA gene sequencing. The feature of the intestinal microbiome of maintenance hemodialysis constipation group and the microbiome differences among the three groups were elucidated by species annotation analysis, α-diversity analysis, β-diversity analysis, species difference analysis, and predictive functional analysis.

RESULTS: The alpha diversity analysis indicated that maintenance hemodialysis constipation group was less diverse and homogeneous than maintenance hemodialysis non-constipation group and healthy control group. At the genus level, the top ten dominant genera in maintenance hemodialysis constipation group patients were Enterococcus, Escherichia-Shigella, Bacteroides, Streptococcus, Bifidobacterium, Ruminococcus_gnavus_group, Lachnospiraceae_unclassified, Faecalibacterium, Akkermansia and UCG-002. Compared with non-constipation group, the Enterococcus, Rhizobiales_unclassified, Filomicrobium, Eggerthella, Allobaculum, Prevotella_7, Gordonibacter, Mitochondria_unclassified, Lachnoanaerobaculum were significantly higher in constipation group (p<0.05). Compared with non-constipation group, the Kineothrix, Rhodopirellula, Weissella were significantly lower in constipation group (p<0.05). The predictive functional analysis revealed that compared with non-constipation group, constipation group was significantly enriched in pathways associated with pyruate metabolism, flavonoid biosynthesis.

CONCLUSIONS: This study describes for the first time the intestinal microbiome characteristics of maintenance hemodialysis patients with constipation. The results of this study suggest that there is a difference in the intestinal flora between maintenance hemodialysis patients with constipation and maintenance hemodialysis patients without constipation.}, } @article {pmid39588438, year = {2024}, author = {Dandamudi, BJ and Dimaano, KAM and Shah, N and AlQassab, O and Al-Sulaitti, Z and Nelakuditi, B and Mohammed, L}, title = {Neurodegenerative Disorders and the Gut-Microbiome-Brain Axis: A Literature Review.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e72427}, pmid = {39588438}, issn = {2168-8184}, abstract = {Neurodegenerative diseases are severe, age-related conditions with complex etiologies that result in significant morbidity and mortality. The gut microbiome, a dynamic symbiotic environment comprising commensal organisms, represents the largest reservoir of these organisms within the human body. It produces short-chain fatty acids, endogenous signals, and neuroactive compounds, which can modulate neuronal function, plasticity, and behavior. Emerging evidence suggests that the gut microbiome plays a pivotal role in neurodevelopment, aging, and brain diseases, including Alzheimer's disease, Parkinson's disease, and stroke. Communication between the gut and brain occurs through a bidirectional channel known as the gut-microbiome-brain axis, which is being explored for therapeutic potential in neurodegenerative disorders. This literature review was conducted through a comprehensive search of five electronic databases - PubMed, Scopus, Ovid Medline, Cochrane Review, and Google Scholar - from inception to June 2024, focusing on English-language studies. Keywords included "gut-brain axis", "microbiome dysbiosis", "neurodegeneration", and disorder-specific terms such as "Alzheimer's disease" and "Parkinson's disease", paired with "gut microbiome". The review examines current knowledge on the relationship between gut microbiota and neurodegenerative disorders, emphasizing potential mechanisms and therapeutic options. Results indicate that gut dysbiosis, characterized by microbial imbalance, is intricately associated with neurodegenerative disease pathogenesis by influencing immune responses, increasing blood-brain barrier permeability, and generating neurotoxic metabolites. Therapeutic approaches targeting the gut microbiome, including probiotics, prebiotics, and fecal microbiota transplantation, show promise in restoring microbial balance and slowing disease progression. However, further research is essential to validate these findings and develop effective clinical interventions.}, } @article {pmid39587707, year = {2024}, author = {Ilozumba, MN and Lin, T and Hardikar, S and Byrd, DA and Round, JL and Stephens, WZ and Holowatyj, AN and Warby, CA and Damerell, V and Li, CI and Figueiredo, JC and Toriola, AT and Shibata, D and Fillmore, GC and Pickron, B and Siegel, EM and Kahlert, C and Florou, V and Gigic, B and Ose, J and Ulrich, CM}, title = {Fusobacterium nucleatum Abundance is Associated with Cachexia in Colorectal Cancer Patients: The ColoCare Study.}, journal = {Cancer medicine}, volume = {13}, number = {22}, pages = {e70431}, pmid = {39587707}, issn = {2045-7634}, support = {//the German Ministry of Education and Research project PerMiCCion (01KD2101D)/ ; //German Cancer Research Center/ ; //the German Consortium of Translational Cancer Research, (DKTK)/ ; R01 CA189184/CA/NCI NIH HHS/United States ; R01 CA207371/CA/NCI NIH HHS/United States ; R01 CA211705/CA/NCI NIH HHS/United States ; R01 CA254108/CA/NCI NIH HHS/United States ; U01 CA206110/CA/NCI NIH HHS/United States ; //University of Utah Immunology, Inflammation, and Infectious Disease Initiative/ ; //Huntsman Cancer Foundation/ ; //Stiftung LebensBlicke, Matthias Lackas Stiftung, Claussen-Simon Stiftung/ ; //the Rahel-Goitein-Straus-Program, Medical Faculty Heidelberg University/ ; //ERA-NET (European Research Area Network) on Translational Cancer Research (TRANSCAN) project/ ; //Cancer Control and Population Health Sciences (CCPS) at the University of Utah/ ; }, mesh = {Humans ; *Colorectal Neoplasms/complications/microbiology ; Male ; *Cachexia/etiology/microbiology ; *Fusobacterium nucleatum/isolation & purification ; Female ; Aged ; Middle Aged ; *Feces/microbiology ; Fusobacterium Infections/complications/microbiology ; Neoplasm Staging ; Risk Factors ; }, abstract = {BACKGROUND: Cachexia accounts for about 20% of all cancer-related deaths and indicates poor prognosis. The impact of Fusobacterium nucleatum (Fn), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established.

METHODS: We evaluated the association between Fn abundance in pre-surgical stool samples and onset of cachexia at 6 months post-surgery in n = 87 patients with stages I-III CRC in the ColoCare Study.

RESULTS: High fecal Fn abundance compared to negative/low fecal Fn abundance was associated with 4-fold increased risk of cachexia onset at 6 months post-surgery (OR = 4.82, 95% CI = 1.15, 20.10, p = 0.03).

CONCLUSION: Our findings suggest that high fecal Fn abundance was associated with an increased risk of cachexia at 6 months post-surgery in CRC patients. This is the first study to link Fn abundance with cachexia in CRC patients, offering novel insights into biological mechanisms and potential management of cancer cachexia. Due to the small sample size, our results should be interpreted with caution. Future studies with larger sample sizes are needed to validate these findings.}, } @article {pmid39587339, year = {2024}, author = {Castells-Nobau, A and Puig, I and Motger-Albertí, A and de la Vega-Correa, L and Rosell-Díaz, M and Arnoriaga-Rodríguez, M and Escrichs, A and Garre-Olmo, J and Puig, J and Ramos, R and Ramió-Torrentà, L and Pérez-Brocal, V and Moya, A and Pamplona, R and Jové, M and Sol, J and Martin-Garcia, E and Martinez-Garcia, M and Deco, G and Maldonado, R and Fernández-Real, JM and Mayneris-Perxachs, J}, title = {Microviridae bacteriophages influence behavioural hallmarks of food addiction via tryptophan and tyrosine signalling pathways.}, journal = {Nature metabolism}, volume = {6}, number = {11}, pages = {2157-2186}, pmid = {39587339}, issn = {2522-5812}, support = {PI15/01934//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; CD20/00051//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; RD16/0017/0020//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; PI20/01090//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; CP18/00009//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; PI23/00575//Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)/ ; SLT017_20_000164//Generalitat de Catalunya (Government of Catalonia)/ ; 2021SGR00990//Generalitat de Catalunya (Government of Catalonia)/ ; 2017 SGR-669//Generalitat de Catalunya (Government of Catalonia)/ ; SLT002/16/00250//Government of Catalonia | Departament de Salut, Generalitat de Catalunya/ ; LCF/PR/HR22/52420017//"la Caixa" Foundation (Caixa Foundation)/ ; PNSD- 2019I006//Ministerio de Sanidad, Servicios Sociales e Igualdad (Ministry of Health, Social Services and Equality)/ ; PNSD- 2021I076//Ministerio de Sanidad, Servicios Sociales e Igualdad (Ministry of Health, Social Services and Equality)/ ; }, abstract = {Food addiction contributes to the obesity pandemic, but the connection between how the gut microbiome is linked to food addiction remains largely unclear. Here we show that Microviridae bacteriophages, particularly Gokushovirus WZ-2015a, are associated with food addiction and obesity across multiple human cohorts. Further analyses reveal that food addiction and Gokushovirus are linked to serotonin and dopamine metabolism. Mice receiving faecal microbiota and viral transplantation from human donors with the highest Gokushovirus load exhibit increased food addiction along with changes in tryptophan, serotonin and dopamine metabolism in different regions of the brain, together with alterations in dopamine receptors. Mechanistically, targeted tryptophan analysis shows lower anthranilic acid (AA) concentrations associated with Gokushovirus. AA supplementation in mice decreases food addiction and alters pathways related to the cycle of neurotransmitter synthesis release. In Drosophila, AA regulates feeding behaviour and addiction-like ethanol preference. In summary, this study proposes that bacteriophages in the gut microbiome contribute to regulating food addiction by modulating tryptophan and tyrosine metabolism.}, } @article {pmid39586550, year = {2024}, author = {Novelle, MG and Naranjo, B and López-Cánovas, JL and Díaz-Ruiz, A}, title = {Fecal Microbiota Transplantation, a tool to transfer healthy longevity.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {102585}, doi = {10.1016/j.arr.2024.102585}, pmid = {39586550}, issn = {1872-9649}, abstract = {The complex gut microbiome influences host aging and plays an important role in the manifestation of age-related diseases. Restoring a healthy gut microbiome via Fecal Microbiota Transplantation (FMT) is receiving extensive consideration to therapeutically transfer healthy longevity. Herein, we comprehensively review the benefits of gut microbial rejuvenation - via FMT - to promote healthy aging, with few studies documenting life length properties. This review explores how preconditioning donors via standard - lifestyle and pharmacological - antiaging interventions reshape gut microbiome, with the resulting benefits being also FMT-transferable. Finally, we expose the current clinical uses of FMT in the context of aging therapy and address FMT challenges - regulatory landscape, protocol standardization, and health risks - that require refinement to effectively utilize microbiome interventions in the elderly.}, } @article {pmid39586125, year = {2024}, author = {Ye, H and Wang, H and Han, B and Chen, K and Wang, X and Ma, F and Cheng, L and Zheng, S and Zhao, X and Zhu, J and Li, J and Hong, M}, title = {Guizhi Shaoyao Zhimu decoction inhibits neutrophil extracellular traps formation to relieve rheumatoid arthritis via gut microbial outer membrane vesicles.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {136}, number = {}, pages = {156254}, doi = {10.1016/j.phymed.2024.156254}, pmid = {39586125}, issn = {1618-095X}, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease with a high disability rate. Accumulating studies suggest that neutrophil extracellular traps (NETs) play a crucial role in the pathogenesis of RA and targeting NETs has emerged as a potential therapeutic strategy for RA. As a traditional Chinese medicine, Guizhi-Shaoyao-Zhimu Decoction (GSZD) has exhibited good efficacy in the treatment of rheumatoid arthritis (RA), while the underly mechanism especially the possibility that GSZD alter NETs formation to relieve RA remains unknown.

PURPOSE: Our study aimed to investigate relationship between GSZD and NETs in RA treatment and revealed underlying mechanism.

METHODS: We constructed collagen-induced arthritis (CIA) model and treated CIA mice with GZSY to validate therapeutic effects of GSZD and examine whether GZSD could inhibit NETs formation in RA. And 16S rRNA sequencing and Fecal microbiota transplantation (FMT) experiment were performed to determine whether GSZD could reduce NETs formation to alleviate RA in gut microbiota-associated manner and identify crucial bacterium in response to GSZD administration. CIA mice treated with effective bacteria and its outer membrane vesicles (OMVs) with oral administration to investigate protective effect against RA and NETs regulative efficiency. We utilized small interfering RNA in vivo and vitro to silence gene mediating effect of GZSD-gut microbiota-NETs.

RESULTS: GSZD could inhibit NETs formation and relive arthritis in CIA mice. Additionally, GSZD alter gut microbiota composition and significantly increase intestinal Parabacteroides goldsteinii (P.goldsteinii) abundance. Mechanistically, P.goldsteinii enriched by GSZD secreted outer membrane vesicles (OMVs) to translocate into joints and activate Cav-1-Nrf2 axis, leading to reduced NETs formation and alleviate arthritis. In clinical, the abundance of P.goldsteinii exhibited negative correlation with NETs indexes and RA disease activities.

CONCLUSION: Our findings suggest that GSZD inhibits NETs formation to relieve RA in P.goldsteinii-Cav-1-Nrf2 associated manner, which could provide new sight of the prevention and treatment of RA.}, } @article {pmid39583974, year = {2024}, author = {Naito, Y and Takagi, T}, title = {Role of gut microbiota in inflammatory bowel disease pathogenesis.}, journal = {Journal of clinical biochemistry and nutrition}, volume = {75}, number = {3}, pages = {175-177}, pmid = {39583974}, issn = {0912-0009}, abstract = {The role of the gut microbiota, especially bacterial flora, in the pathogenesis of inflammatory bowel disease (IBD) is becoming clearer. Advances in gut microbiota analysis and the use of gnotobiotics models have underscored the importance of gut bacteria and their metabolites in the progression of IBD. Fecal microbiota transplantation has shown promise in clinical trials for ulcerative colitis started as Advanced Medical Care B in Japan, raising expectations for its outcomes. This review explores the gut microbiota's role in IBD, encompassing both current knowledge and future prospects.}, } @article {pmid39582897, year = {2024}, author = {Wang, Z and Wu, X and Wang, Y and Wen, Q and Cui, B and Zhang, F}, title = {Colonic transendoscopic enteral tubing is revolutionizing intestinal therapeutics, diagnosis, and microbiome research.}, journal = {Therapeutic advances in gastroenterology}, volume = {17}, number = {}, pages = {17562848241301574}, pmid = {39582897}, issn = {1756-283X}, abstract = {The intestine, as a crucial organ of the human body, has remained enigmatic despite the remarkable advancements in modern medical technology. Over the past decades, the invention of endoscopic technology has made the noninvasive intervention of the intestine a reality, expanding diagnostic and therapeutic options for diseases. However, due to the single-treatment feature of endoscopic procedures, continuous or repeated medication administration, sampling, and decompression drainage within the intestine have yet to be fulfilled. These limitations persisted until the invention of colonic transendoscopic enteral tubing (TET) in 2014, which realized repeated fecal microbiota transplantation, medication administration, and decompression drainage for the treatment of colon perforation and intestinal obstruction, as well as in situ dynamic sampling. These breakthroughs have not gone unnoticed, gaining global attention and recommendations from guidelines and consensuses. TET has emerged as a novel microbial research tool that offers new paradigms for human microbiome research. This review aims to update the research progress based on TET.}, } @article {pmid39581510, year = {2024}, author = {Zhang, X and Klöhn, M and Ouwerkerk-Mahadevan, S and Jagst, M and Vereyken, L and Verboven, P and Goovaerts, Q and Todt, D and Jonckers, THM and Coelmont, L and Fletcher, H and Das, K and Samby, K and Neyts, J and Steinmann, E and Koul, A and Kaptein, SJF}, title = {A pan-genotypic hepatitis E virus replication inhibitor with high potency in a rat infection model.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.10.043}, pmid = {39581510}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Hepatitis E virus (HEV) constitutes a substantial public health burden with ∼20 million human infections annually, including 3.3 million symptomatic cases. Appropriate treatment options for, in particular, HEV-infected immunocompromised patients and pregnant women are lacking, underscoring the urgent need for potent and safe antiviral drugs.

METHODS: HEV subgenomic replicon systems were used to screen a small library of pre-selected nucleoside analogues, originally developed in a hepatitis C virus (HCV) antiviral program. Antiviral activity of the selected hit on HEV infection was evaluated in a variety of cell culture systems; the efficacy of the compound was assessed in the athymic nude rat HEV infection model.

RESULTS: Compound JNJ-9117 exerts pan-genotype antiviral activity against HEV in different cell types as well as in primary human hepatocytes. A high level of conservation is observed between three crucial motifs in the catalytic domain of the HCV and HEV polymerases. This suggests a mechanism of action that is identical to that of the molecule against HCV, whereby the 5'-triphosphate of JNJ-9117 acts as a chain terminator during viral RNA synthesis. JNJ-9117 has a favorable pharmacokinetic and safety profile in rats and results in a pronounced antiviral effect in a chronic rat HEV infection model, both in a prophylactic and therapeutic setting. The combination of JNJ-9117 and ribavirin (each at an intentionally selected suboptimal/inactive dose) was in infected rats highly effective in lowering viral RNA load in liver and feces to (almost) undetectable levels.

CONCLUSIONS: JNJ-9117 has a profile that holds promise for the treatment of life-threatening HEV infections in humans. Phase 1 studies with JNJ-9117 have been initiated in healthy human volunteers.}, } @article {pmid39581509, year = {2024}, author = {Chen, S and Wen, Q and Zhang, F}, title = {An Unusual Cause of Diarrhea and Hematochezia.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2024.11.007}, pmid = {39581509}, issn = {1528-0012}, } @article {pmid39580105, year = {2024}, author = {Fülöpová, N and Brückner, K and Muselík, J and Pavloková, S and Franc, A}, title = {Development and evaluation of innovative enteric-coated capsules for colon-specific delivery of hydrophilic biomaterials.}, journal = {International journal of pharmaceutics}, volume = {}, number = {}, pages = {124991}, doi = {10.1016/j.ijpharm.2024.124991}, pmid = {39580105}, issn = {1873-3476}, abstract = {OBJECTIVE: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract.

METHODS: Hard gelatin capsules and DRcaps[TM]capsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit® E, and polyvinyl acetate) and external (Eudragit® S, Acryl-EZE®, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms.

RESULTS: Combining suitable internal (ethylcellulose 1.0 %) and external (Eudragit® S 20.0 %) coating of DRcaps[TM] capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720 min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480 min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields.

CONCLUSION: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery.}, } @article {pmid39579562, year = {2024}, author = {Yang, Y and Wu, R and Qian, C and Wu, D and Ou, J}, title = {Mume fructus alters the abundance of intestinal microbiota and alleviates damaged intestinal barrier and inflammation in rats with DSS induced colitis.}, journal = {Molecular immunology}, volume = {176}, number = {}, pages = {60-72}, doi = {10.1016/j.molimm.2024.11.008}, pmid = {39579562}, issn = {1872-9142}, abstract = {The gut microbiota plays a crucial role in the development of colitis by influencing the immune response and inflammation in the colon. Previous research has shown that Mume Fructus, a traditional Chinese medicine, can alleviate colitis by reducing the activity of inflammatory pathways. However, the specific connection between Mume Fructus-treated colitis and regulation of gut flora remains unclear, prompting further investigation. This research aims to delve deeper into the possible impact of the gut microbiota in colitis when treated with the aqueous decoction of Mume Fructus (MF). The effects of MF on rats with DSS-induced colitis were assessed through examination of pathological indicators, intestinal barrier proteins, and analysis of 16S rDNA sequencing to investigate its impact on the gut microbiota. In addition, the colon contents of rats after the administration of MF were transplanted into rats with colitis, and the effect of MF on intestinal flora was verified, and "beneficial bacteria" were identified by 16S rDNA sequencing and Spearman's correlation analysis. In summary, our findings suggest that MF has the potential to ameliorate symptoms of colitis through modulation of intestinal microbiota and restoration of intestinal barrier function.}, } @article {pmid39574673, year = {2024}, author = {Wolfe, TM and Jo, J and Pinkham, NV and Garey, KW and Walk, ST}, title = {Microbiome impact of ibezapolstat and other Clostridioides difficile infection relevant antibiotics using humanized mice.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.11.06.622322}, pmid = {39574673}, issn = {2692-8205}, abstract = {BACKGROUND: Ibezapolstat (IBZ) is a competitive inhibitor of the bacterial Pol IIIC enzyme in clinical development for treatment of Clostridioides difficile infection (CDI). Previous studies demonstrated IBZ carries a favorable microbiome diversity profile compared to vancomycin (VAN). However, head-to-head comparisons with other CDI antibiotics have not been done. The purpose of this study was to compare microbiome changes associated with IBZ to other clinically used CDI antibiotics.

METHODS: Groups of germ-free (GF) mice received a fecal microbiota transplant from one of two healthy human donors and were subsequently exposed to either IBZ, VAN, fidaxomicin (FDX), metronidazole (MET), or no antibiotic (control). 16S rRNA encoding gene sequencing of temporally collected stool samples was used to compare gut microbiome perturbation between treatment and no-drug control groups.

RESULTS: Among the tested antibiotics, the most significant change in microbiome diversity was observed in MET-treated mice. Each antibiotic had a unique effect, but changes in alpha and beta diversity following FDX- and IBZ-treated groups were less pronounced compared to those observed in VAN-or MET-treated groups. By the end of therapy, both IBZ and FDZ increased the relative abundance of Bacteroidota (phylum), with IBZ additionally increasing the relative abundance of Actinomycetota (phylum).

CONCLUSION: In microbiome-humanized mice, IBZ and FDX had smaller effects on gut microbiome diversity compared to VAN and MET. Notable differences were observed between the microbiome of IBZ- and FDX-treated groups, which may allow for differentiation of these two antibiotics in future studies.}, } @article {pmid39574251, year = {2024}, author = {Shen, CL and Deshmukh, H and Santos, JM and Elmassry, MM and Presto, P and Driver, Z and Bhakta, V and Yakhnitsa, V and Kiritoshi, T and Ji, G and Lovett, J and Hamood, A and Neugebauer, V}, title = {Fecal Microbiota Transplantation Modulates Gut Microbiome Composition and Glial Signaling in Brain and Colon of Rats with Neuropathic Pain: Evidence for Microbiota-Gut-Brain Axis.}, journal = {The Journal of frailty & aging}, volume = {13}, number = {4}, pages = {319-330}, doi = {10.14283/jfa.2024.65}, pmid = {39574251}, issn = {2260-1341}, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Fecal Microbiota Transplantation ; *Neuralgia/therapy/microbiology/metabolism ; Rats ; Male ; *Brain-Gut Axis/physiology ; Neuroglia/metabolism ; Colon/microbiology ; Brain/metabolism ; Rats, Sprague-Dawley ; Disease Models, Animal ; Signal Transduction ; }, abstract = {Despite evidence linking the gut microbiome to neuropathic pain (NP), it is not known if altering gut microbiota can alleviate NP via the microbiome-gut-brain axis. This study examined if healthy gut microbiota of sham male rats (Sham+V) and dysbiotic gut microbiota of NP rats (spinal nerve ligation: NP, SNL+V) can be disrupted and restored, respectively, via fecal microbiota transplant (FMT) from the opposite group [Sham+(SNL-FMT) and SNL+(Sham-FMT), respectively]. All groups received FMT daily for two weeks, followed by three weeks without FMT. SNL rats showed higher mechanical hypersensitivity [SNL+V vs. Sham+V] throughout the study. After two weeks, the FMT of healthy gut microbiota decreased mechanical hypersensitivity in SNL rats [SNL+(Sham-FMT) vs. SNL+V]. A temporal shift in microbiome profiles after 2-week FMT treatment was observed in Sham+(SNL-FMT) and SNL+(Sham-FMT) groups, while the microbiome profile shifted back a certain extent after FMT ceased. At the end of study, the Sham+(SNL-FMT) group acquired low abundance of UCG-001, Odoribacter, and Peptococcaceae, and high abundance of UBA1819 and Victivallis. The SNL+(Sham-FMT) group maintained high abundance of Butyricimonas and Escherichia-Shigella. The SNL+(Sham-FMT) group had altered glial and macrophage activation/inflammation markers in the brain/colon than the SNL+V group. Relative to the SNL+V group, the SNL+(Sham-FMT) group had significantly lower gene expressions of GFAP (hypothalamus), IBA-1 (colon), and NF-κB (amygdala/colon), but higher gene expressions of complex I (amygdala/hypothalamus) and claudin-3 (amygdala/hypothalamus/colon). In conclusion, FMT containing healthy microbiota given to SNL rats attenuates mechanical hypersensitivity, modulates microbiota composition, and mitigates downstream glial activation/inflammation markers in a NP model.}, } @article {pmid39571844, year = {2024}, author = {Yu, L and Lin, F and Yu, Y and Deng, X and Shi, X and Lu, X and Lu, Y and Wang, D}, title = {Rehmannia glutinosa polysaccharides enhance intestinal immunity of mice through regulating the microbiota.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 3}, pages = {137878}, doi = {10.1016/j.ijbiomac.2024.137878}, pmid = {39571844}, issn = {1879-0003}, abstract = {The Rehmannia glutinosa polysaccharides (RGP) have various benefits such as enhancing immune cell activity, decreasing oxidative stress and delaying or inhibiting tumor occurrence. Although much research has been directed at understanding the role of RGP, its influence on gut immunity is largely understudied. Here, we aimed to dissect the immune-regulating effects of RGP in the mice intestines. In vivo experiments involving the oral administration of RGP to mice at dosages of 100, 200, and 400 mg/kg over seven consecutive days revealed that RGP therapy significantly increased the percentages of CD3[+] T lymphocytes and CD19[+] B lymphocytes in intestines and improved the integrity of the mucosal barrier. Moreover, RGP modified the gut microbiota composition by enhancing the abundance of beneficial bacteria like Lactobacillus and Akkermansia. Fecal microbiota transplantation (FMT) experiments further revealed that RGP modulated the host's intestinal immunological function by altering the gut microbiota composition. These findings indicate that RGP may control the immunological function of the intestines.}, } @article {pmid39571733, year = {2024}, author = {Yu, J and Feng, L and Luo, Z and Yang, J and Zhang, Q and Liu, C and Liang, D and Xie, Y and Li, H and Gong, J and He, Z and Lan, P}, title = {Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis.}, journal = {Journal of advanced research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jare.2024.11.024}, pmid = {39571733}, issn = {2090-1224}, abstract = {INTRODUCTION: The intricate interplay of interleukin-10 (IL-10) and gut microbiota influences tumor development and progression, yet the impacts on colorectal cancer (CRC) metastasis remain incompletely understood.

METHODS: The impact of Il10 deficiency on CRC metastasis was first evaluated in CRC metastasis tumor samples and mouse model. Antibiotic sterilization and fecal microbiota transplantation (FMT) experiment were used to assess the role of gut microbiota in IL-10 mediated CRC metastasis, and full-length 16S rDNA sequencing analysis further identified the potential target bacteria influencing CRC metastasis. The inhibitory effect of Parabacteroides distasonis (P. distasonis) on CRC metastasis was evaluated by oral administration in mice. Key metabolites involved in P. distasonis inhibition of CRC metastasis was identified by widely-targeted metabolome analysis and validated both in vivo and in vitro. The underlying mechanisms of P-hydroxyphenyl acetic acid (4-HPAA) inhibiting CRC metastasis was investigated via RNA-sequencing and validated in cellular experiments.

RESULTS: We revealed that serum IL-10 levels were markedly elevated in metastatic CRC patients compared to non-metastatic cases. In parallel, Il10-deficiency (Il10[-/]) in mice resulted in decreased CRC metastasis in a gut microbiota-dependent manner. Mechanistically, Il10[-/-] mice reshaped gut microbiota composition, notably enriching P. distasonis. The enriched P. distasonis produced 4-HPAA, which activated the aryl hydrocarbon receptor (AHR) and subsequently inhibited the expression of VEGFA, a typical oncogene, thereby sequentially suppressing CRC metastasis. Importantly, engineered bacteria capable of producing 4-HPAA effectively hindered CRC metastasis. Furthermore, AHR depletion significantly disrupted the 4-HPAA-induced reduction in CRC cell migration and the inhibition of metastasis in both in vitro and in vivo lung metastasis mouse models.

CONCLUSIONS: These findings demonstrate the significance of IL-10 deficiency in suppressing CRC metastasis through the 4-HPPA-AHR-VEGFA axis mediated by gut P. distasonis, suggesting that P. distasonis or 4-HPAA supplementation could offer a promising therapeutic strategy for CRC metastasis prevention.}, } @article {pmid39571265, year = {2024}, author = {Mansouri, P and Mansouri, P and Behmard, E and Najafipour, S and Kouhpayeh, A and Farjadfar, A}, title = {Novel targets for mucosal healing in inflammatory bowel disease therapy.}, journal = {International immunopharmacology}, volume = {144}, number = {}, pages = {113544}, doi = {10.1016/j.intimp.2024.113544}, pmid = {39571265}, issn = {1878-1705}, abstract = {Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal tract, primarily manifesting as ulcerative colitis (UC) or Crohn's disease (CD). Both inflammation and disruption of the intestinal epithelial barrier are key factors in IBD pathogenesis. Substantial evidence has revealed a significant association between aberrant immune responses and impairment of the intestinal epithelial barrier in IBD pathogenesis. The components of the intestinal epithelium, particularly goblet cells and Paneth cells, are crucial to gut homeostasis, as they secrete mucin, antimicrobial peptides (AMPs), and cytokines. Furthermore, impairment of epithelial integrity, which is regulated by tight junctions, is a hallmark of IBD pathology. While common treatments for IBD, such as anti-inflammatory drugs, target various signaling pathways with varying efficacies, therapeutic approaches focused on mucosal and epithelial barrier healing have been largely neglected. Moreover, high costs, side effects, and insufficient or inconsistent therapeutic outcomes remain major drawbacks of conventional anti-IBD drugs. Recent studies on epithelial barrier regeneration and permeability reduction have introduced promising therapeutic targets, including farnesoid X receptor (FXR), urokinase-type plasminogen activator (uPA)-urokinase-type plasminogen activator receptor (uPAR) interaction, fecal microbiota transplantation (FMT), and insulin receptor (INSR). Notably, the simultaneous targeting of intestinal inflammation and promotion of epithelial barrier healing shows promise for efficient IBD treatment. Future research should explore targeted therapies and combination treatments, including natural remedies, microbiota colonization, stem cell approaches, and computer-aided drug design. It is also crucial to focus on accurate prognosis and developing a thorough understanding of IBD development mechanisms.}, } @article {pmid39570086, year = {2024}, author = {Justice, J and Kankaria, RA and Johnson, DB}, title = {Immune checkpoint inhibition of metastatic melanoma: achieving high efficacy in the face of high toxicity.}, journal = {Expert review of clinical pharmacology}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/17512433.2024.2431513}, pmid = {39570086}, issn = {1751-2441}, abstract = {INTRODUCTION: Immune checkpoint inhibitors (ICIs) have advanced the treatment of metastatic melanoma by blocking immune system down-regulators enhancing T-cell-mediated anti-tumor responses. However, many ICIs induce immune-related adverse effects (irAEs) that can impact many organ systems.

AREAS COVERED: Strategies used to manage irAEs include corticosteroids, anti-tumor necrosis factor alpha (TNF-α) agents, other biological therapies, fecal microbiota transplantation (FMT), and emerging regimens. In this review, we describe current evidence for the efficacy of ICIs, acute and chronic immune toxicities, and strategies to manage toxicities for patients treated with ICIs.

EXPERT OPINION: IrAE management will likely evolve by developing more tailored approaches to prevent toxicities, improving non-steroidal management strategies and tailoring the dose of steroids, and identifying biomarkers of severe toxicities.}, } @article {pmid39569890, year = {2024}, author = {Jang, S and Yu, J and Park, S and Lim, H and Koh, H and Park, YR}, title = {Development of Time-Aggregated Machine Learning Model for Relapse Prediction in Pediatric Crohn's Disease.}, journal = {Clinical and translational gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ctg.0000000000000794}, pmid = {39569890}, issn = {2155-384X}, support = {//Ministry of Health and Welfare/ ; }, abstract = {INTRODUCTION: Pediatric Crohn's disease (CD) easily progresses to an active disease compared to adult CD, making it important to predict and minimize CD relapses. However, prediction of relapse at various time points (TPs) during pediatric CD remains understudied. We aimed to develop a real-time aggregated model to predict pediatric CD relapse in different TPs and time windows (TWs).

