@article {pmid39030525,
year = {2024},
author = {Lu, L and Li, F and Gao, Y and Kang, S and Li, J and Guo, J},
title = {Microbiome in radiotherapy: an emerging approach to enhance treatment efficacy and reduce tissue injury.},
journal = {Molecular medicine (Cambridge, Mass.)},
volume = {30},
number = {1},
pages = {105},
pmid = {39030525},
issn = {1528-3658},
support = {31920210037//Fundamental Research Funds for Central Universities of the Central South University/ ; No. xbmuyjrc202217//Northwest Minzu University/ ; },
mesh = {Humans ; *Gastrointestinal Microbiome/radiation effects ; *Neoplasms/radiotherapy/microbiology/immunology/therapy ; *Probiotics/therapeutic use ; *Radiotherapy/adverse effects/methods ; Animals ; Microbiota/radiation effects ; Radiation Injuries/microbiology/therapy/etiology ; Treatment Outcome ; },
abstract = {Radiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system's response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.},
}

Humans
*Gastrointestinal Microbiome/radiation effects
*Neoplasms/radiotherapy/microbiology/immunology/therapy
*Probiotics/therapeutic use
*Radiotherapy/adverse effects/methods
Animals
Microbiota/radiation effects
Radiation Injuries/microbiology/therapy/etiology
Treatment Outcome

@article {pmid39030408,
year = {2024},
author = {Gilbert, JA and Hartmann, EM},
title = {The indoors microbiome and human health.},
journal = {Nature reviews. Microbiology},
volume = {},
number = {},
pages = {},
pmid = {39030408},
issn = {1740-1534},
abstract = {Indoor environments serve as habitat for humans and are replete with various reservoirs and niches for microorganisms. Microorganisms enter indoor spaces with their human and non-human hosts, as well as via exchange with outdoor sources, such as ventilation and plumbing. Once inside, many microorganisms do not survive, especially on dry, barren surfaces. Even reduced, this microbial biomass has critical implications for the health of human occupants. As urbanization escalates, exploring the intersection of the indoor environment with the human microbiome and health is increasingly vital. The indoor microbiome, a complex ecosystem of microorganisms influenced by human activities and environmental factors, plays a pivotal role in modulating infectious diseases and fostering healthy immune development. Recent advancements in microbiome research shed light on this unique ecological system, highlighting the need for innovative approaches in creating health-promoting living spaces. In this Review, we explore the microbial ecology of built environments - places where humans spend most of their lives - and its implications for immune, endocrine and neurological health. We further propose strategies to harness the indoor microbiome for better health outcomes.},
}

@article {pmid39026867,
year = {2024},
author = {Rudzite, M and O'Toole, GA},
title = {An energy coupling factor transporter of Streptococcus sanguinis impacts antibiotic susceptibility as well as metal and membrane homeostasis.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.07.12.603315},
pmid = {39026867},
issn = {2692-8205},
abstract = {UNLABELLED: Streptococcus sanguinis is a prevalent member of human microbiome capable of acting as a causative agent of oral and respiratory infections. S. sanguinis competitive success within the infection niche is dependent on acquisition of metal ions and vitamins. Among the systems that bacteria use for micronutrient uptake is the energy coupling factor (ECF) transporter system EcfAAT. Here we describe physiological changes arising from EcfAAT transporter disruption. We found that EcfAAT contributes to S. sanguinis antibiotic sensitivity as well as metal and membrane homeostasis. Specifically, our work found that disruption of EcfAAT results in increased polymyxin susceptibility. We performed assessment of cell-associated metal content and found depletion of iron, magnesium, and manganese. Furthermore, membrane composition analysis revealed significant enrichment in unsaturated fatty acid species resulting in increased membrane fluidity. Our results demonstrate how disruption of a single EcfAAT transporter can have broad consequences on bacterial cell homeostasis. ECF transporters are of interest within the context of infection biology in bacterial species other than streptococci, hence work described here will further the understanding of how micronutrient uptake systems contribute to bacterial pathogenesis.

IMPORTANCE: Proficiency in micronutrient uptake is key for pathogen success in bacteria-bacteria and bacteria-host interactions within the infection context. Micronutrient uptake mechanisms are of interest in furthering the understanding of bacterial physiology within infection niche and as targets for design of antimicrobials. Here we describe how a deletion of a nutrient uptake transporter in S. sanguinis alters bacterial sensitivity to antibiotics. We also show that a defect in this candidate nutrient uptake system has consequences on the intracellular metal content, and also results in changes in membrane fatty acid composition and fluidity. This study demonstrates how disruption of a single nutrient uptake system disrupts bacterial physiology resulting in increased antibiotic sensitivity.},
}

@article {pmid39026688,
year = {2024},
author = {Agnew, A and Humm, E and Zhou, K and Gunsalus, RP and Zhou, ZH},
title = {Reconstruction and identification of the native PLP synthase complex from Methanosarcina acetivorans lysate.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.07.09.602819},
pmid = {39026688},
issn = {2692-8205},
abstract = {Many protein-protein interactions behave differently in biochemically purified forms as compared to their in vivo states. As such, determining native protein structures may elucidate structural states previously unknown for even well-characterized proteins. Here we apply the bottom-up structural proteomics method, cryoID , toward a model methanogenic archaeon. While they are keystone organisms in the global carbon cycle and active members of the human microbiome, there is a general lack of characterization of methanogen enzyme structure and function. Through the cryoID approach, we successfully reconstructed and identified the native Methanosarcina acetivorans pyridoxal 5'-phosphate (PLP) synthase (PdxS) complex directly from cryogenic electron microscopy (cryoEM) images of fractionated cellular lysate. We found that the native PdxS complex exists as a homo-dodecamer of PdxS subunits, and the previously proposed supracomplex containing both the synthase (PdxS) and glutaminase (PdxT) was not observed in cellular lysate. Our structure shows that the native PdxS monomer fashions a single 8α/8β TIM-barrel domain, surrounded by seven additional helices to mediate solvent and interface contacts. A density is present at the active site in the cryoEM map and is interpreted as ribose 5-phosphate. In addition to being the first reconstruction of the PdxS enzyme from a heterogeneous cellular sample, our results reveal a departure from previously published archaeal PdxS crystal structures, lacking the 37 amino acid insertion present in these prior cases. This study demonstrates the potential of applying the cryoID workflow to capture native structural states at atomic resolution for archaeal systems, for which traditional biochemical sample preparation is nontrivial.},
}

@article {pmid39023173,
year = {2024},
author = {Ivashkin, V and Maev, I and Poluektova, E and Sinitsa, A and Avalueva, E and Mnatsakanyan, M and Simanenkov, V and Karpeeva, J and Kopylova, D and Kuprina, I and Kucheryavyy, Y and Lapina, T and Solovyeva, O and Soom, M and Cheremushkina, N and Maevskaya, E and Maslennikov, R},
title = {Efficacy and safety of postbiotic containing inactivated Lactobacillus reuteri (Limosilactobacillus reuteri) DSM 17648 as adjuvant therapy for Helicobacter pylori eradication in adults with functional dyspepsia: A randomized double-blind placebo-contolled trial.},
journal = {Clinical and translational gastroenterology},
volume = {},
number = {},
pages = {},
doi = {10.14309/ctg.0000000000000750},
pmid = {39023173},
issn = {2155-384X},
abstract = {INTRODUCTION: Increasing the effectiveness of eradication therapy is an important task in gastroenterology. The aim was to evaluate the efficacy and safety of postbiotic containing inactivated (non-viable) Limosilactobacillus reuteri DSM17648 (Pylopass) as adjuvant treatment for Helicobacter pylori eradication in patients with functional dyspepsia (FD).

METHODS: This randomized, double-blind, placebo-controlled, multicenter, parallel study included Helicobacter pylori positive patients with FD. The postbiotic group received Pylopass 200 mg bid for 14 days in combination with eradication therapy (esomeprazole 20 mg bid + amoxicillin 1000 mg bid + clarithromycin 500 mg bid for 14 days) and another 14 days after completion of eradication therapy. The study was registered in the ISRCTN registry (ISRCTN20716052).

RESULTS: Eradication efficiency was 96.7% for the postbiotic group versus 86.0% for the placebo group (P=0.039). Both groups showed significant improvements in quality of life and reduction of most gastrointestinal symptoms with no significant differences between groups. The overall number of digestive adverse effects in the postbiotic group was lower than in the placebo group. Serious adverse effects were not registered.

CONCLUSIONS: The postbiotic containing inactivated L. reuteri DSM17648 significantly improves the effectiveness of H. pylori eradication therapy in FD and decreases overall number of digestive adverse effects of this therapy.},
}

@article {pmid39022135,
year = {2020},
author = {Jiang, J and Warren, CM and Browning, RL and Ciaccio, CE and Gupta, RS},
title = {Food allergy epidemiology and racial and/or ethnic differences.},
journal = {Journal of food allergy},
volume = {2},
number = {1},
pages = {11-16},
pmid = {39022135},
issn = {2689-0275},
abstract = {In recent decades, immunoglobulin E (IgE) mediated food allergy has become a growing public health concern. Converging evidence from cross-sectional prevalence studies, health care utilization records, and cohort studies indicate that food allergies are increasingly prevalent and often severe. Although IgE-mediated food allergy has long been considered a predominantly pediatric concern, analysis of recent self-reported data suggests that food allergies may be more prevalent among adult populations than previously acknowledged, with many reported cases of adult-onset allergies as well as persistent childhood-onset allergies. Results of studies also suggest that food allergy-related health care utilization is increasing as more individuals seek emergency treatment for food-induced anaphylaxis. Analysis of epidemiologic data also indicates that the burden of food allergies is unequally distributed. Published prevalence rates are highest in Western countries, e.g., the United States, United Kingdom, and Australia. Within these countries, there also is heterogeneity across racial and/or ethnic groups, with non-White and second-generation immigrant populations disproportionately affected. Importantly, such observations can shed light on the etiology of food allergy and inform improved clinical management, treatment, and prevention efforts. For example, there is a growing consensus that earlier introduction of allergenic foods, e.g., peanut, promotes oral tolerance and can dramatically reduce food allergy risk. In addition, much attention has been paid to the potentially deleterious effects of cutaneous allergen exposure, e.g., through eczematous skin, which can skew the immune response away from tolerance and toward allergic sensitization, thereby increasing food allergy risk. Furthermore, there is a growing appreciation for the potential protective effects of diverse microbial exposures, given mounting evidence for the immunomodulatory effects of the human microbiome. Also, when considering the geographic variability in the prevalence of certain food and environmental allergies as well as their structural similarities at the molecular level, it is believed that co-sensitization between food and environmental allergens may be a key driver of rising food allergy prevalence.},
}

@article {pmid38688858,
year = {2024},
author = {Sminia, TJ and Aalvink, S and de Jong, H and Tempelaars, MH and Zuilhof, H and Abee, T and de Vos, WM and Tytgat, HLP and Wennekes, T},
title = {Probing Peptidoglycan Synthesis in the Gut Commensal Akkermansia Muciniphila with Bioorthogonal Chemical Reporters.},
journal = {Chembiochem : a European journal of chemical biology},
volume = {},
number = {},
pages = {e202400037},
doi = {10.1002/cbic.202400037},
pmid = {38688858},
issn = {1439-7633},
support = {//Netherlands Foundation for Scientific Research (NWO)/ ; 722.011.006//VENI/ ; 723.014.005//VIDI/ ; //Laboratory of Microbiology/ ; //Soehngen Institute of Anaerobic Microbiology/ ; //SIAM/ ; 024.002.002//NWO/ ; //NWO/ ; //WMdV/ ; //Laboratory of Biochemistry, Wageningen University/ ; },
abstract = {Our gut microbiota directly influences human physiology in health and disease. The myriad of surface glycoconjugates in both the bacterial cell envelope and our gut cells dominate the microbiota-host interface and play a critical role in host response and microbiota homeostasis. Among these, peptidoglycan is the basic glycan polymer offering the cell rigidity and a basis on which many other glycoconjugates are anchored. To directly study peptidoglycan in gut commensals and obtain the molecular insight required to understand their functional activities we need effective techniques like chemical probes to label peptidoglycan in live bacteria. Here we report a chemically guided approach to study peptidoglycan in a key mucin-degrading gut microbiota member of the Verrucomicrobia phylum, Akkermansia muciniphila. Two novel non-toxic tetrazine click-compatible peptidoglycan probes with either a cyclopropene or isonitrile handle allowed for the detection and imaging of peptidoglycan synthesis in this intestinal species.},
}

@article {pmid39015605,
year = {2024},
author = {Sermsaksasithorn, P and Asawanonda, P and Phutrakool, P and Ondee, T and Chariyavilaskul, P and Payungporn, S and Pongpirul, K and Hirankarn, N},
title = {Efficacy and Safety of Cannabis Transdermal Patch for Alleviating Psoriasis Symptoms: Protocol for a Randomized Controlled Trial (CanPatch).},
journal = {Medical cannabis and cannabinoids},
volume = {7},
number = {1},
pages = {99-110},
pmid = {39015605},
issn = {2504-3889},
abstract = {INTRODUCTION: Current topical treatments for psoriasis offer limited efficacy and are associated with long-term adverse effects in a subset of patients, highlighting the need for new therapeutic options. Cannabidiol (CBD), a non-psychoactive cannabinoid derived from Cannabis sativa L., has shown potential in reversing psoriasis pathology through its action on skin receptors in preclinical studies. Given the promising properties of CBD, transdermal patches containing this compound represent a novel approach to psoriasis treatment. However, comprehensive data on their efficacy and safety remain scarce.