METHODS: This retrospective study was conducted on children diagnosed with CD between 2015 and 2022 at Severance Hospital. Laboratory test results and demographic data were collected starting at 3 months after diagnosis, and cohorts were formed using data from six different TPs at 1-month intervals. Relapse-defined as a pediatric CD activity index ≥30 points-was predicted, and TWs were 3-7 months with 1-month intervals. The feature importance of the variables in each setting was determined.

RESULTS: Data from 180 patients were used to construct cohorts corresponding to the TPs. We identified the optimal TP and TW to reliably predict pediatric CD relapse with an area under the receiver operating characteristic curve score of 0.89 when predicting with a 3-month TW at a 3-month TP. Variables such as C-reactive protein levels and lymphocyte fraction were found to be important factors.

DISCUSSION: We developed a time-aggregated model to predict pediatric CD relapse in multiple TPs and TWs. This model identified important variables that predicted relapse in pediatric CD to support real-time clinical decision making.}, } @article {pmid39568727, year = {2024}, author = {Alam, M and Abbas, K and Mustafa, M and Usmani, N and Habib, S}, title = {Microbiome-based therapies for Parkinson's disease.}, journal = {Frontiers in nutrition}, volume = {11}, number = {}, pages = {1496616}, pmid = {39568727}, issn = {2296-861X}, abstract = {The human gut microbiome dysbiosis plays an important role in the pathogenesis of Parkinson's disease (PD). The bidirectional relationship between the enteric nervous system (ENS) and central nervous system (CNS) under the mediation of the gut-brain axis control the gastrointestinal functioning. This review article discusses key mechanisms by which modifications in the composition and function of the gut microbiota (GM) influence PD progression and motor control loss. Increased intestinal permeability, chronic inflammation, oxidative stress, α-synuclein aggregation, and neurotransmitter imbalances are some key factors that govern gastrointestinal pathology and PD progression. The bacterial taxa of the gut associated with PD development are discussed with emphasis on the enteric nervous system (ENS), as well as the impact of gut bacteria on dopamine production and levodopa metabolism. The pathophysiology and course of the disease are associated with several inflammatory markers, including TNF-α, IL-1β, and IL-6. Emerging therapeutic strategies targeting the gut microbiome include probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). The article explored how dietary changes may affect the gut microbiota (GM) and the ways that can affect Parkinson's disease (PD), with a focus on nutrition-based, Mediterranean, and ketogenic diets. This comprehensive review synthesizes current evidence on the role of the gut microbiome in PD pathogenesis and explores its potential as a therapeutic target. Understanding these complex interactions may assist in the development of novel diagnostic tools and treatment options for this neurodegenerative disorder.}, } @article {pmid39567117, year = {2025}, author = {Lu, X and Jing, Y and Zhang, N and Chen, L and Tai, J and Cao, Y}, title = {Structural characterization and anti-obesity effect of a novel water-soluble galactomannan isolated from Eurotium cristatum.}, journal = {Carbohydrate polymers}, volume = {348}, number = {Pt B}, pages = {122870}, doi = {10.1016/j.carbpol.2024.122870}, pmid = {39567117}, issn = {1879-1344}, mesh = {Animals ; *Galactose/analogs & derivatives ; *Mannans/chemistry/pharmacology/isolation & purification ; Mice ; *Anti-Obesity Agents/pharmacology/chemistry/isolation & purification ; *Obesity/drug therapy ; Male ; *Diet, High-Fat ; *Eurotium/chemistry ; *Solubility ; Gastrointestinal Microbiome/drug effects ; Water/chemistry ; Mice, Inbred C57BL ; }, abstract = {Obesity is a serious public health challenge worldwide, the present study is aimed to investigate the structural characteristic and anti-obesity effect of a water-soluble galactomannan (PEC) extracted from Eurotium cristatum (E. cristatum). Detailed analysis of the PEC structure showed a weight-average molecular weight of 32,305 Da and a composition of mainly mannose, galactose and small amounts of glucose. Nuclear magnetic resonance spectroscopy combined with methylation analysis indicated that the main chain of PEC is →5)-β-D-Galf-(1 → 6)-α-D-Manp-(1 → glycosidic bond, and the branched chain →2)-α-D-Manp-(1 → through →2,6)-α-D-Manp-(1 → is connected to the main chain by an O-2 bond. Furthermore, PEC was found to ameliorate body weight gain, metabolic disorders, and to modulate the gut microbiota in HFD-fed mice. Fecal microbiota transplantation trial confirmed that PEC prevented obesity development and metabolic disorders by reversing gut dysbiosis in HFD-fed mice. This is the first report of the isolation of PEC from E. cristatum, and the findings suggested that PEC exerted its antiobesity and related beneficial effects by regulating the gut microbiota. In conclusion, as a polysaccharide, PEC could reduce obesity by modulating the gut microbiota and has potential been a prophylactic agent for obesity and related metabolic diseases.}, } @article {pmid39566790, year = {2024}, author = {Liu, Z and Wang, M and Li, J and Liang, Y and Jiang, K and Hu, Y and Gong, W and Guo, X and Guo, Q and Zhu, B}, title = {Hizikia fusiforme polysaccharides synergized with fecal microbiota transplantation to alleviate gut microbiota dysbiosis and intestinal inflammation.}, journal = {International journal of biological macromolecules}, volume = {283}, number = {Pt 4}, pages = {137851}, doi = {10.1016/j.ijbiomac.2024.137851}, pmid = {39566790}, issn = {1879-0003}, abstract = {Ulcerative colitis (UC) is closely associated with disruptions in gut microbiota. Restoring balance to gut microbiota and reducing intestinal inflammation has become a promising therapeutic approach for UC. However, challenges remain, including limited efficacy in some treatments. This study explores the synergistic effects and underlying mechanisms of Hizikia fusiforme polysaccharides (HFP) combined with fecal microbiota transplantation (FMT) to improve UC symptoms. Seven-week-old C57/BL6J mice were induced with UC using dextran sodium sulfate (DSS). Supplementation with either FMT alone or in combination with HFP effectively alleviated UC symptoms, reduced colonic inflammation, and corrected gut microbiota imbalance. Notably, HFP combined with FMT yielded showed better effects in ameliorating DSS-induced UC in mice than did FMT alone. Enrichment of probiotics, such as Bifidobacterium, and upregulation of beneficial metabolites, such as betaine, were identified as potential mechanisms for the enhanced effects of HFP combined with FMT against DSS-induced UC. These findings suggest that the combination of Hizikia fusiforme polysaccharides with FMT has potential applications in rectifying dysbiosis and ameliorating inflammatory bowel diseases.}, } @article {pmid39564459, year = {2024}, author = {Zhao, J and Liu, J and Feng, J and Liu, X and Hu, Q}, title = {The gut microbiota-brain connection: insights into major depressive disorder and bipolar disorder.}, journal = {Frontiers in psychiatry}, volume = {15}, number = {}, pages = {1421490}, pmid = {39564459}, issn = {1664-0640}, abstract = {Major depressive disorder (MDD) and bipolar disorder (BD) are two of the most prevalent mood disorders that seriously jeopardize both physical and mental health. The current diagnosis of MDD and BD relies primarily on clinical symptoms. However, correctly differentiating between MDD and BD during depressive episode states remains a substantial clinical challenge. The human gut hosts a large and diverse microbiota, which plays a pivotal role in various physiological processes. Emerging evidence suggests that the gut microbiota (GM) exerts beneficial effects on mental health disorders, including MDD, BD, and schizophrenia, through the microbe-gut-brain axis (MGBA). In recent years, the relationship between GM and mood disorders has garnered considerable attention, leading to intensive research in this area. The MGBA is a bidirectional communication system between the gut and the brain. Growing evidence indicates that the brain can influence the GM, which in turn may modulate the brain through this axis. This review aims to explore the changes in the GM of patients with MDD and BD and evaluate the effects of different treatments on their GM, including medication, probiotic, prebiotic and synbiotic interventions, and fecal microbiota transplantation (FMT). By doing so, we seek to identify potential disease-specific biomarkers, improve differential diagnosis, and offer novel therapeutic avenues for these disorders.}, } @article {pmid39562050, year = {2024}, author = {Li, N and Li, Y and Huang, Z and Cao, Z and Cao, C and Gao, X and Zuo, T}, title = {Faecal phageome transplantation alleviates intermittent intestinal inflammation in IBD and the timing of transplantation matters: a preclinical proof-of-concept study in mice.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2024-333598}, pmid = {39562050}, issn = {1468-3288}, } @article {pmid39557804, year = {2024}, author = {Lee, JY and Kim, Y and Kim, J and Kim, JK}, title = {Fecal Microbiota Transplantation: Indications, Methods, and Challenges.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {}, number = {}, pages = {}, pmid = {39557804}, issn = {1976-3794}, support = {RS-2024-00340833//National Research Foundation of Korea/ ; }, abstract = {Over the past two decades, as the importance of gut microbiota to human health has become widely known, attempts have been made to treat diseases by correcting dysbiosis of gut microbiota through fecal microbiota transplantation (FMT). Apart from current knowledge of gut microbiota, FMT to treat disease has a long history, from the treatment of food poisoning in the fourth century to the treatment of Clostridioides difficile infections in the twentieth century. In 2013, FMT was recognized as a standard treatment for recurrent C. difficile because it consistently showed high efficacy. Though recurrent C. difficile is the only disease internationally recognized for FMT efficacy, FMT has been tested for other diseases and shown some promising preliminary results. Different FMT methods have been developed using various formulations and administration routes. Despite advances in FMT, some issues remain to be resolved, such as donor screening, manufacturing protocols, and unknown components in the fecal microbiota. In this review, we discuss the mechanisms, clinical indications, methods, and challenges of current FMT. We also discuss the development of alternative therapies to overcome the challenges of FMT.}, } @article {pmid39555931, year = {2024}, author = {Wang, J and Xiang, J-H and Peng, X-Y and Liu, M and Sun, L-J and Zhang, M and Zhang, L-Y and Chen, Z-B and Tang, Z-Q and Cheng, L}, title = {Characteristic alterations of gut microbiota and serum metabolites in patients with chronic tinnitus: a multi-omics analysis.}, journal = {Microbiology spectrum}, volume = {}, number = {}, pages = {e0187824}, doi = {10.1128/spectrum.01878-24}, pmid = {39555931}, issn = {2165-0497}, abstract = {Chronic tinnitus is a central nervous system disorder. Currently, the effects of gut microbiota on tinnitus remain unexplored. To explore the connection between gut microbiota and tinnitus, we conducted 16S rRNA sequencing of fecal microbiota and serum metabolomic analysis in a cohort of 70 patients with tinnitus and 30 healthy volunteers. We used the weighted gene co-expression network method to analyze the relationship between the gut microbiota and the serum metabolites. The random forest technique was utilized to select metabolites and gut taxa to construct predictive models. A pronounced gut dysbiosis in the tinnitus group, characterized by reduced bacterial diversity, an increased Firmicutes/Bacteroidetes ratio, and some opportunistic bacteria including Aeromonas and Acinetobacter were enriched. In contrast, some beneficial gut probiotics decreased, including Lactobacillales and Lactobacillaceae. In serum metabolomic analysis, serum metabolic disturbances in tinnitus patients and these differential metabolites were enriched in pathways of neuroinflammation, neurotransmitter activity, and synaptic function. The predictive models exhibited great diagnostic performance, achieving 0.94 (95% CI: 0.85-0.98) and 0.96 (95% CI: 0.86-0.99) in the test set. Our study suggests that changes in gut microbiota could potentially influence the occurrence and chronicity of tinnitus, and exert regulatory effects through changes in serum metabolites. Overall, this research provides new perceptions into the potential role of gut microbiota and serum metabolite in the pathogenesis of tinnitus, and proposes the "gut-brain-ear" concept as a pathomechanism underlying tinnitus, with significant clinical diagnostic implications and therapeutic potential.IMPORTANCETinnitus affects millions of people worldwide. Severe cases may lead to sleep disorders, anxiety, and depression, subsequently impacting patients' lives and increasing societal healthcare expenditures. However, tinnitus mechanisms are poorly understood, and effective therapeutic interventions are currently lacking. We discovered the gut microbiota and serum metabolomics changes in patients with tinnitus, and provided the potential pathological mechanisms of dysregulated gut flora in chronic tinnitus. We proposed the innovative concept of the "gut-brain-ear axis," which underscores the exploration of gut microbiota impact on susceptibility to chronic tinnitus through serum metabolic profile modulation. We also reveal novel biomarkers associated with chronic tinnitus, offering a new conceptual framework for further investigations into the susceptibility of patients, potential treatment targets for tinnitus, and assessing patient prognosis. Subsequently, gut microbiota and serum metabolites can be used as molecular markers to assess the susceptibility and prognosis of tinnitus.Furthermore, fecal transplantation may be used to treat tinnitus.}, } @article {pmid39555739, year = {2024}, author = {Liu, X and Kang, W and Li, J and Li, X and Yang, P and Shi, M and Wang, Z and Wang, Y and Medina, ADPA and Liu, D and Zhu, F and Shen, H and Huang, K and Chen, X and Liu, Y}, title = {Melatonin Ameliorates Cadmium-Induced Liver Fibrosis Via Modulating Gut Microbiota and Bile Acid Metabolism.}, journal = {Journal of pineal research}, volume = {76}, number = {8}, pages = {e70005}, doi = {10.1111/jpi.70005}, pmid = {39555739}, issn = {1600-079X}, support = {//This study was funded by the National Natural Science Foundation of China (32102741) and Fundamental Research Funds for the Central Universities (Grant No. KJYQ2024010; KYT2023004)./ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Bile Acids and Salts/metabolism ; *Melatonin/pharmacology ; Mice ; *Liver Cirrhosis/metabolism/chemically induced/pathology ; Male ; *Cadmium/toxicity ; Mice, Knockout ; Mice, Inbred C57BL ; Receptors, Cytoplasmic and Nuclear/metabolism ; }, abstract = {Cadmium (Cd) is a widespread environmental contaminant with high toxicity to human health. Melatonin has been shown to improve Cd-induced liver damage. However, its mechanism has not yet been elucidated. In this study, we aimed to investigate the effects of melatonin on Cd-induced liver damage and fibrosis. A combination of 16S rRNA gene sequencing and mass spectrometry-based metabolomics was adopted to investigate changes in the gut microbiome and its metabolites on the regulation of melatonin in Cd-induced liver injury and fibrosis of mice. Further, nonabsorbable antibiotics, a fecal microbiota transplantation (FMT) program and intestine-specific farnesoid X receptor (FXR) knockout mice were employed to explore the mechanism of melatonin (MT) on liver injury and fibrosis in Cd treated mice. MT significantly improved hepatic inflammation, bile duct hyperplasia, liver damage, and liver fibrosis, with a notable decrease in liver bile acid levels in Cd-exposed mice. MT treatment remodeled the gut microbiota, improved gut barrier function, and reduced the production of gut-derived lipopolysaccharide (LPS). MT significantly decreased the intestinal tauro-β-muricholic acid levels, which are known as FXR antagonists. Notably, MT prominently activated the intestinal FXR signaling, subsequently inhibiting liver bile acid synthesis and decreasing hepatic inflammation in Cd-exposed mice. However, MT could not ameliorate Cd-induced liver damage and fibrosis in Abx-treated mice. Conversely, MT still exerted a protective effect on Cd-induced liver damage and fibrosis in FMT mice. Interestingly, MT failed to reverse liver damage and fibrosis in Cd-exposed intestinal epithelial cell-specific FXR gene knockout mice, indicating that intestinal FXR signaling mediated the protective effect of MT treatment. MT improves Cd-induced liver damage and fibrosis through reshaping the intestinal flora, activating the intestinal FXR-mediated suppression of liver bile acid synthesis and reducing LPS leakage in mice.}, } @article {pmid39552646, year = {2024}, author = {Dong, X and Su, Y and Luo, Z and Li, C and Gao, J and Han, X and Yao, S and Wu, W and Tian, L and Bai, Y and Wang, G and Ren, W}, title = {Fecal microbiota transplantation alleviates cognitive impairment by improving gut microbiome composition and barrier function in male rats of traumatic brain injury following gas explosion.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1485936}, pmid = {39552646}, issn = {1664-302X}, abstract = {BACKGROUND: Dysbiosis of gut microbiota (GM) is intricately linked with cognitive impairment and the incidence of traumatic brain injury (TBI) in both animal models and human subjects. However, there is limited understanding of the impact and mechanisms of fecal microbiota transplantation (FMT) on brain and gut barrier function in the treatment of TBI induced by gas explosion (GE).

METHODS: We have employed FMT technology to establish models of gut microbiota dysbiosis in male rats, and subsequently conducted non-targeted metabolomics and microbiota diversity analysis to explore the bacteria with potential functional roles.

RESULTS: Hematoxylin-eosin and transmission electron microscopy revealed that GE induced significant pathological damage and inflammation responses, as well as varying degrees of mitochondrial impairment in neuronal cells in the brains of rats, which was associated with cognitive decline. Furthermore, GE markedly elevated the levels of regulatory T cell (Tregs)-related factors interleukin-10, programmed death 1, and fork head box protein P3 in the brains of rats. Similar changes in these indicators were also observed in the colon; however, these alterations were reversed upon transfer of normal flora into the GE-exposed rats. Combined microbiome and metabolome analysis indicated up-regulation of Clostridium_T and Allobaculum, along with activation of fatty acid biosynthesis after FMT. Correlation network analysis indirectly suggested a causal relationship between FMT and alleviation of GE-induced TBI. FMT improved intestinal structure and up-regulated expression of tight junction proteins Claudin-1, Occludin, and ZO-1, potentially contributing to its protective effects on both brain and gut.

CONCLUSION: Transplantation of gut microbiota from healthy rats significantly enhanced cognitive function in male rats with traumatic brain injury caused by a gas explosion, through the modulation of gut microbiome composition and the improvement of both gut and brain barrier integrity via the gut-brain axis. These findings may offer a scientific foundation for potential clinical interventions targeting gas explosion-induced TBI using FMT.}, } @article {pmid39548908, year = {2024}, author = {Gopal, RK and Ganesh, PS and Pathoor, NN}, title = {Synergistic Interplay of Diet, Gut Microbiota, and Insulin Resistance: Unraveling the Molecular Nexus.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2400677}, doi = {10.1002/mnfr.202400677}, pmid = {39548908}, issn = {1613-4133}, abstract = {This comprehensive review explores the intricate relationship between gut microbiota, diet, and insulin resistance, emphasizing the novel roles of diet-induced microbial changes in influencing metabolic health. It highlights how diet significantly influences gut microbiota composition, with different dietary patterns fostering diverse microbial communities. These diet-induced changes in the microbiome impact human metabolism by affecting inflammation, energy balance, and insulin sensitivity, particularly through microbial metabolites like short-chain fatty acids (SCFAs). Focusing the key mediators like endotoxemia and systemic inflammation, and introduces personalized microbiome-based therapeutic strategies, it also investigates the effects of dietary components-fiber, polyphenols, and lipids-on microbiota and insulin sensitivity, along with the roles of protein intake and amino acid metabolism. The study compares the effects of Western and Mediterranean diets on the microbiota-insulin resistance axis. Therapeutic implications, including probiotics, fecal microbiota transplantation (FMT), and personalized diets, are discussed. Key findings reveal that high-fat diets, especially those rich in saturated fats, contribute to dysbiosis and increased intestinal permeability, while high-fiber diets promote beneficial bacteria and SCFAs. The review underscores the future potential of food and microbiota interventions for preventing or managing insulin resistance.}, } @article {pmid39548468, year = {2024}, author = {Song, Q and Gao, Y and Liu, K and Tang, Y and Man, Y and Wu, H}, title = {Gut microbial and metabolomics profiles reveal the potential mechanism of fecal microbiota transplantation in modulating the progression of colitis-associated colorectal cancer in mice.}, journal = {Journal of translational medicine}, volume = {22}, number = {1}, pages = {1028}, pmid = {39548468}, issn = {1479-5876}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Metabolomics ; Humans ; *Disease Progression ; *Colitis-Associated Neoplasms/microbiology/pathology/metabolism ; Mice, Inbred C57BL ; Male ; Colorectal Neoplasms/microbiology/pathology/metabolism ; Dextran Sulfate ; Metabolome ; Mice ; Female ; Azoxymethane ; Wnt Signaling Pathway ; Feces/microbiology ; }, abstract = {PURPOSE: Intestinal flora promotes the pathogenesis of colorectal cancer (CRC) through microorganisms and their metabolites. This study aimed to investigate the composition of intestinal flora in different stages of CRC progression and the effect of fecal microbiota transplantation (FMT) on CRC mice.

METHODS: The fecal microbiome from healthy volunteers (HC), colorectal adenoma (CRA), inflammatory bowel disease (IBD), and CRC patients were analyzed by 16s rRNA gene sequencing. In an azoxymethane (AOM)/dextran-sulfate-sodium (DSS)-induced CRC mouse, the effect of FMT from HC, CRA, CRC, and IBD patients on CRC mice was assessed by histological analysis. Expression of inflammation- EMT-associated proteins and Wnt/β-catenin pathway were assessed using qRT-PCR and western blot. The ratio of the fecal microorganisms and metabolomics alteration after FMT were also assessed.

RESULT: Prevotella, Faecalibacterium, Phascolarctobacterium, Veillonella, Alistipes, Fusobacterium, Oscillibacter, Blautia, and Ruminococcus abundance was different among HC, IBD, CRC, and CRA patients. HC-FMT alleviated disease progression and inflammatory response in CRC mice, inhibited splenic T help (Th)1 and Th17 cell numbers, and suppressed the EMT and Wnt/β-catenin pathways in tumor tissues of CRC mice. IBD-FMT, CRA-FMT, and CRC-FMT played deleterious roles; the CRC-FMT mice exhibited the most malignant phenotype. Compared with the non-FMT CRC mice, Muribaculaceae abundance was lower after FMT, especially lowest in the IBD-FMT group; while Lactobacillus abundance was higher after FMT and especially high in HC-FMT. Akkermansia and Ileibacterium abundance increased after FMT-HC compared to other groups. Metabolite correlation analysis revealed that Muribaculaceae abundance was significantly correlated with metabolites such as Betaine, LysoPC, and Soyasaponin III. Lactobacillus abundance was positively correlated with Taurocholic acid 3-sulfate, and Ileibacterium abundance was positively correlated with Linoleoyl ethanolamide.

CONCLUSION: The different intestinal microbiota communities of HC, IBD, CRA, and CRC patients may be attributed to the different modulation effects of FMT on CRC mice. CRC-FMT promoted, while HC-FMT inhibited the progress of CRC. Increased linoleoyl ethanolamide levels and abundance of Muribaculaceae, Akkermansia, and Ileibacterium and reduced Fusobacterium might participate in inhibiting CRC initiation and development. This study demonstrated that FMT intervention could restore the intestinal microbiota and metabolomics of CRC mice, suggesting FMT as a potential strategy for CRC therapy.}, } @article {pmid39548040, year = {2024}, author = {Wang, J and Yang, R and Zhong, H and Liu, YJ}, title = {Fecal microbiota transplants in pediatric autism: opportunities and challenges.}, journal = {World journal of pediatrics : WJP}, volume = {}, number = {}, pages = {}, pmid = {39548040}, issn = {1867-0687}, support = {82070823//National Natural Science Foundation of China/ ; }, } @article {pmid39547534, year = {2024}, author = {Birch, CR and Paaske, SE and Jensen, MB and Baunwall, SMD and Ehlers, LH and Hvas, CL}, title = {Cost-effectiveness of faecal microbiota transplantation compared with vancomycin monotherapy for early Clostridioides difficile infection: economic evaluation alongside a randomised controlled trial.}, journal = {The Journal of hospital infection}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhin.2024.11.003}, pmid = {39547534}, issn = {1532-2939}, abstract = {For Clostridioides difficile infection (CDI), faecal microbiota transplantation (FMT) is currently recommended for patients with three or more CDI episodes. A recent randomised controlled trial (RCT) show that FMT may be considered early, defined as intervention during the first or second CDI episode. Compared with standard care for first or second CDI, patients randomised to FMT had €1,645 lower hospital costs over 26 weeks owing to fewer admissions and hospital contacts and less medication use.}, } @article {pmid39547500, year = {2024}, author = {Huang, ZB and Zhang, GP and Lu, CX and Gong, C and Gao, X and Lin, Y and Su, P and Xu, W and Lin, Y and Lin, N and Wu, X and Chen, X and Zheng, T and Zheng, X}, title = {Gut microbiota-derived 3-indoleacetic acid confers a protection against sepsis-associated encephalopathy through microglial aryl hydrocarbon receptors.}, journal = {Experimental neurology}, volume = {384}, number = {}, pages = {115055}, doi = {10.1016/j.expneurol.2024.115055}, pmid = {39547500}, issn = {1090-2430}, abstract = {BACKGROUND: The gut microbiota significantly contributes to the pathogenesis of central nervous system disorders. Among the bioactive molecules produced by the gut microbiota, 3-indoleacetic acid (IAA) has been shown to attenuate oxidative stress and inflammatory responses. This experiment aimed to determine the impacts of IAA on sepsis-associated encephalopathy (SAE) and the underlying mechanisms.

METHODS: A total of 34 septic patients and 24 healthy controls were included in the analysis of the clinical correlation between fecal IAA and septic encephalopathy. Fecal microbiota transplantation was used to verify the role of the gut microbiota and its metabolites in SAE. Male C57BL/6 mice aged six to eight weeks, pre-treated with IAA via oral gavage, were subjected to the cecal ligation and puncture (CLP) procedures. This treatment was administered either in combination with an aryl hydrocarbon receptor (AhR) antagonist, CH223191, or a CSF1R inhibitor, PLX3397, to eliminate microglia. Both immunofluorescence staining and enzyme-linked immunosorbent assays were used to evaluate microglia activation and inflammatory cytokine secretion. Behavioral assessments were conducted to quantify neurological deficits.

RESULTS: A decreased fecal level of IAA was observed in the patients with sepsis-associated delirium (SAD), a manifestation of SAE. A reduced IAA level was significantly associated with worsen clinical outcomes. Fecal microbiota transplantation from the SAD patients induced an SAE-like phenotype in mice, but supplementing exogenous IAA improved the SAE-like phenotype, mediated by microglia. IAA effectively binded with the aryl hydrocarbon receptor (AhR). Furthermore, IAA increased the nuclear activity of AhR in the lipopolysaccharide (LPS)-treated microglial cells, leading to reduced secretion of inflammatory cytokines. The AhR inhibitor CH223191 counteracted the protective effect of IAA against SAE in mice.

CONCLUSIONS: Gut microbiota-derived IAA confers a protection against SAE by activating AhR in microglia, improving neuronal and cognitive impairments. Thus, IAA holds the promise as a potential therapeutic agent for managing SAE.}, } @article {pmid39547012, year = {2024}, author = {Wang, J and Hou, Y and Mu, L and Yang, M and Ai, X}, title = {Gut microbiota contributes to the intestinal and extraintestinal immune homeostasis by balancing Th17/Treg cells.}, journal = {International immunopharmacology}, volume = {143}, number = {Pt 3}, pages = {113570}, doi = {10.1016/j.intimp.2024.113570}, pmid = {39547012}, issn = {1878-1705}, abstract = {Gut microbiota is generally considered to play an important role in host health due to its extensive immunomodulatory activities. Th17 and Treg cells are two important CD4+ T cell subsets involved in immune regulation, and their imbalance is closely tied to many immune diseases. Recently, abundant researches have highlighted the importance of gut microbiota in supporting intestinal and extraintestinal immunity through the balance of Th17 and Treg cells. Here, we presented a comprehensive review of these findings. This review first provided an overview of gut microbiota, along with Th17/Treg cell differentiation and cytokine production. Subsequently, the review summarized the regulatory effects of gut microbiota (in terms of species, components, and metabolites) on the Th17/Treg cell balance in the local intestines and extraintestinal organs, such as lung, liver, brain, kidney, and bone. Specifically, the Th17 and Treg cells that can be modulated by gut microbiota originate not only from the gut and extraintestinal organs, but also from peripheral blood and spleen. Then, the microbial therapeutics, including probiotics, prebiotics, postbiotics, and fecal microbiota transplantation (FMT), were also reviewed because of their therapeutic potentials in addressing intestinal and extraintestinal diseases via the Th17/Treg axis. Finally, the review discussed the clinical applications and future study prospects of microbial therapeutics by targeting the Th17/Treg cell balance. In conclusion, this review focused on elucidating the regulatory effects of gut microbiota in balancing Th17/Treg cells to maintain intestinal and extraintestinal immune homeostasis, contributing to the further development and promotion of microbial therapeutics.}, } @article {pmid39546851, year = {2024}, author = {Peña-Ocaña, BA and Silva-Flores, M and Shotaro, T and García-Gálvez, L and Hernández-Esquivel, L and Robledo-Cadena, DX and Barrera-Oviedo, D and Pérez-Torres, I and Tostado-Islas, O and Maeda, T and Rodríguez-Zavala, JS and Marín-Hernández, Á and García-Contreras, R and Jasso-Chávez, R}, title = {Transplant of gut microbiota ameliorates metabolic and heart disorders in rats fed with a hypercaloric diet by modulating microbial metabolism and diversity.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {181}, number = {}, pages = {117667}, doi = {10.1016/j.biopha.2024.117667}, pmid = {39546851}, issn = {1950-6007}, abstract = {Metabolic syndrome (MS) is a cluster of metabolic disorders which have a tight correlation with dysbiosis of gut microbiota (GM) that have to be treated to avoid higher risks for health. In this work, probiotics obtained from healthy cultured GM were provided to rats with metabolic syndrome (MSR) as therapy in treating MS through the correction of dysbiosis. MSR showed obesity, high blood pressure, abnormal blood chemistry parameters and high heart rate respect to control rats (CNTR). Cultivated GM from feces of MSR in media favoring anaerobic species, showed dysbiosis as judged by differences in the 16S rRNA metabarcoding analysis and by affected intermediary metabolism (methane and SCFA production, nutrients consumption and enzyme activities) compared to CNTR. The metabarcoding analysis of cultured healthy GM identified 211 species, which were further transplanted alive in MSR once a week for 9 weeks. Thereafter, in transplanted MSR the excess of Clostridium and Lactobacillus diminished, while Prevotella, Eubacterium, Faecalibacterium and methanogens, among others increased, leading to the recovery of the microbial metabolic capacity. The presence of butyric acid-producing bacteria in the transplanted GM correlated with increased levels of anti-inflammatory cytokines. Therefore, transplanted MSR recovered the normal levels of weight, blood glucose, triglycerides and cholesterol as well as the heart function. Data suggested that the great diversity of species contained in the GM transplanted restored the microbial metabolism, consuming excessive nutrients and secondary metabolites produced by MS. The use of cultivated GM as probiotics may be a safer alternative for the treatment of different diseases.}, } @article {pmid39545921, year = {2024}, author = {Ullern, A and Holm, K and Røssevold, AH and Andresen, NK and Bang, C and Lingjærde, OC and Naume, B and Hov, JR and Kyte, JA}, title = {Gut microbiota diversity is prognostic and associated with benefit from chemo-immunotherapy in metastatic triple-negative breast cancer.}, journal = {Molecular oncology}, volume = {}, number = {}, pages = {}, doi = {10.1002/1878-0261.13760}, pmid = {39545921}, issn = {1878-0261}, support = {2017100//Helse Sør-Øst RHF/ ; 2017122//Helse Sør-Øst RHF/ ; 182632//Kreftforeningen/ ; 214972/WT_/Wellcome Trust/United Kingdom ; 802544/ERC_/European Research Council/International ; }, abstract = {The gut microbiota influences multiple aspects of human health and disease. Several studies have indicated an association between the gut microbiota and response to immune checkpoint inhibitors in various cancers, but there is scarce data from breast cancer. The randomized ALICE trial demonstrated improved progression-free survival (PFS) from adding the programmed cell death 1 ligand 1 (PD-L1) inhibitor atezolizumab (atezo) to immunomodulating chemotherapy (chemo) in metastatic triple-negative breast cancer (mTNBC), even for PD-L1[negative] disease. Herein, we investigated the microbiota composition and dynamics in the ALICE patients and their association with clinical outcome, by analyzing fecal samples collected at baseline and after 8 weeks. We applied 16S (V3-V4) rRNA sequencing to characterize the diversity and taxonomic composition. Kaplan-Meier and Cox proportional hazard models were used for time-to-event analyses. We found that high alpha diversity by Faith's phylogenetic diversity (PD) at baseline was associated with prolonged PFS in the total study population and in the atezo-chemo arm, but not in the placebo-chemo arm. Moreover, Faith's PD appeared to be predictive of benefit from atezolizumab. Patients with high Faith's PD exhibited a PFS hazard ratio of 0.34 (P = 0.018) in favor of the atezo-chemo arm, compared to 0.83 (P = 0.62) in the low Faith's PD group. Faith's PD was significantly reduced during treatment. At baseline, Bifidobacterium was significantly overrepresented in patients without clinical benefit in the atezo-chemo arm, but not in the placebo-chemo arm. These findings suggest that alpha diversity by Faith's PD should be further investigated as a prognostic and predictive biomarker in patients with mTNBC receiving chemo-immunotherapy.}, } @article {pmid39543390, year = {2024}, author = {Islam, J and Ohtani, N and Shimizu, Y and Tanimizu, M and Goto, Y and Sato, M and Makino, E and Shimada, T and Ueda, C and Matsuo, A and Suyama, Y and Sakai, Y and Karrow, NA and Yoneyama, H and Hirakawa, R and Furukawa, M and Tanaka, H and Nochi, T}, title = {Freeze-dried fecal microorganisms as an effective biomaterial for the treatment of calves suffering from diarrhea.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {28078}, pmid = {39543390}, issn = {2045-2322}, support = {Livestock Promotional Subsidy//Japan Racing Association/ ; 20K15478//Japan Society for the Promotion of Science/ ; 22H00393//Japan Society for the Promotion of Science/ ; 18H03969//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Cattle ; *Diarrhea/therapy/microbiology/veterinary ; *Fecal Microbiota Transplantation/methods ; *Feces/microbiology ; *Freeze Drying ; Gastrointestinal Microbiome ; Cattle Diseases/therapy/microbiology ; Biocompatible Materials ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is a therapeutic modality for treating neonatal calf diarrhea. Several practical barriers, including donor selection, fecal collection, and a limited timeframe for FMT, are the main constraints to using fresh feces for implementing on-farm FMT. We report the utility of FMT with pretreated ready-to-use frozen (F) or freeze-dried (FD) microorganisms for treating calf diarrhea. In total, 19 FMT (F-FMT, n = 10 and FD-FMT, n = 9) treatments were conducted. Both FMT treatments were 100% clinically effective; however, multi-omics analysis showed that FD-FMT was superior to F-FMT. Machine learning analysis with SourceTracker confirmed that donor microbiota was retained four times better in the recipient calves treated with FD-FMT than F-FMT. A predictive model based on receiver operating characteristic curve analysis and area under the curve showed that FD-FMT was more discriminative than F-FMT of the observed changes in microbiota and metabolites during disease recovery. These results provide new insights into establishing methods for preparing fecal microorganisms to increase the quality of FMT in animals and may contribute to FMT in humans.}, } @article {pmid39541983, year = {2024}, author = {Urtecho, G and Moody, T and Huang, Y and Sheth, RU and Richardson, M and Descamps, HC and Kaufman, A and Lekan, O and Zhang, Z and Velez-Cortes, F and Qu, Y and Cohen, L and Ricaurte, D and Gibson, TE and Gerber, GK and Thaiss, CA and Wang, HH}, title = {Spatiotemporal dynamics during niche remodeling by super-colonizing microbiota in the mammalian gut.}, journal = {Cell systems}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cels.2024.10.007}, pmid = {39541983}, issn = {2405-4720}, abstract = {While fecal microbiota transplantation (FMT) has been shown to be effective in reversing gut dysbiosis, we lack an understanding of the fundamental processes underlying microbial engraftment in the mammalian gut. Here, we explored a murine gut colonization model leveraging natural inter-individual variations in gut microbiomes to elucidate the spatiotemporal dynamics of FMT. We identified a natural "super-donor" consortium that robustly engrafts into diverse recipients and resists reciprocal colonization. Temporal profiling of the gut microbiome showed an ordered succession of rapid engraftment by early colonizers within 72 h, followed by a slower emergence of late colonizers over 15-30 days. Moreover, engraftment was localized to distinct compartments of the gastrointestinal tract in a species-specific manner. Spatial metagenomic characterization suggested engraftment was mediated by simultaneous transfer of spatially co-localizing species from the super-donor consortia. These results offer a mechanism of super-donor colonization by which nutritional niches are expanded in a spatiotemporally dependent manner. A record of this paper's transparent peer review process is included in the supplemental information.}, } @article {pmid39540836, year = {2024}, author = {Charles, P and Kumar, S and Girish Kumar, CP and Parameswaran, S and Viswanathan, P and Nachiappa Ganesh, R}, title = {Association of gut microbiota with allograft injury in kidney transplant recipients: a comparative profiling through 16S metagenomics and quantitative PCR.}, journal = {Journal of medical microbiology}, volume = {73}, number = {11}, pages = {}, doi = {10.1099/jmm.0.001934}, pmid = {39540836}, issn = {1473-5644}, mesh = {Humans ; *Kidney Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Male ; *RNA, Ribosomal, 16S/genetics ; Female ; Middle Aged ; *Metagenomics/methods ; Adult ; Prospective Studies ; Longitudinal Studies ; *Graft Rejection/microbiology ; Real-Time Polymerase Chain Reaction/methods ; Bacteria/classification/genetics/isolation & purification ; Feces/microbiology ; Allografts/microbiology ; Transplant Recipients ; }, abstract = {Introduction. The existence of a mutual relationship between gut microbiota and immune homeostasis highlights its importance in the context of kidney transplantation.Gap statement. The translational utility of gut microbiota as a biomarker for allograft injury has not been assessed before.Aim. In this study, we aimed to characterize the gut microbial diversity in kidney transplant recipients and investigate the alterations in the gut microbial composition in association with allograft injury such as histopathological graft rejection and calcineurin inhibitor toxicity. In addition, we compared the gut microbial quantitation using 16S metagenomics and quantitative PCR (qPCR) to assess its translational utility.Methodology. In this prospective longitudinal cohort study, we enrolled 38 kidney transplant recipients and collected serial faecal specimens (n=114), once before the induction therapy, and twice after transplant, during the first and third month. We characterized the gut microbial composition through 16S rRNA sequencing and qPCR from the DNA isolates of the samples. The recipients were clinically followed up for a median of 600 days post-transplant. Histopathological evidence of allograft rejection and calcineurin inhibitor toxicity were used for the correlational analysis with gut microbial diversity.Results. Significant differences in the gut microbial diversity were observed between the pre- and post-transplant samples. Pre-transplant gut microbiota revealed a higher relative abundance of phylum Bacteroidetes in the allograft rejection group, and a higher relative abundance of phylum Firmicutes was observed in the histopathological features of calcineurin inhibitor toxicity (hCNI toxicity) group. We found a high concordance between 16S metagenomics and qPCR outputs for assessing the gut microbial diversity. Furthermore, the receiver operating characteristic curve analysis has also proven that the pre-transplant levels of gut microbial dysbiosis, as a potential predictive biomarker for allograft injury.Conclusion. Our pilot study found a strong statistical association of gut microbial dysbiosis with kidney allograft injury, highlighting the potential of gut microbiota as a predictive biomarker and that qPCR serves as a more reliable and economic tool for assessing dysbiosis paving the way for its translational utility.}, } @article {pmid39539436, year = {2024}, author = {Abood, NA and Kadhim, DJ and Hussein, RJ}, title = {Medication-related burden among Iraqi patients with ulcerative colitis: a cross-sectional study.}, journal = {Journal of medicine and life}, volume = {17}, number = {8}, pages = {800-805}, pmid = {39539436}, issn = {1844-3117}, mesh = {Humans ; *Colitis, Ulcerative/drug therapy ; Iraq ; Male ; Cross-Sectional Studies ; Female ; Adult ; Surveys and Questionnaires ; Middle Aged ; Cost of Illness ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; }, abstract = {Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurring periods of inflammation and remission, primarily affecting the colon. The concept of medication-related burden, which refers to the adverse effects experienced by patients due to conventional medical treatments, is relatively new in the field. This study aimed to measure medication-related burden among patients with ulcerative colitis in Iraq. The study was conducted at the Gastroenterology and Hepatology Teaching Hospital, Medical City, Baghdad, Iraq, from December 2022 to May 2023. We used the Arabic version of the Living with Medicines Questionnaire version 3 (LMQ-3) to explore medication-related burdens experienced by patients with UC. Eighty-six patients with ulcerative colitis were included. The mean of the total medication-related burden score was 107.5 ± 20.7. The findings showed that 45.3% of patients with UC had a moderate degree of medication-related burden, followed by minimum burden (44.2%), high burden (5.8%), and no burden (4.7%). The lowest median burden scores emerged in five domains: interactions with healthcare professionals, practical difficulties with medication use, medication side effects, medication effectiveness, and the impact on daily life. Conversely, the highest-burden scores were noted in the cost, concerns about medication use, and autonomy to vary the regimen domains. In multivariate analysis, none of the patient-related variables was independently correlated with the total medication-related burden score. A large proportion of the patients with UC who participated in the current study reported varying degrees of medication-related burden, with the majority having a minimum to moderate medication-related burden.}, } @article {pmid39539028, year = {2024}, author = {Kovynev, A and Ying, Z and Zhang, S and Olgiati, E and Lambooij, JM and Visentin, C and Guigas, B and Ducarmon, QR and Rensen, PCN and Schönke, M}, title = {Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice.}, journal = {Journal of pineal research}, volume = {76}, number = {8}, pages = {e70003}, doi = {10.1111/jpi.70003}, pmid = {39539028}, issn = {1600-079X}, support = {//This work was supported by the Novo Nordisk Foundation (grant NNF18OC0032394 to M.S.), The Netherlands Cardiovascular Research Initiative CVON-GENIUS-2 (grant to P.C.N.R.), the Chinese Scholarship Council (grants to Z.Y. and S.Z.). A.K. is supported by a PhD grant from Leiden University Medical Center (to M.S.)./ ; }, mesh = {Animals ; Mice ; Male ; *Physical Conditioning, Animal ; *Gastrointestinal Microbiome ; *Liver/metabolism ; Fatty Liver/therapy/metabolism ; Non-alcoholic Fatty Liver Disease/metabolism/therapy ; Diet, High-Fat ; Mice, Transgenic ; }, abstract = {Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; L-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as Akkermansia, Lachnospiraceae, and Rikenella. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis.}, } @article {pmid38978509, year = {2024}, author = {Cantón, R and De Lucas Ramos, P and García-Botella, A and García-Lledó, A and Hernández-Sampelayo, T and Gómez-Pavón, J and González Del Castillo, J and Martín-Delgado, MC and Martín Sánchez, FJ and Martínez-Sellés, M and Molero García, JM and Moreno Guillén, S and Rodríguez-Artalejo, FJ and Reigadas, E and Del Campo, R and Serrano, S and Ruiz-Galiana, J and Bouza, E}, title = {Human intestinal microbiome: Role in health and disease.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {37}, number = {6}, pages = {438-453}, doi = {10.37201/req/056.2024}, pmid = {38978509}, issn = {1988-9518}, mesh = {Humans ; *Gastrointestinal Microbiome ; *Probiotics/therapeutic use ; Prebiotics ; Fecal Microbiota Transplantation ; }, abstract = {The study of the microbiota and the microbiome, and specifically the intestinal one, has determined great interest due to the possible association of their alterations with numerous diseases. These include entities as diverse as Crohn's disease, autism, diabetes, cancer or situations as prevalent today as obesity. In view of this situation, different recommendations have been performed regarding the use of probiotics, prebiotics, and postbiotics as modulators of the microbiota and the microbiome, seeking both preventive and therapeutic effects, and faecal material transfer (FMT) is proposed as an alternative. The latter has emerged as the only proven beneficial intervention on the intestinal microbiome, specifically in the treatment of recurrent colitis associated with Clostridioides difficile (R-CDI). In the rest of the entities, the lowering of laboratory costs has favored the study of the microbiome, which is resolved by delivering reports with catalogs of microorganisms, metabolites or supposed biomarkers without consensus on their composition associated with healthy or diseased microbiota and the disease. There is still insufficient evidence in any disease for interventions on the microbiome beyond FMT and R-CDI. Multi- and multi-disciplinary work with extensive research and the application of artificial intelligence in this field may shed light on the questions raised currently. Ethical issues must also be resolved in light of possible interventions within the umbrella of personalized medicine.}, } @article {pmid39538028, year = {2024}, author = {Emile, SH and Wignakumar, A and Horesh, N and Garoufalia, Z and Strassmann, V and Boutros, M and Wexner, SD}, title = {Systematic literature review and meta-analysis of surgical treatment of complete rectal prolapse in male patients.}, journal = {Techniques in coloproctology}, volume = {28}, number = {1}, pages = {158}, pmid = {39538028}, issn = {1128-045X}, mesh = {Adult ; Humans ; Male ; Middle Aged ; Constipation/etiology/surgery/epidemiology ; Digestive System Surgical Procedures/methods/adverse effects ; Fecal Incontinence/etiology/epidemiology ; Operative Time ; Perineum/surgery ; Postoperative Complications/etiology/epidemiology ; *Rectal Prolapse/surgery ; Rectum/surgery ; Recurrence ; Surgical Mesh ; Treatment Outcome ; }, abstract = {BACKGROUND: Rectal prolapse often affects women but may also affect men. This systematic review aimed to provide outcomes of surgery for complete rectal prolapse reported in studies with a predominantly male population.

METHODS: This PRISMA-compliant systematic literature review searched PubMed and Scopus between January 2000 and February 2024; Google Scholar was queried for studies reporting outcomes of complete rectal prolapse surgery in predominately (> 90%) male populations. Main outcome measures were recurrence, complications, operative time, and bowel function.

RESULTS: Eight studies (452 patients; median age 45.6 years) were included; 80.5% of patients underwent abdominal procedures whereas 19.5% underwent perineal procedures. The prevalence of recurrence was 11.2% after ventral mesh rectopexy (VMR), 0.8% after posterior mesh rectopexy (PMR), 0 after resection rectopexy, and 19.3% after perineal procedures. The prevalence of complications was 13.9% after VMR, 13.1% after PMR, 43.3% after resection rectopexy, and 17.4% after perineal procedures. The most improvement in constipation was noted after resection rectopexy (83.3-100%) and in fecal incontinence (FI) was noted after posterior mesh rectopexy (86.4-90%). Abdominal procedures had lower rates of recurrence (6% vs. 19.3%, RR 0.50, 95% CI 0.21-1.18, p = 0.113), similar complication rates (14.3% vs. 13.6%, RR 0.41, 95% CI 0.06-2.9, p = 0.374), and longer operative times (116 ± 47.2 vs. 74.2 ± 23.6 min, p < 0.001).

CONCLUSIONS: Treatment of rectal prolapse in male patients undergoing abdominal procedures was associated with longer operative times, lower recurrence rates, and similar complications to perineal procedures. PMR and resection rectopexy had the lowest recurrence. The most improvement in FI and constipation was noted after PMR and resection rectopexy, respectively.}, } @article {pmid39536754, year = {2024}, author = {Wang, T and Fan, Y and Tan, S and Wang, Z and Li, M and Guo, X and Yu, X and Lin, Q and Song, X and Xu, L and Li, L and Li, S and Gao, L and Liang, X and Li, C and Ma, C}, title = {Probiotics and their metabolite spermidine enhance IFN-γ[+]CD4[+] T cell immunity to inhibit hepatitis B virus.}, journal = {Cell reports. Medicine}, volume = {}, number = {}, pages = {101822}, doi = {10.1016/j.xcrm.2024.101822}, pmid = {39536754}, issn = {2666-3791}, abstract = {The therapeutic potential of commensal microbes and their metabolites is promising in the functional cure of chronic hepatitis B virus (HBV) infection, which is defined as hepatitis B surface antigen (HBsAg) loss. Here, using both specific-pathogen-free and germ-free mice, we report that probiotics significantly promote the decline of HBsAg and inhibit HBV replication by enhancing intestinal homeostasis and provoking intrahepatic interferon (IFN)-γ[+]CD4[+] T cell immune response. Depletion of CD4[+] T cells or blockage of IFN-γ abolishes probiotics-mediated HBV inhibition. Specifically, probiotics-derived spermidine accumulates in the gut and transports to the liver, where it exhibits a similar anti-HBV effect. Mechanistically, spermidine enhances IFN-γ[+]CD4[+] T cell immunity by autophagy. Strikingly, administration of probiotics in HBV patients reveals a preliminary trend to accelerate the decline of serum HBsAg. In conclusion, probiotics and their derived spermidine promote HBV clearance via autophagy-enhanced IFN-γ[+]CD4[+] T cell immunity, highlighting the therapeutic potential of probiotics and spermidine for the functional cure of HBV patients.}, } @article {pmid39534584, year = {2024}, author = {Hrubesz, G and Leigh, J and Ng, TL}, title = {Understanding the relationship between breast cancer, immune checkpoint inhibitors, and gut microbiota: a narrative review.}, journal = {Translational breast cancer research : a journal focusing on translational research in breast cancer}, volume = {5}, number = {}, pages = {31}, pmid = {39534584}, issn = {2218-6778}, abstract = {BACKGROUND AND OBJECTIVE: The composition of gut microbiota plays an important role in predicting and influencing outcomes of cancer treated with immunotherapy. Our objective is to summarize the role of gut microbiota and immunotherapy in breast cancer.

METHODS: A systematic search from inception until July 2024 of key search terms including immunity, breast neoplasm, gastrointestinal microbiome/microbiota, fecal microbiota transplantation, pro- and prebiotics, antibiotics and immunotherapy using EMBASE, MEDLINE and CENTRAL was conducted. The results were screened by two reviewers independently and synthesized and presented descriptively.

KEY CONTENT AND FINDINGS: Thirteen studies (5 clinical, 8 pre-clinical) met the eligibility criteria and were published from 2020-2024. Clinical studies showed that the composition and diversity of gut microbiota was associated with patient response to immunotherapy. In pre-clinical studies, dysbiotic states induced by obesity, antibiotics, and diet were associated with immunosuppression and influenced response to programmed cell death-ligand 1 (PD-L1) inhibitors. Microbiota-modulating treatments such as probiotics showed the ability to enhance response to immunotherapy, indicating their potential use as adjunct therapies in breast cancer treatment.

CONCLUSIONS: The composition of gut microbiota could help predict the chance of response to immunotherapy, and modulating gut microbiota has the potential to enhance the efficacy of chemo-immunotherapy in breast cancer. However, the available data relating to breast cancer are limited. Larger prospective studies are required to further elucidate their role as a biomarker and treatment.}, } @article {pmid39534519, year = {2024}, author = {Jeyaraman, N and Jeyaraman, M and Mariappan, T and Muthu, S and Ramasubramanian, S and Sharma, S and Santos, GS and da Fonseca, LF and Lana, JF}, title = {Insights of gut-liver axis in hepatic diseases: Mechanisms, clinical implications, and therapeutic potentials.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {15}, number = {6}, pages = {98146}, pmid = {39534519}, issn = {2150-5349}, abstract = {With the rising prevalence of chronic liver diseases worldwide, there exists a need to diversify our artillery to incorporate a plethora of diagnostic and therapeutic methods to combat this disease. Currently, the most common causes of liver disease are non-alcoholic fatty liver disease, hepatitis, and alcoholic liver disease. Some of these chronic diseases have the potential to transform into hepatocellular carcinoma with advancing fibrosis. In this review, we analyse the relationship between the gut and liver and their significance in liver disease. This two-way relationship has interesting effects on each other in liver diseases. The gut microbiota, through its metabolites, influences the metabolism in numerous ways. Careful manipulation of its composition can lead to the discovery of numerous therapeutic potentials that can be applied in the treatment of various liver diseases. Numerous cohort studies with a pan-omics approach are required to understand the association between the gut microbiome and hepatic disease progression through which we can identify effective ways to deal with this issue.}, } @article {pmid39534419, year = {2024}, author = {Wang, J and Meng, Y and Guo, ZG}, title = {Contribution of gut microbiota to the development of Crohn's disease: Insights gained from fecal microbiota transplantation studies in mice.}, journal = {World journal of gastroenterology}, volume = {30}, number = {41}, pages = {4514-4517}, pmid = {39534419}, issn = {2219-2840}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Crohn Disease/microbiology/immunology/therapy ; *Gastrointestinal Microbiome/immunology ; Mice ; *Disease Models, Animal ; Humans ; Mesentery ; Feces/microbiology ; Intestines/microbiology/immunology ; Adipose Tissue/immunology ; }, abstract = {We would like to present some new thoughts on the publication in the journal published in August 2024 in World Journal of Gastroenterology. We specifically focused on the alterations in the intestinal tract, mesenteric adipose tissue (MAT), and systemic inflammatory changes in mice following fecal flora transplantation into a mouse model of Crohn's disease (CD). Accumulating evidence suggests that the occurrence of CD is influenced by environmental factors, host immune status, genetic susceptibility, and flora imbalance. One microbiota-based intervention, fecal microbiota transplantation, has emerged as a potential treatment option for CD. The MAT is considered a "second barrier" around the inflamed intestine. The interaction between gut microbes and inflammatory changes in MAT has attracted considerable interest. In the study under discussion, the authors transplanted fetal fecal microorganisms from patients with CD and clinically healthy donors, respectively, into 2,4,6-trinitrobenzene sulfonic acid-induced CD mice. The research explored the complex interplay between MAT, creeping fat, inflammation, and intestinal flora in CD by evaluating intestinal and mesenteric lesions, along with the systemic inflammatory state in the mice. This article provides several important insights. First, the transplantation of intestinal flora holds significant potential as a therapeutic strategy for CD, offering hope for patients with CD. Second, it presents a novel approach to the diagnosis and treatment of CD: The inflammatory response in CD could potentially be assessed through pathological or imaging changes in the MAT, and CD could be treated by targeting the inflammation of the MAT.}, } @article {pmid39533632, year = {2024}, author = {Philips, CA and Ahamed, R and Oommen, TT and Nahaz, N and Tharakan, A and Rajesh, S and Augustine, P}, title = {Clinical outcomes and associated bacterial and fungal microbiota changes after high dose probiotic therapy for severe alcohol-associated hepatitis: An observational study.}, journal = {Medicine}, volume = {103}, number = {45}, pages = {e40429}, pmid = {39533632}, issn = {1536-5964}, mesh = {Humans ; *Hepatitis, Alcoholic/therapy ; Male ; *Probiotics/administration & dosage/therapeutic use ; Middle Aged ; Female ; *Gastrointestinal Microbiome/drug effects ; *Fecal Microbiota Transplantation/methods ; Adult ; Treatment Outcome ; Adrenal Cortex Hormones/administration & dosage/therapeutic use ; Mycobiome ; Dysbiosis/therapy/microbiology ; }, abstract = {Alcohol-associated hepatitis (AH) is a critical condition with high mortality rates and is worsened by infections. Organ failure is strongly associated with intestinal dysbiosis. Emerging research suggests that gut microbiota modulation with probiotics can improve AH outcomes. This study investigated the clinical and microbiome effects of high-dose probiotic infusion (HDPI) compared with corticosteroid therapy (CST) and fecal microbiota transplantation (FMT) in severe AH. Patients with biopsy-proven severe-AH were enrolled from March 2019 to June 2020 and matched for age and disease severity. The patients received HDPI (n = 20), FMT (n = 16), or CST (n = 14). HDPI consists of a potent probiotic mix delivered via a nasoduodenal tube for 6 days. The primary outcome was survival at 90-days. Stool samples were subjected to 16S and 18S rRNA sequencing to assess significant bacterial and fungal taxa and their interactions at baseline and post treatment. At 90-days, survival rates were 55%, 64.3%, and 87.5% (HDPI, CST, respectively). HDPI did not beneficially impact bacterial alpha-diversity but significantly altered beta-diversity. Notably, the number of pathogenic bacteria, such as Bilophila and Roseburia increased. Fungal analysis revealed no significant changes in alpha diversity, but significant dissimilarities in beta diversity post-HDPI. New fungal genera such as Basidiomycota and Phragmoplastophyta have emerged, with significant deleterious expansion in fungal communities and damaging modifications between fungal-bacterial interactions. HDPI failed to outperform CST in improving the clinical outcomes of patients with severe AH. While HDPI influenced both bacterial and fungal microbiomes, it also led to the persistence of pathogenic communities. FMT showed superior survival outcomes, highlighting the urgent need for further controlled trials.}, } @article {pmid39533343, year = {2024}, author = {Guo, X and Xu, J and Zhao, Y and Wang, J and Fu, T and Richard, ML and Sokol, H and Wang, M and Li, Y and Liu, Y and Wang, H and Wang, C and Wang, X and He, H and Wang, Y and Ma, B and Peng, S}, title = {Melatonin alleviates heat stress-induced spermatogenesis dysfunction in male dairy goats by regulating arachidonic acid metabolism mediated by remodeling the gut microbiota.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {233}, pmid = {39533343}, issn = {2049-2618}, support = {32072815//National Natural Science Foundation of China/ ; 2022YFD1300200//National Key Research and Development Program of China/ ; 2023-YBNY-140//General Project of the Key R & D Plan of Shaanxi Province/ ; TG20221184//Ningbo Second Hormone Factory/ ; }, mesh = {Animals ; *Melatonin/pharmacology ; Male ; *Spermatogenesis/drug effects ; *Goats ; *Gastrointestinal Microbiome/drug effects ; *Testis/drug effects/metabolism ; Mice ; *Heat-Shock Response/drug effects ; *Arachidonic Acid/metabolism ; Spermatozoa/drug effects ; Oxidative Stress/drug effects ; }, abstract = {BACKGROUND: Heat stress (HS) commonly occurring in summer has gradually become a factor threatening the reproductive performance of male dairy goats by reducing their fecundity. Despite the melatonin is applied to relieve HS, it is still unclear whether melatonin protects against reproductive damage induced by HS in dairy goats and how it works. The purpose of the present study is to evaluate the role of melatonin in alleviating HS-induced spermatogenesis dysfunction in male dairy goats and further explore its mechanism.

RESULTS: HS impaired spermatogenesis, sperm formation in the testes, and sperm maturation in the epididymis of dairy goats, resulting in decreased sperm quality. Melatonin rescued the decrease of sperm quality induced by HS via decreasing inflammatory and oxidative stress levels in testicular tissue and enhancing intercellular barrier function within the testes. Amplicon-based microbiota analysis revealed that despite gut microbiota differences between melatonin-treated dairy goats and NC dairy goats to some extent, melatonin administration tends to return the gut microbiota of male dairy goats under HS to the levels of natural control dairy goats. To explore whether the protective role of melatonin in sperm quality is mediated by regulating gut microbiota, fecal microbiota of HS dairy goats with or without melatonin treatment were transferred to HS mice, respectively. We found HS mice that had received fecal bacteria of HS dairy goats experienced serious testicular injury and dyszoospermia, while this phenomenon was ameliorated in HS mice that had received fecal bacteria of dairy goats treated with melatonin, indicating melatonin alleviates HS-induced spermatogenic damage in a microbiota dependent manner. We further found that the testicular tissue of both HS dairy goats and mice transplanted with HS dairy goat feces produced large amounts of arachidonic acid (AA)-related metabolites, which were closely associated with semen quality. Consistently, supplementation with AA has been shown to elevate the levels of inflammation and oxidative stress in the testicular tissue of mice, disrupting intercellular connections and ultimately leading to spermatogenic disorders.

CONCLUSION: This study has revealed that melatonin can effectively alleviate spermatogenic disorders in dairy goats caused by HS. This beneficial effect was primarily achieved through the modulation of gut microbiota, which subsequently inhibited the excessive synthesis of AA in testicular tissue. These discoveries are of great significance for preventing or improving the decline in male livestock reproductive performance caused by HS, enhancing the reproductive efficiency of elite male breeds, and ultimately improving the production efficiency of animal husbandry. Video Abstract.}, } @article {pmid39531305, year = {2024}, author = {Tursumetova, DR and Khan, Y and Tkacheva, LV and Rayevskii, KP}, title = {[The role and features of the gut microbiota in Alzheimer's disease.].}, journal = {Advances in gerontology = Uspekhi gerontologii}, volume = {37}, number = {4}, pages = {442-452}, pmid = {39531305}, issn = {1561-9125}, mesh = {*Alzheimer Disease/microbiology/therapy/physiopathology ; Humans ; *Gastrointestinal Microbiome/physiology ; *Probiotics/administration & dosage/therapeutic use ; Fecal Microbiota Transplantation/methods ; Prebiotics/administration & dosage ; Brain-Gut Axis/physiology ; Disease Progression ; }, abstract = {Alzheimer's disease causes gradual, persistent deterioration of cognitive function in the elderly, causing social and economic damage to society. Over the past decades, mankind has made significant progress in the study of Alzheimer's disease, but there are no methods to fully control the disease. The lack of effectiveness of existing treatment methods emphasizes the need to search for new approaches. The present review is devoted to the study of the latest data regarding the role of microbiota in the mechanisms of formation and progression of Alzheimer's disease, possible therapeutic ways to influence the processes of neurodegeneration through microbiota and taking into account identified relationships. The article considers the axis «gut microbiota-brain» as a link in the pathogenesis of neuroinflammation. New data on the influence of gut microbiota on neurodegenerative processes through metabolic, nervous, and immune mechanisms is analyzed. New data reveals correlations between microbiota specifics and the origin and/or progression of Alzheimer's disease, expanding the understanding of disease pathogenesis. The role of the oral microbiota in neurodegeneration processes is mentioned, emphasizing the diverse mechanisms of this disease. Available therapies for Alzheimer's disease are discussed, including probiotics and prebiotics, fecal microbiota transplantation, and dietary correction.}, } @article {pmid39529641, year = {2024}, author = {Kirsch, P and Rauch, J and Delau, O and Axelrad, J and Chang, S and Shaukat, A}, title = {Prevalence of Active Pouch Symptoms and Patient Perception of Symptom Control and Quality of Life in an Outpatient Practice.}, journal = {Gastro hep advances}, volume = {3}, number = {8}, pages = {1069-1078}, pmid = {39529641}, issn = {2772-5723}, abstract = {BACKGROUND AND AIMS: Pouchitis is an inflammatory condition affecting the ileal pouch in patients' status after ileal pouch anal anastomosis (IPAA). This affects a significant portion of IPAA patients. Our aim was to study the prevalence of active pouch symptoms among currently treated outpatients with endoscopic pouchitis and understand patients' perspective of disease control and quality of life.

METHODS: We cross-sectionally reviewed the medical charts of patients who had undergone pouchoscopy at NYU Langone Health from 2010 to 2022 and recorded demographic, clinical, and endoscopic data. Based on the most recent data in the medical record, we defined active pouch symptoms as 2 or more current clinical symptoms and "endoscopic pouchitis" as "moderate" or "severe" by pouchoscopy. We also administered surveys in March 2023 to 296 patients with an IPAA to understand symptom control, quality of life, and interest in fecal microbiota transplant.

RESULTS: We identified 282 unique patients. The median age of patients was 46 (interquartile range 33-59), with 54.3% males. Of these, 37.2% of patients currently had active pouch symptoms, 36.9% had endoscopic pouchitis, and 14.9% met the criteria for both. Of the 296 surveys sent to patients with IPAA, 74 (25%) responded. The median age of respondents was 49.5 (interquartile range 34-62). 59.5% were male. Average treatment satisfaction score (scale of 0-10) was 6.4 and quality of life score was 5.8. A majority (64.9%) expressed interest in fecal microbiota transplant.

CONCLUSION: Outpatients with active pouch symptoms or endoscopic pouchitis have high prevalence of active disease and report ongoing symptoms. The results underscore the inadequacy of current treatments and highlight the need for additional therapeutic options.}, } @article {pmid39524804, year = {2024}, author = {Zhang, Y and Wu, Y and Guan, Y and Lu, Y and Zhu, W and Ping, F and Wang, Y}, title = {Maidong Dishao Decoction mitigates submandibular gland injury in NOD mice through modulation of gut microbiota and restoration of Th17/Treg immune balance.}, journal = {Heliyon}, volume = {10}, number = {21}, pages = {e38421}, pmid = {39524804}, issn = {2405-8440}, abstract = {BACKGROUND: Primary Sjogren's syndrome (pSS) is a common chronic autoimmune disease that presents limited treatment options and poses significant challenges for patients. Maidong Dishao Decoction (MDDST), a traditional Chinese medicine compound, has demonstrated potential in alleviating dryness symptoms associated with pSS. Therefore, it is important to study the specific mechanism of its therapeutic effect.