METHODS: We outline a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of CBD transdermal patches with minimal tetrahydrocannabinol (THC) in 60 patients with mild to moderate plaque-type psoriasis at a university hospital in Thailand (n = 60). This study aims to evaluate the changes in the local psoriasis severity index (LPSI), itch score via a visual analog scale, and occurrence of adverse events on day 0, 30, 60, and 90 of the study. Additionally, we will examine the alteration in the skin, gut, and oral microbiome in a subset of participants to explore potential correlations with treatment outcomes. The primary outcome will focus on the difference in LPSI scores at the end of the study period, employing an intention-to-treat analysis. Multivariate logistic regression will be used to identify baseline clinical and microbiological predictors of treatment response.

CONCLUSION: This study aims to investigate the efficacy and safety of CBD transdermal patches in alleviating the symptoms of psoriasis. The results of this study may highlight a novel topical treatment option that reduces suffering in patients with psoriasis. We also designed to provide a holistic evaluation by considering both clinical outcomes and the underlying biological mechanisms, including the interaction with the human microbiome. Through this trial, we aim to contribute valuable insights into personalized psoriasis management strategies.},
}

@article {pmid39013264,
year = {2024},
author = {Kim, J and Park, S and Kim, SJ and Yoo, I and Kim, H and Hwang, S and Sim, KM and Kim, I and Jun, E},
title = {High-throughput drug screening using a library of antibiotics targeting cancer cell lines that are resistant and sensitive to gemcitabine.},
journal = {Biochemical and biophysical research communications},
volume = {730},
number = {},
pages = {150369},
doi = {10.1016/j.bbrc.2024.150369},
pmid = {39013264},
issn = {1090-2104},
abstract = {Gemcitabine is a nucleoside analog widely used as an anticancer agent against several types of cancer. Although gemcitabine sometimes shows excellent effectiveness, cancer cells are often poorly responsive to or resistant to the drug. Recently, specific strains or dysbiosis of the human microbiome were correlated with drug reactivity and resistance acquisition. Therefore, we aimed to identify antibiotic compounds that can modulate the microbiome to enhance the responsiveness to gemcitabine. To achieve this, we confirmed the gemcitabine responsiveness based on public data and conducted drug screening on a set of 250 antibiotics compounds. Subsequently, we performed experiments to investigate whether the selected compounds could enhance the responsiveness to gemcitabine. First, we grouped a total of seven tumor cell lines into resistant and sensitive group based on the IC50 value (1 μM) of gemcitabine obtained from the public data. Second, we performed high-throughput screening with compound treatments, identifying seven compounds from the resistant group and five from the sensitive group based on dose dependency. Finally, the combination of the selected compound, puromycin dihydrochloride, with gemcitabine in gemcitabine-resistant cell lines resulted in extensive cell death and a significant increase in cytotoxic efficacy. Additionally, mRNA levels associated with cell viability and stemness were reduced. Through this study, we screened antibiotics to further improve the efficacy of existing anticancer drugs and overcome resistance. By combining existing anticancer agents and antibiotic substances, we hope to establish various drug combination therapies and ultimately improve cancer treatment efficacy.},
}

@article {pmid39011022,
year = {2024},
author = {Sarkar, P and Chintaluri, S and Sarkar, S and Unnisa, M and Jakkampudi, A and Mulukutla, AP and Kumari, S and Reddy, DN and Talukdar, R},
title = {Evaluation of the Crosstalk Between the Host Mycobiome and Bacteriome in Patients with Chronic Pancreatitis.},
journal = {Indian journal of microbiology},
volume = {64},
number = {2},
pages = {603-617},
pmid = {39011022},
issn = {0046-8991},
abstract = {UNLABELLED: The human microbiome is a diverse consortium of microbial kingdoms that play pivotal roles in host health and diseases. We previously reported a dysbiotic bacteriome in chronic pancreatitis patients with diabetes (CPD) compared with patients with it's nondiabetic (CPND) phenotype. In this study, we extended our exploration to elucidate the intricate interactions between the mycobiome, bacteriome, and hosts' plasma metabolome with the disease phenotypes. A total of 25 participants (CPD, n = 7; CPND, n = 10; healthy control, n = 8) were recruited for the study. We observed elevated species richness in both the bacterial and fungal profiles within the CP diabetic cohort compared to the nondiabetic CP phenotype and healthy control cohorts. Notably, the CP group displayed heterogeneous fungal diversity, with only 40% of the CP nondiabetic patients and 20% of the CP diabetic patients exhibiting common core gut fungal profiles. Specific microbial taxa alterations were identified, including a reduction in Bifidobacterium adolescentis and an increase in the prevalence of Aspergillus penicilloides and Klebsiella sp. in the disease groups. In silico analysis revealed the enrichment of pathways related to lipopolysaccharide (LPS), apoptosis, and peptidase, as well as reduced counts of the genes responsible for carbohydrate metabolism in the CP groups. Additionally, distinct plasma metabolome signatures were observed, with CPD group exhibiting higher concentrations of sugars and glycerolipids, while the CPND cohort displayed elevated levels of amino acids in their blood. The fatty acid-binding protein (FABP) concentration was notably greater in the CPD group than in the HC group (4.220 vs. 1.10 ng/ml, p = 0.04). Furthermore, compared with healthy controls, disease groups exhibited fewer correlations between key fungal taxa (Aspergillus sp., Candida sp.) and bacterial taxa (Prevotella copri, Bifidobacteria sp., Rumminococcaceae). Our study unveils, for the first time, a dysbiotic mycobiome and emphasizes unique host bacterial-mycobial interactions in CP patient with diabetes, potentially influencing disease severity. These findings provide crucial insights for future mechanistic studies aiming to unravel the determinants of disease severity in this complex clinical context.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-024-01207-8.},
}

@article {pmid39009231,
year = {2024},
author = {Réthi-Nagy, Z and Juhász, S},
title = {Microbiome's Universe: Impact on health, disease and cancer treatment.},
journal = {Journal of biotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jbiotec.2024.07.002},
pmid = {39009231},
issn = {1873-4863},
abstract = {The human microbiome is a diverse ecosystem of microorganisms that reside in the body and influence various aspects of health and well-being. Recent advances in sequencing technology have brought to light microbial communities in organs and tissues that were previously considered sterile. The gut microbiota plays an important role in host physiology, including metabolic functions and immune modulation. Disruptions in the balance of the microbiome, known as dysbiosis, have been linked to diseases such as cancer, inflammatory bowel disease and metabolic disorders. In addition, the administration of antibiotics can lead to dysbiosis by disrupting the structure and function of the gut microbial community. Targeting strategies are the key to rebalancing the microbiome and fighting disease, including cancer, through interventions such as probiotics, fecal microbiota transplantation (FMT), and bacteria-based therapies. Future research must focus on understanding the complex interactions between diet, the microbiome and cancer in order to optimize personalized interventions. Multidisciplinary collaborations are essential if we are going to translate microbiome research into clinical practice. This will revolutionize approaches to cancer prevention and treatment.},
}

@article {pmid39006241,
year = {2024},
author = {Hu, Y and Zhang, R and Li, J and Wang, H and Wang, M and Ren, Q and Fang, Y and Tian, L},
title = {Association Between Gut and Nasal Microbiota and Allergic Rhinitis: A Systematic Review.},
journal = {Journal of asthma and allergy},
volume = {17},
number = {},
pages = {633-651},
pmid = {39006241},
issn = {1178-6965},
abstract = {Allergic rhinitis is a chronic non-infectious inflammation of the nasal mucosa mediated by specific IgE. Recently, the human microbiome has drawn broad interest as a potential new target for treating this condition. This paper succinctly summarizes the main findings of 17 eligible studies published by February 2024, involving 1044 allergic rhinitis patients and 954 healthy controls from 5 countries. These studies examine differences in the human microbiome across important mucosal interfaces, including the nasal and intestinal areas, between patients and controls. Overall, findings suggest variations in the gut microbiota between allergic rhinitis patients and healthy individuals, although the specific bacterial taxa that significantly changed were not always consistent across studies. Due to the limited scope of existing research and patient coverage, the relationship between the nasal microbiome and allergic rhinitis remains inconclusive. The article discusses the potential immune-regulating role of the gut microbiome in allergic rhinitis. Further well-designed clinical trials with large-scale recruitment of allergic rhinitis patients are encouraged.},
}

@article {pmid38979233,
year = {2024},
author = {Dong, PT and Shi, W and He, X and Borisy, GG},
title = {Adhesive interactions within microbial consortia can be differentiated at the single-cell level through expansion microscopy.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {38979233},
issn = {2692-8205},
support = {R01 DE022586/DE/NIDCR NIH HHS/United States ; R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE030943/DE/NIDCR NIH HHS/United States ; T90 DE026110/DE/NIDCR NIH HHS/United States ; },
abstract = {Investigating microbe-microbe interactions at the single-cell level is critical to unraveling the ecology and dynamics of microbial communities. In many situations, microbes assemble themselves into densely packed multi-species biofilms. The density and complexity pose acute difficulties for visualizing individual cells and analyzing their interactions. Here, we address this problem through an unconventional application of expansion microscopy, which allows for the 'decrowding' of individual bacterial cells within a multispecies community. Expansion microscopy generally has been carried out under isotropic expansion conditions and used as a resolution-enhancing method. In our variation of expansion microscopy, we carry out expansion under heterotropic conditions; that is, we expand the space between bacterial cells but not the space within individual cells. The separation of individual bacterial cells from each other reflects the competition between the expansion force pulling them apart and the adhesion force holding them together. We employed heterotropic expansion microscopy to study the relative strength of adhesion in model biofilm communities. These included mono and dual-species Streptococcus biofilms, and a three-species synthetic community (Fusobacterium nucleatum, Streptococcus mutans, and Streptococcus sanguinis) under conditions that facilitated interspecies coaggregation. Using adhesion mutants, we investigated the interplay between F. nucleatum outer membrane protein RadD and different Streptococcus species. We also examined the Schaalia-TM7 epibiont association. Quantitative proximity analysis was used to evaluate the separation of individual microbial members. Our study demonstrates that heterotropic expansion microscopy can 'decrowd' dense biofilm communities, improve visualization of individual bacterial members, and enable analysis of microbe-microbe adhesive interactions at the single-cell level.},
}

@article {pmid39002973,
year = {2024},
author = {Vich Vila, A and Zhang, J and Liu, M and Faber, KN and Weersma, RK},
title = {Untargeted faecal metabolomics for the discovery of biomarkers and treatment targets for inflammatory bowel diseases.},
journal = {Gut},
volume = {},
number = {},
pages = {},
doi = {10.1136/gutjnl-2023-329969},
pmid = {39002973},
issn = {1468-3288},
abstract = {The gut microbiome has been recognised as a key component in the pathogenesis of inflammatory bowel diseases (IBD), and the wide range of metabolites produced by gut bacteria are an important mechanism by which the human microbiome interacts with host immunity or host metabolism. High-throughput metabolomic profiling and novel computational approaches now allow for comprehensive assessment of thousands of metabolites in diverse biomaterials, including faecal samples. Several groups of metabolites, including short-chain fatty acids, tryptophan metabolites and bile acids, have been associated with IBD. In this Recent Advances article, we describe the contribution of metabolomics research to the field of IBD, with a focus on faecal metabolomics. We discuss the latest findings on the significance of these metabolites for IBD prognosis and therapeutic interventions and offer insights into the future directions of metabolomics research.},
}

@article {pmid38997154,
year = {2024},
author = {Rysbekov, K and Abrakhmanova, S and Satybaeva, R and Starosvetova, Y and Kushugulova, A},
title = {Helicobacter pylori eradication therapy for children.},
journal = {Drug metabolism and personalized therapy},
volume = {},
number = {},
pages = {},
pmid = {38997154},
issn = {2363-8915},
abstract = {OBJECTIVES: The research aims to investigate the effect of vitamin D supplementation on the efficacy of Helicobacter pylori eradication therapy and to find new drug combinations for the eradication of the bacterium.