OBJECTIVE: This study aims to investigate the effects of MDDST on gut microbiota, short-chain fatty acids (SCFAs), and the Th17/Treg immune balance in non-obese diabetes (NOD) mice.

METHODS: The study employed ultrahigh-performance liquid chromatography coupled with quadrupole-exactive mass spectrometry (UHPLC-QE-MS) to identify the primary components of MDDST. Subsequently, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assays (ELISA), and flow cytometry analyses were conducted to evaluate the therapeutic effects of MDDST in NOD mice. Additionally, 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS) were utilized to assess the influence of MDDST on gut microbiota and SCFAs. Finally, fecal microbiota transplantation (FMT) and SCFA-based interventions were performed to elucidate the mechanisms through which MDDST exerts its effects.

RESULTS: The research findings demonstrate that MDDST exerts therapeutic effects on NOD mice, primarily manifested as reduced inflammation, decreased water intake, ameliorated pathological changes and lowered levels of Sjogren's syndrome antigen A (SSA) and immunoglobulin G (IgG). Additionally, MDDST significantly decreased serum levels of interleukin-6 (IL-6) and interleukin-17 (IL-17), while enhancing levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), thereby regulating the Th17/Treg immune balance. Further investigations revealed that MDDST treatment induces alterations in gut microbiota composition and elevates SCFA levels in the gut. Subsequent FMT and SCFA intervention experiments demonstrated a downregulation of pSS-related phenotypes.

CONCLUSION: In summary, MDDST demonstrates protective effects against pSS by restoring the balance between Th17 and Treg cells. The therapeutic effects can be partially attributed to its regulation of gut microbiota and SCFAs. Our finding provides a new option for treating pSS.}, } @article {pmid39530534, year = {2024}, author = {Kao, D and Wong, K and Jijon, H and Moayyedi, P and Franz, R and McDougall, C and Hotte, N and Panaccione, R and Semlacher, E and Kroeker, KI and Peerani, F and MacDonald, KV and Xu, H and Narula, N and Turbide, C and Marshall, DA and Madsen, KL}, title = {Preliminary results from a multicenter, randomized trial using fecal microbial transplantation to induce remission in patients with mild to moderate Crohn's disease.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000003196}, pmid = {39530534}, issn = {1572-0241}, abstract = {INTRODUCTION: Fecal microbial transplantation (FMT) has shown promise at inducing remission in ulcerative colitis. This study is the first of its kind to evaluate the efficacy and safety of FMT at inducing remission in Crohn's disease (CD).

METHODS: This double-blind, placebo-controlled trial was conducted in three Canadian academic centers; randomized patients with mild to moderate CD received FMT or placebo. The first treatment was administered by colonoscopy followed by weekly fecal capsules for 7 weeks. Primary endpoint was clinical and endoscopic remission at week 8. Secondary outcomes included clinical and endoscopic response, adverse events, and health-related quality of life using generic and disease-specific instruments.

RESULTS: From July 2017 to June 2021, 21 and 13 patients were randomized to FMT and placebo groups, respectively. The trial terminated early due to futility. At week 8, 0% (0/15) of patients in the FMT group versus 8.3% (1/11) in the placebo group reached the primary endpoint of combined clinical and endoscopic remission as per protocol analysis. There were no differences between the groups in clinical or endoscopic responses. One participant in each group had worsening of CD. Although both groups experienced statistically significant improvements in health-related quality of life, only the FMT group had a significant decrease in activity impairment. Although there were no significant changes in microbial diversity or composition, participants who achieved clinical response became more similar to their donors in stool microbial composition.

DISCUSSION: FMT was not effective at inducing clinical and endoscopic remission in CD using the FMT regimen in this study. Future studies may use other strategies to enhance treatment response, including longer intervention, antibiotic pretreatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet, biologic or small molecule therapies.}, } @article {pmid39528920, year = {2024}, author = {Laperrousaz, B and Levast, B and Fontaine, M and Nancey, S and Dechelotte, P and Doré, J and Lehert, P}, title = {Safety comparison of single-donor and pooled fecal microbiota transfer product preparation in ulcerative colitis: systematic review and meta-analysis.}, journal = {BMC gastroenterology}, volume = {24}, number = {1}, pages = {402}, pmid = {39528920}, issn = {1471-230X}, mesh = {*Colitis, Ulcerative/therapy/microbiology ; Humans ; *Fecal Microbiota Transplantation/methods ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {BACKGROUND: Multiple studies have evaluated fecal microbiota transfer (FMT) in patients with ulcerative colitis (UC) using single-donor (SDN) and multidonor (MDN) products. Systematic review and meta-analysis were performed to compare the safety of SDN and MDN products.

METHODS: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence to identify studies that compared FMT products manufactured using SDN or MDN strategies against control treatment in patients with UC. Fifteen controlled studies were selected for meta-analysis (11 randomized controlled trials and 4 controlled cohort trials). Safety of each treatment type was assessed using the counts of adverse events and serious adverse events using fixed- and random-effects models. Significance of the indirect difference between FMT preparations was assessed using a network approach. Benefit-risk ratios were calculated by multiplicative utility model, incorporating geometric mean of risk ratios (RRs) of efficacy and safety.

RESULTS: Safety data was collected for a total of 587 patients (193 exposed to SDN products, 114 exposed to MDN products and 280 exposed to control treatment). The 12 studies showed similar overall safety event counts for MDN and SDN versus placebo (RRs: 0.90 and 1.09, respectively [P = 0.206 and P = 0.420, respectively]). Results indicated similar risk of safety events for MDN compared to SDN (RR: 0.83, P = 0.159). Positive benefit-risk ratios were demonstrated for MDN and SDN versus placebo (RRs: 1.70 and 1.16, respectively [P = 0.003 and P = 0.173, respectively]). MDN had a greater benefit-risk ratio compared to SDN (RR: 1.46, P = 0.072).

CONCLUSION: Similar safety profiles were observed for MDN and SDN strategies. Alongside previously described superior efficacy, treatment with MDN has greater benefit-risk ratio than SDN in patients with UC. Further development of MDN FMT treatment for UC should be considered.}, } @article {pmid39526563, year = {2024}, author = {Tessier, MEM and Schraw, JM and Beer, S and Harpavat, S and Kyle Jensen, M and Magee, JC and Ng, V and Scheurer, ME and Taylor, SA and Shneider, BL}, title = {The association of human milk intake and outcomes in biliary atresia.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1002/jpn3.12403}, pmid = {39526563}, issn = {1536-4801}, support = {5K23-DK119567//National Institute of Diabetes, Digestive and Kidney Diseases/ ; U01DK103140//University of Utah/ ; U01DK062453//Children's Hospital Colorado/ ; U01DK062456//The University of Michigan/ ; U01DK103149//Texas Children's Hospital/ ; U01DK103135//The Hospital for Sick Children/ ; U24DK062456//ChiLDReN's Scientific Data Coordinating Center, Ann Arbor, MI/ ; }, abstract = {OBJECTIVES: Human milk intake has many benefits which could influence outcomes in biliary atresia (BA). However, the role of human milk in BA has not been examined. We hypothesized that human milk intake would be associated with improved outcomes in BA.

METHODS: We assessed the impact of any human milk (AHM) as compared to formula only (FO) intake before Kasai portoenterostomy (KP) on outcomes in 447 infants with BA using the PROBE database (NCT00061828) post hoc. The primary outcome was clearance of jaundice (COJ = total bilirubin (TB) < 2 mg/dL by 3 months post-KP). Secondary outcomes included 2-year native liver survival (SNL), bilirubin levels, cholangitis, ascites, and growth. We assessed the fecal microbiome (n = 8) comparing AHM versus FO.

RESULTS: At baseline, 211 infants received AHM and 215 received FO. 53.9% of AHM and 50.5% of FO achieved COJ (p = NS). SNL was insignificantly increased in AHM (odds ratio = 1.47, 95% confidence interval: 1.00-2.12, p = 0.053). TB decreased in AHM from 4 weeks to 3 months post-KP [4.8-4.0 mg/dL (p = 0.01)] unlike the FO group (4.9-4.9 mg/dL, p = 0.4). At 3 months post-KP, AHM infants had greater weight gain (1.88 ± 0.66 vs. 1.57 ± 0.73 kg, p < 0.001) and mid-upper arm circumference (12.9 ± 1.4 vs. 12.2 ± 1.7 cm, p < 0.001). Other secondary outcomes were not different. Microbiome differences were seen between AHM and FO.

CONCLUSIONS: Human milk intake in infants with BA did not significantly improve COJ or SNL. However, growth parameters were improved, and TB 3 months post-KP was decreased. Thus, human milk intake should not be discouraged. Prospective studies with detailed assessment of human milk intake are needed.}, } @article {pmid39515099, year = {2024}, author = {Yu, ZQ and Du, HX and Gao, S and Liang, CZ}, title = {Eriocalyxin B ameliorated experimental autoimmune prostatitis via modulation of macrophage polarization through gut microbiota-mediated vitamin D3 alteration.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156191}, doi = {10.1016/j.phymed.2024.156191}, pmid = {39515099}, issn = {1618-095X}, abstract = {BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a often heterogeneous condition in urology. Accumulating evidence suggests that the autoimmune response against prostate antigens is related to CP/CPPS. The gut microbiota may be a possible cause of a number of autoimmune diseases. Eriocalyxin B (EriB) is used as an anti-inflammatory treatment for autoimmune disorders. The underlying mechanism of fecal metabolome involved in CP/CPPS treatment by EriB remains unclear.

METHODS: The experimental autoimmune prostatitis (EAP) mouse model was generated by subcutaneous immunization. Macrophages, inflammatory cytokines, intestinal microbiota, and fecal metabolome of the mice were analyzed. The alteration of the fecal metabolome was investigated in detail in EriB-treated EAP mice and confirmed by in vitro experiments.

RESULTS: EriB ameliorated significantly decreased prostate inflammation in EAP mice and promoted macrophage phenotype polarizing from M1 to M2. The gut microbiome was altered, and intestinal barrier damage was improved by EriB treatment. Furthermore, the enrichment of vitamin digestion and absorption pathways in the fecal metabolome revealed that vitamin D3 was altered by EriB. In vitro experiments confirmed that macrophage polarization from M1 to M2 was promoted by vitamin D3. Finally, fecal transplantation from EriB-treated mice markedly reduced inflammatory indicators and the macrophage M1/M2 ratio in pseudogerm-free EAP mice. In our study, the immune state of macrophage regulated by gut microbiota-mediated vitamin D3 alteration was first time revealed in EAP treatment.

CONCLUSIONS: EriB ameliorated in mice with EAP, the gut microbiota mediates vitamin D3 alterations to modulate macrophage phenotype polarizing from M1 to M2.}, } @article {pmid39515036, year = {2024}, author = {Sun, B and Hu, C and Li, J and Yang, Z and Chen, L}, title = {Interaction between young fecal transplantation and perfluorobutanesulfonate endocrine disrupting toxicity in aged recipients: An estrobolome perspective.}, journal = {Environment international}, volume = {193}, number = {}, pages = {109133}, doi = {10.1016/j.envint.2024.109133}, pmid = {39515036}, issn = {1873-6750}, abstract = {Transplanting young feces into the aged was found to effectively counteract the endocrine disrupting effects of perfluorobutanesulfonate (PFBS) pollutant, showing promise in the maintenance of healthy aging. However, the interactive mechanisms between young fecal transplantation and PFBS endocrine disruption during aging remain unclear. In this follow-up study, aged zebrafish were administered young donor feces and then exposed to environmentally relevant concentrations of PFBS (0 and 100 μg/L). Alterations in the holistic estrobolome along gut-liver axis were investigated. The results showed that PFBS singular exposure significantly increased blood estradiol concentration in the aged, inducing an estrogenic activity. Concentrations of other estrogen forms, including estrone and estriol, were also disrupted by PFBS. Interestingly, young fecal transplant effectively mitigated the estrogenic toxicity of PFBS and largely restored estrogen equilibrium. After PFBS exposure, the transcriptions of estrogen metabolic genes were consistently upregulated in aged livers, causing the accumulation of 2-methoxyestradiol-3-methylether metabolite. In contrast, aged livers coexposed to young fecal transplant and PFBS enhanced the glucuronidation process, successfully facilitating the elimination and detoxification of estrogen metabolites. In aged gut, PFBS exposure inhibited β-glucuronidase enzyme activity, implying the suppression of estrogen deconjugation and recycle. However, in the combined group, β-glucuronidase activity was significantly stimulated, thus reestablishing estrobolome dynamics. Overall, current findings provide mechanistic insights into the antagonistic interaction between young fecal transplant and PFBS on reproductive endocrinology. Gut microbiota manipulation appears appealing to maintain healthy aging progression albeit the interruption of environmental xenobiotics.}, } @article {pmid39513042, year = {2024}, author = {Park, KJ and Gao, Y}, title = {Gut-brain axis and neurodegeneration: mechanisms and therapeutic potentials.}, journal = {Frontiers in neuroscience}, volume = {18}, number = {}, pages = {1481390}, pmid = {39513042}, issn = {1662-4548}, abstract = {This paper reviews the effects of gut microbiota in regulating neurodegenerative diseases through controlling gut-brain axis. Specific microbial populations and their metabolites (short-chain fatty acids and tryptophan derivatives) regulate neuroinflammation, neurogenesis and neural barrier integrity. We then discuss ways by which these insights lead to possible interventions - probiotics, prebiotics, dietary modification, and fecal microbiota transplantation (FMT). We also describe what epidemiological and clinical studies have related certain microbiota profiles with the courses of neurodegenerative diseases and how these impact the establishment of microbiome-based diagnostics and individualized treatment options. We aim to guide microbial ecology research on this key link to neurodegenerative disorders and also to highlight collaborative approaches to manage neurological health by targeting microbiome-related factors.}, } @article {pmid39510500, year = {2024}, author = {Scull, CE and Hu, Y and Jennings, S and Wang, G}, title = {Normalization of CF Immune System Reverses Intestinal Neutrophilic Inflammation and Significantly Improves the Survival of CF Mice.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {}, number = {}, pages = {101424}, doi = {10.1016/j.jcmgh.2024.101424}, pmid = {39510500}, issn = {2352-345X}, abstract = {BACKGROUND & AIMS: Cystic fibrosis (CF) is an autosomal recessive genetic disorder, affecting multiple organ systems. CF intestinal disease develops early, manifesting as intestinal bacterial overgrowth/dysbiosis, neutrophilic inflammation and obstruction. As unresolvable infection and inflammation reflect host immune deficiency, we sought to determine if the CF-affected immune system plays any significant role in CF intestinal disease pathogenesis.

METHODS: CF and sibling wild-type (WT) mice underwent reciprocal bone marrow transplantation. After immune reconstitution, their mortality, intestinal transit, fecal inflammatory markers, and mucosal immune cell composition were assessed. Moreover, reciprocal neutrophil transfusion was conducted to determine if neutrophil function affects intestinal movement. Furthermore, expression of induced nitric oxide synthase (iNOS) and production of nitric oxide (NO) in CF and WT neutrophils were compared. Lastly, specific iNOS inhibitor 1400W was tested to prevent CF intestinal obstruction.

RESULTS: Immune restoration in CF mice reversed the intestinal neutrophilic inflammation, improved the intestinal dysmotility, and rescued the mice from mortality. Transfusion of WT neutrophils into CF mice ameliorated the retarded bowel movement. CF neutrophils expressed significantly more iNOS and produced significantly more NO. Pharmaceutical blocking of iNOS significantly improved intestinal transit and survival of CF mice.

CONCLUSION: CF immune defect plays a critical role in CF intestinal disease development. Activation of iNOS in inflammatory cells produces excessive NO, slows the bowel movement, and facilitates intestinal paralysis and obstruction in CF. Thus, normalization of the CF immune system may offer a novel therapy to treat CF intestinal disease.}, } @article {pmid39510376, year = {2024}, author = {Huang, Y and You, Y and Wang, W and Chen, YH and Zhang, H and Li, QP and Liu, L and Tong, K and Sun, N and Hao, JR and Gao, C}, title = {Adenosine regulates depressive behavior in mice with chronic social defeat stress through gut microbiota.}, journal = {Neuropharmacology}, volume = {262}, number = {}, pages = {110209}, doi = {10.1016/j.neuropharm.2024.110209}, pmid = {39510376}, issn = {1873-7064}, abstract = {Major depressive disorder (MDD) is recognized as the most prevalent affective disorder worldwide. Metagenomic studies increasingly support a critical role for dysbiosis of gut microbiota in the development of depression. Previous studies have demonstrated that adenosine alleviates gut dysbiosis, suggesting that elevating adenosine levels could be a novel intervention for MDD; however, the mechanisms underlying this effect remain unclear. This study utilized 16S rRNA gene sequencing, fecal microbiota transplantation (FMT) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to test the hypothesis that increased adenosine alleviates depressive behaviors in male mice subjected to chronic social defeat stress (CSDS) through alterations to gut microbiota. The data showed that depression-susceptible (SUS) mice exhibited gut dysbiosis, and FMT from SUS mice increased depression-like behaviors in healthy recipients. In SUS mice, adenosine supplementation ameliorated both depression-like behaviors and abnormalities in gut microbiota, and co-administration of probiotics and adenosine not only mitigated depression-like behaviors but also enhanced gut barrier integrity. By including 83 depressed adolescents and 67 healthy controls, this study found that the level of short-chain fatty acids (SCFAs) in the depression group was reduced, this finding parallels reductions seen in SUS mice and in recipient mice after FMT from SUS donors. Conversely, supplementation with either adenosine or probiotics led increased SCFAs concentrations in the serum of SUS mice. These findings suggest that adenosine may alleviate depression-like behaviors in CSDS mice by modulating the gut microbiota. This effect is likely associated with increased serum SCFAs, metabolites produced by the gut microbiota, following adenosine supplementation.}, } @article {pmid39510013, year = {2024}, author = {Yang, D and Lv, G and Wu, Y and Guo, W and Wang, Y and Hu, J and Li, N and Zheng, F and Dai, Y and Pi, Z and Yue, H}, title = {Licorice-regulated gut-joint axis for alleviating collagen-induced rheumatoid arthritis.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156203}, doi = {10.1016/j.phymed.2024.156203}, pmid = {39510013}, issn = {1618-095X}, abstract = {BACKGROUND: Rheumatoid arthritis (RA) is partially affected by the integrity of the intestinal barrier. Licorice (GC), a medicinal and food-related herb, exhibits potent anti-inflammatory activity; however, studies on its mechanisms of action in RA are limited.

METHOD: Using a bovine type-II collagen-induced arthritis rat model, this study examined how GC influences the gut-joint axis to decrease RA. The Th17/Treg cell ratios in the blood, colon, and joints were also measured. Metabolomics and 16S rRNA sequencing were applied to explore the effects of variations in gut flora and metabolites.

RESULTS: The arthropathological slices, inflammation markers, and joint inflammation index scores in the GC treatment group significantly differed from those in the CIA group. Studies on the effect of GC on the gut-joint axis showed changes in the levels of lipopolysaccharide and diamine oxidase, both directly associated with intestinal permeability. ZO-1, occludin, and claudin-1, three intestinal tight-junction proteins, may express themselves more when exposed to GC. By maintaining an appropriate Th17/Treg cell ratio in the blood, colon, and joints, GC may reduce impaired to the intestinal barrier. An imbalance in the intestinal microenvironment, caused by modifications in gut flora and endogenous substances, can damage the intestinal barrier. GC may modify the relative abundances of Papillibacter, Clostridium, Eubacterium, Helicobacter, Provotella, and Barnesiella during RA treatment by repairing the intestinal barrier. The metabolic differences were mainly related to primary bile acid biosynthesis, pyrimidine metabolism, steroid biosynthesis, biotin metabolism, and sphingolipid metabolism. A fecal microbiota transplantation experiment confirmed the involvement of the gut microbiota and its metabolites in GC-mediated RA therapy.

CONCLUSION: The results demonstrated that GC repairs the intestinal barrier and adjusts the gut-joint axis to manage immunological imbalance in RA.}, } @article {pmid39509684, year = {2024}, author = {L'Huillier, JC and Guo, WA}, title = {The always evolving diagnosis and management of Clostridioides difficile colitis: What you need to know.}, journal = {The journal of trauma and acute care surgery}, volume = {}, number = {}, pages = {}, doi = {10.1097/TA.0000000000004474}, pmid = {39509684}, issn = {2163-0763}, abstract = {The diagnosis, pharmacologic management, and surgical options for Clostridioides difficile infection (CDI) are rapidly evolving, which presents a challenge for the busy surgeon to remain up to date on the latest clinical guidelines. This review provides an evidence-based practical guide for CDI management tailored to the needs of surgeons and surgical intensivists. Historically, the diagnosis of CDI relied on slow cell culture cytotoxicity neutralization assays, but now, the rapidly resulting nucleic acid amplification tests and enzyme immunoassays have become mainstream. In terms of antibiotic therapy, metronidazole and oral vancomycin were the main "workhorse" antibiotics in the early 2000s, but large randomized controlled trials have now demonstrated that fidaxomicin produces superior results. Regarding surgical intervention, total abdominal colectomy was once the only procedure of choice; however, diverting loop ileostomy with colonic lavage is emerging as a viable alternative. Finally, novel adjuncts such as fecal microbiota transplantation and targeted therapy against toxin B (bezlotoxumab) are playing an increasingly important role in the management of CDI.}, } @article {pmid39507519, year = {2024}, author = {Claassen-Weitz, S and du Toit, E and Gardner-Lubbe, S and Kullin, B and Bellairs, G and Hilton, C and Chicken, A and Welp, K and Livingstone, H and Brink, A}, title = {Knowledge and perceptions of South African blood donors towards biobanking and stool donation.}, journal = {Southern African journal of infectious diseases}, volume = {39}, number = {1}, pages = {645}, pmid = {39507519}, issn = {2313-1810}, abstract = {BACKGROUND: The complexity of contexts and varied purposes for which biome donation are requested are unknown in South Africa.

OBJECTIVES: The aim of this study was to provide strategic data towards actualisation of whether a stool donor bank may be established as a collaborative between Western Cape Blood Services (WCBS) and the University of Cape Town (UCT).

METHOD: We designed a cross-sectional, questionnaire-based survey to determine willingness of WCBS blood donors to donate stool specimens for microbiome biobanking. The study was conducted between 01 June 2022 and 01 July 2022 at three WCBS donation centres in Cape Town, South Africa. Anonymous blood donors who met the inclusion criteria were enrolled. Anonymised demographic and interview data were analysed statistically.

RESULTS: Analysis of responses from 209/231 blood donors demonstrated in a logistic regression model that compensation (p < 0.001) and 'societal benefit outweighs inconvenience' beliefs (p = 7.751e-05) were covariates significantly associated with willingness to donate stool. Age was borderline significant at a 5% level (p = 0.0556). Most willing stool donors indicated that donating stool samples would not affect blood donations (140/157, 90%). Factors decreasing willingness to donate were stool collection being unpleasant or embarrassing.

CONCLUSION: The survey provides strategic data for the establishment of a stool bank and provided an understanding of the underlying determinants regarding becoming potential donors.

CONTRIBUTION: This is the first report on the perspectives of potential participants in donating samples towards a stool microbiome biobank in South Africa, a necessity for faecal microbiota transplantation (FMT).}, } @article {pmid39523344, year = {2024}, author = {You, X and Yan, J and Herzog, J and Nobakhti, S and Campbell, R and Hoke, A and Hammamieh, R and Sartor, RB and Shefelbine, S and Kacena, MA and Chakraborty, N and Charles, JF}, title = {Bone loss with aging is independent of gut microbiome in mice.}, journal = {Bone research}, volume = {12}, number = {1}, pages = {65}, pmid = {39523344}, issn = {2095-4700}, support = {R01-AG046257//U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ ; P30-AR070253//U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/ ; P40-OD010995//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; P30-DK034987//U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ ; 997397//Crohn's and Colitis Foundation (Crohn's & Colitis Foundation)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/physiology ; *Aging/physiology ; Male ; Mice ; Feces/microbiology ; RNA, Ribosomal, 16S/genetics ; Bone Resorption/microbiology ; Germ-Free Life ; }, abstract = {Emerging evidence suggests a significant role of gut microbiome in bone health. Aging is well recognized as a crucial factor influencing the gut microbiome. In this study, we investigated whether age-dependent microbial change contributes to age-related bone loss in CB6F1 mice. The bone phenotype of 24-month-old germ-free (GF) mice was indistinguishable compared to their littermates colonized by fecal transplant at 1-month-old. Moreover, bone loss from 3 to 24-month-old was comparable between GF and specific pathogen-free (SPF) mice. Thus, GF mice were not protected from age-related bone loss. 16S rRNA gene sequencing of fecal samples from 3-month and 24-month-old SPF males indicated an age-dependent microbial shift with an alteration in energy and nutrient metabolism potential. An integrative analysis of 16S predicted metagenome function and LC-MS fecal metabolome revealed an enrichment of protein and amino acid biosynthesis pathways in aged mice. Microbial S-adenosyl methionine metabolism was increased in the aged mice, which has previously been associated with the host aging process. Collectively, aging caused microbial taxonomic and functional alteration in mice. To demonstrate the functional importance of young and old microbiome to bone, we colonized GF mice with fecal microbiome from 3-month or 24-month-old SPF donor mice for 1 and 8 months. The effect of microbial colonization on bone phenotypes was independent of the microbiome donors' age. In conclusion, our study indicates age-related bone loss occurs independent of gut microbiome.}, } @article {pmid39522895, year = {2024}, author = {Wan, J and Wang, F and Xiao, Y and Cheng, Y and Zhen, S and Jiang, Q and Tan, B and Li, X and Chen, J and Liao, S}, title = {Poria cocos polysaccharides alleviate dextran sulphate sodium-induced ulcerative colitis in mice by modulating intestinal inflammatory responses and microbial dysbiosis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {137450}, doi = {10.1016/j.ijbiomac.2024.137450}, pmid = {39522895}, issn = {1879-0003}, abstract = {Poria cocos polysaccharide (PCP), one of the main active components of P. cocos, is extensively used worldwide and exhibits strong pharmacological effects. However, whether PCP can attenuate inflammatory bowel disease remains unclear. In this study, we assessed the effects of PCP supplementation on dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) in mice. We found that PCP supplementation mitigated UC symptoms in DSS-treated mice, as evidenced by reductions in body weight loss, colon length shortening and disease activity index score. Importantly, PCP supplementation enhanced colonic barrier integrity by increasing tight junction protein abundance and exerted anti-inflammatory effects by suppressing nuclear factor-κB (NF-κB) activation in DSS-treated mice. Furthermore, PCP supplementation reversed DSS-induced dysbiosis in colonic microbiota by increasing the colonic abundance of beneficial bacteria (e.g. Akkermansiaceae) and decreasing the colonic abundance of harmful bacteria (e.g. Erysipelotrichaceae) in DSS-treated mice. Although PCP supplementation failed to ameliorate DSS-induced UC in antibiotic-treated mice, faecal microbiota transplantation from PCP-administered mice ameliorated DSS-induced UC in antibiotic-treated mice. In summary, PCP alleviates UC in mice by attenuating intestinal inflammation via the inhibition of NF-κB activation and modulating the intestinal microbiota.}, } @article {pmid39522254, year = {2024}, author = {Li, X and Khan, I and Han, R and Huang, G and Xia, W and Yin, L and Leong, WK and Su, L and Law, BY and Wong, VKW and Wu, Q and Guo, X and Hsiao, WLW}, title = {Gynostemma pentaphyllum saponins shield mice from peanut allergy by modulation of gut microbiota: A novel approach for peanut allergy management.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {135}, number = {}, pages = {156101}, doi = {10.1016/j.phymed.2024.156101}, pmid = {39522254}, issn = {1618-095X}, abstract = {BACKGROUND: Food allergies, particularly peanut (PN) allergies, are a growing concern, with fatal anaphylaxis incidents often reported. While palforzia is the sole FDA-approved drug for managing PN allergies, it is not universally effective.

PURPOSE: This study aimed to investigate the potential of Gynostemma pentaphyllum saponins (GpS) as a novel therapeutic agent for PN allergy through modulation of gut microbiota, addressing the limitations of current treatments.

METHODS: To elucidate the role of GpS on peanut allergy, we first built a PN-sensitized C57BL/6J model mice. Through comprehensive sequencing analysis, we identified Parabacteroides distasonis as a key bacterium triggering PN sensitization. Employing the same mouse model, GpS was evaluated for its effects on anaphylactic symptoms, serum immunoglobulin levels, and allergy-related biomarkers. 16S rRNA sequencing and transcriptomic analysis were applied to investigate the impact of GpS on the host's gut epithelium and microbiome.

RESULTS: GpS treatment effectively reduced anaphylactic symptoms in PN-sensitized mice, as shown by decreased IgG1, total IgE, and PN-specific IgE levels. It also modulated the immune response by suppressing proinflammatory cytokines (IL-1β, IFN-γ, IL-21) and chemokines (CCL5, CCL12, CCL17, CCL22), while enhancing anti-inflammatory cytokines (IL-4, IL-10, IL-12, IL-13). Fecal microbial transplant from GpS-treated Model mice to PN-sensitized mice displayed anti-peanut allergy effects. Additionally, the administration of GpS-enhanced bacteria (Clostridium aldenese or Lactobacillus murinus), alleviated anaphylactic symptoms and reduced serum allergy markers in PN-sensitized mice.

CONCLUSION: To conclude, we revealed the intestinal environment, signaling molecules, mucosal cytokines, and commensal microbial profiles in the peanut-sensitized mouse model. We further presented evidence for the protective effect of GpS against PN allergen sensitization by downregulating a series of food-allergy-associated biomarkers and cytokines via the modulation of gut bacteria. More importantly, supported by both in vitro and in vivo experiments, we demonstrated that the protective effect of GpS against PN-allergy is through the enhancement of two commensal bacteria, Clostridium aldenese, and Lactobacillus murinus.}, } @article {pmid39521596, year = {2024}, author = {Hurtado-Lorenzo, A and Swantek, JL}, title = {The landscape of new therapeutic opportunities for IBD.}, journal = {Advances in pharmacology (San Diego, Calif.)}, volume = {101}, number = {}, pages = {1-83}, doi = {10.1016/bs.apha.2024.10.011}, pmid = {39521596}, issn = {1557-8925}, mesh = {Humans ; *Inflammatory Bowel Diseases/drug therapy/therapy/immunology ; Animals ; Gastrointestinal Microbiome ; Fecal Microbiota Transplantation ; }, abstract = {This chapter presents an overview of the emerging strategies to address the unmet needs in the management of inflammatory bowel diseases (IBD). IBD poses significant challenges, as over half of patients experience disease progression despite interventions, leading to irreversible complications, and a substantial proportion do not respond to existing therapies, such as biologics. To overcome these limitations, we describe a diverse array of novel therapeutic approaches. In the area of immune homeostasis restoration, the focus is on targeting cytokine networks, leukocyte trafficking, novel immune pathways, and cell therapies involving regulatory T cells and mesenchymal stem cells (MSC). Recognizing the critical role of impaired intestinal barrier integrity in IBD, we highlight therapies aimed at restoring barrier function and promoting mucosal healing, such as those targeting cell proliferation, tight junctions, and lipid mediators. Addressing the challenges posed by fibrosis and fistulas, we describe emerging targets for reversing fibrosis like kinase and cytokine inhibitors and nuclear receptor agonists, as well as the potential of MSC for fistulas. The restoration of a healthy gut microbiome, through strategies like fecal microbiota transplantation, rationally defined bacterial consortia, and targeted antimicrobials, is also highlighted. We also describe innovative approaches to gut-targeted drug delivery to enhance efficacy and minimize side effects. Reinforcing these advancements is the critical role of precision medicine, which emphasizes the use of multiomics analysis for the discovery of biomarkers to enable personalized IBD care. Overall, the emerging landscape of therapeutic opportunities for IBD holds great potential to surpass the therapeutic ceiling of current treatments.}, } @article {pmid39521225, year = {2024}, author = {Yang, X and Zhang, X and Ma, Y and Li, S and Wang, Q and Hong, JS and Yu, G and Qi, B and Wang, J and Liu, C and Shang, Q and Wu, X and Zhao, J}, title = {Fucoidan ameliorates rotenone-induced Parkinsonism in mice by regulating the microbiota-gut-brain axis.}, journal = {International journal of biological macromolecules}, volume = {}, number = {}, pages = {137373}, doi = {10.1016/j.ijbiomac.2024.137373}, pmid = {39521225}, issn = {1879-0003}, abstract = {Microbiota-gut-brain axis, the bidirectional relationship between the gut microbiota and the brain, has been increasingly appreciated in the pathogenesis of Parkinson's disease (PD). Fucoidan, a sulphate-rich polysaccharide, has been shown to be neuroprotective by reducing oxidative stress in PD models. However, the role of microbiota-gut-brain axis in the neuroprotective activity of fucoidan has not been revealed. In this study, the therapeutic effects of fucoidan and involvement of microbiota-gut-brain axis in rotenone (ROT)-induced PD were investigated. The results showed that fucoidan gavage attenuated neuroinflammation, dopamine neuronal damage and motor dysfunction in ROT-induced PD mice. In addition, fucoidan treatment ameliorated gut dysfunction, intestinal inflammation and disruption of the intestinal barrier in PD mice. Fucoidan also affected the composition of gut microbiota in PD mice, indicated particularly by decreased abundance of Akkermansia muciniphila and Lactobacillus johnsonii and increased abundance of Lactobacillus murinus. Mechanistic studies showed that fecal microbiota transplantation (FMT) from the fucoidan-treated mice and probiotic Lactobacillus murinus supplement are as potent as fucoidan treatment in attenuating peripheral and central inflammation and ameliorating dopamine neuronal damage, which might be attributed to the downregulation of LPS/TLR4/NF-κB signaling pathway. Our study suggests that fucoidan might be potential candidates for the treatment of PD.}, } @article {pmid39519488, year = {2024}, author = {Pinto, C and Carrasco-Loncharic, T and González-Mienert, E and de Solminihac, J and Gálvez-Jirón, F and Cifuentes, F and Pino-Lagos, K}, title = {IL-33 Induces a Switch in Intestinal Metabolites Revealing the Tryptophan Pathway as a Target for Inducing Allograft Survival.}, journal = {Nutrients}, volume = {16}, number = {21}, pages = {}, doi = {10.3390/nu16213655}, pmid = {39519488}, issn = {2072-6643}, support = {1210654//Fondo Nacional de Desarrollo Científico y Tecnológico (Fondecyt)/ ; }, mesh = {Animals ; *Tryptophan/metabolism ; *Gastrointestinal Microbiome/drug effects ; *Graft Survival/drug effects ; *Interleukin-33/metabolism ; *Skin Transplantation ; *T-Lymphocytes, Regulatory/metabolism ; Mice ; *Mice, Inbred C57BL ; Intestines/drug effects ; Allografts ; Mice, Inbred BALB C ; Male ; Kynurenic Acid/metabolism ; Dysbiosis ; }, abstract = {BACKGROUND: IL-33, a pleiotropic cytokine, has been associated with a plethora of immune-related processes, both inflammatory and anti-inflammatory. T regulatory (Treg) cells, the main leukocyte population involved in immune tolerance, can be induced by the administration of IL-33, the local microbiota, and its metabolites. Here, we demonstrate that IL-33 drastically induces the production of intestinal metabolites involved on tryptophan (Trp) metabolism.

METHODS: naïve mice were treated with IL-33 for 4 days and leukocyte populations were analyzed by flow cytometry, and feces were processed for microbiota and intestinal metabolites studies. Using a murine skin transplantation model, the effect of Kynurenic acid (KA) on allograft survival was tested.

RESULTS: Under homeostatic conditions, animals treated with IL-33 showed an increment in Treg cell frequencies. Intestinal bacterial abundance analysis indicates that IL-33 provokes dysbiosis, demonstrated by a reduction in Enterobacteria and an increment in Lactobacillus genera. Furthermore, metabolomics analysis showed a dramatic IL-33 effect on the abundance of intestinal metabolites related to amino acid synthesis pathways, highlighting molecules linked to Trp metabolism, such as kynurenic acid (KA), 5-Hydroxyindoleacetic acid (5-HIAA), and 6-Hydroxynicotinic acid (6-HNA), which was supported by an enhanced expression of Ido and Kat mRNA in MLN cells, which are two enzymes involved on KA synthesis. Interestingly, animals receiving KA in drinking water and subjected to skin transplantation showed allograft acceptance, which is associated with an increment in Treg cell frequencies.

CONCLUSIONS: Our study reveals a new property for IL-33 as a modulator of the intestinal microbiota and metabolites, especially those involved with Trp metabolism. In addition, we demonstrate that KA favors Tregs in vivo, positively affecting skin transplantation survival.}, } @article {pmid39519055, year = {2024}, author = {Misiąg, P and Molik, K and Kisielewska, M and Typek, P and Skowron, I and Karwowska, A and Kuźnicki, J and Wojno, A and Ekiert, M and Choromańska, A}, title = {Amelanotic Melanoma-Biochemical and Molecular Induction Pathways.}, journal = {International journal of molecular sciences}, volume = {25}, number = {21}, pages = {}, doi = {10.3390/ijms252111502}, pmid = {39519055}, issn = {1422-0067}, mesh = {Humans ; *Melanoma, Amelanotic/metabolism/genetics/pathology ; Proto-Oncogene Proteins B-raf/genetics/metabolism/antagonists & inhibitors ; Biomarkers, Tumor/metabolism ; Proto-Oncogene Proteins c-kit/genetics/metabolism/antagonists & inhibitors ; Skin Neoplasms/metabolism/genetics/pathology/therapy ; Melanins/metabolism/biosynthesis ; Signal Transduction ; }, abstract = {Amelanotic melanoma (AM) is a subtype of hypomelanotic or completely amelanotic melanoma. AM is a rare subtype of melanoma that exhibits a higher recurrence rate and aggressiveness as well as worse surveillance than typical melanoma. AM shows a dysregulation of melanin production, cell cycle control, and apoptosis pathways. Knowing these pathways has an application in medicine due to targeted therapies based on the inhibiting elements of the abovementioned pathways. Therefore, we summarized and discussed AM biochemical and molecular induction pathways and personalized medicine approaches, clinical management, and future directions due to the fact that AM is relatively rare. AM is commonly misdiagnosed. Hence, the role of biomarkers is becoming significant. Nonetheless, there is a shortage of biomarkers specific to AM. BRAF, NRAS, and c-KIT genes are the main targets of therapy. However, the role of BRAF and KIT in AM varied among studies. BRAF inhibitors combined with MAK inhibitors demonstrate better results. Immune checkpoint inhibitors targeting CTLA-4 combined with a programmed death receptor 1 (PD-1) show better outcomes than separately. Fecal microbiota transplantation may overcome resistance to immune checkpoint therapy of AM. Immune-modulatory vaccines against indoleamine 2,3-dioxygenase (IDO) and PD ligand (PD-L1) combined with nivolumab may be efficient in melanoma treatment.}, } @article {pmid39518717, year = {2024}, author = {Brusnic, O and Onisor, D and Boicean, A and Hasegan, A and Ichim, C and Guzun, A and Chicea, R and Todor, SB and Vintila, BI and Anderco, P and Porr, C and Dura, H and Fleaca, SR and Cristian, AN}, title = {Fecal Microbiota Transplantation: Insights into Colon Carcinogenesis and Immune Regulation.}, journal = {Journal of clinical medicine}, volume = {13}, number = {21}, pages = {}, doi = {10.3390/jcm13216578}, pmid = {39518717}, issn = {2077-0383}, abstract = {Colorectal cancer (CRC) constitutes a significant global health challenge, with recent studies underscoring the pivotal role of the gut microbiome in its pathogenesis and progression. Fecal microbiota transplantation (FMT) has emerged as a compelling therapeutic approach, offering the potential to modulate microbial composition and optimize treatment outcomes. Research suggests that specific bacterial strains are closely linked to CRC, influencing both its clinical management and therapeutic interventions. Moreover, the gut microbiome's impact on immunotherapy responsiveness heralds new avenues for personalized medicine. Despite the promise of FMT, safety concerns, particularly in immunocompromised individuals, remain a critical issue. Clinical outcomes vary widely, influenced by genetic predispositions and the specific transplantation methodologies employed. Additionally, rigorous donor selection and screening protocols are paramount to minimize risks and maximize therapeutic efficacy. The current body of literature advocates for the establishment of standardized protocols and further clinical trials to substantiate FMT's role in CRC management. As our understanding of the microbiome deepens, FMT is poised to become a cornerstone in CRC treatment, underscoring the imperative for continued research and clinical validation.}, } @article {pmid39508236, year = {2024}, author = {Shen, H and Zhang, C and Zhang, Q and Lv, Q and Liu, H and Yuan, H and Wang, C and Meng, F and Guo, Y and Pei, J and Yu, C and Tie, J and Chen, X and Yu, H and Zhang, G and Wang, X}, title = {Gut microbiota modulates depressive-like behaviors induced by chronic ethanol exposure through short-chain fatty acids.}, journal = {Journal of neuroinflammation}, volume = {21}, number = {1}, pages = {290}, pmid = {39508236}, issn = {1742-2094}, support = {82271931//National Natural Science Foundation of China/ ; 82101979//National Natural Science Foundation of China/ ; 2022-MS-220//Natural Science Foundation of Liaoning Province/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects/physiology ; Mice ; *Ethanol/toxicity/administration & dosage/pharmacology ; *Depression/chemically induced/metabolism ; *Fatty Acids, Volatile/metabolism ; Male ; *Mice, Inbred C57BL ; Fecal Microbiota Transplantation ; Anxiety/chemically induced ; Central Nervous System Depressants/pharmacology/toxicity ; }, abstract = {BACKGROUND: Chronic ethanol exposure (CEE) is recognized as an important risk factor for depression, and the gut-brain axis has emerged as a key mechanism underlying chronic ethanol exposure-induced anxiety and depression-like behaviors. Short-chain fatty acids (SCFAs), which are the key metabolites generated by gut microbiota from insoluble dietary fiber, exert protective roles on the central nervous system, including the reduction of neuroinflammation. However, the link between gut microbial disturbances caused by chronic ethanol exposure, production of SCFAs, and anxiety and depression-like behaviors remains unclear.

METHODS: Initially, a 90-day chronic ethanol exposure model was established, followed by fecal microbiota transplantation model, which was supplemented with SCFAs via gavage. Anxiety and depression-like behaviors were determined by open field test, forced swim test, and elevated plus-maze. Serum and intestinal SCFAs levels were quantified using GC-MS. Changes in related indicators, including the intestinal barrier, intestinal inflammation, neuroinflammation, neurotrophy, and nerve damage, were detected using Western blotting, immunofluorescence, and Nissl staining.

RESULTS: Chronic ethanol exposure disrupted with gut microbial homeostasis, reduced the production of SCFAs, and led to anxiety and depression-like behaviors. Recipient mice transplanted with fecal microbiota that had been affected by chronic ethanol exposure exhibited impaired intestinal structure and function, low levels of SCFAs, intestinal inflammation, activation of neuroinflammation, a compromised blood-brain barrier, neurotrophic defects, alterations in the GABA system, anxiety and depression-like behaviors. Notably, the negative effects observed in these recipient mice were significantly alleviated through the supplementation of SCFAs.

CONCLUSION: SCFAs not only mitigate damage to intestinal structure and function but also alleviate various lesions in the central nervous system, such as neuroinflammation, and reduce anxiety and depression-like behaviors, which were triggered by transplantation with fecal microbiota that had been affected by chronic ethanol exposure, adding more support that SCFAs serve as a bridge between the gut and the brain.}, } @article {pmid39502702, year = {2024}, author = {Han, YJ and Kim, S and Shin, H and Kim, HW and Park, JD}, title = {Protective effect of gut microbiota restored by fecal microbiota transplantation in a sepsis model in juvenile mice.}, journal = {Frontiers in immunology}, volume = {15}, number = {}, pages = {1451356}, pmid = {39502702}, issn = {1664-3224}, mesh = {Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Sepsis/therapy/microbiology/immunology ; Mice ; *Disease Models, Animal ; Male ; Cytokines/metabolism/blood ; Anti-Bacterial Agents/therapeutic use ; Dysbiosis/therapy ; Feces/microbiology ; Mice, Inbred C57BL ; }, abstract = {INTRODUCTION: Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice.

METHODS: Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP.

RESULTS: Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1β (IL-1β), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-α, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%).

CONCLUSION: FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children.}, } @article {pmid39502523, year = {2024}, author = {Anouti, A and Kerr, TA and Mitchell, MC and Cotter, TG}, title = {Advances in the management of alcohol-associated liver disease.}, journal = {Gastroenterology report}, volume = {12}, number = {}, pages = {goae097}, pmid = {39502523}, issn = {2052-0034}, abstract = {Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.}, } @article {pmid39500537, year = {2024}, author = {Slizovskiy, IB and Bonin, N and Bravo, JE and Ferm, PM and Singer, J and Boucher, C and Noyes, NR}, title = {Factors impacting target-enriched long-read sequencing of resistomes and mobilomes.}, journal = {Genome research}, volume = {}, number = {}, pages = {}, doi = {10.1101/gr.279226.124}, pmid = {39500537}, issn = {1549-5469}, abstract = {We investigated the efficiency of target-enriched long-read sequencing (TELSeq) for detecting antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs) within complex matrices. We aimed to overcome limitations associated with traditional antimicrobial resistance (AMR) detection methods, including short-read shotgun metagenomics, which can lack sensitivity, specificity, and the ability to provide detailed genomic context. By combining biotinylated probe-based enrichment with long-read sequencing, we facilitated the amplification and sequencing of ARGs, eliminating the need for bioinformatic reconstruction. Our experimental design included replicates of human fecal microbiota transplant material, bovine feces, pristine prairie soil, and a mock human gut microbial community, allowing us to examine variables including genomic DNA input and probe set composition. Our findings demonstrated that TELSeq markedly improves the detection rates of ARGs and MGEs compared to traditional sequencing methods, underlining its potential for accurate AMR monitoring. A key insight from our research is the importance of incorporating mobilome profiles to better predict the transferability of ARGs within microbial communities, prompting a recommendation for the use of combined ARG-MGE probe sets for future studies. We also reveal limitations for ARG detection from low-input workflows, and describe the next steps for ongoing protocol refinement to minimize technical variability and expand utility in clinical and public health settings. This effort is part of our broader commitment to advancing methodologies that address the global challenge of AMR.}, } @article {pmid39500027, year = {2024}, author = {Hua, Y and Zhou, C and Fan, R and Benazzouz, S and Shen, J and Xiao, R and Ma, W}, title = {Altered intestinal microbiota induced by high-fat diets affect cognition differently in mice.}, journal = {Nutrition research (New York, N.Y.)}, volume = {132}, number = {}, pages = {67-84}, doi = {10.1016/j.nutres.2024.09.019}, pmid = {39500027}, issn = {1879-0739}, abstract = {The role of the gut microbiota in the association between high-fat diet and cognition is not clear. We hypothesized that a high-fat diet may influence cognition by altering the intestinal microbiota. Fecal microbiota isolated from male C57BL/6J mice feeding on various high-fat diets and a control basic diet were transplanted to antibiotic-treated recipient mice. The measurement of weight and plasma lipids, novel object recognition test, 16S rRNA gene sequencing of feces, and hematoxylin-eosin staining of the hippocampal cornu ammonis 1 and cornu ammonis 3 areas were performed for all mice. Compared with those in the control and n-3 polyunsaturated fatty acid (n-3 PUFA) groups, donor obese mice fed with diets high in long-chain saturated fatty acids, n-6 polyunsaturated fatty acids (n-6 PUFAs), and trans fatty acids exhibited significant cognitive impairment (all P < .05). There were fewer neurons in the hippocampal area in the n-6 PUFA group than in the n-3 PUFA group (P < .05). Similar effect on cognition and neurons in hippocampal area in corresponding recipient mice were revealed after fecal microbiota transplantation. In addition, the composition of intestinal microbiota differed among recipient mice after fecal microbiota transplantation from donor mice. According to these results, it was concluded that diets rich in long-chain saturated fatty acids, n-6 PUFAs, and trans fatty acids may lead to cognitive impairment by damaging the structure of the hippocampus through influencing the intestinal microbiota in mice, whereas a diet high in n-3 PUFAs may exhibit a beneficial effect.}, } @article {pmid39499189, year = {2024}, author = {Ghani, R and Chrysostomou, D and Roberts, LA and Pandiaraja, M and Marchesi, JR and Mullish, BH}, title = {Faecal (or intestinal) microbiota transplant: a tool for repairing the gut microbiome.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2423026}, pmid = {39499189}, issn = {1949-0984}, mesh = {*Fecal Microbiota Transplantation/methods ; Humans ; *Gastrointestinal Microbiome ; *Clostridium Infections/therapy/microbiology ; Animals ; Feces/microbiology ; Clostridioides difficile/physiology ; Treatment Outcome ; Donor Selection ; }, abstract = {Faecal/intestinal microbiota transplant (FMT/IMT) is an efficacious treatment option for recurrent Clostridioides difficile infection, which has prompted substantial interest in FMT's potential role in the management of a much broader range of diseases associated with the gut microbiome. Despite its promise, the success rates of FMT in these other settings have been variable. This review critically evaluates the current evidence on the impact of clinical, biological, and procedural factors upon the therapeutic efficacy of FMT, and identifies areas that remain nebulous. Due to some of these factors, the optimal therapeutic approach remains unclear; for example, the preferred timing of FMT administration in a heavily antibiotic-exposed hematopoietic cell transplant recipient is not standardized, with arguments that can be made in alternate directions. We explore how these factors may impact upon more informed selection of donors, potential matching of donors to recipients, and aspects of clinical care of FMT recipients. This includes consideration of how gut microbiome composition and functionality may strategically inform donor selection criteria. Furthermore, we review how the most productive advances within the FMT space are those where clinical and translational outcomes are assessed together, and where this model has been used productively in recent years to better understand the contribution of the gut microbiome to human disease, and start the process toward development of more targeted microbiome therapeutics.}, } @article {pmid39495286, year = {2024}, author = {Zhang, H and Zhou, W and Gao, P and Li, Z and Li, C and Li, J and Bian, J and Gong, L and He, C and Han, L and Wang, M}, title = {Ellagic Acid Protects against Alcohol-Related Liver Disease by Modulating the Hepatic Circadian Rhythm Signaling through the Gut Microbiota-NPAS2 Axis.}, journal = {Journal of agricultural and food chemistry}, volume = {72}, number = {45}, pages = {25103-25117}, doi = {10.1021/acs.jafc.4c06992}, pmid = {39495286}, issn = {1520-5118}, mesh = {*Gastrointestinal Microbiome/drug effects ; *Circadian Rhythm ; Animals ; *Basic Helix-Loop-Helix Transcription Factors/metabolism/genetics ; *Liver/metabolism/drug effects ; *Liver Diseases, Alcoholic/metabolism/prevention & control/microbiology/drug therapy ; Mice ; Male ; Humans ; *Ellagic Acid/pharmacology ; *Mice, Inbred C57BL ; Signal Transduction/drug effects ; Nerve Tissue Proteins/genetics/metabolism ; Bacteria/classification/genetics/metabolism/isolation & purification/drug effects ; Protective Agents/pharmacology/administration & dosage ; }, abstract = {Alcohol-related liver disease (ALD) encompasses a spectrum of hepatic disorders resulting from alcohol abuse, which constitutes the predominant etiology of morbidity and mortality associated with hepatic pathologies globally. Excessive alcohol consumption disrupts the integrity of the intestinal barrier and perturbs the balance of gut microbiota, thereby facilitating the progression of ALD. Ellagic acid (EA) has been extensively reported to be an effective intervention for alleviating liver symptoms. However, the target molecules of EA in improving ALD and its underlying mechanism remain elusive. First, our study indicates that EA ameliorated ALD through the hepatic circadian rhythm signaling by up-regulating neuronal PAS domain protein 2 (NPAS2). Furthermore, analysis of the intestinal microbiome showed that EA significantly enhanced the abundance of beneficial bacteria, which was positively correlated with NPAS2 expression and negatively correlated with liver injury. Finally, antibiotic treatment and fecal microbiota transplantation (FMT) experiments established a causal relationship between the reshaped microbiota and NPAS2 in the amelioration of ALD. In summary, our study demonstrates novel evidence that EA attenuated ALD by modulating the hepatic circadian rhythm signaling pathway via the gut microbiota-NPAS2 axis, providing valuable insights for EA and microbiome-targeted interventions against ALD.}, } @article {pmid39494101, year = {2024}, author = {Singh, AK and Durairajan, SSK and Iyaswamy, A and Williams, LL}, title = {Elucidating the role of gut microbiota dysbiosis in hyperuricemia and gout: Insights and therapeutic strategies.}, journal = {World journal of gastroenterology}, volume = {30}, number = {40}, pages = {4404-4410}, pmid = {39494101}, issn = {2219-2840}, mesh = {*Dysbiosis ; Humans ; *Gout/microbiology/therapy/complications ; *Gastrointestinal Microbiome/physiology ; *Hyperuricemia/microbiology/blood/therapy/diagnosis ; *Uric Acid/blood/metabolism ; *Probiotics/therapeutic use/administration & dosage ; *Prebiotics/administration & dosage ; Gout Suppressants/therapeutic use ; }, abstract = {Hyperuricemia (HUA) is a condition associated with a high concentration of uric acid (UA) in the bloodstream and can cause gout and chronic kidney disease. The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people. This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder. Some studies have suggested that changes in the composition, diversity, and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis. Therefore, we discussed how the gut microbiota contributes to HUA through purine metabolism, UA excretion, and intestinal inflammatory responses. We examined specific changes in the composition of the gut microbiota associated with gout and HUA, highlighting key bacterial taxa and the metabolic pathways involved. Additionally, we discussed the effect of conventional gout treatments on the gut microbiota composition, along with emerging therapeutic approaches that target the gut microbiome, such as the use of probiotics and prebiotics. We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.}, } @article {pmid39493843, year = {2024}, author = {Duan, X and Nie, Y and Xie, X and Zhang, Q and Zhu, C and Zhu, H and Chen, R and Xu, J and Zhang, J and Yang, C and Yu, Q and Cai, K and Wang, Y and Tian, W}, title = {Sex differences and testosterone interfere with the structure of the gut microbiota through the bile acid signaling pathway.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1421608}, pmid = {39493843}, issn = {1664-302X}, abstract = {BACKGROUND: The gut microbiome has a significant impact on human wellness, contributing to the emergence and progression of a range of health issues including inflammatory and autoimmune conditions, metabolic disorders, cardiovascular problems, and psychiatric disorders. Notably, clinical observations have revealed that these illnesses can display differences in incidence and presentation between genders. The present study aimed to evaluate whether the composition of gut microbiota is associated with sex-specific differences and to elucidate the mechanism.

METHODS: 16S-rRNA-sequencing technology, hormone analysis, gut microbiota transplantation, gonadectomy, and hormone treatment were employed to investigate the correlation between the gut microbiome and sex or sex hormones. Meanwhile, genes and proteins involved bile acid signaling pathway were analyzed both in the liver and ileum tissues.

RESULTS: The composition and diversity of the microbiota from the jejunum and feces and the level of sex hormones in the serum differed between the sexes in young and middle-aged Sprague Dawley (SD) rats. However, no similar phenomenon was found in geriatric rats. Interestingly, whether in young, middle-aged, or old rats, the composition of the microbiota and bacterial diversity differed between the jejunum and feces in rats. Gut microbiota transplantation, gonadectomy, and hormone replacement also suggested that hormones, particularly testosterone (T), influenced the composition of the gut microbiota in rats. Meanwhile, the mRNA and protein level of genes involved bile acid signaling pathway (specifically SHP, FXR, CYP7A1, and ASBT) exhibited gender-specific differences, and T may play a significant role in mediating the expression of this pathway.

CONCLUSION: Sex-specific differences in the structure of the gut microbiota are mediated by T through the bile acid signaling pathway, pointing to potential targets for disease prevention and management techniques by indicating that sex differences and T levels may alter the composition of the gut microbiota via the bile acid signaling pathway.}, } @article {pmid39493719, year = {2024}, author = {Wang, L and Yu, L and Liu, Z and Che, C and Wang, Y and Zhao, Y and Zhu, M and Yang, G and Cao, A}, title = {FMT intervention decreases urine 5-HIAA levels: a randomized double-blind controlled study.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1411089}, pmid = {39493719}, issn = {2296-858X}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is often linked to gastrointestinal issues and altered serotonin metabolism. Emerging evidence suggests gut microbiota influence both, with fecal microbiota transplantation (FMT) offering a potential therapeutic approach. However, its impact on serotonin metabolism and ASD symptoms is not well understood. In this study, we aimed to evaluate the clinical effects of FMT and examine changes in specific urinary metabolites in children with ASD.

METHODS: A randomized double-blind controlled trial was performed to evaluate the clinical effects of FMT on GI and ASD-related symptoms. Gastrointestinal symptoms were assessed using the Gastrointestinal Symptom Rating Scale (GSRS), and the ASD-related symptoms were assessed using the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), and Social Responsiveness Scale (SRS) scores. Urinary metabolites were analyzed by homogeneous enzyme immunoassay using commercially available kits.

RESULTS: Significant improvements in GI and core ASD symptoms were observed following FMT intervention. The average GSRS scores decreased from 30.17 (before) to 19 (after; p < 0.0001), CARS scores decreased from 36.22 to 33.33 (p < 0.0001), SRS scores decreased from 151.17 to 137.5 (p = 0.0002), and the ABC scores decreased 76.39 to 53.17 (p < 0.0001) in the FMT group. However, in the placebo group, GSRS, CARS, and SRS scores showed no significant changes, while ABC scores decreased from 72 to 58.75 (p = 0.034). The FMT group also showed a significant reduction in urinary 5-hydroxyindoleacetic acid (5-HIAA) levels from 8.6 to 7.32 mg/L (p = 0.022), while other metabolites showed no significant changes.

CONCLUSION: FMT is a safe and effective treatment for improving GI and core symptoms in children with ASD, with 5-HIAA showing potential as a urinary biomarker for treatment response.}, } @article {pmid39492827, year = {2024}, author = {Jiang, L and Fan, JG}, title = {Gut microbiota in gastrointestinal diseases: Insights and therapeutic strategies.}, journal = {World journal of gastroenterology}, volume = {30}, number = {39}, pages = {4329-4332}, pmid = {39492827}, issn = {2219-2840}, mesh = {Humans ; *Gastrointestinal Microbiome/physiology ; Dysbiosis ; Inflammatory Bowel Diseases/microbiology/therapy ; Hypertension, Portal/microbiology/therapy/diagnosis/etiology ; Liver/microbiology/metabolism ; Gastrointestinal Diseases/microbiology/therapy ; Probiotics/therapeutic use ; Animals ; Fecal Microbiota Transplantation ; }, abstract = {Considering the bidirectional crosstalk along the gut-liver axis, gut-derived microorganisms and metabolites can be released into the liver, potentially leading to liver injury. In this editorial, we comment on several studies published in the recent issue of the World Journal of Gastroenterology. We focus specifically on the roles of gut microbiota in selected gastrointestinal (GI) diseases that are prevalent, such as inflammatory bowel disease, metabolic dysfunction-associated steatotic liver disease, and hepatitis B virus-related portal hypertension. Over the past few decades, findings from both preclinical and clinical studies have indicated an association between compositional and metabolic changes in the gut microbiota and the pathogenesis of the aforementioned GI disorders. However, studies elucidating the mechanisms underlying the host-microbiota interactions remain limited. The purpose of this editorial is to summarize current findings and provide insights regarding the context-specific roles of gut microbiota. Ultimately, the discovery of microbiome-based biomarkers may facilitate disease diagnosis and the development of personalized medicine.}, } @article {pmid39492826, year = {2024}, author = {Kong, MW and Yu, Y and Wang, P and Wan, Y and Gao, Y and Zhang, CX}, title = {Advances in the research of intestinal fungi in Crohn's disease.}, journal = {World journal of gastroenterology}, volume = {30}, number = {39}, pages = {4318-4323}, pmid = {39492826}, issn = {2219-2840}, mesh = {*Crohn Disease/microbiology/immunology ; Humans ; *Gastrointestinal Microbiome ; Animals ; *Dysbiosis/microbiology ; *Fecal Microbiota Transplantation ; *Fungi/pathogenicity ; *Disease Models, Animal ; Intestines/microbiology ; Mice ; Adipose Tissue/microbiology ; Mesentery/microbiology ; }, abstract = {This article reviews of the original research published by Wu et al in the World Journal of Gastroenterology, delving into the pivotal role of the gut microbiota in the pathogenesis of Crohn's disease (CD). Insights were gained from fecal microbiota transplantation (FMT) in mouse models, revealing the intricate interplay between the gut microbiota, mesenteric adipose tissue (MAT), and creeping fat. The study uncovered the characteristics of inflammation and fibrosis in the MAT and intestinal tissues of patients with CD; moreover, through the FMT mouse model, it observed the impact of samples from healthy patients and those with CD on symptoms. The pathogenesis of CD is complex, and its etiology remains unclear; however, it is widely believed that gut microbiota dysbiosis plays a significant role. Recently, with the development and application of next-generation sequencing technology, research on the role of fungi in the pathogenesis and chronicity of CD has deepened. This editorial serves as a supplement to the research by Wu et al who discussed advances related to the study of fungi in CD.}, } @article {pmid39491642, year = {2024}, author = {Shimokawa, C}, title = {The gut microbiome-helminth-immune axis in autoimmune diseases.}, journal = {Parasitology international}, volume = {104}, number = {}, pages = {102985}, doi = {10.1016/j.parint.2024.102985}, pmid = {39491642}, issn = {1873-0329}, abstract = {The global prevalence of autoimmune diseases has surged in recent decades. Consequently, environmental triggers have emerged as crucial contributors to autoimmune diseases, equally relevant to classical risk factors, such as genetic polymorphisms, infections, and smoking. Sequencing-based approaches have demonstrated distinct gut microbiota compositions in individuals with autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus (T1D), and systemic lupus erythematosus, compared to healthy controls. Furthermore, fecal microbiota transplantation and microbial inoculation experiments have supported the hypothesis that alterations in the gut microbiota can influence autoimmune responses and disease outcomes. Herein, we propose that intestinal helminths may serve as a critical factor in inducing alterations in the gut microbiota. The concept of helminth-mediated suppression of autoimmune diseases in humans is supported by substantial evidence, aligning with the long-standing "hygiene hypothesis." This review focused on T1D to explore the interactions between parasites, gut microbiota, and the immune system-a topic that remains a black box within this intricate triangular relationship.}, } @article {pmid39491609, year = {2024}, author = {Chen, D and Xie, J and Chen, X and Qin, B and Kong, D and Luo, J}, title = {Fecal microbiota transplantation alleviates neuronal Apoptosis, necroptosis and M1 polarization of microglia after ischemic stroke.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2024.10.053}, pmid = {39491609}, issn = {1873-7544}, abstract = {OBJECTIVE: This study aims to delve into the mechanisms underlying the improvement of neurological function in rats with ischemic stroke through fecal microbiota transplantation.

METHODS: A total of fifty male Sprague-Dawley rats were categorized into three groups: sham surgery, model, and fecal transplantation. We assessed behavioral and pathological alterations in the rats using modified neurological function scoring and TTC staining. Additionally, Western blot and immunofluorescence techniques were employed to examine the expression levels of RIP1, RIP3, MLKL, p-MLKL, Bcl-2, Bax, and cleaved caspase-3 in neurons of ischemic brain tissue, while iNOS and Arg1 were analyzed to evaluate microglial polarization.

RESULTS: The fecal transplantation group exhibited a decline in neurological function score compared to the model group, accompanied by a reduction in infarct volume (P < 0.05). Relative to the sham surgery group, the model group displayed a significant increase in the expression levels of necroptosis-related proteins RIP1, RIP3, p-MLKL, apoptotic proteins Bax and cleaved caspase-3, and the M1 microglial cell marker iNOS in ischemic brain tissue, while Bcl-2 expression was notably decreased (P < 0.05). Conversely, compared to the model group, the fecal transplantation group demonstrated decreased expression levels of RIP1, RIP3, p-MLKL, Bax, cleaved caspase-3, and iNOS, along with increased expression of Bcl-2.