METHODS: A total of 128 children participated in the research. They were distributed under the following criteria: group A were children who tested positive for H. pylori and were treated with the standard so-called triple therapy including vitamin D; group B were children who tested positive for H. pylori and received the standard triple therapy without including vitamin D in the treatment; and group C were children who tested negative for H. pylori. After endoscopic examination, additional venous blood samples were taken from the children to determine vitamin D levels. A controlled study was carried out 45 days after the initial treatment.

RESULTS: The overall success rate of eradication therapy was 84.1 %. In group A, the success rate of treatment was 93.5 %, contrary to group B, where the success rate was 75 %. Although there was a difference in the percentage of H. pylori eradication therapy in the main group compared to the control group, there was no significant difference in group B. The success rate of eradication is p=0.082.

CONCLUSIONS: Following the research results, the addition of vitamin D to the standard triple therapy regimen for H. pylori had no effect. It can therefore be concluded that vitamin D does not significantly increase the efficacy of eradication therapy.},
}

@article {pmid38996003,
year = {2024},
author = {Byndloss, M and Devkota, S and Duca, F and Niess, JH and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L},
title = {The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.},
journal = {Diabetes care},
volume = {},
number = {},
pages = {},
doi = {10.2337/dci24-0052},
pmid = {38996003},
issn = {1935-5548},
support = {//Novo Nordisk/ ; },
abstract = {This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single-time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.},
}

@article {pmid38993286,
year = {2022},
author = {Reynoso-García, J and Miranda-Santiago, AE and Meléndez-Vázquez, NM and Acosta-Pagán, K and Sánchez-Rosado, M and Díaz-Rivera, J and Rosado-Quiñones, AM and Acevedo-Márquez, L and Cruz-Roldán, L and Tosado-Rodríguez, EL and Figueroa-Gispert, MDM and Godoy-Vitorino, F},
title = {A complete guide to human microbiomes: Body niches, transmission, development, dysbiosis, and restoration.},
journal = {Frontiers in systems biology},
volume = {2},
number = {},
pages = {},
pmid = {38993286},
issn = {2674-0702},
support = {U54 MD007600/MD/NIMHD NIH HHS/United States ; P20 GM103475/GM/NIGMS NIH HHS/United States ; U54 CA096297/CA/NCI NIH HHS/United States ; R25 GM061838/GM/NIGMS NIH HHS/United States ; U54 MD007587/MD/NIMHD NIH HHS/United States ; S21 MD001830/MD/NIMHD NIH HHS/United States ; R25 GM061151/GM/NIGMS NIH HHS/United States ; },
abstract = {Humans are supra-organisms co-evolved with microbial communities (Prokaryotic and Eukaryotic), named the microbiome. These microbiomes supply essential ecosystem services that play critical roles in human health. A loss of indigenous microbes through modern lifestyles leads to microbial extinctions, associated with many diseases and epidemics. This narrative review conforms a complete guide to the human holobiont-comprising the host and all its symbiont populations- summarizes the latest and most significant research findings in human microbiome. It pretends to be a comprehensive resource in the field, describing all human body niches and their dominant microbial taxa while discussing common perturbations on microbial homeostasis, impacts of urbanization and restoration and humanitarian efforts to preserve good microbes from extinction.},
}

@article {pmid38992611,
year = {2024},
author = {Chen, L and Li, Q and Huang, X and Li, Z},
title = {Association between sleep duration and possible sarcopenia in middle-aged and elderly Chinese individuals: evidence from the China health and retirement longitudinal study.},
journal = {BMC geriatrics},
volume = {24},
number = {1},
pages = {594},
pmid = {38992611},
issn = {1471-2318},
support = {2021B1515140026//The Guangdong Basic and Applied Basic Research Fund Local Incubation Projects/ ; 20211800904952//Dongguan City Social Science and Technology Development Project (Key)/ ; 202206010142//The Key Project of Guangzhou Science and Technology Program, China/ ; 2023B1212060018//The Science and Technology Planning Project of Guangdong Province, China/ ; },
mesh = {Humans ; *Sarcopenia/epidemiology/diagnosis/physiopathology ; Male ; Female ; Longitudinal Studies ; China/epidemiology ; Aged ; Middle Aged ; *Sleep/physiology ; Time Factors ; Prevalence ; Sleep Duration ; East Asian People ; },
abstract = {BACKGROUND: Sarcopenia is a common cause of disability in the aging population, and managing sarcopenia is an important step in building intrinsic capacity and promoting healthy aging. A growing body of evidence suggests that sleep deprivation may be a mediator of the development of sarcopenia. The purpose of this study was to explore the longitudinal association between sleep duration and possible sarcopenia using data from a national sample.

METHODS: Two waves of data from the CHARLS database for 2011 and 2015 were used in this study. All possible sarcopenia participants met the Asia Working Group for Sarcopenia 2019 (AWGS 2019) diagnostic criteria. Sleep duration was assessed using a self-report questionnaire, and sleep duration was categorized as short (≤ 6 h), medium (6-8 h), or long (> 8 h) based on previous studies. Longitudinal associations between sleep duration and possible sarcopenia will be calculated by univariate and multifactorial logistic regression analyses and expressed as odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: A total of 5654 individuals participated in the follow-up study, with a prevalence of possible sarcopenia of 53.72% (578) in the short sleep duration group, 38.29% (412) in the medium sleep duration group, and 7.99% (86) in the long sleep duration group. According to the crude model of the second-wave follow-up study, short sleep durations were significantly more strongly associated with possible sarcopenia than were medium and long sleep durations (OR: 1.35, 95% CI: 1.17-1.55, P = 0.000). The association between short sleep duration and possible sarcopenia was maintained even after adjustment for covariates such as age, gender, residence, education level, BMI, smoking status, alcohol consumption and comorbidities (OR: 1.18, 95% CI: 1.02-1.36, P = 0.029). In the subgroup analysis, short sleep duration was associated with low grip strength (OR: 1.20, 95% CI: 1.02-1.41, P = 0.031).

CONCLUSIONS: Sleep deprivation may be closely associated with the development of possible sarcopenia in middle-aged and elderly people, which provides new insights and ideas for sarcopenia intervention, and further studies are needed to reveal the underlying mechanisms involved.},
}

Humans
*Sarcopenia/epidemiology/diagnosis/physiopathology
Male
Female
Longitudinal Studies
China/epidemiology
Aged
Middle Aged
*Sleep/physiology
Time Factors
Prevalence
Sleep Duration
East Asian People

@article {pmid38987933,
year = {2024},
author = {Zhao, Y and Bitzer, A and Power, JJ and Belikova, D and Salazar, BOT and Adolf, LA and Gerlach, DL and Krismer, B and Heilbronner, S},
title = {Nasal commensals reduce Staphylococcus aureus proliferation by restricting siderophore availability.},
journal = {The ISME journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/ismejo/wrae123},
pmid = {38987933},
issn = {1751-7370},
abstract = {The human microbiome is critically associated with human health and disease. One aspect of this is that antibiotic-resistant opportunistic bacterial pathogens such as methicillin-resistant Staphylococcus aureus can reside within the nasal microbiota which increases the risk of infections. Epidemiological studies of the nasal microbiome have revealed positive and negative correlations between non-pathogenic species and S. aureus, but the underlying molecular mechanisms remain poorly understood. The nasal cavity is iron-limited and bacteria are known to produce iron-scavenging siderophores to proliferate in such environments. Siderophores are public goods that can be consumed by all members of a bacterial community. Accordingly, siderophores are known to mediate bacterial competition and collaboration but their role in the nasal microbiome is unknown. Here we show that siderophore acquisition is crucial for S. aureus nasal colonization in vivo. We screened 94 nasal bacterial strains from seven genera for their capacity to produce siderophores as well as to consume the siderophores produced by S. aureus. We found that 80% of the strains engaged in siderophore mediated interactions with S. aureus. Non-pathogenic corynebacterial species were found to be prominent consumers of S. aureus siderophores. In co-culture experiments, consumption of siderophores by competitors reduced S. aureus growth in an iron dependent fashion. Our data show a wide network of siderophore mediated interactions between the species of the human nasal microbiome and provide mechanistic evidence for inter-species competition and collaboration impacting pathogen proliferation. This opens avenues for designing nasal probiotics to displace S. aureus from the nasal cavity of humans.},
}

@article {pmid38987811,
year = {2024},
author = {Won, C and Yim, SS},
title = {Emerging methylation-based approaches in microbiome engineering.},
journal = {Biotechnology for biofuels and bioproducts},
volume = {17},
number = {1},
pages = {96},
pmid = {38987811},
issn = {2731-3654},
support = {G04220037//KAIST/ ; N10230105//KAIST/ ; N11230043//KAIST/ ; N10240028//KAIST/ ; N10240039//KAIST/ ; },
abstract = {Bacterial epigenetics, particularly through DNA methylation, exerts significant influence over various biological processes such as DNA replication, uptake, and gene regulation in bacteria. In this review, we explore recent advances in characterizing bacterial epigenomes, accompanied by emerging strategies that harness bacterial epigenetics to elucidate and engineer diverse bacterial species with precision and effectiveness. Furthermore, we delve into the potential of epigenetic modifications to steer microbial functions and influence community dynamics, offering promising opportunities for understanding and modulating microbiomes. Additionally, we investigate the extensive diversity of DNA methyltransferases and emphasize their potential utility in the context of the human microbiome. In summary, this review highlights the potential of DNA methylation as a powerful toolkit for engineering microbiomes.},
}

@article {pmid38977511,
year = {2024},
author = {Rahim, MA and Seo, H and Kim, S and Barman, I and Ghorbanian, F and Hossain, MS and Shuvo, MSH and Lee, S and Song, HY},
title = {Exploring the potential of Lactocaseibacillus rhamnosus PMC203 in inducing autophagy to reduce the burden of Mycobacterium tuberculosis.},
journal = {Medical microbiology and immunology},
volume = {213},
number = {1},
pages = {14},
pmid = {38977511},
issn = {1432-1831},
support = {RS-2023-00219563//National Research Foundation of Korea/ ; Soonchunhyang University Research Fund//Soonchunhyang University/ ; 20018499//Korean Ministry of Trade, Industry, and Energy (MOTIE, Korea)/ ; },
mesh = {*Autophagy ; *Mycobacterium tuberculosis/genetics ; *Lacticaseibacillus rhamnosus/physiology/metabolism ; *Probiotics ; *Macrophages/microbiology ; Humans ; Lysosomes/metabolism ; Microtubule-Associated Proteins/metabolism/genetics ; Bacterial Load ; Tuberculosis/microbiology ; },
abstract = {Mycobacterium tuberculosis, a lethal pathogen in human history, causes millions of deaths annually, which demands the development of new concepts of drugs. Considering this fact, earlier research has explored the anti-tuberculosis potential of a probiotic strain, Lactocaseibacillus rhamnosus PMC203, leading to a subsequent focus on the molecular mechanism involved in its effect, particularly on autophagy. In this current study, immunoblotting-based assay exhibited a remarkable expression of autophagy marker LC3-II in the PMC203 treated group compared to an untreated group. A remarkable degradation of p62 was also noticed within treated cells compared to control. Furthermore, the immunofluorescence-based assay showed significant fold change in fluorescence intensity for alexa-647-LC3 and alexa-488-LC3, whereas p62 was degraded noticeably. Moreover, lysosomal biogenesis generation was elevated significantly in terms of LAMP1 and acidic vesicular organelles. As a result, PMC203-induced autophagy played a vital role in reducing M. tuberculosis burden within the macrophages in treated groups compared to untreated group. A colony -forming unit assay also revealed a significant reduction in M. tuberculosis in the treated cells over time. Additionally, the candidate strain significantly upregulated the expression of autophagy induction and lysosomal biogenesis genes. Together, these results could enrich our current knowledge of probiotics-mediated autophagy in tuberculosis and suggest its implications for innovatively managing tuberculosis.},
}

*Autophagy
*Mycobacterium tuberculosis/genetics
*Lacticaseibacillus rhamnosus/physiology/metabolism
*Probiotics
*Macrophages/microbiology
Humans
Lysosomes/metabolism
Microtubule-Associated Proteins/metabolism/genetics
Bacterial Load
Tuberculosis/microbiology

@article {pmid38974672,
year = {2024},
author = {Castaño-Henao, L and Mendez, DFG and Egan, S and Sanabria, J},
title = {Changes in groundwater and surface water bacterial communities under disinfection processes: Chlorination, ozonization, photo-fenton and ultraviolet radiation.},
journal = {Current research in microbial sciences},
volume = {7},
number = {},
pages = {100244},
pmid = {38974672},
issn = {2666-5174},
abstract = {Pathogenic bacteria, introduced in water sources through faecal contamination, have traditionally been investigated as individual species, leading to the establishment of microbial, sanitary, and environmental quality indicators. Recent advancements in our understanding of the microbiome and its intricate interactions within the human-microbiome-environment network advocate for a broader evaluation of the impact of disinfection on the entire microbial community. In this study, we conducted a comprehensive screening experiment involving four disinfection processes; ozone, ultraviolet radiation with wavelengths between 200 - 280 nm (UV-C), photo-Fenton, and chlorination, applied to two distinct water sources; surface (SW) and groundwater (GW). The cells that remained viable after treatment were recovered using Brain Heart Infusion (BHI) broth, and 16S rRNA gene sequencing was used for their identification. Our findings confirmed the presence of faecal contamination in the water sources and revealed distinct effects of each treatment on the recovered bacterial populations. The chlorination of groundwater samples likely had a greater impact on bacteria in a vegetative state than on spores. Consequently, this led to a higher abundance in the BHI cultures of sporulating bacteria such as Bacillus (increasing from 0.36 to 93.62 %), while ozonation led to an elevated recovery of Pseudomonas (increasing from 45.2 to 69.9 %). Conversely, in surface water, calcium hypochlorite and ozone treatments favored the selection of Staphylococcus and Bacillus, whose relative abundance in the cultures increased from 0 to 39.22 % and from 0.35 to 96.6 %, respectively. In groundwater, Pseudomonas was resistant to UV-C radiation and their relative abundance increased from 45.2 % to 93.56 %, while photo-Fenton was effective against this bacterial group decreasing its relative abundance to 0.46 %. However, other genera such as Bacteroides, Aeromonas, and Citrobacter seemed to be less injured by this disinfection process. BHI broth was successful in recovering various bacterial groups that exhibited resistance to sublethal water disinfection.},
}

@article {pmid38967872,
year = {2024},
author = {Lyytinen, OL and Dapuliga, C and Wallinger, D and Patpatia, S and Audu, BJ and Kiljunen, SJ},
title = {Three novel Enterobacter cloacae bacteriophages for therapeutic use from Ghanaian natural waters.},
journal = {Archives of virology},
volume = {169},
number = {8},
pages = {156},
pmid = {38967872},
issn = {1432-8798},
mesh = {*Enterobacter cloacae/virology/drug effects ; Ghana ; *Bacteriophages/genetics/isolation & purification/physiology/classification ; *Anti-Bacterial Agents/pharmacology ; Phage Therapy/methods ; Genome, Viral ; Enterobacteriaceae Infections/therapy/microbiology ; Drug Resistance, Multiple, Bacterial ; Finland ; Humans ; Microbial Sensitivity Tests ; Ciprofloxacin/pharmacology ; Meropenem/pharmacology ; },
abstract = {Infections caused by multidrug-resistant (MDR) bacteria are a growing global concern. Enterobacter cloacae complex (ECC) species are particularly adept at developing antibiotic resistance. Phage therapy is proposed as an alternative treatment for pathogens that no longer respond to antibiotics. Unfortunately, ECC phages are understudied when compared to phages of many other bacterial species. In this Ghanaian-Finnish study, we isolated two ECC strains from ready-to-eat food samples and three novel phages from natural waters against these strains. We sequenced the genomic DNA of the novel Enterobacter phages, fGh-Ecl01, fGh-Ecl02, and fGh-Ecl04, and assessed their therapeutic potential. All of the phages were found to be lytic, easy to propagate, and lacking any toxic, integrase, or antibiotic resistance genes and were thus considered suitable for therapy purposes. They all were found to be related to T4-type viruses: fGh-Ecl01 and fGh-Ecl04 to karamviruses and fGh-Ecl02 to agtreviruses. Testing of Finnish clinical ECC strains showed promising susceptibility to these novel phages. As many as 61.1% of the strains were susceptible to fGh-Ecl01 and fGh-Ecl04, and 7.4% were susceptible to fGh-Ecl02. Finally, we investigated the susceptibility of the newly isolated ECC strains to three antibiotics - meropenem, ciprofloxacin, and cefepime - in combination with the novel phages. The use of phages and antibiotics together had synergistic effects. When using an antibiotic-phage combination, even low concentrations of antibiotics fully inhibited the growth of bacteria.},
}

*Enterobacter cloacae/virology/drug effects
Ghana
*Bacteriophages/genetics/isolation & purification/physiology/classification
*Anti-Bacterial Agents/pharmacology
Phage Therapy/methods
Genome, Viral
Enterobacteriaceae Infections/therapy/microbiology
Drug Resistance, Multiple, Bacterial
Finland
Humans
Microbial Sensitivity Tests
Ciprofloxacin/pharmacology
Meropenem/pharmacology

@article {pmid38963518,
year = {2024},
author = {Wang, B and Luan, J and Zhao, W and Yu, J and Li, A and Li, X and Zhong, X and Cao, H and Wang, R and Liu, B and Lu, S and Shi, M},
title = {Comprehensive multiomics analysis of the signatures of gastric mucosal bacteria and plasma metabolites across different stomach microhabitats in the development of gastric cancer.},
journal = {Cellular oncology (Dordrecht)},
volume = {},
number = {},
pages = {},
pmid = {38963518},
issn = {2211-3436},
support = {2021YFA0717002//National Key Research and Development Program of China/ ; 22-3-7-smjk-8-nsh//Funds for Qingdao Science and Technology Benefit People Demonstration Guide Special Project/ ; },
abstract = {PURPOSE: As an important component of the microenvironment, the gastric microbiota and its metabolites are associated with tumour occurrence, progression, and metastasis. However, the relationship between the gastric microbiota and the development of gastric cancer is unclear. The present study investigated the role of the gastric mucosa microbiome and metabolites as aetiological factors in gastric carcinogenesis.

METHODS: Gastric biopsies from different stomach microhabitats (n = 70) were subjected to 16S rRNA gene sequencing, and blood samples (n = 95) were subjected to untargeted metabolome (gas chromatography‒mass spectrometry, GC‒MS) analyses. The datasets were analysed using various bioinformatics approaches.

RESULTS: The microbiota diversity and community composition markedly changed during gastric carcinogenesis. High Helicobacter. pylori colonization modified the overall diversity and composition of the microbiota associated with gastritis and cancer in the stomach. Most importantly, analysis of the functional features of the microbiota revealed that nitrate reductase genes were significantly enriched in the tumoral microbiota, while urease-producing genes were significantly enriched in the microbiota of H. pylori-positive patients. A panel of 81 metabolites was constructed to discriminate gastric cancer patients from gastritis patients, and a panel of 15 metabolites was constructed to discriminate H. pylori-positive patients from H. pylori-negative patients. receiver operator characteristic (ROC) curve analysis identified a series of gastric microbes and plasma metabolites as potential biomarkers of gastric cancer.

CONCLUSION: The present study identified a series of signatures that may play important roles in gastric carcinogenesis and have the potential to be used as biomarkers for diagnosis and for the surveillance of gastric cancer patients with minimal invasiveness.},
}

@article {pmid38962127,
year = {2024},
author = {Lange, E and Kranert, L and Krüger, J and Benndorf, D and Heyer, R},
title = {Microbiome modeling: a beginner's guide.},
journal = {Frontiers in microbiology},
volume = {15},
number = {},
pages = {1368377},
pmid = {38962127},
issn = {1664-302X},
abstract = {Microbiomes, comprised of diverse microbial species and viruses, play pivotal roles in human health, environmental processes, and biotechnological applications and interact with each other, their environment, and hosts via ecological interactions. Our understanding of microbiomes is still limited and hampered by their complexity. A concept improving this understanding is systems biology, which focuses on the holistic description of biological systems utilizing experimental and computational methods. An important set of such experimental methods are metaomics methods which analyze microbiomes and output lists of molecular features. These lists of data are integrated, interpreted, and compiled into computational microbiome models, to predict, optimize, and control microbiome behavior. There exists a gap in understanding between microbiologists and modelers/bioinformaticians, stemming from a lack of interdisciplinary knowledge. This knowledge gap hinders the establishment of computational models in microbiome analysis. This review aims to bridge this gap and is tailored for microbiologists, researchers new to microbiome modeling, and bioinformaticians. To achieve this goal, it provides an interdisciplinary overview of microbiome modeling, starting with fundamental knowledge of microbiomes, metaomics methods, common modeling formalisms, and how models facilitate microbiome control. It concludes with guidelines and repositories for modeling. Each section provides entry-level information, example applications, and important references, serving as a valuable resource for comprehending and navigating the complex landscape of microbiome research and modeling.},
}

@article {pmid38955124,
year = {2024},
author = {Maryam, and Rehman, MU and Hussain, I and Tayara, H and Chong, KT},
title = {A graph neural network approach for predicting drug susceptibility in the human microbiome.},
journal = {Computers in biology and medicine},
volume = {179},
number = {},
pages = {108729},
doi = {10.1016/j.compbiomed.2024.108729},
pmid = {38955124},
issn = {1879-0534},
abstract = {Recent studies have illuminated the critical role of the human microbiome in maintaining health and influencing the pharmacological responses of drugs. Clinical trials, encompassing approximately 150 drugs, have unveiled interactions with the gastrointestinal microbiome, resulting in the conversion of these drugs into inactive metabolites. It is imperative to explore the field of pharmacomicrobiomics during the early stages of drug discovery, prior to clinical trials. To achieve this, the utilization of machine learning and deep learning models is highly desirable. In this study, we have proposed graph-based neural network models, namely GCN, GAT, and GINCOV models, utilizing the SMILES dataset of drug microbiome. Our primary objective was to classify the susceptibility of drugs to depletion by gut microbiota. Our results indicate that the GINCOV surpassed the other models, achieving impressive performance metrics, with an accuracy of 93% on the test dataset. This proposed Graph Neural Network (GNN) model offers a rapid and efficient method for screening drugs susceptible to gut microbiota depletion and also encourages the improvement of patient-specific dosage responses and formulations.},
}

@article {pmid38951769,
year = {2024},
author = {Ranta, K and Skurnik, M and Kiljunen, S},
title = {fENko-Kae01 is a flagellum-specific jumbo phage infecting Klebsiella aerogenes.},
journal = {BMC microbiology},
volume = {24},
number = {1},
pages = {234},
pmid = {38951769},
issn = {1471-2180},
mesh = {*Bacteriophages/genetics/classification/isolation & purification/physiology ; *Genome, Viral ; *Flagella/virology/genetics ; *Enterobacter aerogenes/virology/genetics ; *Host Specificity ; Whole Genome Sequencing ; Myoviridae/genetics/isolation & purification/classification/physiology ; },
abstract = {BACKGROUND: Klebsiella aerogenes is an opportunistic pathogen that causes a wide variety of infections. Due to the rising problem of antibiotic resistance, novel antibiotics and strategies to combat bacterial infections are needed. Host-specific bacteriophages are natural enemies of bacteria and can be used in phage therapy as an alternative form of treatment against bacterial infections. Jumbo phages are defined as phages with genomes larger than 200 kb. Relatively few studies have been done on jumbo phages compared to smaller phages.