CONCLUSION: Fecal microbiota transplantation presents a promising avenue for enhancing neurological function in rats with ischemic stroke by inhibiting neuronal apoptosis, necroptosis, and M1 polarization of microglial cells.}, } @article {pmid39491142, year = {2023}, author = {Zhao, T and Lv, J and Peng, M and Mi, J and Zhang, S and Liu, J and Chen, T and Sun, Z and Niu, R}, title = {Fecal microbiota transplantation and short-chain fatty acids improve learning and memory in fluorosis mice by BDNF-PI3K/AKT pathway.}, journal = {Chemico-biological interactions}, volume = {}, number = {}, pages = {110786}, doi = {10.1016/j.cbi.2023.110786}, pmid = {39491142}, issn = {1872-7786}, abstract = {Fluoride, an environmental toxicant, not only arouses intestinal microbiota dysbiosis, but also causes neuronal apoptosis and a decline in learning and memory ability. The purpose of this study was to explore whether fecal microbiota transplantation (FMT) from healthy mice and bacteria-derived metabolites short-chain fatty acids (SCFAs) supplement protect against fluoride-induced learning and memory impairment. Results showed that FMT reversed the elevated percentage of working memory errors (WME) and reference memory errors (RME) in fluorosis mice during the eight-arm maze test. Nissl and TUNEL staining presented that fluoride led to a decreased proportion of Nissl bodies area in the hippocampal CA3 region and an increased apoptotic ratio of nerve cells in CA1, CA3 and DG areas, whereas FMT alleviated those pathological damages. Moreover, the expressions of mRNA in hippocampal BDNF, PDK1, AKT, Bcl-2, and Bcl-xL were downregulated in mice exposed to fluoride, but the levels of PI3K, Bax, Bak, and Caspase-7 mRNA were upregulated. NaF treatment had an increase in PI3K and Caspase-3 protein levels and reduced the expressions of these four proteins, including BDNF, p-PI3K, AKT and p-AKT. By contrast, FMT enhanced the expression of BDNF and thus activated the PI3K/AKT pathway. Besides, the 16S rRNA sequencing revealed that fluoride caused a reduction in certain SCFA producers in the colon as evidenced by a decline in Erysipelatoclostridiaceae, and a downward trend in Akkermansia, Blautia and Alistipes. However, the disordered gut microbiome was restored via frequent FMT. Of note, SCFAs administration also increased BDNF levels and regulated its downstream pathways, which contributed to cell survival and learning and memory function recovery. In conclusion, FMT and SCFAs may activate the BDNF-PI3K/AKT pathway to play an anti-apoptotic role and ultimately improve learning and memory deficits in fluorosis mice.}, } @article {pmid39490563, year = {2024}, author = {Wu, J and Zhang, R and Yin, Z and Chen, X and Mao, R and Zheng, X and Yuan, M and Li, H and Lu, Y and Liu, S and Gao, X and Sun, Q}, title = {Gut microbiota-driven metabolic alterations reveal the distinct pathogenicity of chemotherapy-induced cachexia in gastric cancer.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {107476}, doi = {10.1016/j.phrs.2024.107476}, pmid = {39490563}, issn = {1096-1186}, abstract = {Cachexia affects approximately 50-80% of advanced cancer patients, particularly those with gastric cancer (GC). Therefore, early detection of cachexia is essential to prevent its progression. Targeting the gut microbiota may be a promising approach for preventing and treating cachexia in patients with GC. Chemotherapy significantly reduced gut microbiota diversity in GC patients. Specifically, the abundance of bacterial genera such as Bacteroides, Streptococcus, and Prevotella was increased in the gut of patients postchemotherapy, which was closely associated with the development of cachexia. Serum metabolic analysis revealed a strong link between specific microbes and metabolite in patients with chemotherapy-induced GC cachexia. We further constructed a random forest model based on the top 6 genera in terms of abundance for the prediction of chemotherapy-related GC cachexia development; this model had an area under the receiver operating characteristic curve (AUC) of 93.5% [95% confidence interval (CI), 86.6%-100%], with a specificity and accuracy above 75%. Additionally, we identified Enterotoxin Bacteroides fragilis (ETBF) as a key factor in chemotherapy-induced GC cachexia. In an in vivo GC model, the colonization of ETBF in the intestines of mice significantly accelerated the muscle and adipose tissue consumption induced by chemotherapy, resulting in cachexia symptoms. Furthermore, ETBF damaged the intestinal mucosal barrier by disrupting cell connections and attracting M1 macrophages, which advances GC cachexia. In conclusion, our findings indicate that gut microbiota imbalance is crucial in GC cachexia development, suggesting potential biomarkers for early diagnosis. Clinical trial registration: http://www.chictr.org.cn, Identification No: ChiCTR2200064547.}, } @article {pmid39489477, year = {2024}, author = {Chen, W and Liu, Y and Pu, J and Gui, S and Wang, D and Zhong, X and Tao, W and Chen, X and Chen, X and Chen, Y and Zhao, L and Wu, Q and Chen, X and Zhang, Y and Xie, A and Xie, P}, title = {Comparative transcriptional analyses of the striatum in the chronic social defeat stress model in C57BL/6J male mice and the gut microbiota-dysbiosis model in Kumming mice.}, journal = {Neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.neuroscience.2024.10.057}, pmid = {39489477}, issn = {1873-7544}, abstract = {Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression.}, } @article {pmid39487198, year = {2024}, author = {Chatthanathon, P and Leelahavanichkul, A and Cheibchalard, T and Wilantho, A and Hirankarn, N and Somboonna, N}, title = {Comparative time-series analyses of gut microbiome profiles in genetically and chemically induced lupus-prone mice and the impacts of fecal transplantation.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {26371}, pmid = {39487198}, issn = {2045-2322}, support = {CU_FRB65_hea(68)_131_23_61//Thailand Science Research and Innovation Fund Chulalongkorn University/ ; }, mesh = {Animals ; *Lupus Erythematosus, Systemic/microbiology/immunology/genetics ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Mice ; *Receptors, IgG/genetics ; *Dysbiosis/microbiology ; *Disease Models, Animal ; Female ; Feces/microbiology ; Mice, Knockout ; Terpenes ; Mice, Inbred C57BL ; }, abstract = {Although the association between gut dysbiosis (imbalance of the microbiota) in systemic lupus erythematosus (SLE) is well-known, the simultaneous exploration in gut dysbiosis in fecal and different intestinal sections before and after lupus onset (at 2, 4, 6, 8, and 10 months old) resulting from the loss of inhibitory Fc gamma receptor IIb (FcGIIb) and pristane induction have never been conducted. Anti-dsDNA (an important lupus autoantibody) and proteinuria developed as early as 6 months old in both models, with higher levels in FcGRIIb deficient (FcGRIIb-/-) mice. Compared to the healthy control at 2 and 4 months, the lupus mice (both FcGRRIIb-/- and pristane) and healthy mice at 6 months old demonstrated an alteration as indicated by the Shannon alpha diversity index, highlighting influences of lupus- and age-induced dysbiosis, respectively. Non-metric multidimensional scaling (NMDS) revealed that the fecal microbiota of FcGRIIb-/- mice were distinct from the age-matched healthy control at all timepoints (at 6 month, p < 0.05), while pristane mice showed divergence at only some timepoints. Analyses of different intestinal sections revealed similarity among microbiota in the cecum, colon, and feces, contrasting with those in the small intestines (duodenum, jejunum, and ileum). Subtle differences were found between FcGRIIb-/- and pristane mice in feces and the intestinal sections as assessed by several analyses, for examples, the similar or dissimilar distances (NMDS), the neighbor-joining clustering, and the potential metabolisms (KEGG pathway analysis). Due to the differences between the gut microbiota (feces and intestinal sections) in the lupus mice and the healthy control, rebalancing of the microbiota using rectal administration of feces from the healthy control (fecal transplantation; FMT) to 7-month-old FcGIIb-/- mice (the established lupus; positive anti-dsDNA and proteinuria) was performed. In comparison to FcGRIIb-/- mice without FMT, FMT mice (more effect on the female than the male mice) showed the lower anti-dsDNA levels with similar fecal microbiome diversity (16s DNA gene copy number) and microbiota patterns to the healthy control. In conclusion, gut microbiota (feces and intestinal sections) of lupus mice (FcGRIIb-/- and pristane) diverged from the control as early as 4-6 months old, correlating with lupus characteristics (anti-dsDNA and proteinuria). The different gut microbiota in FcGRIIb-/- and pristane suggested a possible different gut microbiota in lupus with various molecular causes. Furthermore, FMT appeared to mitigate gut dysbiosis and reduce anti-dsDNA, supporting the benefit of the rebalancing gut microbiota in lupus, with more studies are warranted.}, } @article {pmid39488230, year = {2024}, author = {Rubak, T and Baunwall, SMD and Gregersen, M and Paaske, SE and Asferg, M and Barat, I and Secher-Johnsen, J and Riis, MG and Rosenbæk, JB and Hansen, TK and Ørum, M and Steves, CJ and Veilbæk, H and Hvas, CL and Damsgaard, EMS}, title = {Early geriatric assessment and management in older patients with Clostridioides difficile infection in Denmark (CLODIfrail): a randomised trial.}, journal = {The lancet. Healthy longevity}, volume = {}, number = {}, pages = {100648}, doi = {10.1016/j.lanhl.2024.100648}, pmid = {39488230}, issn = {2666-7568}, abstract = {BACKGROUND: Clostridioides difficile infection causes diarrhoea and colitis. Older patients with C difficile infection are often frail and have comorbidities, leading to high mortality rates. The frailty burden in older people might restrict access to treatments, such as C difficile infection-specific antibiotics and faecal microbiota transplantation. We aimed to investigate the clinical effects of early comprehensive geriatric assessment (CGA) and frailty evaluation, including home visits and assessment for faecal microbiota transplantation, in older patients with C difficile infection.

METHODS: In this randomised, quality improvement trial with a pragmatic design, patients from the Central Denmark Region aged 70 years or older with a positive PCR test for C difficile toxin were randomly assigned (1:1) to CGA or standard care, both with equal access to faecal microbiota transplantation. Patients and investigators were unmasked to treatment. The primary outcome was 90-day mortality, and was compared in the study groups according to the intention-to-treat principle. The study is registered with ClinicalTrials.gov, NCT05447533.

FINDINGS: Between Sept 1, 2022, and May 3, 2023, we randomly assigned 217 patients to CGA (n=109) or standard care (n=108). The median patient age was 78 years (IQR 74-84). 116 (53%) of 217 patients were female and 101 (47%) were male. 16 (15%; 95% CI 9-23) of 109 patients in the CGA group and 22 (20%; 14-29) of 108 patients in the standard-care group died within 90 days (odds ratio 0·66, 95% CI 0·32-1·38. No serious adverse events or deaths related to patient assessment or faecal microbiota transplantation were recorded in either group. Deaths directly attributable to C difficile infection were lower in the CGA group (seven [44%] of 16 deaths vs 18 [82%] of 22 deaths in the standard-care group; p=0·020).

INTERPRETATION: Older patients who received CGA had a 90-day mortality rate similar to that of patients who received standard care, but with fewer deaths directly attributable to C difficile infection.

FUNDING: Innovation Fund Denmark, Novo Nordisk Foundation, and Helsefonden.}, } @article {pmid39484201, year = {2024}, author = {Cheng, X and Ren, C and Mei, X and Jiang, Y and Zhou, Y}, title = {Gut microbiota and irritable bowel syndrome: status and prospect.}, journal = {Frontiers in medicine}, volume = {11}, number = {}, pages = {1429133}, pmid = {39484201}, issn = {2296-858X}, abstract = {Irritable bowel syndrome (IBS) is a very common gastrointestinal disease that, although not as aggressive as tumors, affects patients' quality of life in different ways. The cause of IBS is still unclear, but more and more studies have shown that the characteristics of the gut microbiota, such as diversity, abundance, and composition, are altered in patients with IBS, compared to the healthy population, which confirms that the gut microbiota plays a crucial role in the development of IBS. This paper aims to identify the commonalities by reviewing a large body of literature. Changes in the characteristics of gut microbiota in patients with different types of IBS are discussed, relevant mechanisms are described, and the treatment modalities of gut microbiota in IBS are summarized. Although there are more clinical trials that have made good progress, more standardized, more generalized, larger-scale, multi-omics clinical studies are what is missing. Overall, gut microbiota plays a crucial role in the development of IBS, and there is even more potential for treating IBS by modulating gut microbiota.}, } @article {pmid39484168, year = {2024}, author = {Duo, H and Yang, Y and Zhang, G and Chen, Y and Cao, Y and Luo, L and Pan, H and Ye, Q}, title = {Comparative effectiveness of treatments for recurrent Clostridioides difficile infection: a network meta-analysis of randomized controlled trials.}, journal = {Frontiers in pharmacology}, volume = {15}, number = {}, pages = {1430724}, pmid = {39484168}, issn = {1663-9812}, abstract = {BACKGROUND: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infectious diarrhea. A major clinical challenge is recurrent CDI (rCDI) without effective standard drug-based therapy. Additionally, a comprehensive comparison of various therapy effectiveness in rCDI patients is still under investigation.

METHODS: A Bayesian network meta-analysis (NMA) of randomized control trials up to March 2024 was performed to investigate the efficacy of rCDI interventions.

RESULTS: Seventeen trials were included, comprising 4,148 CDI patients with ten interventions, including fecal microbiota transplantation (FMT) by lower gastrointestinal (LGI), FMT by upper gastrointestinal (UGI), Autologous FMT (AFMT), vancomycin + FMT, vancomycin, placebo, fidaxomicin, Vowst (SER109), Rebyota (RBX2660), and monoclonal antibody. NMA showed that FMT by LGI had the highest efficacy in treating rCDIs with an odds ratio (95% confidence interval) of 32.33 (4.03, 248.69) compared with placebo. FMT by UGI also showed high efficacy, whereas the efficacy comparison between FMT by LGI and UGI was not statistically significant (ORs) (95% CI), 1.72 (0.65, 5.21). The rankogram and surface under the cumulative ranking curve (SUCRA) also showed FMT by LGI ranked at the top and FMT by UGI ranked second in the curative effect.

CONCLUSION: NMA demonstrates FMT's significant efficacy in rCDI management, regardless of administration route (lower or upper gastrointestinal). Despite its significant benefits, FMT's safety is a concern due to the lack of standardized FDAcompliant manufacturing and oversight. Microbiota-based therapies also exhibit potential. However, limited research mandates further clinical exploration. Antibiotics, in contrast, display comparatively reduced efficacy in rCDI, potentially linked to disruptions in native gut microflora balance.

SYSTEMATIC REVIEW: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=368435, Identifier CRD42022368435.}, } @article {pmid39483608, year = {2024}, author = {Aslam, MR and Perala, A and Wishart, AV and Hamouda, RK and Elsaady, E and Khan, S}, title = {Therapeutic Potential of Fecal Microbiota Transplantation in Type 2 Diabetes Mellitus: A Systematic Review.}, journal = {Cureus}, volume = {16}, number = {10}, pages = {e70642}, pmid = {39483608}, issn = {2168-8184}, abstract = {Diabetes mellitus is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. It can cause various complications, which result in significant morbidity and mortality. There are multiple treatment options available to combat this disease; however, despite this, the incidence of type 2 diabetes mellitus is continuously increasing. Some promising results have shown that dysbiosis has a role in the pathogenesis of type 2 diabetes mellitus and fecal microbiota transplantation (FMT) in animals; however, the usage of FMT in humans needs further clarification and review. We explored PubMed, Popline, and Cochrane Library to identify relevant papers. Eight articles were then finalized after screening and applying eligibility criteria. These articles explored the role of the therapeutic efficacy of FMT in insulin resistance and hyperglycemia. The studies showed that the FMT had a positive impact on managing hyperglycemia and insulin resistance, which is evident in the decline of blood glucose and HBA1c levels and the rise of insulin and C-peptides. In addition, FMT also helped to control other risk factors such as hyperlipidemia and blood pressure; however, the impact on weight loss is not convincing. FMT also influenced the levels of some microbiota, which could be involved in controlling hyperglycemia and insulin resistance. Due to limited control trials and study periods and the small sample size of diabetic patients, more research is needed to explore the impact of FMT in controlling type 2 diabetes mellitus.}, } @article {pmid39482760, year = {2024}, author = {Nie, D and Wang, D and Wang, Z and Fang, Q and Wang, H and Xie, W and Li, C and Zhang, Y}, title = {The gut microbiome in patients with Cushing's disease affects depression- and anxiety-like behavior in mice.}, journal = {Microbiome}, volume = {12}, number = {1}, pages = {225}, pmid = {39482760}, issn = {2049-2618}, mesh = {Animals ; *Gastrointestinal Microbiome ; Mice ; *Pituitary ACTH Hypersecretion/microbiology/psychology/physiopathology ; *Depression/microbiology ; *Anxiety/microbiology ; Humans ; *Disease Models, Animal ; Male ; Behavior, Animal ; Feces/microbiology ; Female ; Corticosterone/blood ; Bacteria/classification/isolation & purification ; Adult ; Middle Aged ; Fecal Microbiota Transplantation ; Mice, Inbred C57BL ; }, abstract = {BACKGROUND: Depression and anxiety significantly impact the quality of life in individuals with Cushing's disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology.

RESULTS: The gut bacterial phenotype of patients with Cushing's disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased. However, this effect can be alleviated by supplementing with 2-(14, 15-epoxyeicosatrienoyl) glycerol (2-14,15-EG) which was found at reduced levels in the peripheral blood of mice treated with coprofecal bacteria from Cushing's disease. In this process, the effects of hormone levels and immune factors were not significant. In addition, in an animal model, corticosterone has been observed to affect behavioral changes in mice through gut microbiota composition, clarifying the cause-and-effect relationship between hormones, microbiota, and behavior. Finally, there was no significant difference in gut microbiome composition and its effects on mouse behavior in patients with Cushing's disease with different levels of depression and anxiety.

CONCLUSIONS: In summary, this research enhances our current understanding of how gut microbes in patients with Cushing's disease contribute to depression and anxiety, offering novel insights for clinical treatment approaches. Video Abstract.}, } @article {pmid39486524, year = {2024}, author = {Kapoor, B and Biswas, P and Gulati, M and Rani, P and Gupta, R}, title = {Gut microbiome and Alzheimer's disease: what we know and what remains to be explored.}, journal = {Ageing research reviews}, volume = {}, number = {}, pages = {102570}, doi = {10.1016/j.arr.2024.102570}, pmid = {39486524}, issn = {1872-9649}, abstract = {With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut-brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut-brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.}, } @article {pmid39486483, year = {2024}, author = {Lu, H and Xie, L and Guo, L and Gu, X and Zhu, R and Yang, Y and Tang, F and Li, M and Liu, C and Wang, D and Li, M and Tian, Y and Cai, S}, title = {EGCG protects intestines of mice and pelvic cancer patients against radiation injury via the gut microbiota/D-tagatose/AMPK axis.}, journal = {Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology}, volume = {}, number = {}, pages = {110608}, doi = {10.1016/j.radonc.2024.110608}, pmid = {39486483}, issn = {1879-0887}, abstract = {BACKGROUND AND PURPOSE: Radiation-induced intestinal injury (RIII) compromises the clinical utility of pelvic radiotherapy (RT). We aimed to explore the protective effect and underlying mechanism of (-)-epigallocatechin-3-gallate (EGCG) on RIII.

MATERIALS AND METHODS: We evaluated the protective effect of EGCG on intestine in RIII mouse model and pelvic cancer patients, while explored the underlying mechanism through (1) 16S rRNA sequencing, (2) metabolomic profiles, (3) fresh sterile fecal filtrate (SFF) transplantation, and (4) transcriptome sequencing.

RESULTS: EGCG efficiently prevented RIII in mouse, as reflected by improved survival, alleviated intestinal structure damage, promoted intestinal regeneration, and ameliorated gut microbiota dysbiosis. Prophylactic EGCG intervention reduced the severity of RIII in patients receiving pelvic RT. Mechanistically, the protective effect of EGCG could be transferred to other mice by SFF transplantation. EGCG enriched gut microbiota-derived metabolite D-tagatose, and oral administration of D-tagatose reproduced the radio-protective effect of EGCG via activating AMPK.

CONCLUSION: Oral EGCG may be a promising strategy for preventing RIII clinically, and warrant further investigation in prospective randomized phase III trials.}, } @article {pmid39486191, year = {2024}, author = {Singh, R and Panganiban, K and Au, E and Ravikumar, R and Pereira, S and Prevot, TD and Mueller, DJ and Remington, G and Agarwal, SM and Verdu, EF and Bercik, P and De Palma, G and Hahn, MK}, title = {Human-fecal microbiota transplantation in relation to gut microbiome signatures in animal models for schizophrenia: A scoping review.}, journal = {Asian journal of psychiatry}, volume = {102}, number = {}, pages = {104285}, doi = {10.1016/j.ajp.2024.104285}, pmid = {39486191}, issn = {1876-2026}, abstract = {More recently, attention has turned to the putative role of gut microbiome (GMB) in pathogenesis, symptomatology, treatment response and/or resistance in schizophrenia (SCZ). It is foreseeable that fecal microbiota transplantation (FMT) from SCZ patients (SCZ-FMT) to germ-free mice could represent a suitable experimental framework for a better understanding of the relationship between GMB and SCZ. Thus, we set out to identify literature (i) characterizing the GMB in animal models of SCZ, and (ii) employing SCZ-FMT into rodents to model SCZ in relation to behavioral and molecular phenotypes. Five studies examining animal models of SCZ suggest distinct GMB composition compared to respective control groups, which was correlated with SCZ-like behavioral phenotypes. Four additional studies investigated SCZ-FMT into rodents in relation to behavioral phenotypes, including spontaneous hyperlocomotion, social deficits, exaggerated startle response, and cognitive impairments, resembling those observed in SCZ patients. Mice receiving SCZ-FMT showed altered neurochemical and metabolic pathways in the brain. Animal models of SCZ have shown altered GMB composition, whereas reported behavioral and neurochemical alterations following FMT from patients into rodents suggest early face and construct validity for SCZ-FMT animal models. However, the predictive validity of these models remains to be validated.}, } @article {pmid39485288, year = {2024}, author = {Minaya, DM and Kim, JS and Kirkland, R and Allen, J and Cullinan, S and Maclang, N and de Lartigue, G and de La Serre, C}, title = {Transfer of microbiota from lean donors in combination with prebiotics prevents excessive weight gain and improves gut-brain vagal signaling in obese rats.}, journal = {Gut microbes}, volume = {16}, number = {1}, pages = {2421581}, doi = {10.1080/19490976.2024.2421581}, pmid = {39485288}, issn = {1949-0984}, mesh = {Animals ; *Obesity/microbiology/metabolism ; Male ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Prebiotics/administration & dosage ; *Brain-Gut Axis/physiology ; *Diet, High-Fat/adverse effects ; *Vagus Nerve ; *Weight Gain/drug effects ; Dysbiosis/microbiology ; Rats, Sprague-Dawley ; Bacteria/classification/isolation & purification/genetics/metabolism ; Fecal Microbiota Transplantation ; Brain/metabolism ; Signal Transduction ; }, abstract = {Gastrointestinal (GI) microbiota plays an active role in regulating the host's immune system and metabolism, as well as certain pathophysiological processes. Diet is the main factor modulating GI microbiota composition and studies have shown that high fat (HF) diets induce detrimental changes (dysbiosis) in the GI bacterial makeup. HF diet induced dysbiosis has been associated with structural and functional changes in gut-brain vagally mediated signaling system, associated with overeating and obesity. Although HF-driven changes in microbiota composition are sufficient to alter vagal signaling, it is unknown if improving microbiota composition after diet-induced obesity has been established can ameliorate gut-brain signaling and metabolic outcomes. In this study, we evaluated the effect of lean gut microbiota transfer in obese, vagally compromised, rats on gut-brain communication, food intake, and body weight. Male rats were maintained on regular chow or 45% HF diet for nine weeks followed by three weeks of microbiota depletion using antibiotics. The animals were then divided into four groups (n = 10 each): LF - control fed regular chow, LF-LF - chow fed animals that received microbiota from chow fed donors, HF-LF - HF fed animals that received microbiota from chow fed donors, and HF-HF - HF fed animals that received microbiota from HF fed donors. HF-LF animals received inulin as a prebiotic to aid the establishment of the lean microbiome. We found that transferring a LF microbiota to HF fed animals (HF-LF) reduced caloric intake during the light phase when compared with HF-HF rats and prevented additional excessive weight gain. HF-LF animals displayed an increase in postprandial activation of both primary sensory neurons innervating the GI tract and brainstem secondary neurons. We concluded from these data that improving microbiota composition in obese rats is sufficient to ameliorate gut-brain communication and restore normal feeding patterns which was associated with a reduction in weight gain.}, } @article {pmid39484785, year = {2024}, author = {Li, Y and Song, X and Dai, L and Wang, Y and Luo, Q and Lei, L and Pu, Y}, title = {Mechanism of action of exercise regulating intestinal microflora to improve spontaneous hypertension in rats.}, journal = {Biomolecules & biomedicine}, volume = {}, number = {}, pages = {}, doi = {10.17305/bb.2024.11174}, pmid = {39484785}, issn = {2831-090X}, abstract = {Hypertension is a prevalent cardiovascular disease. Exercise is widely recognized as an effective treatment for hypertension, and it may also influence the composition of the intestinal microflora. However, it remains unclear whether exercise can specifically regulate the intestinal microflora in the context of hypertension treatment. In this study, tail blood pressure in spontaneously hypertensive rats (SHR) was measured using a blood pressure meter after exercise intervention and fecal bacteria transplantation following exercise. Blood lipid levels were assessed using an automatic biochemical analyzer, and 16S rRNA sequencing was employed to analyze the intestinal microflora. Histological examinations of ileal tissue were conducted using HE and Masson staining. Intestinal permeability, inflammatory status, and sympathetic activity were evaluated by measuring the levels of diamine oxidase, D-lactic acid, C-reactive protein, interleukin-6, tumor necrosis factor-α, lipopolysaccharide, norepinephrine, angiotensin II, cyclic adenosine monophosphate, and cyclic guanosine monophosphate. Exercise was found to reduce blood pressure and blood lipid levels in SHR. It also improved the composition of the intestinal microflora, as evidenced by a reduced Firmicutes/Bacteroidetes ratio, an increase in bacteria that produce acetic and butyric acid, and higher Chao 1 and Shannon diversity indices. Furthermore, exercise reduced the thickness of the fibrotic and muscular layers in the ileum, increased the goblet cell/villus ratio and villus length, and decreased intestinal permeability, inflammatory markers, and sympathetic nerve activity. The intestinal microbial flora regulated by exercise demonstrated similar effects on hypertension. In conclusion, exercise appears to regulate the intestinal microflora, and this exercise-induced change in flora may contribute to improvements in hypertension in rats.}, } @article {pmid39482823, year = {2024}, author = {Zhang, T and Li, X and Li, J and Sun, F and Duan, L}, title = {Gut microbiome-targeted therapies as adjuvant treatments in inflammatory bowel diseases: a systematic review and network meta-analysis.}, journal = {Journal of gastroenterology and hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jgh.16795}, pmid = {39482823}, issn = {1440-1746}, support = {2021YFA1301300//National Key Research and Development Program of China/ ; 82170557//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND AND AIM: Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD).

METHODS: We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values.

RESULTS: Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD.

CONCLUSIONS: FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.}, } @article {pmid38988278, year = {2024}, author = {Yan, M and Man, S and Ma, L and Guo, L and Huang, L and Gao, W}, title = {Immunological mechanisms in steatotic liver diseases: An overview and clinical perspectives.}, journal = {Clinical and molecular hepatology}, volume = {30}, number = {4}, pages = {620-648}, doi = {10.3350/cmh.2024.0315}, pmid = {38988278}, issn = {2287-285X}, support = {82074069//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; Fatty Liver/complications/therapy/pathology ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; Animals ; }, abstract = {Steatotic liver diseases (SLD) are the principal worldwide cause of cirrhosis and end-stage liver cancer, affecting nearly a quarter of the global population. SLD includes metabolic dysfunction-associated alcoholic liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD), resulting in asymptomatic liver steatosis, fibrosis, cirrhosis and associated complications. The immune processes include gut dysbiosis, adiposeliver organ crosstalk, hepatocyte death and immune cell-mediated inflammatory processes. Notably, various immune cells such as B cells, plasma cells, dendritic cells, conventional CD4+ and CD8+ T cells, innate-like T cells, platelets, neutrophils and macrophages play vital roles in the development of MetALD and MASLD. Immunological modulations targeting hepatocyte death, inflammatory reactions and gut microbiome include N-acetylcysteine, selonsertib, F-652, prednisone, pentoxifylline, anakinra, JKB-121, HA35, obeticholic acid, probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Understanding the immunological mechanisms underlying SLD is crucial for advancing clinical therapeutic strategies.}, } @article {pmid38052097, year = {2024}, author = {Cooper, J and Markovinovic, A and Coward, S and Herauf, M and Shaheen, AA and Swain, M and Panaccione, R and Ma, C and Lu, C and Novak, K and Kroeker, KI and Ng, SC and Kaplan, GG}, title = {Incidence and Prevalence of Primary Sclerosing Cholangitis: A Meta-analysis of Population-based Studies.}, journal = {Inflammatory bowel diseases}, volume = {30}, number = {11}, pages = {2019-2026}, pmid = {38052097}, issn = {1536-4844}, support = {PJT-162393/CAPMC/CIHR/Canada ; G-2106-04697//Leona M. and Harry B. Helmsley Charitable Trust/ ; //Study of Inflammatory Bowel Disease/ ; PJT-162393/CAPMC/CIHR/Canada ; }, mesh = {*Cholangitis, Sclerosing/epidemiology ; Humans ; Incidence ; Prevalence ; Asia/epidemiology ; }, abstract = {BACKGROUND: Primary sclerosing cholangitis is a chronic liver disease associated with significant morbidity, mortality, and healthcare utilization. We conducted a systematic review and meta-analysis of population-based studies of the incidence and prevalence of primary sclerosing cholangitis.

METHODS: Medline and Embase were systematically searched to identify population-based studies of a defined geographic area and reported the incidence or prevalence of primary sclerosing cholangitis in the general population. Meta-analyses, using random-effects, were performed to calculate overall and country-specific incidence (per 100 000 persons/year) and prevalence rates (per 100 000 persons) with 95% confidence intervals.

RESULTS: The 14 studies on incidence and the 12 for prevalence originated from North America, Asia, Europe, and Oceania. Incidence and prevalence rates of primary sclerosing cholangitis were 0.87 (95% confidence interval, 0.59-1.29) and 13.53 (95% confidence interval, 10.20-17.94) per 100 000 persons, respectively.

CONCLUSIONS: Both the prevalence and incidence of primary sclerosing cholangitis is low in the general population. Future studies on the incidence and prevalence of primary sclerosing cholangitis in the general population should be directed at Asia, Africa, and Latin America to allow for a more robust assessment of the global epidemiology of primary sclerosing cholangitis.}, } @article {pmid39481287, year = {2024}, author = {Gautam, R and Maan, P and Patel, AK and Vasudevan, S and Arora, T}, title = {Unveiling the complex interplay between gut microbiota and polycystic ovary syndrome: A narrative review.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {12}, pages = {199-208}, doi = {10.1016/j.clnu.2024.10.028}, pmid = {39481287}, issn = {1532-1983}, abstract = {BACKGROUND & AIM: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects women throughout their reproductive age and characterised via polycystic ovaries, hyperandrogenism, and irregular menstruation. There is rising evidence that the pathophysiology of PCOS is significantly affected via the gut microbiota and its metabolic products.

METHODS: This narrative review synthesizes current literature exploring the relationship between gut microbiota and PCOS. A comprehensive search of electronic databases was conducted to identify relevant studies. Further this review also analysed therapeutic options of probiotics, prebiotics, Fecal Microbiota Transplant (FMT), high fiber and poly phenol rich diet and novel therapeutic agents in treatment of PCOS.

RESULTS: Emerging evidence suggests alterations in the composition and diversity of gut microbiota in women with PCOS. The current literature showed a complex relationship of gut microbiota, short chain fatty acids (SCFAs) metabolism, intestinal permeability and LPS (Lipid Polysaccharide) metabolism, gut-brain axis and bile acid (BA) pathway within etiology and pathophysiology of PCOS. Additionally, the factors such as diet, lifestyle, genetics, and environmental influences may all contribute to alterations in gut microbiota that could potentially exacerbate or mitigate PCOS symptoms.

CONCLUSION: The review provides valuable insights into the intricate interplay between the gut and female reproductive health. The present evidence suggested that alterations in diversity and function of the gut microbiota may lead to specific pathogenic changes that lead to development of PCOS. A comprehensive understanding of these microbial dynamics may lead to new therapeutic approaches that target the gut micro biome.}, } @article {pmid39480487, year = {2024}, author = {Deda, O and Armitage, EG and Mouskeftara, T and Kachrimanidou, M and Zervos, I and Malousi, A and Loftus, NJ and Taitzoglou, I and Gika, H}, title = {Unraveling Cecal Alterations in Clostridioides difficile Colonized Mice through Comprehensive Metabolic Profiling.}, journal = {Journal of proteome research}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jproteome.4c00578}, pmid = {39480487}, issn = {1535-3907}, abstract = {The disruption of gut microbiota caused by antibiotics favors the intestinal colonization of Clostridioides difficile - a Gram-positive, spore-forming anaerobic bacterium that causes potentially fatal gastrointestinal infections. In an endeavor to elucidate the complexities of the gut-brain axis in the context of Clostridium difficile infection (CDI), a murine model has been used to investigate the potential effects of antibiotic administration and subsequent colonization by C. difficile, as well as the impact of three different 10-day treatments (metronidazole, probiotics, and fecal microbiota transplantation), on the cecal metabolome for the first time. This follows our previous research which highlighted the metabolic effect of CDI and these treatments in the brain and employs the same four different metabolomics-based methods (targeted GC-MS/MS, targeted HILIC-MS/MS, untargeted RP-LC-HRMS/MS and untargeted GC-MS). A total of 286 unique metabolites have been identified in the mouse cecal profiles and statistical analysis revealed that CDI, as well as the subsequent treatments, significantly alters cecal metabolites and lipids implicated in various biochemical pathways centered around amino acid metabolism, glycerophospholipid metabolism, and central carbon metabolism. To our knowledge, this study represents the first exploration of the effects of C. difficile-induced colitis and potential treatments on the cecal tissue metabolome.}, } @article {pmid39479215, year = {2024}, author = {Huang, J and Xu, T and Quan, G and Li, Y and Yang, X and Xie, W}, title = {Current progress on the microbial therapies for acute liver failure.}, journal = {Frontiers in microbiology}, volume = {15}, number = {}, pages = {1452663}, pmid = {39479215}, issn = {1664-302X}, abstract = {Acute liver failure (ALF), associated with a clinical fatality rate exceeding 80%, is characterized by severe liver damage resulting from various factors in the absence of pre-existing liver disease. The role of microbiota in the progression of diverse liver diseases, including ALF, has been increasingly recognized, with the interactions between the microbiota and the host significantly influencing both disease onset and progression. Despite growing interest in the microbiological aspects of ALF, comprehensive reviews remain limited. This review critically examines the mechanisms and efficacy of microbiota-based treatments for ALF, focusing on their role in prevention, treatment, and prognosis over the past decade.}, } @article {pmid39473963, year = {2024}, author = {Wang, YN and Zhai, XY and Wang, Z and Gao, CL and Mi, SC and Tang, WL and Fu, XM and Li, HB and Yue, LF and Li, PF and Xi, SY}, title = {Jianpi-Huatan-Huoxue-Anshen formula ameliorates gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with H22 hepatocellular carcinoma.}, journal = {World journal of gastrointestinal oncology}, volume = {16}, number = {10}, pages = {4209-4231}, pmid = {39473963}, issn = {1948-5204}, abstract = {BACKGROUND: Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing & life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear.

AIM: To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC).

METHODS: Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1β, IL-6, IL-8, IL-10, IL-22, TNF-α, and TGF-β, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-κB, Occludin, MUC-2, Claudin-1, and IκB-α in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing.

RESULTS: TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-β, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-κB, IL-1β, IL-6, TNF-α, IL-22, IL-8, and IκB-α were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria, AF12, Adlercreutzia, Clostridium, Coriobacteriaceae, and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum, Odoribacter, RF32, YS2, and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora.

CONCLUSION: TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy.}, } @article {pmid39471749, year = {2024}, author = {Liu, X and Lu, B and Tang, H and Jia, X and Zhou, Q and Zeng, Y and Gao, X and Chen, M and Xu, Y and Wang, M and Tan, B and Li, J}, title = {Gut microbiome metabolites, molecular mimicry, and species-level variation drive long-term efficacy and adverse event outcomes in lung cancer survivors.}, journal = {EBioMedicine}, volume = {109}, number = {}, pages = {105427}, doi = {10.1016/j.ebiom.2024.105427}, pmid = {39471749}, issn = {2352-3964}, abstract = {BACKGROUND: The influence of the gut microbiota on long-term immune checkpoint inhibitor (ICI) efficacy and immune-related adverse events (irAEs) is poorly understood, as are the underlying mechanisms.

METHODS: We performed gut metagenome and metabolome sequencing of gut microbiotas from patients with lung cancer initially treated with anti-PD-1/PD-L1 therapy and explored the underlying mechanisms mediating long-term (median follow-up 1167 days) ICI responses and immune-related adverse events (irAEs). Results were validated in external, publicly-available datasets (Routy, Lee, and McCulloch cohorts).

FINDINGS: The ICI benefit group was enriched for propionate (P = 0.01) and butyrate/isobutyrate (P = 0.12) compared with the resistance group, which was validated in the McCulloch cohort (propionate P < 0.001, butyrate/isobutyrate P = 0.002). The acetyl-CoA pathway (P = 0.02) in beneficial species mainly mediated butyrate production. Microbiota sequences from irAE patients aligned with antigenic epitopes found in autoimmune diseases. Microbiotas of responsive patients contained more lung cancer-related antigens (P = 0.07), which was validated in the Routy cohort (P = 0.02). Escherichia coli and SGB15342 of Faecalibacterium prausnitzii showed strain-level variations corresponding to clinical phenotypes. Metabolome validation reviewed more abundant acetic acid (P = 0.03), propionic acid (P = 0.09), and butyric acid (P = 0.02) in the benefit group than the resistance group, and patients with higher acetic, propionic, and butyric acid levels had a longer progression-free survival and lower risk of tumor progression after adjusting for histopathological subtype and stage (P < 0.05).

INTERPRETATION: Long-term ICI survivors have coevolved a compact microbial community with high butyrate production, and molecular mimicry of autoimmune and tumor antigens by microbiota contribute to outcomes. These results not only characterize the gut microbiotas of patients who benefit long term from ICIs but pave the way for "smart" fecal microbiota transplantation. Registered in the Chinese Clinical Trial Registry (ChiCTR2000032088).

FUNDING: This work was supported by Beijing Natural Science Foundation (7232110), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-072, 2023-PUMCH-C-054), CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-C&T-B-010).}, } @article {pmid39471538, year = {2024}, author = {Levitte, S and Nilkant, R and Jensen, AR and Zhang, KY}, title = {Unlocking the promise of mesenchymal stem cells and extracorporeal photopheresis to address rejection and graft failure in intestinal transplant recipients.}, journal = {Human immunology}, volume = {85}, number = {6}, pages = {111160}, doi = {10.1016/j.humimm.2024.111160}, pmid = {39471538}, issn = {1879-1166}, abstract = {INTRODUCTION: In patients with irreversible intestinal failure, intestinal transplant has become a standard treatment option. Graft failure secondary to acute or chronic cellular rejection continues to be a significant challenge following transplant. Even with optimal immune suppression, some patients continue to struggle with refractory rejection. Both extracorporeal photopheresis (ECP) and extracellular vesicles derived from mesenchymal stem cells (EVs) have been used to treat refractory rejection following intestinal transplantation, although their use remains limited and consistent treatment protocols are lacking.

METHODS: Intestinal transplant recipients who received ECP only or ECP and EVs as rescue therapy for acute cellular rejection or chronic inflammation between 2016 and 2022 were included in this single-center retrospective analysis. Baseline demographics, pre- and post-treatment histopathology, endoscopic and biochemical findings, and long-term transplant outcomes were analyzed.

RESULTS: Three patients (two pediatric and one adult) with acute steroid- and biologic-refractory rejection were treated with ECP and/or EVs, as was one patient (pediatric) with chronic graft rejection and inflammation. Patients received twice weekly ECP for 4 weeks and once weekly thereafter. EVs were administered in three doses each separated by 72 h. Immunosuppression at the time of treatment initiation included high-dose tacrolimus and sirolimus. Histologic resolution of rejection was achieved in all patients over 12-16 weeks. Steroids were weaned to low-dose or withdrawn in every patient within 4 weeks of ECP/EV treatment. C-reactive protein decreased from an average of 14.75 to 1.6 mg/dL post-treatment and fecal calprotectin decreased from average 800 mg/g to 31 mg/g. Donor-induced cytotoxic T cell populations were quantified for two of the patients with acute rejection, and in both cases decreased dramatically following treatment. There were no complications associated with either treatment.

CONCLUSION: Both ECP and EVs present novel opportunities to address graft rejection and inflammation in bowel transplant recipients. More work will be needed to define the optimal therapeutic parameters for each treatment modality.}, } @article {pmid39470619, year = {2024}, author = {Liu, X and Luo, Y and Chen, X and Wu, M and Xu, X and Tian, J and Gao, Y and Zhu, J and Wang, Z and Zhou, Y and Zhang, Y and Wang, X and Li, W and Lu, Q and Yao, X}, title = {Fecal microbiota transplantation against moderate-to-severe atopic dermatitis: A randomized, double-blind controlled explorer trial.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.16372}, pmid = {39470619}, issn = {1398-9995}, support = {//Nanjing Incubation Program for National Clinical Research Center/ ; //National Key Research and Development Program of China/ ; //CAMS Innovation Fund for Medical Sciences/ ; //Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ ; //National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a novel treatment for inflammatory diseases. Herein, we assess its safety, efficacy, and immunological impact in patients with moderate-to-severe atopic dermatitis (AD).

METHODS: In this randomized, double-blind, placebo-controlled clinical trial, we performed the efficacy and safety assessment of FMT for moderate-to-severe adult patients with AD. All patients received FMT or placebo once a week for 3 weeks, in addition to their standard background treatments. Patients underwent disease severity assessments at weeks 0, 1, 2, 4, 8, 12, and 16, and blood and fecal samples were collected for immunologic analysis and metagenomic shotgun sequencing, respectively. Safety was monitored throughout the trial.

RESULTS: Improvements in eczema area and severity index (EASI) scores and percentage of patients achieving EASI 50 (50% reduction in EASI score) were greater in patients treated with FMT than in placebo-treated patients. No serious adverse reactions occurred during the trial. FMT treatment decreased the Th2 and Th17 cell proportions among the peripheral blood mononuclear cells, and the levels of TNF-α, and total IgE in serum. By contrast, the expression levels of IL-12p70 and perforin on NK cells were increased. Moreover, FMT altered the abundance of species and functional pathways of the gut microbiota in the patients, especially the abundance of Megamonas funiformis and the pathway for 1,4-dihydroxy-6-naphthoate biosynthesis II.

CONCLUSION: FMT was a safe and effective therapy in moderate-to-severe adult patients with AD; the treatment changed the gut microbiota compositions and functions.}, } @article {pmid39470206, year = {2024}, author = {Todd, CL and Johnson, EE and Stewart, F and Wallace, SA and Bryant, A and Woodward, S and Norton, C}, title = {Conservative, physical and surgical interventions for managing faecal incontinence and constipation in adults with central neurological diseases.}, journal = {The Cochrane database of systematic reviews}, volume = {10}, number = {10}, pages = {CD002115}, pmid = {39470206}, issn = {1469-493X}, mesh = {Humans ; *Constipation/therapy/etiology ; *Fecal Incontinence/therapy/etiology ; *Randomized Controlled Trials as Topic ; Adult ; *Central Nervous System Diseases/complications ; Conservative Treatment/methods ; Quality of Life ; Bias ; }, abstract = {BACKGROUND: People with central neurological disease or injury have a much higher risk of both faecal incontinence (FI) and constipation than the general population. There is often a fine line between the two symptoms, with management intended to ameliorate one risking precipitating the other. Bowel problems are observed to be the cause of much anxiety and may reduce quality of life in these people. Current bowel management is largely empirical, with a limited research base. The review is relevant to individuals with any disease directly and chronically affecting the central nervous system (post-traumatic, degenerative, ischaemic or neoplastic), such as multiple sclerosis, spinal cord injury, cerebrovascular disease, Parkinson's disease and Alzheimer's disease. This is an update of a Cochrane Review first published in 2001 and subsequently updated in 2003, 2006 and 2014.

OBJECTIVES: To assess the effects of conservative, physical and surgical interventions for managing FI and constipation in people with a neurological disease or injury affecting the central nervous system.

SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register (searched 27 March 2023), which includes searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, ClinicalTrials.gov, WHO ICTRP as well as handsearching of journals and conference proceedings; and all reference lists of relevant articles.

SELECTION CRITERIA: We included randomised, quasi-randomised (where allocation is not strictly random), cross-over and cluster-randomised trials evaluating any type of conservative, physical or surgical intervention against placebo, usual care or no intervention for the management of FI and constipation in people with central neurological disease or injury.

DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed the risk of bias in eligible trials using Cochrane's 'Risk of bias' tool and independently extracted data from the included trials using a range of prespecified outcome measures. We produced summary of findings tables for our main outcome measures and assessed the certainty of the evidence using GRADE.

MAIN RESULTS: We included 25 studies with 1598 participants. The studies were generally at high risk of bias due to lack of blinding of participants and personnel to the intervention. Half of the included studies were also at high risk of bias in terms of selective reporting. Outcomes were often reported heterogeneously across studies, making it difficult to pool data. We did not find enough evidence to be able to analyse the effects of interventions on individual central neurological diseases. Additionally, very few studies reported on the primary outcomes of self-reported improvement in FI or constipation, or Neurogenic Bowel Dysfunction Score. Conservative interventions compared with usual care, no active treatment or placebo Thirteen studies assessed this comparison. The interventions included assessment-based nursing, holistic nursing, probiotics, psyllium, faecal microbiota transplantation, and a stepwise protocol of increasingly invasive evacuation methods. Conservative interventions may result in a large improvement in faecal incontinence (standardised mean difference (SMD) -1.85, 95% confidence interval (CI) -3.47 to -0.23; 3 studies; n = 410; low-certainty evidence). We interpreted SMD ≥ 0.80 as a large effect. It was not possible to pool all data from studies that assessed improvement in constipation, but the evidence suggested that conservative interventions may improve constipation symptoms (data not pooled; 8 studies; n = 612; low-certainty evidence). Conservative interventions may lead to a reduction in mean time taken on bowel care (data not pooled; 5 studies; n = 526; low-certainty evidence). The evidence is uncertain about the effects of conservative interventions on condition-specific quality of life and adverse events. Neurogenic Bowel Dysfunction Score was not reported. Physical therapy compared with usual care, no active treatment or placebo Twelve studies assessed this comparison. The interventions included massage therapy, standing, osteopathic manipulative treatment, electrical stimulation, transanal irrigation, and conventional physical therapy with visceral mobilisation. Physical therapies may make little to no difference to self-reported faecal continence assessed using the St Mark's Faecal Incontinence Score, where the minimally important difference is five, or the Cleveland Constipation Score (MD -2.60, 95% CI -4.91 to -0.29; 3 studies; n = 155; low-certainty evidence). Physical therapies may result in a moderate improvement in constipation symptoms (SMD -0.62, 95% CI -1.10 to -0.14; 9 studies; n = 431; low-certainty evidence). We interpreted SMD ≥ 0.5 as a moderate effect. However, physical therapies may make little to no difference in Neurogenic Bowel Dysfunction Score as the minimally important difference for this tool is 3 (MD -1.94, 95% CI -3.36 to -0.51; 7 studies; n = 358; low-certainty evidence). We are very uncertain about the effects of physical therapies on the time spent on bowel care, condition-specific quality of life and adverse effects (all very low-certainty evidence). Surgical interventions compared with usual care, no active treatment or placebo No studies were found for surgical interventions that met the inclusion criteria for this review.

AUTHORS' CONCLUSIONS: There remains little research on this common and, for patients, very significant issue of bowel management. The available evidence is almost uniformly of low methodological quality. The clinical significance of some of the research findings presented here is difficult to interpret, not least because each intervention has only been addressed in individual trials, against control rather than compared against each other, and the interventions are very different from each other. Understanding whether there is a clinically-meaningful difference from the results of available trials is largely hampered by the lack of uniform outcome measures. This is due to an absence of core outcome sets, and development of these needs to be a research priority to allow studies to be compared directly. Some studies used validated constipation, incontinence or condition-specific measures; however, others used unvalidated analogue scales to report effectiveness. Some studies did not use any patient-reported outcomes and focused on physiological outcome measures, which is of relatively limited significance in terms of clinical implementation. There was evidence in favour of some conservative interventions, but these findings need to be confirmed by larger, well-designed controlled trials, which should include evaluation of the acceptability of the intervention to patients and the effect on their quality of life.}, } @article {pmid39468666, year = {2024}, author = {Lian, J and Xia, L and Wang, G and Wu, W and Yi, P and Li, M and Su, X and Chen, Y and Li, X and Dou, F and Wang, Z}, title = {Multi-omics evaluation of clinical-grade human umbilical cord-derived mesenchymal stem cells in synergistic improvement of aging related disorders in a senescence-accelerated mouse model.}, journal = {Stem cell research & therapy}, volume = {15}, number = {1}, pages = {383}, pmid = {39468666}, issn = {1757-6512}, support = {3502220214001//Xiamen Cell Therapy Research Center/ ; 3502Z20234008//Key Healthcare Projects of Xiamen City/ ; 202212631066//Xiamen Medical College Undergraduate Innovation and Entrepreneurship Training Program/ ; 2022//Xiamen Medical College Undergraduate Innovation and Entrepreneurship Training Program/ ; 2023QNB003//Health science and technology project of Fujian Province/ ; 3502Z202372072//Natural Science Foundation of Xiamen/ ; 3502Z20244ZD1009//Natural Science Foundation of Xiamen/ ; }, mesh = {Animals ; Mice ; *Mesenchymal Stem Cells/metabolism/cytology ; Humans ; *Umbilical Cord/cytology/metabolism ; *Aging ; *Disease Models, Animal ; Mesenchymal Stem Cell Transplantation/methods ; Gastrointestinal Microbiome ; Male ; DNA Damage ; Multiomics ; }, abstract = {BACKGROUND: The prevalence of age-related disorders, particularly in neurological and cardiovascular systems, is an increasing global health concern. Mesenchymal stem cell (MSC) therapy, particularly using human umbilical cord-derived MSCs (HUCMSCs), has shown promise in mitigating these disorders. This study investigates the effects of HUCMSCs on aging-related conditions in a senescence-accelerated mouse model (SAMP8), with a focus on DNA damage, gut microbiota alterations, and metabolic changes.

METHODS: SAMP8 mice were treated with clinical-grade HUCMSCs via intraperitoneal injections. Behavioral and physical assessments were conducted to evaluate cognitive and motor functions. The Single-Strand Break Mapping at Nucleotide Genome Level (SSiNGLe) method was employed to assess DNA single-strand breaks (SSBs) across the genome, with particular attention to exonic regions and transcription start sites. Gut microbiota composition was analyzed using 16S rRNA sequencing, and carboxyl metabolomic profiling was performed to identify changes in circulating metabolites.

RESULTS: HUCMSC treatment significantly improved motor coordination and reduced anxiety in SAMP8 mice. SSiNGLe analysis revealed a notable reduction in DNA SSBs in MSC-treated mice, especially in critical genomic regions, suggesting that HUCMSCs may mitigate age-related DNA damage. The functional annotation of the DNA breaktome indicated a potential link between reduced DNA damage and altered metabolic pathways. Additionally, beneficial alterations in gut microbiota were observed, including an increase in short-chain fatty acid (SCFA)-producing bacteria, which correlated with improved metabolic profiles.

CONCLUSION: The administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism. The observed alterations in DNA break patterns, along with specific changes in microbiota and metabolic profiles, suggest that these could serve as potential biomarkers for evaluating the efficacy of HUCMSCs in treating age-related disorders. This highlights a promising avenue for the development of new therapeutic strategies that leverage these biomarkers, to enhance the effectiveness of HUCMSC-based treatments for aging-associated diseases.}, } @article {pmid39468065, year = {2024}, author = {Wang, G and Cao, L and Li, S and Zhang, M and Li, Y and Duan, J and Li, Y and Hu, Z and Wu, J and Ni, J and Lan, D and Li, T and Lu, J}, title = {Gut microbiota dysbiosis-mediated ceramides elevation contributes to corticosterone-induced depression by impairing mitochondrial function.}, journal = {NPJ biofilms and microbiomes}, volume = {10}, number = {1}, pages = {111}, pmid = {39468065}, issn = {2055-5008}, support = {82371176//National Natural Science Foundation of China (National Science Foundation of China)/ ; 81801331//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, mesh = {Animals ; *Gastrointestinal Microbiome/drug effects ; *Mitochondria/metabolism ; *Corticosterone ; Mice ; *Depression ; *Ceramides/metabolism ; *Dysbiosis ; *Hippocampus/metabolism ; Fecal Microbiota Transplantation ; Male ; Disease Models, Animal ; Feces/microbiology ; Mice, Inbred C57BL ; Neurogenesis ; Behavior, Animal/drug effects ; }, abstract = {The role of gut microbiota (GM) dysbiosis in the pathogenesis of depression has received widespread attention, but the mechanism remains elusive. Corticosterone (CORT)-treated mice showed depression-like behaviors, reduced hippocampal neurogenesis, and altered composition of the GM. Fecal microbial transplantation from CORT-treated mice transferred depression-like phenotypes and their dominant GM to the recipients. Fecal metabolic profiling exposed remarkable increase of gut ceramides in CORT-treated and recipient mice. Oral gavage with Bifidobacterium pseudolongum and Lactobacillus reuteri could induce elevations of gut ceramides in mice. Ceramides-treated mice showed depressive-like phenotypes, significant downregulation of oxidative phosphorylation-associated genes, and hippocampal mitochondrial dysfunction. Our study demonstrated a link between chronic exposure to CORT and its impact on GM composition, which induces ceramides accumulation, ultimately leading to hippocampal mitochondrial dysfunction. This cascade of events plays a critical role in reducing adult hippocampal neurogenesis and is strongly associated with the development of depression-like behaviors.}, } @article {pmid39467697, year = {2024}, author = {Qu, J and Meng, F and Wang, Z and Xu, W}, title = {Unlocking Cardioprotective Potential of Gut Microbiome: Exploring Therapeutic Strategies.}, journal = {Journal of microbiology and biotechnology}, volume = {34}, number = {12}, pages = {1-12}, doi = {10.4014/jmb.2405.05019}, pmid = {39467697}, issn = {1738-8872}, abstract = {The microbial community inhabiting the human gut resembles a bustling metropolis, wherein beneficial bacteria play pivotal roles in regulating our bodily functions. These microorganisms adeptly break down resilient dietary fibers to fuel our energy, synthesize essential vitamins crucial for our well-being, and maintain the delicate balance of our immune system. Recent research indicates a potential correlation between alterations in the composition and activities of these gut microbes and the development of coronary artery disease (CAD). Consequently, scientists are delving into the intriguing realm of manipulating these gut inhabitants to potentially mitigate disease risks. Various promising strategies have emerged in this endeavor. Studies have evidenced that probiotics can mitigate inflammation and enhance the endothelial health of our blood vessels. Notably, strains such as Lactobacilli and Bifidobacteria have garnered substantial attention in both laboratory settings and clinical trials. Conversely, prebiotics exhibit anti-inflammatory properties and hold potential in managing conditions like hypertension and hypercholesterolemia. Synbiotics, which synergistically combine probiotics and prebiotics, show promise in regulating glucose metabolism and abnormal lipid profiles. However, uncertainties persist regarding postbiotics, while antibiotics are deemed unsuitable due to their potential adverse effects. On the other hand, TMAO blockers, such as 3,3-dimethyl-1-butanol, demonstrate encouraging outcomes in laboratory experiments owing to their anti-inflammatory and tissue-protective properties. Moreover, fecal transplantation, despite yielding mixed results, warrants further exploration and refinement. In this comprehensive review, we delve into the intricate interplay between the gut microbiota and CAD, shedding light on the multifaceted approaches researchers are employing to leverage this understanding for therapeutic advancements.}, } @article {pmid39466773, year = {2024}, author = {Partida-Rodríguez, O and Brown, EM and Woodward, SE and Cirstea, M and Reynolds, LA and Petersen, C and Vogt, SL and Peña-Díaz, J and Thorson, L and Arrieta, MC and Hernández, EG and Rojas-Velázquez, L and Moran, P and González Rivas, E and Serrano-Vázquez, A and Pérez-Juárez, H and Torres, J and Ximénez, C and Finlay, BB}, title = {Fecal microbiota transplantation from protozoa-exposed donors downregulates immune response in a germ-free mouse model, its role in immune response and physiology of the intestine.}, journal = {PloS one}, volume = {19}, number = {10}, pages = {e0312775}, pmid = {39466773}, issn = {1932-6203}, mesh = {Animals ; *Fecal Microbiota Transplantation ; Mice ; *Germ-Free Life ; Gastrointestinal Microbiome/immunology ; Cytokines/metabolism ; T-Lymphocytes, Regulatory/immunology ; Intestines/immunology/parasitology/microbiology ; Mice, Inbred C57BL ; Intestinal Mucosa/immunology/metabolism ; Down-Regulation ; Female ; Spleen/immunology/metabolism ; }, abstract = {Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP). We determined the production of intestinal cytokines, the lymphocyte populations in both the colon and the spleen, and the genetic expression of markers of intestinal epithelial integrity. We observed a general downregulation of the intestinal immune response in mice receiving FMT-P. We found significantly lower intestinal production of the cytokines IL-6, TNF, IFN-γ, MCP-1, IL-10, and IL-12 in the FMT-P. Furthermore, a significant decrease in the proportion of CD3+, CD4+, and Foxp3+ T regulatory cells (Treg) was observed in both, the colon and spleen with FMT-P in contrast to FMT-NP. We also found that in FMT-P mice there was a significant decrease in tjp1 expression in all three regions of the small intestine; ocln in the ileum; reg3γ in the duodenum and relmβ in both the duodenum and ileum. We also found an increase in colonic mucus layer thickness in mice colonized with FMT-P in contrast with FMT-NP. Finally, our results suggest that gut protozoa, such as Blastocystis hominis, Entamoeba coli, Endolimax nana, Entamoeba histolytica/E. dispar, Iodamoeba bütschlii, and Chilomastix mesnili consortia affect the immunoinflammatory state and induce functional changes in the intestine via the gut microbiota. Likewise, it allows us to establish an FMT model in germ-free mice as a viable alternative to explore the effects that exposure to intestinal parasites could have on the immune response in humans.}, } @article {pmid39463943, year = {2024}, author = {Dai, A and Adintori, PA and Funnell, T and Jogia, WP and Fei, T and Waters, NR and Rangesa, M and Ballweg, A and Gipson, B and Raj, S and Hayase, E and Markey, KA and Burgos da Silva, M and Miltiadous, O and Brambilla, CZ and Buchan, ML and Peets, T and Gradissimo, A and Smith, N and Katsamakis, Z and Warren, A and Amoretti, LA and Duan, C and Zhang, C and Matheis, F and Sullivan, AP and Slingerland, JB and Clurman, A and Brereton, DG and Giardina, PA and Gomes, ALC and Johnson, AJ and Knights, D and Jenq, RR and Perales, MA and Giralt, SA and Schluter, J and van den Brink, MRM and Peled, J}, title = {Sugar-rich foods exacerbate antibiotic-induced microbiome injury.}, journal = {bioRxiv : the preprint server for biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/2024.10.14.617881}, pmid = {39463943}, issn = {2692-8205}, abstract = {Intestinal microbiota composition is implicated in several diseases; understanding the factors that influence it are key to elucidating host-commensal interactions and to designing microbiome-targeted therapies. We quantified how diet influences microbiome dynamics in hospitalized patients. We recorded 9,419 meals consumed by 173 patients undergoing hematopoietic cell transplantation and profiled the microbiome in 1,009 longitudinally collected stool samples from 158 of them. Caloric intake was correlated with fecal microbiota diversity. Bayesian inference revealed associations between intake of sweets or sugars during antibiotic exposure with microbiome disruption, as assessed by low diversity or expansion of the pathobiont Enterococcus. We validated this observation experimentally, finding that sucrose exacerbated antibiotic-induced Enterococcus expansion in mice. Taken together, our results suggest that avoiding sugar-rich foods during antibiotic treatment may reduce microbiome injury.}, } @article {pmid39462615, year = {2024}, author = {Ozaki, Y and Suzuki, Y and Suzuki, H}, title = {[Gut Microbiota as a Potential Biomarker for Immune Checkpoint Inhibitors].}, journal = {Gan to kagaku ryoho. Cancer & chemotherapy}, volume = {51}, number = {9}, pages = {862-864}, pmid = {39462615}, issn = {0385-0684}, mesh = {Humans ; *Gastrointestinal Microbiome/drug effects ; *Immune Checkpoint Inhibitors/therapeutic use ; *Lung Neoplasms/drug therapy/immunology/microbiology ; Biomarkers, Tumor/immunology ; }, abstract = {Immune checkpoint inhibitors(ICIs)currently play a predominant role in the standard treatment of non-small cell lung cancer(NSCLC)across all stages. While PD-L1 positivity has traditionally been used as the sole effective biomarker, evidence suggests that certain efficacy exists even in PD-L1-negative lung cancers. Various investigations have been conducted to identify biomarkers predicting the therapeutic efficacy of ICIs, focusing on both tumor-local and host-related factors. Among indicators reflecting the host status, the gut microbiota has garnered attention, with its composition and diversity potentially influencing the efficacy of ICI therapy. The presence of specific gut microbiota has been frequently reported to enhance the effectiveness of ICI treatment. Furthermore, the use of antibiotics may diminish the effects of ICIs, while fecal microbiota transplantation has shown potential to enhance ICI therapy. In our department, analysis of the gut microbiota in patients receiving anti-PD-1 antibody treatment has been conducted, yielding promising results through the identification of specific bacterial species and the search for these species using real-time PCR, suggesting avenues for further research. Recently, attention has also been drawn to the lung microbiota and tumor microbiota in the context of lung cancer, with reports suggesting that increased diversity in these microbial communities may correlate with the efficacy of ICI therapy. However, none of these findings alone provide sufficient evidence as standalone biomarkers, necessitating future research to advance from both the host environment, including the gut microbiota, and the microenvironment of the tumor site, such as the lung and tumor microbiota.}, } @article {pmid39462312, year = {2024}, author = {Garcia-Martinez, Y and Alexandrova, E and Iebba, V and Ferravante, C and Spinelli, M and Franci, G and Amoresano, A and Weisz, A and Trepiccione, F and Borriello, M and Ingrosso, D and Perna, AF}, title = {Does gut microbiota dysbiosis impact the metabolic alterations of hydrogen sulfide and lanthionine in patients with chronic kidney disease?.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {436}, pmid = {39462312}, issn = {1471-2180}, support = {Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; Grant agreement No [860329]//European Union's Horizon 2020 research and innovation program/ ; }, mesh = {Humans ; *Gastrointestinal Microbiome ; *Hydrogen Sulfide/metabolism ; *Renal Insufficiency, Chronic/microbiology/metabolism ; Male ; Female ; Middle Aged ; *Dysbiosis/microbiology ; *Feces/microbiology/chemistry ; Aged ; Sulfides/metabolism ; Adult ; Renal Dialysis ; Bacteria/classification/isolation & purification/metabolism/genetics ; Alanine/analogs & derivatives/metabolism ; Case-Control Studies ; }, abstract = {BACKGROUND: Chronic Kidney Disease (CKD) is characterized by a methionine-related metabolic disorder involving reduced plasma levels of hydrogen sulfide (H2S) and increased lanthionine. The gut microbiota influences methionine metabolism, potentially impacting sulfur metabolite dysfunctions in CKD. We evaluated whether gut microbiota dysbiosis contributes to H2S and lanthionine metabolic alterations in CKD.