RESULTS: A novel phage, fENko-Kae01, was isolated from a commercial phage cocktail. Genomic analysis revealed that fENko-Kae01 is a lytic jumbo phage with a 360 kb genome encoding 578 predicted genes. No highly similar phage genomes were identified and fENko-Kae01 may be a completely new genus representative. No known genes associated with lysogenic life cycle, bacterial virulence, or antibiotic resistance were identified. The phage had myovirus morphology and a narrow host range. Phage resistant bacterial mutants emerged under phage selection. Whole genome sequencing revealed that the biogenesis of the flagellum was affected in four mutants and the lack of functional flagellum was confirmed in motility assays. Furthermore, phage fENKo-Kae01 failed to adsorb on the non-motile mutants indicating that the bacterial flagellum is the phage-binding receptor.

CONCLUSIONS: fENko-Kae01 is a novel jumbo bacteriophage that is considered safe for phage therapy. fENko-Kae01 uses the flagellum as the phage-binding receptor and may represent a completely novel genus.},
}

*Bacteriophages/genetics/classification/isolation & purification/physiology
*Genome, Viral
*Flagella/virology/genetics
*Enterobacter aerogenes/virology/genetics
*Host Specificity
Whole Genome Sequencing
Myoviridae/genetics/isolation & purification/classification/physiology

@article {pmid38950441,
year = {2024},
author = {Chen, Y},
title = {Beyond Meta-Omics: Functional Genomics in Future Marine Microbiome Research.},
journal = {Annual review of marine science},
volume = {},
number = {},
pages = {},
doi = {10.1146/annurev-marine-020123-100931},
pmid = {38950441},
issn = {1941-0611},
abstract = {When President Bill Clinton and Francis Collins, then the director of the National Human Genome Research Institute, celebrated the near completion of the human genome sequence at the White House in the summer of 2000, it is unlikely that they or anyone else could have predicted the blossoming of meta-omics in the following two decades and their applications in modern human microbiome and environmental microbiome research. This transformation was enabled by the development of high-throughput sequencing technologies and sophisticated computational biology tools and bioinformatics software packages. Today, environmental meta-omics has undoubtedly revolutionized our understanding of ocean ecosystems, providing the genetic blueprint of oceanic microscopic organisms. In this review, I discuss the importance of functional genomics in future marine microbiome research and advocate a position for a gene-centric, bottom-up approach in modern oceanography. I propose that a synthesis of multidimensional approaches is required for a better understanding of the true functionality of the marine microbiome.},
}

@article {pmid38948147,
year = {2024},
author = {Guan, Y and Wu, D and Wang, H and Liu, NN},
title = {Microbiome-driven anticancer therapy: A step forward from natural products.},
journal = {mLife},
volume = {3},
number = {2},
pages = {219-230},
pmid = {38948147},
issn = {2770-100X},
abstract = {Human microbiomes, considered as a new emerging and enabling cancer hallmark, are increasingly recognized as critical effectors in cancer development and progression. Manipulation of microbiome revitalizing anticancer therapy from natural products shows promise toward improving cancer outcomes. Herein, we summarize our current understanding of the human microbiome-driven molecular mechanisms impacting cancer progression and anticancer therapy. We highlight the potential translational and clinical implications of natural products for cancer prevention and treatment by developing targeted therapeutic strategies as adjuvants for chemotherapy and immunotherapy against tumorigenesis. The challenges and opportunities for future investigations using modulation of the microbiome for cancer treatment are further discussed in this review.},
}

@article {pmid38945961,
year = {2024},
author = {Kim, N and Ma, J and Kim, W and Kim, J and Belenky, P and Lee, I},
title = {Genome-resolved metagenomics: a game changer for microbiome medicine.},
journal = {Experimental & molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {38945961},
issn = {2092-6413},
support = {HI19C1344//Korea Health Industry Development Institute (KHIDI)/ ; R01 DK125382/DK/NIDDK NIH HHS/United States ; },
abstract = {Recent substantial evidence implicating commensal bacteria in human diseases has given rise to a new domain in biomedical research: microbiome medicine. This emerging field aims to understand and leverage the human microbiota and derivative molecules for disease prevention and treatment. Despite the complex and hierarchical organization of this ecosystem, most research over the years has relied on 16S amplicon sequencing, a legacy of bacterial phylogeny and taxonomy. Although advanced sequencing technologies have enabled cost-effective analysis of entire microbiota, translating the relatively short nucleotide information into the functional and taxonomic organization of the microbiome has posed challenges until recently. In the last decade, genome-resolved metagenomics, which aims to reconstruct microbial genomes directly from whole-metagenome sequencing data, has made significant strides and continues to unveil the mysteries of various human-associated microbial communities. There has been a rapid increase in the volume of whole metagenome sequencing data and in the compilation of novel metagenome-assembled genomes and protein sequences in public depositories. This review provides an overview of the capabilities and methods of genome-resolved metagenomics for studying the human microbiome, with a focus on investigating the prokaryotic microbiota of the human gut. Just as decoding the human genome and its variations marked the beginning of the genomic medicine era, unraveling the genomes of commensal microbes and their sequence variations is ushering us into the era of microbiome medicine. Genome-resolved metagenomics stands as a pivotal tool in this transition and can accelerate our journey toward achieving these scientific and medical milestones.},
}

@article {pmid38944815,
year = {2024},
author = {Del Chierico, F and Masi, L and Petito, V and Baldelli, V and Puca, P and Benvenuto, R and Fidaleo, M and Palucci, I and Lopetuso, LR and Caristo, ME and Carrozza, C and Giustiniani, MC and Nakamichi, N and Kato, Y and Putignani, L and Gasbarrini, A and Pani, G and Scaldaferri, F},
title = {Solute Transporter OCTN1/Slc22a4 Affects Disease Severity and Response to Infliximab in Experimental Colitis: Role of Gut Microbiota and Immune Modulation.},
journal = {Inflammatory bowel diseases},
volume = {},
number = {},
pages = {},
doi = {10.1093/ibd/izae135},
pmid = {38944815},
issn = {1536-4844},
support = {GR-2016-02364891//Italian Ministry of Health/ ; },
abstract = {BACKGROUND: Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial etiology, still incompletely understood. OCTN1, an organic cation transporter, could have a role in modulating the inflammatory response, and some genetic polymorphisms of this molecule have been associated with increased risk of inflammatory bowel diseases. Until now, limited information exists on its potential in predicting/modulating patient's response to therapies. The aim of this study was to evaluate the role of OCTN1 in modifying gut microbiota and mucosal immunity in response to infliximab therapy in murine colitis.

METHODS: A dextran sodium sulphate model of colitis was used to assess the clinical efficacy of infliximab administered intravenously in ocnt1 gene knockout mice and their C57BL/6 controls. Stool, colon, and mesenteric lymph node samples were collected to evaluate differences in gut microbiota composition, histology, and T cell populations, respectively.

RESULTS: Octn1 -/- influences the microbiota profile and is associated with a worse dysbiosis in mice with colitis. Infliximab treatment attenuates colitis-associated dysbiosis, with an increase of bacterial richness and evenness in both strains. In comparison with wild type, octn1-/- mice have milder disease and a higher baseline percentage of Treg, Tmemory, Th2 and Th17 cells.

CONCLUSIONS: Our data support the murine model to study OCTN1 genetic contribution to inflammatory bowel diseases. This could be the first step towards the recognition of this membrane transporter as a biomarker in inflammatory conditions and a predictor of response to therapies.},
}

@article {pmid38942021,
year = {2024},
author = {Chen, W and Li, Y and Wang, W and Gao, S and Hu, J and Xiang, B and Wu, D and Jiao, N and Xu, T and Zhi, M and Zhu, L and Zhu, R},
title = {Enhanced microbiota profiling in patients with quiescent Crohn's disease through comparison with paired healthy first-degree relatives.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {101624},
doi = {10.1016/j.xcrm.2024.101624},
pmid = {38942021},
issn = {2666-3791},
abstract = {Prior studies indicate no correlation between the gut microbes of healthy first-degree relatives (HFDRs) of patients with Crohn's disease (CD) and the development of CD. Here, we utilize HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. When compared to non-relative controls, the use of HFDR controls identifies fewer differential taxa. Faecalibacterium, Dorea, and Fusicatenibacter are decreased in CD-R, independent of inflammation, and correlated with fecal short-chain fatty acids (SCFAs). Validation with a large multi-center cohort confirms decreased Faecalibacterium and other SCFA-producing genera in CD-R. Classification models based on these genera distinguish CD from healthy individuals and demonstrate superior diagnostic power than models constructed with markers identified using unrelated controls. Furthermore, these markers exhibited limited discriminatory capabilities for other diseases. Finally, our results are validated across multiple cohorts, underscoring their robustness and potential for diagnostic and therapeutic applications.},
}

@article {pmid38935049,
year = {2024},
author = {Bai, X and Nielsen, SD and Kunisaki, KM and Trøseid, M},
title = {Pulmonary comorbidities in people with HIV- the microbiome connection.},
journal = {Current opinion in HIV and AIDS},
volume = {},
number = {},
pages = {},
doi = {10.1097/COH.0000000000000871},
pmid = {38935049},
issn = {1746-6318},
abstract = {PURPOSE OF REVIEW: To report recent evidence on associations between human microbiome, particularly airway and gut, and pulmonary comorbidities in people with HIV (PWH). Furthermore, we explore how changes in the microbiome may contribute to pulmonary immune dysregulation and higher rates of pulmonary comorbidities among PWH. Finally, we propose future directions in the field.

RECENT FINDINGS: Increased risk of pulmonary comorbidities and rapid lung function decline have been reported in even well treated PWH. Altered microbiota profiles have been reported in PWH with pulmonary comorbidities and rapid lung function decline as compared to those without. The most consistent data have been the association between HIV-related pulmonary comorbidities, lung and oral microbiota dysbiosis, which has been also associated with distinct respiratory mucosal inflammatory profiles and short-term mortality. However, a possible causal link remains to be elucidated.