METHODS: The gut microbiota of 88 CKD patients (non-dialysis, hemodialysis, and transplant patients) and 26 healthy controls were profiled using 16 S-amplicon sequencing. H2S and lanthionine concentrations were measured in serum and fecal samples using the methylene blue method and LC-MS/MS, respectively.

RESULTS: The CKD population exhibited a tenfold increase in serum lanthionine associated with kidney dysfunction. Despite lanthionine retention, hemodialysis and transplant patients had significantly lower serum H2S than healthy controls. Fecal H2S levels were not altered or related to bloodstream H2S concentrations. Conversely, fecal lanthionine was significantly increased in CKD compared to healthy controls and associated with kidney dysfunction. Microbiota composition varied among CKD groups and healthy controls, with the greatest dissimilarity observed between hemodialysis and transplant patients. Changes relative to the healthy group included uneven Ruminococcus gnavus distribution (higher in transplant patients and lower in non-dialysis CKD patients), reduced abundance of the short-chain fatty acid-producing bacteria Alistipes indistinctus and Coprococcus eutactus among transplant patients, and depleted Streptococcus salivarius in non-dialysis CKD patients. A higher abundance of Methanobrevibacter smithii, Christensenella minuta, and Negativibacillus massiliensis differentiated hemodialysis patients from controls. No correlation was found between differentially abundant species and the metabolic profile that could account for the H2S and lanthionine alterations observed.

CONCLUSIONS: The metabolic deregulation of H2S and lanthionine observed in the study was not associated with alterations in the gut microbiota composition in CKD patients. Further research on microbial sulfur pathways may provide a better understanding of the role of gut microbiota in maintaining H2S and lanthionine homeostasis.}, } @article {pmid39462039, year = {2024}, author = {Zhou, X and Shen, S and Wang, Z}, title = {Genetic evidence of bidirectional mendelian randomization study on the causality between gut microbiome and respiratory diseases contributes to gut-lung axis.}, journal = {Scientific reports}, volume = {14}, number = {1}, pages = {25550}, pmid = {39462039}, issn = {2045-2322}, support = {82174302//National Natural Science Foundation of China/ ; }, mesh = {Humans ; *Mendelian Randomization Analysis ; *Gastrointestinal Microbiome/genetics ; *Genome-Wide Association Study ; Lung/microbiology/pathology ; Respiratory Tract Diseases/microbiology/genetics ; Risk Factors ; }, abstract = {Observational studies and clinical trials have suggested the relationship between the gut microbiome and respiratory diseases, but the causality between them remains unclear. Firstly, we selected eight respiratory diseases Genome-wide association study (GWAS) datasets mainly from the FinnGen collaboration as outcomes. The exposure was based on GWAS statistics about the gut microbiome, sourced from the MiBioGen consortium, including gut microbial taxa. The causal link between the gut microbiome and respiratory illnesses was then estimated using a Two-sample Mendelian randomization (MR) analysis, including the inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure reliability, F-statistics and sensitivity tests were conducted. Furthermore, we performed a reverse MR analysis of the pre-Mendelian positive findings to possible reverse causality. For the 196 gut microbe taxa, the IVW analysis suggested 88 potential associations with eight clinically prevalent respiratory diseases. Among them, 30 causal associations were found in more than one MR method. Multiple statistical corrections have confirmed three causal associations: genus Holdemanella was a risk factor for chronic obstructive pulmonary disease (COPD) (P = 1.3 × 10[-4], OR = 1.18), family FamilyXIII was a protective factor for COPD (P = 1.3 × 10[-3], OR = 0.75), and genus Oxalobacter was a risk factor for asthma (P = 2.1 × 10[-4], OR = 1.09). Our MR analysis results indicate that there would be a causal relationship between the gut microbiome and respiratory diseases, contributing to the gut-lung axis. This finding offers new insights into the gut microbiome's roles in respiratory diseases' clinical prevention, pathogenesis, and improvement of clinical symptoms. Further randomized controlled trials are necessary to clarify the protective effect of probiotics and fecal microbial transplantation on respiratory health.}, } @article {pmid39461299, year = {2024}, author = {Verbiest, A and Hvistendahl, MK and Bolognani, F and Li, C and Youssef, NN and Huh, S and Menys, A and Bhatnagar, G and Vanslembrouck, R and Peeters, R and Sartoris, R and Vermeersch, P and Wauters, L and Verbeke, K and Jeppesen, PB and Joly, F and Vanuytsel, T}, title = {Efficacy and safety of apraglutide in short bowel syndrome with intestinal failure and colon-in-continuity: A multicenter, open-label, metabolic balance study.}, journal = {Clinical nutrition (Edinburgh, Scotland)}, volume = {43}, number = {12}, pages = {158-166}, doi = {10.1016/j.clnu.2024.10.011}, pmid = {39461299}, issn = {1532-1983}, abstract = {BACKGROUND: Apraglutide is a novel long-acting GLP-2 analog in development for short bowel syndrome with intestinal failure (SBS-IF). This multicenter, open-label, phase 2 study in SBS-IF and colon-in-continuity (CiC) investigates the safety and efficacy of apraglutide.

METHODS: This was a 52-week phase 2 metabolic balance study (MBS) in 9 adult patients with SBS-IF-CiC receiving once-weekly subcutaneous apraglutide injections. Safety was the primary endpoint. Secondary endpoints included changes in absorption parameters (MBS at baseline, after 4 weeks with stable parenteral support (PS), and 48 weeks), PS needs (48-week PS adjustment period based on monthly 48-h fluid balances) and intestinal morphology and motility (static and cine MRI at baseline and 4, 24 and 48 weeks).

RESULTS: PS volume decreased by -4702 mL/week (-52 %; p < 0.001) at week 52. Seven patients (78 %) achieved ≥1 day off PS at week 52. At 4 weeks, fecal output was reduced by 253 g/day (p = 0.013). At 48 weeks, increases in wet weight absorption by 316 g/day (p = 0.039), energy absorption by 1134 kJ/day (p = 0.041) and carbohydrate absorption by 56.1 g/day (p = 0.024) were observed. Moreover, small bowel length increased from 29.7 to 40.7 cm (p = 0.012), duodenal wall thickness increased by 0.8 mm (p = 0.02) and motility in the proximal colon was reduced (p = 0.031). A total of 127 adverse events was reported, which were mostly mild to moderate.

CONCLUSION: Apraglutide had an acceptable safety profile and was associated with significant reductions in PS needs and days off PS, improvements in intestinal absorption, and structural and functional intestinal changes in patients with SBS-IF-CiC.

CLINICALTRIALS: gov, Number NCT04964986.}, } @article {pmid39460926, year = {2024}, author = {Magnusson, C and Ölfvingsson, E and Hjortswang, H and Östholm, Å and Serrander, L}, title = {Improved health-related quality of life in patients with recurrent Clostridioides difficile infection after treatment with faecal microbiota transplantation.}, journal = {Infectious diseases (London, England)}, volume = {}, number = {}, pages = {1-8}, doi = {10.1080/23744235.2024.2415694}, pmid = {39460926}, issn = {2374-4243}, abstract = {BACKGROUND: Clostridioides difficile is a major burden for both healthcare systems and the patients. Faecal microbiota transplantation (FMT) is becoming more common as a treatment since it reduces the risk of recurrent Clostridioides difficile infection (rCDI).

OBJECTIVES: To evaluate how treatment with FMT is affecting the health-related quality of life (HRQoL) in patients with rCDI.

METHODS: A prospective observational cohort study was conducted where patients who were offered FMT as a treatment for rCDI were asked to fill in a questionnaire based on the Short Health Scale (SHS) and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) about their HRQoL before and after treatment.

RESULTS: Patients with rCDI had poor HRQoL, which improved following FMT.

CONCLUSIONS: Since FMT cures, reduces the risk of new recurrences of CDI and improves the HRQoL of the patients, it should be offered as a treatment for patients with rCDI. Also, SHS is a useful and reliable instrument for measuring HRQoL in patients with rCDI.}, } @article {pmid39460538, year = {2024}, author = {Yang, J and Liang, J and Hu, N and He, N and Liu, B and Liu, G and Qin, Y}, title = {The Gut Microbiota Modulates Neuroinflammation in Alzheimer's Disease: Elucidating Crucial Factors and Mechanistic Underpinnings.}, journal = {CNS neuroscience & therapeutics}, volume = {30}, number = {10}, pages = {e70091}, pmid = {39460538}, issn = {1755-5949}, support = {2024yjscx013//Innovative Research Project for Postgraduate Students of Heilongjiang University of Traditional Chinese Medicine/ ; }, mesh = {*Gastrointestinal Microbiome/physiology ; *Alzheimer Disease/microbiology/metabolism/pathology ; Humans ; *Neuroinflammatory Diseases/microbiology/metabolism ; Animals ; Dysbiosis ; Blood-Brain Barrier/metabolism/microbiology ; Fecal Microbiota Transplantation ; Probiotics ; }, abstract = {BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is characterized by progressive cognitive decline and neuronal loss, commonly linked to amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Recent research highlights the gut microbiota as a key player in modulating neuroinflammation, a critical pathological feature of AD. Understanding the role of the gut microbiota in this process is essential for uncovering new therapeutic avenues and gaining deeper insights into AD pathogenesis.

METHODS: This review provides a comprehensive analysis of how gut microbiota influences neuroinflammation and glial cell function in AD. A systematic literature search was conducted, covering studies from 2014 to 2024, including reviews, clinical trials, and animal studies. Keywords such as "gut microbiota," "Alzheimer's disease," "neuroinflammation," and "blood-brain barrier" were used.

RESULTS: Dysbiosis, or the imbalance in gut microbiota composition, has been implicated in the modulation of key AD-related mechanisms, including neuroinflammation, blood-brain barrier integrity, and neurotransmitter regulation. These disruptions may accelerate the onset and progression of AD. Additionally, therapeutic strategies targeting gut microbiota, such as probiotics, prebiotics, and fecal microbiota transplantation, show promise in modulating AD pathology.

CONCLUSIONS: The gut microbiota is a pivotal factor in AD pathogenesis, influencing neuroinflammation and disease progression. Understanding the role of gut microbiota in AD opens avenues for innovative diagnostic, preventive, and therapeutic strategies.}, } @article {pmid39459579, year = {2024}, author = {Alswat, AS}, title = {The Influence of the Gut Microbiota on Host Health: A Focus on the Gut-Lung Axis and Therapeutic Approaches.}, journal = {Life (Basel, Switzerland)}, volume = {14}, number = {10}, pages = {}, pmid = {39459579}, issn = {2075-1729}, abstract = {The human gut microbiota is a complex ecosystem harboring thousands of microbial strains that play a crucial role in maintaining the overall well-being of its host. The composition of the gut microbiota varies with age from infancy to adulthood and is influenced by dietary habits, environment, and genetic disposition. Recent advances in culture-independent techniques and nucleic acid sequencing have improved our understanding of the diversity of the gut microbiota. The microbial species present in the gut release short-chain fatty acids (SCFAs), which have anti-inflammatory properties. The gut microbiota also plays a substantial role in modulating the host's immune system, promoting immune tolerance, and maintaining homeostasis. The impact of the gut microbiota on the health of the host is quite evident, as gut dysbiosis has been linked to various diseases, including metabolic disorders, autoimmune diseases, allergies, and inflammatory bowel diseases. The gut microbiota has bidirectional communication with the respiratory system, creating the gut-lung axis, which has been associated with different respiratory diseases. Therapeutic approaches targeting the gut microbiota, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), aim to restore microbial balance and promote the growth of beneficial strains in the gut. Nonetheless, gaining knowledge of the complex interactions between the gut microbiota and the host is necessary to develop personalized medicine approaches and microbiota-based therapies for various conditions. This review summarizes studies related to the gut-lung axis with particular emphasis on the role of the microbiota. Future research directions are also discussed.}, } @article {pmid39458553, year = {2024}, author = {Borrego-Ruiz, A and Borrego, JJ}, title = {Nutritional and Microbial Strategies for Treating Acne, Alopecia, and Atopic Dermatitis.}, journal = {Nutrients}, volume = {16}, number = {20}, pages = {}, pmid = {39458553}, issn = {2072-6643}, mesh = {Humans ; *Dermatitis, Atopic/therapy/microbiology ; *Gastrointestinal Microbiome ; *Acne Vulgaris/therapy/microbiology ; *Probiotics/therapeutic use/administration & dosage ; *Alopecia/therapy/microbiology ; Synbiotics/administration & dosage ; Dysbiosis/therapy ; Fecal Microbiota Transplantation ; Diet ; Skin/microbiology ; }, abstract = {BACKGROUND/OBJECTIVES: Diet is one of the major determinants of the composition and function of the gut microbiome, and diverse studies have established directional connections between gut microbiome dysbiosis and skin dyshomeostasis. Furthermore, a significant link between the gut and certain skin-related disorders has been reported. This work reviews the mechanisms underlying the relationship between nutritional factors, gut microbiome, and certain skin diseases such as acne vulgaris, alopecia, and atopic dermatitis. In addition, it explores how the modulation of the gut microbiome and human skin through diet and various microbial strategies, including probiotics, synbiotics, postbiotics, and fecal microbiota transplantation, may serve as future treatments for skin diseases, possibly replacing traditional methods such as antibiotic, topical corticosteroid, and laser therapies.

RESULTS: The adequate intake of certain foods can promote a balanced gut microbiome, potentially reducing skin inflammation and improving overall skin health, while poor dietary choices may lead to worse outcomes by disrupting gut homeostasis. In this regard, diets high in antioxidants, fiber, and phytonutrients appear to be beneficial for enhancing skin health and preventing associated comorbidities. In addition, the administration of probiotics, synbiotics, and postbiotics in the treatment of cutaneous diseases has been shown to restore skin dyshomeostasis and to improve the symptoms of the reviewed skin conditions.

CONCLUSIONS: Consuming a healthy, plant-based diet can reduce skin inflammation and enhance overall skin health. Although the application of probiotics, synbiotics, and postbiotics has demonstrated promise in modulating inflammation, enhancing tissue regeneration, and inhibiting pathogenic colonization, further research is required.}, } @article {pmid39458486, year = {2024}, author = {Gómez-Pérez, AM and Muñoz-Garach, A and Lasserrot-Cuadrado, A and Moreno-Indias, I and Tinahones, FJ}, title = {Microbiota Transplantation in Individuals with Type 2 Diabetes and a High Degree of Insulin Resistance.}, journal = {Nutrients}, volume = {16}, number = {20}, pages = {}, pmid = {39458486}, issn = {2072-6643}, support = {PI15/011114//Instituto de Salud Carlos III/ ; EPIGEN-MICROBIOTA NCT05076656, PI15/01114//CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Fondo de Investigación para la Salud/ ; CPII21/00013//Instituto de Salud Carlos III-FEDER: Miguel Servet II programm/ ; B-0033-2014//Servicio Andaluz de Salud/ ; }, mesh = {Humans ; *Diabetes Mellitus, Type 2/therapy/blood/microbiology ; Female ; Male ; *Insulin Resistance ; Middle Aged ; *Fecal Microbiota Transplantation ; *Probiotics/therapeutic use ; Aged ; *Blood Glucose/metabolism ; Single-Blind Method ; Glucose Tolerance Test ; Gastrointestinal Microbiome ; Insulin/blood ; Body Mass Index ; Lactobacillus delbrueckii ; Treatment Outcome ; Glycated Hemoglobin/metabolism ; }, abstract = {The objective of this study was to determine the results of fecal microbiota transplantation (FMT) from healthy lean subjects in patients with type 2 diabetes (T2D); Methods: We designed a phase II, randomized, single-blind, parallel-arm clinical trial. Twenty-one subjects (12 men [57.1%] and 9 women [42.9%]), who had previously signed an informed consent were randomized to FMT from lean donors, a probiotic (Lactobacillus delbrueckii spp. bulgaricus LB-14), or placebo. Mean age at baseline was 62.5 ± 5.8 years and mean body mass index (BMI) at baseline was approximately 32.4 ± 2.4 kg/m[2]. Anthropometric measures, biochemical variables, oral glucose tolerance test (OGTT), and a stool microbiota analysis were performed (baseline, 4 and 12 weeks). The trial was conducted following the Declaration of Helsinki, Good Clinical Practice Guides (CPMP/ICH/135/95) and the current Spanish legislation regarding clinical trials (RD 223/2004).; Results: FMT changes occurred at the expense of the species found in the donor. No differences in weight, body mass index, HbA1c, or the results of the OGTT for glucose and insulin were found between groups after the intervention, although a decrease in uric acid was observed in the probiotic group (-0.5 mg/dL; p = 0.037) and a mild increase in HbA1c in the FMT group (+0.25%; p = 0.041); Conclusions: In our sample, neither FMT from healthy and lean donors nor a probiotic were effective in improving insulin sensitivity and HbA1c in patients with T2D.}, } @article {pmid39458368, year = {2024}, author = {Marsiglia, R and Pane, S and Del Chierico, F and Russo, A and Vernocchi, P and Romani, L and Cardile, S and Diamanti, A and Galli, L and Tamborino, A and Terlizzi, V and De Angelis, P and Angelino, G and Putignani, L}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infections in a Cystic Fibrosis Child Previously Screen Positive, Inconclusive Diagnosis (CFSPID): A Case Report.}, journal = {Microorganisms}, volume = {12}, number = {10}, pages = {}, pmid = {39458368}, issn = {2076-2607}, support = {Current Research funds//Italian Ministry of Health/ ; }, abstract = {Clostridioides difficile infection (CDI) is generally treated with vancomycin, metronidazole or fidaxomicin, although fecal microbiota transplantation (FMT) represents a promising therapeutic option for antibiotic-resistant recurrent C. difficile infections (rCDIs) in adults. In pediatric cystic fibrosis (CF) patients, CDIs are generally asymptomatic and respond to treatment. Here, we present the case of an 8-year-old female, initially diagnosed as "CFTR-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis" (CMRS/CFSPID), who then progressed to CF at 12 months. In the absence of CF-related symptoms, she presented multiple and disabling episodes of bloody diarrhoea with positive tests for C. difficile antigen and A/B toxin. After conventional treatments failed and several CDI relapses, FMT was proposed. Donor screening and GM donor-receiver matching identified her mother as a donor. Metataxonomy and targeted metabolomics provided, through a pre- and post-FMT time course, gut microbiota (GM) profiling to assess GM engraftment. At first, the GM map revealed severe dysbiosis, with a prevalence of Bacteroidetes and Proteobacteria (i.e., Klebsiella spp., Escherichia coli), a reduction in Firmicutes, a GM nearly entirely composed of Enterococcaceae (i.e., Enterococcus) and an almost complete depletion of Verrucomicrobia and Actinobacteria, mostly represented by Veillonella dispar. Post FMT, an increment in Bifidobacterium spp. and Collinsella spp. with a decrease in V. dispar restored intestinal eubiosis. Consistently, four weeks after FMT treatment, the child's gut symptoms cleared, without CDI recurrence.}, } @article {pmid39458032, year = {2024}, author = {Piccioni, A and Spagnuolo, F and Candelli, M and Voza, A and Covino, M and Gasbarrini, A and Franceschi, F}, title = {The Gut Microbiome in Sepsis: From Dysbiosis to Personalized Therapy.}, journal = {Journal of clinical medicine}, volume = {13}, number = {20}, pages = {}, pmid = {39458032}, issn = {2077-0383}, abstract = {Sepsis is a complex clinical syndrome characterized by an uncontrolled inflammatory response to an infection that may result in septic shock and death. Recent research has revealed a crucial link between sepsis and alterations in the gut microbiota, showing that the microbiome could serve an essential function in its pathogenesis and prognosis. In sepsis, the gut microbiota undergoes significant dysbiosis, transitioning from a beneficial commensal flora to a predominance of pathobionts. This transformation can lead to a dysfunction of the intestinal barrier, compromising the host's immune response, which contributes to the severity of the disease. The gut microbiota is an intricate system of protozoa, fungi, bacteria, and viruses that are essential for maintaining immunity and metabolic balance. In sepsis, there is a reduction in microbial heterogeneity and a predominance of pathogenic bacteria, such as proteobacteria, which can exacerbate inflammation and negatively influence clinical outcomes. Microbial compounds, such as short-chain fatty acids (SCFAs), perform a crucial task in modulating the inflammatory response and maintaining intestinal barrier function. However, the role of other microbiota components, such as viruses and fungi, in sepsis remains unclear. Innovative therapeutic strategies aim to modulate the gut microbiota to improve the management of sepsis. These include selective digestive decontamination (SDD), probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT), all of which have shown potential, although variable, results. The future of sepsis management could benefit greatly from personalized treatment based on the microbiota. Rapid and easy-to-implement tests to assess microbiome profiles and metabolites associated with sepsis could revolutionize the disease's diagnosis and management. These approaches could not only improve patient prognosis but also reduce dependence on antibiotic therapies and promote more targeted and sustainable treatment strategies. Nevertheless, there is still limited clarity regarding the ideal composition of the microbiota, which should be further characterized in the near future. Similarly, the benefits of therapeutic approaches should be validated through additional studies.}, } @article {pmid39457652, year = {2024}, author = {Zhang, J and Gan, H and Duan, X and Li, G}, title = {Targeting the Intestinal Microbiota: A Novel Direction in the Treatment of Inflammatory Bowel Disease.}, journal = {Biomedicines}, volume = {12}, number = {10}, pages = {}, pmid = {39457652}, issn = {2227-9059}, support = {82170617//National Natural Science Foundation of China/ ; }, abstract = {Over the past decade, there has been a rapid increase in the incidence of inflammatory bowel disease. It has been suggested that multifactorial interactions of environmental factors, genetic factors, immune response and intestinal microbiota are involved in the pathogenesis of inflammatory bowel disease. It is widely recognized that the intestinal microbiota are essential for human metabolism, the immune system and pathogen resistance, and are integral to human health. Therefore, the dysbiosis of the microbiota is a critical step leading to intestinal mucosal damage and a key factor in the pathogenesis of inflammatory bowel disease. Regulating the microbiota through interventions such as enteral nutrition, fecal microbiota transplantation, and probiotic supplementation has the potential to prevent or even reverse intestinal dysbiosis, opening up new perspectives for the treatment of inflammatory bowel disease.}, } @article {pmid39457040, year = {2024}, author = {Mousa, WK and Al Ali, A}, title = {The Gut Microbiome Advances Precision Medicine and Diagnostics for Inflammatory Bowel Diseases.}, journal = {International journal of molecular sciences}, volume = {25}, number = {20}, pages = {}, pmid = {39457040}, issn = {1422-0067}, mesh = {Humans ; *Inflammatory Bowel Diseases/microbiology/therapy/diagnosis/genetics ; *Gastrointestinal Microbiome ; *Precision Medicine/methods ; *Probiotics/therapeutic use ; Fecal Microbiota Transplantation ; Animals ; Metabolomics/methods ; }, abstract = {The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.}, } @article {pmid39456641, year = {2024}, author = {Wu, M and Tian, C and Zou, Z and Jin, M and Liu, H}, title = {Gastrointestinal Microbiota in Gastric Cancer: Potential Mechanisms and Clinical Applications-A Literature Review.}, journal = {Cancers}, volume = {16}, number = {20}, pages = {}, pmid = {39456641}, issn = {2072-6694}, support = {WJ2023M92//Scientific research project of Hubei Provincial Health Commission/ ; 320.6750.2023-19-7 and 320.6750.2024-10-2//Clinical Research Special Fund of Wu Jieping Medical Foundation/ ; WX23A31//Medical Science Research Fundation of Wuhan/ ; }, abstract = {Emerging evidence highlights the crucial role of gastrointestinal microbiota in the pathogenesis of gastric cancer. Helicobacter pylori (H. pylori) infection stands out as a primary pathogenic factor. However, interventions such as anti-H. pylori therapy, gastric surgeries, immunotherapy, and chronic inflammation significantly remodel the gastric microbiome, implicating a broader spectrum of microorganisms in cancer development. These microbial populations can modulate gastric carcinogenesis through various mechanisms, including sustained chronic inflammation, bacterial genotoxins, alterations in short-chain fatty acids, elevated gastrointestinal bile acids, impaired mucus barrier function, and increased concentrations of N-nitrosamines and lactic acid. The dynamic changes in gut microbiota also critically influence the outcomes of anti-cancer therapies by modifying drug bioavailability and metabolism, thus affecting therapeutic efficacy and side effect profiles. Additionally, the effectiveness of radiotherapy can be significantly impacted by gut microbiota alterations. Novel therapeutic strategies targeting the microbiome, such as dietary interventions, probiotic and synbiotic supplementation, and fecal microbiota transplantation, are showing promise in cancer treatment. Understanding the intricate relationship between the gut microbiota and gastric cancer is essential for developing new, evidence-based approaches to the prevention and treatment of this malignancy.}, } @article {pmid39455910, year = {2024}, author = {Tang, BB and Su, CX and Wen, N and Zhang, Q and Chen, JH and Liu, BB and Wang, YQ and Huang, CQ and Hu, YL}, title = {FMT and TCM to treat diarrhoeal irritable bowel syndrome with induced spleen deficiency syndrome- microbiomic and metabolomic insights.}, journal = {BMC microbiology}, volume = {24}, number = {1}, pages = {433}, pmid = {39455910}, issn = {1471-2180}, support = {2023ZR004//TCM science and technology project of Zhejiang Province/ ; 2024KY869//Zhejiang Provincial Medical and Health Science and Technology Project/ ; 2022020801020508//Knowledge Innovation Program of Wuhan Shuguang Project/ ; 2022020801020584//Knowledge Innovation Program of Wuhan Shuguang Project/ ; 82374205//National Natural Science Foundation of China/ ; 2020020601012244//Wuhan Applied Foundational Frontier Project/ ; }, mesh = {Animals ; *Irritable Bowel Syndrome/therapy/microbiology/drug therapy ; *Gastrointestinal Microbiome/drug effects ; Rats ; *Fecal Microbiota Transplantation ; *Diarrhea/microbiology/therapy/drug therapy ; *Medicine, Chinese Traditional/methods ; *Drugs, Chinese Herbal/pharmacology/therapeutic use ; *Disease Models, Animal ; *Metabolomics ; Splenic Diseases/therapy/microbiology/drug therapy ; Male ; RNA, Ribosomal, 16S/genetics ; Feces/microbiology ; Spleen/microbiology/metabolism ; }, abstract = {BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D) is a functional bowel disease with diarrhea, and can be associated with common spleen deficiency syndrome of the prevelent traditional Chinese medicine (TCM) syndrome. Fecal microbiota transplantation (FMT) could help treating IBS-D, but may provide variable effects. Our study evaluated the efficacy of TCM- shenling Baizhu decoction and FMT in treating IBS-D with spleen deficiency syndrome, with significant implications on gut microbiome and serum metabolites.

METHODS: The new borne rats were procured from SPF facility and separated as healthy (1 group) and IBS-D model (3 groups) rats were prepared articially using mother's separation and senna leaf treatment. 2 groups of IBS-D models were further treated with TCM- shenling Baizhu decoction and FMT. The efficacy was evaluated by defecation frequency, bristol stool score, and intestinal tight junction proteins (occludin-1 and claudin-1) expression. Microbiomic analysis was conducted using 16 S rRNA sequencing and bioinformatics tools. Metabolomics were detected in sera of rats by LC-MS and annotated by using KEGG database.

RESULTS: Significant increment in occludin-1 and claudin-1 protein expression alleviated the diarrheal severity in IBS-D rats (P < 0.05) after treatment with FMT and TCM. FMT and TCM altered the gut microbiota and regulated the tryptophan metabolism, steroid hormone biosynthesis and glycerophospholipid metabolism of IBS-D rats with spleen deficiency syndrome.The microbial abundance were changed in each case e.g., Monoglobus, Dubosiella, and Akkermansia and othe metabolic profiles.

CONCLUSION: FMT and TCM treatment improved the intestinal barrier function by regulating gut microbiota and improved metabolic pathways in IBS-D with spleen deficiency syndrome.}, } @article {pmid39454127, year = {2024}, author = {Ran, X and Li, Y and Guo, W and Li, K and Guo, W and Wang, X and Liu, J and Bi, J and Fu, S}, title = {Angelica sinensis Polysaccharide Alleviates Staphylococcus aureus-Induced Mastitis by Regulating The Intestinal Flora and Gut Metabolites.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.4c06094}, pmid = {39454127}, issn = {1520-5118}, abstract = {The modulation of intestinal flora by various polysaccharides has been shown to mitigate disease progression. Recent research reveals a significant link between intestinal flora and the progression of mastitis. This study demonstrates that the oral administration of Angelica sinensis polysaccharide (ASP) reduces mammary inflammation and blood-milk barrier (BMB) damage induced by Staphylococcus aureus in mice, primarily through the modulation of intestinal flora. The beneficial effects of ASP were negated when antibiotics disrupted the gut microbiota in mice. Furthermore, fecal microbiota transplantation (FMT) from ASP-treated mice to recipients markedly alleviated symptoms of S. aureus-induced mastitis. Oral ASP not only enhances gut microbial diversity but also shifts its composition, increasing the abundance of Lachnospiraceae_NK4A136 while reducing Erysipelatoclostridium. Metabolomic analysis revealed that ASP alters intestinal metabolic pathways, elevating levels of metabolites, such as tabersonine and riboflavin. Notably, tabersonine was found to ameliorate S. aureus-induced mastitis. These results suggest that targeting intestinal flora and metabolism through polysaccharides could serve as a promising strategy for mastitis intervention and potentially for other infectious diseases, as well.}, } @article {pmid39452187, year = {2024}, author = {Niyazi, D and Vergiev, S and Markovska, R and Stoeva, T}, title = {Prevalence and Molecular Epidemiology of Intestinal Colonization by Multidrug-Resistant Bacteria among Hematopoietic Stem-Cell Transplantation Recipients: A Bulgarian Single-Center Study.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {13}, number = {10}, pages = {}, pmid = {39452187}, issn = {2079-6382}, support = {19019/2019//Medical University of Varna/ ; }, abstract = {Background/Objectives: Intestinal colonization by multidrug-resistant (MDR) bacteria is considered one of the main risk factors for invasive infections in the hematopoietic stem-cell transplant (HSCT) setting, associated with hard-to-eradicate microorganisms. The aim of this study was to assess the rate of intestinal colonization by MDR bacteria and their microbial spectrum in a group of post-HSCT patients to study the genetic determinants of beta-lactam and glycopeptide resistance in the recovered isolates, as well as to determine the epidemiological relation between them. Methods: The intestinal colonization status of 74 patients admitted to the transplantation center of University Hospital "St. Marina"-Varna in the period January 2019 to December 2021 was investigated. Stool samples/rectal swabs were screened for third-generation cephalosporin and/or carbapenem-resistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Stenotrophomonas maltophilia. Identification and antimicrobial susceptibility testing were performed by Phoenix (BD, Sparks, MD, USA) and MALDI Biotyper sirius (Bruker, Bremen, Germany). Molecular genetic methods (PCR, DNA sequencing) were used to study the mechanisms of beta-lactam and glycopeptide resistance in the collected isolates, as well as the epidemiological relationship between them. Results: A total of 28 patients (37.8%) were detected with intestinal colonization by MDR bacteria. Forty-eight non-duplicate MDR bacteria were isolated from their stool samples. Amongst them, the Gram-negative bacteria prevailed (68.8%), dominated by ESBL-producing Escherichia coli (30.3%), and followed by carbapenem-resistant Pseudomonas sp. (24.2%). The Gram-positive bacteria were represented exclusively by Enterococcus faecium (31.2%). The main beta-lactam resistance mechanisms were associated with CTX-M and VIM production. VanA was detected in all vancomycin-resistant enterococci. A clonal relationship was observed among Enterobacter cloacae complex and among E. faecium isolates. Conclusions: To the best of our knowledge, this is the first Bulgarian study that presents detailed information about the prevalence, resistance genetic determinants, and molecular epidemiology of MDR gut-colonizing bacteria in HSCT patients.}, } @article {pmid39449276, year = {2024}, author = {Zhang, H and Luo, M and Li, Y and Liu, L and Bian, J and Gong, L and He, C and Han, L and Wang, M}, title = {Ellagic acid ameliorates alcohol-induced cognitive and social dysfunction through the gut microbiota-mediated CCL21-CCR7 axis.}, journal = {Food & function}, volume = {}, number = {}, pages = {}, doi = {10.1039/d4fo03985h}, pmid =