SUMMARY: Associations between the lung and oral microbiome, HIV-associated pulmonary comorbidities and rapid lung function decline have been reported in recent studies. Yet the underlying mechanism underpinning the observed associations is largely unknown and substantial knowledge gaps remain. Future research is warranted to unveil the role and mechanism of human microbiome from different anatomical compartments in relation to pulmonary comorbidities in PWH.},
}

@article {pmid38932188,
year = {2024},
author = {Alipour-Khezri, E and Moqadami, A and Barzegar, A and Mahdavi, M and Skurnik, M and Zarrini, G},
title = {Bacteriophages and Green Synthesized Zinc Oxide Nanoparticles in Combination Are Efficient against Biofilm Formation of Pseudomonas aeruginosa.},
journal = {Viruses},
volume = {16},
number = {6},
pages = {},
pmid = {38932188},
issn = {1999-4915},
mesh = {*Zinc Oxide/pharmacology ; *Pseudomonas aeruginosa/virology/drug effects/physiology ; *Biofilms/drug effects ; *Metal Nanoparticles/chemistry ; Green Chemistry Technology ; Bacteriophages/physiology ; Anti-Bacterial Agents/pharmacology ; Nanoparticles/chemistry ; },
abstract = {Bacteriophages (phages) are viruses that infect the bacteria within which their reproduction cycle takes place, a process that ends in the lysis and death of the bacterial cell. Some phages are also able to destroy bacterial biofilms. Due to increased antibiotics resistance, Pseudomonas aeruginosa, another biofilm-forming pathogen, is a problem in many parts of the world. Zinc oxide (ZnO) and other metal nanoparticles (NPs) are biologically active and also possess anti-biofilm properties. ZnO-NPs were prepared by the green synthesis method using orange peels. The vibrational peaks of the ZnO-NPs were analyzed using FTIR analysis, and their size and morphological properties were determined using scanning electron microscopy (SEM). The ability of the ZnO-NPs to reduce or eliminate P. aeruginosa biofilm alone or in combination with phages PB10 and PA19 was investigated. The P. aeruginosa cells were effectively killed in the preformed 48 h biofilms during a 24 h incubation with the ZnO-NP-phage combination, in comparison with the control or ZnO-NPs alone. The treatments on growing biofilms were most efficient in the final stages of biofilm development. All five treatment groups showed a significant biofilm reduction compared to the control group (p < 0.0001) at 48 h of incubation. The influence of the ZnO-NPs and phages on the quorum sensing system of P. aeruginosa was monitored by quantitative real-time PCR (qRT-PCR) of the autoinducer biosynthesis gene lasI. While the ZnO-NPs repressed the lasI gene transcription, the phages slightly activated it at 24 and 48 h of incubation. Also, the effect of the ZnO-NPs and phage PA19 on the viability of HFF2 cells was investigated and the results showed that the combination of NPs with PA19 reduced the toxic effect of ZnO-NPs and also stimulated the growth in normal cells.},
}

*Zinc Oxide/pharmacology
*Pseudomonas aeruginosa/virology/drug effects/physiology
*Biofilms/drug effects
*Metal Nanoparticles/chemistry
Green Chemistry Technology
Bacteriophages/physiology
Anti-Bacterial Agents/pharmacology
Nanoparticles/chemistry

@article {pmid38930571,
year = {2024},
author = {Sprague, KL and Rajakaruna, S and Bandow, B and Burchat, N and Bottomley, M and Sampath, H and Paliy, O},
title = {Gut Microbiota Fermentation of Digested Almond-Psyllium-Flax Seed-Based Artisan Bread Promotes Mediterranean Diet-Resembling Microbial Community.},
journal = {Microorganisms},
volume = {12},
number = {6},
pages = {},
pmid = {38930571},
issn = {2076-2607},
support = {DBI-1335772//National Science Foundation/ ; },
abstract = {Different modifications of the standard bread recipe have been proposed to improve its nutritional and health benefits. Here, we utilized the in vitro Human Gut Simulator (HGS) to assess the fermentation of one such artisan bread by human gut microbiota. Dried and milled bread, composed of almond flour, psyllium husks, and flax seeds as its three main ingredients, was first subjected to an in vitro protocol designed to mimic human oro-gastro-intestinal digestion. The bread digest was then supplied to complex human gut microbial communities, replacing the typical Western diet-based medium (WM) of the GHS system. Switching the medium from WM to bread digest resulted in statistically significant alterations in the community structure, encoded functions, produced short-chain fatty acids, and available antioxidants. The abundances of dietary fiber degraders Enterocloster, Mitsuokella, and Prevotella increased; levels of Gemmiger, Faecalibacterium, and Blautia decreased. These community alterations resembled the previously revealed differences in the distal gut microbiota of healthy human subjects consuming typical Mediterranean vs. Western-pattern diets. Therefore, the consumption of bread high in dietary fiber and unsaturated fatty acids might recapitulate the beneficial effects of the Mediterranean diet on the gut microbiota.},
}

@article {pmid38930451,
year = {2024},
author = {Balleza-Alejandri, LR and Peña-Durán, E and Beltrán-Ramírez, A and Reynoso-Roa, AS and Sánchez-Abundis, LD and García-Galindo, JJ and Suárez-Rico, DO},
title = {Decoding the Gut Microbiota-Gestational Diabetes Link: Insights from the Last Seven Years.},
journal = {Microorganisms},
volume = {12},
number = {6},
pages = {},
doi = {10.3390/microorganisms12061070},
pmid = {38930451},
issn = {2076-2607},
abstract = {The human microbiome, a complex ecosystem of bacteria, viruses, and protozoans living in symbiosis with the host, plays a crucial role in human health, influencing everything from metabolism to immune function. Dysbiosis, or an imbalance in this ecosystem, has been linked to various health issues, including diabetes and gestational diabetes (GD). In diabetes, dysbiosis affects the function of adipose tissue, leading to the release of adipokines and cytokines, which increase inflammation and insulin resistance. During pregnancy, changes to the microbiome can exacerbate glucose intolerance, a common feature of GD. Over the past years, burgeoning insights into the gut microbiota have unveiled its pivotal role in human health. This article comprehensively reviews literature from the last seven years, highlighting the association between gut microbiota dysbiosis and GD, as well as the metabolism of antidiabetic drugs and the potential influences of diet and probiotics. The underlying pathophysiological mechanisms discussed include the impact of dysbiosis on systemic inflammation and the interplay with genetic and environmental factors. By focusing on recent studies, the importance of considering microbial health in the prevention and treatment of GD is emphasized, providing insights into future research directions and clinical applications to improve maternal-infant health outcomes.},
}

@article {pmid38929681,
year = {2024},
author = {Lee, J and Kim, H and Park, JS},
title = {Beyond the Bile: Exploring the Microbiome and Metabolites in Cholangiocarcinoma.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {6},
pages = {},
doi = {10.3390/life14060698},
pmid = {38929681},
issn = {2075-1729},
support = {N/A//INHA UNIVERSITY HOSPITAL Research Grant/ ; N/A//Shihwa medical center research fund/ ; },
abstract = {INTRODUCTION: Cholangiocarcinoma (CCC) still has a high mortality rate despite improvements in diagnostic and therapeutic techniques. The role of the human microbiome in CCC is poorly understood, and a recent metagenomic analysis demonstrated a significant correlation between microbiome-associated carcinogenesis and CCC. This study aimed to investigate changes in microbiome composition associated with CCC and its metabolic signature by integrating taxonomic and functional information with metabolomics data and in vitro experimental results.

METHODS: From February 2019 to January 2021, this study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), both with and without a diagnosis of CCC. Bile samples were collected via endoscopic nasobiliary drainages (ENBD) and subjected to DNA extraction, PCR amplification of the bacterial 16S rRNA gene V3-V4 region, and data analysis using QIIME2. In vitro Carboxyfluorescein succinimidyl ester (CFSE) proliferation and Annexin V/PI apoptosis assays were performed to investigate the effects of metabolites on CCC cells.

RESULTS: A total of 24 patients were included in the study. Bile fluid analysis revealed a significantly higher abundance of Escherichia coli in the CCC group. Alpha diversity analyses exhibited significant differences between the CCC and non-CCC groups, and Nuclear Magnetic Resonance (NMR) spectroscopy metabolic profiling identified 15 metabolites with significant concentration differences; isoleucine showed the most notable difference. In vitro experiments demonstrated that isoleucine suppressed CCC cell proliferation but did not induce apoptosis.

CONCLUSIONS: This research underlines the significance of biliary dysbiosis and specific bile metabolites, such as isoleucine, in influencing the development and progression of CCC.},
}

@article {pmid38927134,
year = {2024},
author = {Martins, D and Silva, C and Ferreira, AC and Dourado, S and Albuquerque, A and Saraiva, F and Batista, AB and Castro, P and Leite-Moreira, A and Barros, AS and Miranda, IM},
title = {Unravelling the Gut Microbiome Role in Cardiovascular Disease: A Systematic Review and a Meta-Analysis.},
journal = {Biomolecules},
volume = {14},
number = {6},
pages = {},
doi = {10.3390/biom14060731},
pmid = {38927134},
issn = {2218-273X},
support = {UIDB/00051/2020//Fundação para a Ciência e Tecnologia/ ; UIDP/00051/2020//Fundação para a Ciência e Tecnologia/ ; 2021.06947.BD//Fundação para a Ciência e Tecnologia/ ; },
mesh = {*Gastrointestinal Microbiome ; Humans ; *Cardiovascular Diseases/microbiology/metabolism ; Bacteria/metabolism/classification/genetics ; Methylamines/metabolism/blood ; },
abstract = {A notable shift in understanding the human microbiome's influence on cardiovascular disease (CVD) is underway, although the causal association remains elusive. A systematic review and meta-analysis were conducted to synthesise current knowledge on microbial taxonomy and metabolite variations between healthy controls (HCs) and those with CVD. An extensive search encompassing three databases identified 67 relevant studies (2012-2023) covering CVD pathologies from 4707 reports. Metagenomic and metabolomic data, both qualitative and quantitative, were obtained. Analysis revealed substantial variability in microbial alpha and beta diversities. Moreover, specific changes in bacterial populations were shown, including increased Streptococcus and Proteobacteria and decreased Faecalibacterium in patients with CVD compared with HC. Additionally, elevated trimethylamine N-oxide levels were reported in CVD cases. Biochemical parameter analysis indicated increased fasting glucose and triglycerides and decreased total cholesterol and low- and high-density lipoprotein cholesterol levels in diseased individuals. This study revealed a significant relationship between certain bacterial species and CVD. Additionally, it has become clear that there are substantial inconsistencies in the methodologies employed and the reporting standards adhered to in various studies. Undoubtedly, standardising research methodologies and developing extensive guidelines for microbiome studies are crucial for advancing the field.},
}

*Gastrointestinal Microbiome
Humans
*Cardiovascular Diseases/microbiology/metabolism
Bacteria/metabolism/classification/genetics
Methylamines/metabolism/blood

@article {pmid38926732,
year = {2024},
author = {Li, Q and Huang, Z and Yang, H and Tang, J and Zuo, T and Yang, Q and Huang, Z and Guo, Q and Li, M and Gao, X and Chao, K},
title = {Intestinal mRNA expression profiles associated with mucosal healing in ustekinumab-treated Crohn's disease patients: bioinformatics analysis and prospective cohort validation.},
journal = {Journal of translational medicine},
volume = {22},
number = {1},
pages = {595},
pmid = {38926732},
issn = {1479-5876},
support = {2022JBGS05//the Sixth Affiliated Hospital of Sun Yat-Sen University/ ; 2022JBGS03//the Sixth Affiliated Hospital of Sun Yat-Sen University/ ; 2020B1111170004//the program of Guangdong Provincial Clinical Research Center for Digestive Diseases/ ; 1010CG(2023)-12//the Sixth Affiliated Hospital of Sun Yat-Sen University Clinical Research-'1010' Program/ ; },
mesh = {Adult ; Female ; Humans ; Male ; Cluster Analysis ; *Computational Biology/methods ; *Crohn Disease/genetics/drug therapy ; Gene Expression Profiling ; Gene Ontology ; Intestinal Mucosa/metabolism/pathology ; Prospective Studies ; Reproducibility of Results ; *RNA, Messenger/genetics/metabolism ; ROC Curve ; Transcriptome/genetics ; *Ustekinumab/therapeutic use/pharmacology ; },
abstract = {BACKGROUND: Variations exist in the response of patients with Crohn's disease (CD) to ustekinumab (UST) treatment, but the underlying cause remains unknown. Our objective was to investigate the involvement of immune cells and identify potential biomarkers that could predict the response to interleukin (IL) 12/23 inhibitors in patients with CD.

METHODS: The GSE207022 dataset, which consisted of 54 non-responders and 9 responders to UST in a CD cohort, was analyzed. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Least absolute shrinkage and selection operator (LASSO) regression was used to screen the most powerful hub genes. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performances of these genes. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to estimate the proportions of immune cell types. These significantly altered genes were subjected to cluster analysis into immune cell-related infiltration. To validate the reliability of the candidates, patients prescribed UST as a first-line biologic in a prospective cohort were included as an independent validation dataset.

RESULTS: A total of 99 DEGs were identified in the integrated dataset. GO and KEGG analyses revealed significant enrichment of immune response pathways in patients with CD. Thirteen genes (SOCS3, CD55, KDM5D, IGFBP5, LCN2, SLC15A1, XPNPEP2, HLA-DQA2, HMGCS2, DDX3Y, ITGB2, CDKN2B and HLA-DQA1), which were primarily associated with the response versus nonresponse patients, were identified and included in the LASSO analysis. These genes accurately predicted treatment response, with an area under the curve (AUC) of 0.938. T helper cell type 1 (Th1) cell polarization was comparatively strong in nonresponse individuals. Positive connections were observed between Th1 cells and the LCN2 and KDM5D genes. Furthermore, we employed an independent validation dataset and early experimental verification to validate the LCN2 and KDM5D genes as effective predictive markers.

CONCLUSIONS: Th1 cell polarization is an important cause of nonresponse to UST therapy in patients with CD. LCN2 and KDM5D can be used as predictive markers to effectively identify nonresponse patients.

TRIAL REGISTRATION: Trial registration number: NCT05542459; Date of registration: 2022-09-14; URL: https://www.

CLINICALTRIALS: gov .},
}

Adult
Female
Humans
Male
Cluster Analysis
*Computational Biology/methods
*Crohn Disease/genetics/drug therapy
Gene Expression Profiling
Gene Ontology
Intestinal Mucosa/metabolism/pathology
Prospective Studies
Reproducibility of Results
*RNA, Messenger/genetics/metabolism
ROC Curve
Transcriptome/genetics
*Ustekinumab/therapeutic use/pharmacology

@article {pmid38924840,
year = {2024},
author = {Yang, Y and Olah, P and Radai, Z and Maia, G and Salava, A and Salo, V and Barker, J and Lauerma, A and Andersson, B and Homey, B and Fyhrquist, N and Alenius, H},
title = {Exploratory multi-omics analysis reveals host-microbe interactions associated with disease severity in psoriatic skin.},
journal = {EBioMedicine},
volume = {105},
number = {},
pages = {105222},
doi = {10.1016/j.ebiom.2024.105222},
pmid = {38924840},
issn = {2352-3964},
abstract = {BACKGROUND: Psoriasis (Pso) is a chronic inflammatory skin disease that poses both physical and psychological challenges. Dysbiosis of the skin microbiome has been implicated in Pso, yet a comprehensive multi-omics analysis of host-microbe interactions is still lacking. To bridge this gap, we conducted an exploratory study by adopting the integrated approach that combines whole metagenomic shotgun sequencing with skin transcriptomics.

METHODS: This was a cross-sectional study, adult patients with plaque-type Psoriasis (Pso) and healthy volunteers were included. Skin microbiota samples and biopsies were collected from both lesional and non-lesional skin areas on the lower back. Weighted Gene Correlation Network Analysis (WGCNA) was employed for co-expression network analysis, and cell deconvolution was conducted to estimate cell fractions. Taxonomic and functional features of the microbiome were identified using whole metagenomic shotgun sequencing. Association between host genes and microbes was analyzed using Spearman correlation.

FINDINGS: Host anti-viral responses and interferon-related networks were identified and correlated with the severity of psoriasis. The skin microbiome showed a greater prevalence of Corynebacterium simulans in the PASI severe-moderate groups, which correlated with interferon-induced host genes. Two distinct psoriatic clusters with varying disease severities were identified. Variations in the expression of cell apoptosis-associated antimicrobial peptides (AMPs) and microbial aerobic respiration I pathway may partly account for these differences in disease severity.

INTERPRETATION: Our multi-omics analysis revealed for the first time anti-viral responses and the presence of C. simulans associated with psoriasis severity. It also identified two psoriatic subtypes with distinct AMP and metabolic pathway expression. Our study provides new insights into understanding the host-microbe interaction in psoriasis and lays the groundwork for developing subtype-specific strategies for managing this chronic skin disease.

FUNDING: The research has received funding from the FP7 (MAARS-Grant 261366) and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the author's view and the JU is not responsible for any use that may be made of the information it contains. GAM was supported by a scholarship provided by CAPES-PRINT, financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES (Brazilian Government Agency). The authors thank all patients who participated in our study.},
}

@article {pmid38923832,
year = {2024},
author = {Del Giudice, G and Serra, A and Pavel, A and Torres Maia, M and Saarimäki, LA and Fratello, M and Federico, A and Alenius, H and Fadeel, B and Greco, D},
title = {A Network Toxicology Approach for Mechanistic Modelling of Nanomaterial Hazard and Adverse Outcomes.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e2400389},
doi = {10.1002/advs.202400389},
pmid = {38923832},
issn = {2198-3844},
support = {309329//EU FP7 project "NANOSOLUTIONS"/ ; 322761//Academy of Finland/ ; 101043848/ERC_/European Research Council/International ; 101137742//EU project "INSIGHT"/ ; 101008099//CompSafeNano project/ ; },
abstract = {Hazard assessment is the first step in evaluating the potential adverse effects of chemicals. Traditionally, toxicological assessment has focused on the exposure, overlooking the impact of the exposed system on the observed toxicity. However, systems toxicology emphasizes how system properties significantly contribute to the observed response. Hence, systems theory states that interactions store more information than individual elements, leading to the adoption of network based models to represent complex systems in many fields of life sciences. Here, they develop a network-based approach to characterize toxicological responses in the context of a biological system, inferring biological system specific networks. They directly link molecular alterations to the adverse outcome pathway (AOP) framework, establishing direct connections between omics data and toxicologically relevant phenotypic events. They apply this framework to a dataset including 31 engineered nanomaterials with different physicochemical properties in two different in vitro and one in vivo models and demonstrate how the biological system is the driving force of the observed response. This work highlights the potential of network-based methods to significantly improve their understanding of toxicological mechanisms from a systems biology perspective and provides relevant considerations and future data-driven approaches for the hazard assessment of nanomaterials and other advanced materials.},
}

@article {pmid38912690,
year = {2024},
author = {Byndloss, M and Devkota, S and Duca, F and Hendrik Niess, J and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L},
title = {The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.},
journal = {Diabetes},
volume = {},
number = {},
pages = {},
doi = {10.2337/dbi24-0028},
pmid = {38912690},
issn = {1939-327X},
support = {2020 (09150182010020)//ZONMW-VICI/ ; 875534//European Union’s Innovative Medicine Initiative/ ; 310030_219210//Swiss National Science Foundation (SNSF)/ ; CEX2021-001189-S/10.13039/501100011033//Severo Ochoa Center of Excellence/ ; //Novo Nordisk Foundation/ ; 2020 (2020.10.002)//DFN-DON/ ; 1DP1 DK130687/DK/NIDDK NIH HHS/United States ; PID2020-119536RB-I00//Spanish Ministry of Science, Innovation and Universities MICIU/AEI/ ; },
abstract = {This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single-time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.},
}

@article {pmid38910152,
year = {2024},
author = {Byndloss, M and Devkota, S and Duca, F and Niess, JH and Nieuwdorp, M and Orho-Melander, M and Sanz, Y and Tremaroli, V and Zhao, L},
title = {The gut microbiota and diabetes: research, translation, and clinical applications - 2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.},
journal = {Diabetologia},
volume = {},
number = {},
pages = {},
pmid = {38910152},
issn = {1432-0428},
abstract = {This article summarises the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organised by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: (1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g. genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomisation in humans; (2) the highly individualised nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; (3) because single time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and (4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal.},
}

@article {pmid38909617,
year = {2024},
author = {Kullberg, RFJ and Wikki, I and Haak, BW and Kauko, A and Galenkamp, H and Peters-Sengers, H and Butler, JM and Havulinna, AS and Palmu, J and McDonald, D and Benchraka, C and Abdel-Aziz, MI and Prins, M and Maitland van der Zee, AH and van den Born, BJ and Jousilahti, P and de Vos, WM and Salomaa, V and Knight, R and Lahti, L and Nieuwdorp, M and Niiranen, T and Wiersinga, WJ},
title = {Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies.},
journal = {The Lancet. Microbe},
volume = {},
number = {},
pages = {},
doi = {10.1016/S2666-5247(24)00079-X},
pmid = {38909617},
issn = {2666-5247},
abstract = {BACKGROUND: Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts.

METHODS: In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18-70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25-74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5-7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards.

FINDINGS: We profiled gut microbiota from 10 699 participants (4248 [39·7%] from the derivation cohort and 6451 [60·3%] from the validation cohort). 602 (5·6%) participants (152 [3·6%] from the derivation cohort; 450 [7·0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0·041; validation p=0·0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0·75 [95% CI 0·60-0·94] per 10% increase in butyrate producers, p=0·013; validation cohort 0·86 [0·77-0·96] per 10% increase, p=0·0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities.

INTERPRETATION: Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections.

FUNDING: Amsterdam UMC, Porticus, National Institutes of Health, Netherlands Organisation for Health Research and Development (ZonMw), and Leducq Foundation.},
}

@article {pmid38904934,
year = {2024},
author = {Peer, A and Samuelson, DR},
title = {The Role of the Microbiome in Allergy, Asthma, and Occupational Lung Disease.},
journal = {Current allergy and asthma reports},
volume = {},
number = {},
pages = {},
pmid = {38904934},
issn = {1534-6315},
support = {R01-DK131990-01/DK/NIDDK NIH HHS/United States ; R01-DK131990-01/DK/NIDDK NIH HHS/United States ; P50-AA030407/AA/NIAAA NIH HHS/United States ; },
abstract = {PURPOSE OF REVIEW: The human commensal microbiota is now widely accepted as a key regulator of human health and disease. The composition of the mucosal associated microbiota has been shown to play a critical role in the lung health. The role of the mucosal microbiota in the development and severity of allergy, asthma, and occupational lung disease is only beginning to take shape. However, advances in our understanding of these links have tremendous potential to led to new clinical interventions to reduce allergy, asthma, and occupational lung disease morbidity.

RECENT FINDINGS: We review recent work describing the relationship and role of the commensal microbiota in the development of allergy, asthma, and occupational lung disease. Our review primarily focuses on occupational exposures and the effects of the microbiome, both in composition and function. Data generated from these studies may lead to the development of interventions targeted at establishing and maintaining a healthy microbiota. We also highlight the role of environmental exposures and the effects on the commensal microbial community and their potential association with occupational lung disease. This review explores the current research describing the role of the human microbiome in the regulation of pulmonary health and disease, with a specific focus on the role of the mucosal microbiota in the development of allergy, asthma, and occupational lung disease.},
}

@article {pmid38899893,
year = {2024},
author = {He, J and Ma, M and Xu, Z and Guo, J and Chen, H and Yang, X and Chen, P and Liu, G},
title = {Association between semen microbiome disorder and sperm DNA damage.},
journal = {Microbiology spectrum},
volume = {},
number = {},
pages = {e0075924},
doi = {10.1128/spectrum.00759-24},
pmid = {38899893},
issn = {2165-0497},
abstract = {DNA fragmentation index (DFI), a new biomarker to diagnose male infertility, is closely associated with poor reproductive outcomes. Previous research reported that seminal microbiome correlated with sperm DNA integrity, suggesting that the microbiome may be one of the causes of DNA damage in sperm. However, it has not been elucidated how the microbiota exerts their effects. Here, we used a combination of 16S rRNA sequencing and untargeted metabolomics techniques to investigate the role of microbiota in high sperm DNA fragmentation index (HDFI). We report that increased specific microbial profiles contribute to high sperm DNA fragmentation, thus implicating the seminal microbiome as a new therapeutic target for HDFI patients. Additionally, we found that the amount of Lactobacillus species was altered: Lactobacillus iners was enriched in HDFI patients, shedding light on the potential influence of L. iners on male reproductive health. Finally, we also identified enrichment of the acetyl-CoA fermentation to butanoate II and purine nucleobase degradation I in the high sperm DNA fragmentation samples, suggesting that butanoate may be the target metabolite of sperm DNA damage. These findings provide valuable insights into the complex interplay between microbiota and sperm quality in HDFI patients, laying the foundation for further research and potential clinical interventions.IMPORTANCEThe DNA fragmentation index (DFI) is a measure of sperm DNA fragmentation. Because high sperm DNA fragmentation index (HDFI) has been strongly associated with adverse reproductive outcomes, this has been linked to the seminal microbiome. Because the number of current treatments for HDFI is limited and most of them have no clear efficacy, it is critical to understand how semen microbiome exerts their effects on sperm DNA. Here, we evaluated the semen microbiome and its metabolites in patients with high and low sperm DNA fragmentation. We found that increased specific microbial profiles contribute to high sperm DNA fragmentation. In particular, Lactobacillus iners was uniquely correlated with high sperm DNA fragmentation. Additionally, butanoate may be the target metabolite produced by the microbiome to damage sperm DNA. Our findings support the interaction between semen microbiome and sperm DNA damage and suggest that seminal microbiome should be a new therapeutic target for HDFI patients.},
}

@article {pmid38898695,
year = {2024},
author = {Wisgrill, L and Martens, A and Kasbauer, R and Eigenschink, M and Pummer, L and Redlberger-Fritz, M and Végvári, Á and Warth, B and Berger, A and Fyhrquist, N and Alenius, H},
title = {Network analysis reveals age- and virus-specific circuits in nasal epithelial cells of extremely premature infants.},
journal = {Allergy},
volume = {},
number = {},
pages = {},
doi = {10.1111/all.16196},
pmid = {38898695},
issn = {1398-9995},
support = {[10.47379/LS20025]//Vienna Science and Technology Fund/ ; 2020-02090//Vetenskapsrådet/ ; },
abstract = {BACKGROUND AND OBJECTIVES: Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health-care burdens. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms.

METHODS: Using a trans-well pseudostratified nasal epithelial cell system, we examined age-dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches.

RESULTS: Our studies revealed differences in innate-receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular-viral networks, emphasizing highly relevant virus-specific pathways, independent of viral replication kinetics.

CONCLUSION: This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers crucial insights that allow for a deeper understanding of age-related differences in nasal epithelial cell immunity following respiratory virus infections.},
}

@article {pmid38898021,
year = {2024},
author = {Zhu, B and Edwards, DJ and Spaine, KM and Edupuganti, L and Matveyev, A and Serrano, MG and Buck, GA},
title = {The association of maternal factors with the neonatal microbiota and health.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {5260},
pmid = {38898021},
issn = {2041-1723},
support = {R01HD092415//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; UH3AI083263//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; UH3 AI083263/AI/NIAID NIH HHS/United States ; R01 HD092415/HD/NICHD NIH HHS/United States ; U54 HD080784/HD/NICHD NIH HHS/United States ; U54HD080784//Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)/ ; },
mesh = {Humans ; Female ; Infant, Newborn ; Pregnancy ; *Feces/microbiology ; *Microbiota ; Adult ; Cesarean Section ; Premature Birth/microbiology ; Gastrointestinal Microbiome/physiology ; Mouth/microbiology ; Rectum/microbiology ; Male ; },
abstract = {The human microbiome plays a crucial role in human health. However, the influence of maternal factors on the neonatal microbiota remains obscure. Herein, our observations suggest that the neonatal microbiotas, particularly the buccal microbiota, change rapidly within 24-48 h of birth but begin to stabilize by 48-72 h after parturition. Network analysis clustered over 200 maternal factors into thirteen distinct groups, and most associated factors were in the same group. Multiple maternal factor groups were associated with the neonatal buccal, rectal, and stool microbiotas. Particularly, a higher maternal inflammatory state and a lower maternal socioeconomic position were associated with a higher alpha diversity of the neonatal buccal microbiota and beta diversity of the neonatal stool microbiota was influenced by maternal diet and cesarean section by 24-72 h postpartum. The risk of admission of a neonate to the newborn intensive care unit was associated with preterm birth as well as higher cytokine levels and probably higher alpha diversity of the maternal buccal microbiota.},
}

Humans
Female
Infant, Newborn
Pregnancy
*Feces/microbiology
*Microbiota
Adult
Cesarean Section
Premature Birth/microbiology
Gastrointestinal Microbiome/physiology
Mouth/microbiology
Rectum/microbiology
Male

@article {pmid38892281,
year = {2024},
author = {Bose, D and Saha, P and Roy, S and Trivedi, A and More, M and Klimas, N and Tuteja, A and Chatterjee, S},
title = {A Double-Humanized Mouse Model for Studying Host Gut Microbiome-Immune Interactions in Gulf War Illness.},
journal = {International journal of molecular sciences},
volume = {25},
number = {11},
pages = {},
pmid = {38892281},
issn = {1422-0067},
support = {I01CX0001923//United States Department of Veterans Affairs/ ; },
mesh = {Animals ; *Gastrointestinal Microbiome ; *Persian Gulf Syndrome/immunology/microbiology ; Humans ; Mice ; *Disease Models, Animal ; *Cytokines/metabolism ; Fecal Microbiota Transplantation ; },
abstract = {Unraveling the multisymptomatic Gulf War Illness (GWI) pathology and finding an effective cure have eluded researchers for decades. The chronic symptom persistence and limitations for studying the etiologies in mouse models that differ significantly from those in humans pose challenges for drug discovery and finding effective therapeutic regimens. The GWI exposome differs significantly in the study cohorts, and the above makes it difficult to recreate a model closely resembling the GWI symptom pathology. We have used a double engraftment strategy for reconstituting a human immune system coupled with human microbiome transfer to create a humanized-mouse model for GWI. Using whole-genome shotgun sequencing and blood immune cytokine enzyme linked immunosorbent assay (ELISA), we show that our double humanized mice treated with Gulf War (GW) chemicals show significantly altered gut microbiomes, similar to those reported in a Veteran cohort of GWI. The results also showed similar cytokine profiles, such as increased levels of IL-1β, IL-6, and TNF R-1, in the double humanized model, as found previously in a human cohort. Further, a novel GWI Veteran fecal microbiota transfer was used to create a second alternative model that closely resembled the microbiome and immune-system-associated pathology of a GWI Veteran. A GWI Veteran microbiota transplant in humanized mice showed a human microbiome reconstitution and a systemic inflammatory pathology, as reflected by increases in interleukins 1β, 6, 8 (IL-1β, IL-6, IL-8), tumor necrosis factor receptor 1 (TNF R-1), and endotoxemia. In conclusion, though preliminary, we report a novel in vivo model with a human microbiome reconstitution and an engrafted human immune phenotype that may help to better understand gut-immune interactions in GWI.},
}

Animals
*Gastrointestinal Microbiome
*Persian Gulf Syndrome/immunology/microbiology
Humans
Mice
*Disease Models, Animal
*Cytokines/metabolism
Fecal Microbiota Transplantation

@article {pmid38890378,
year = {2024},
author = {Khawaja, T and Mäklin, T and Kallonen, T and Gladstone, RA and Pöntinen, AK and Mero, S and Thorpe, HA and Samuelsen, Ø and Parkhill, J and Izhar, M and Akhtar, MW and Corander, J and Kantele, A},
title = {Deep sequencing of Escherichia coli exposes colonisation diversity and impact of antibiotics in Punjab, Pakistan.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {5196},
pmid = {38890378},
issn = {2041-1723},
support = {206194/WT_/Wellcome Trust/United Kingdom ; EuroHPC//Academy of Finland (Suomen Akatemia)/ ; AMRIWA//Academy of Finland (Suomen Akatemia)/ ; },
mesh = {Pakistan/epidemiology ; Humans ; *Escherichia coli/genetics/drug effects/isolation & purification ; *Anti-Bacterial Agents/pharmacology ; *Escherichia coli Infections/epidemiology/microbiology/drug therapy ; *Drug Resistance, Multiple, Bacterial/genetics ; *High-Throughput Nucleotide Sequencing ; Feces/microbiology ; Female ; Male ; Genome, Bacterial/genetics ; Adult ; Genetic Variation ; Middle Aged ; Young Adult ; Phylogeny ; Adolescent ; Child ; },
abstract = {Multi-drug resistant (MDR) E. coli constitute a major public health burden globally, reaching the highest prevalence in the global south yet frequently flowing with travellers to other regions. However, our comprehension of the entire genetic diversity of E. coli colonising local populations remains limited. We quantified this diversity, its associated antimicrobial resistance (AMR), and assessed the impact of antibiotic use by recruiting 494 outpatients and 423 community dwellers in the Punjab province, Pakistan. Rectal swab and stool samples were cultured on CLED agar and DNA extracted from plate sweeps was sequenced en masse to capture both the genetic and AMR diversity of E. coli. We assembled 5,247 E. coli genomes from 1,411 samples, displaying marked genetic diversity in gut colonisation. Compared with high income countries, the Punjabi population generally showed a markedly different distribution of genetic lineages and AMR determinants, while use of antibiotics elevated the prevalence of well-known globally circulating MDR clinical strains. These findings implicate that longitudinal multi-regional genomics-based surveillance of both colonisation and infections is a prerequisite for developing mechanistic understanding of the interplay between ecology and evolution in the maintenance and dissemination of (MDR) E. coli.},
}

Pakistan/epidemiology
Humans
*Escherichia coli/genetics/drug effects/isolation & purification
*Anti-Bacterial Agents/pharmacology
*Escherichia coli Infections/epidemiology/microbiology/drug therapy
*Drug Resistance, Multiple, Bacterial/genetics
*High-Throughput Nucleotide Sequencing
Feces/microbiology
Female
Male
Genome, Bacterial/genetics
Adult
Genetic Variation
Middle Aged
Young Adult
Phylogeny
Adolescent
Child

@article {pmid38890150,
year = {2024},
author = {Fu, C and Zhang, Y and Liang, L and Lin, H and Shan, K and Liu, F and Feng, N},
title = {The microbiota in patients with interstitial cystitis/bladder pain syndrome: a systematic review.},
journal = {BJU international},
volume = {},
number = {},
pages = {},
doi = {10.1111/bju.16439},
pmid = {38890150},
issn = {1464-410X},
support = {THRCJH20200104//Wuxi Taihu Lake Talent Plan, Leading Talents in Medical and Health Profession Project/ ; },
abstract = {OBJECTIVE: To comprehensively review and critically assess the literature on microbiota differences between patients with interstitial cystitis (IC)/bladder pain syndrome (BPS) and normal controls and to provide clinical practice guidelines.

MATERIALS AND METHODS: In this systematic review, we evaluated previous research on microbiota disparities between IC/BPS and normal controls, as well as distinctions among IC/BPS subgroups. A comprehensive literature search was conducted across PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials. Relevant studies were shortlisted based on predetermined inclusion and exclusion criteria, followed by quality assessment. The primary focus was identifying specific taxonomic variations among these cohorts.

RESULTS: A total of 12 studies met the selection criteria. Discrepancies were adjudicated by a third reviewer. The Newcastle-Ottawa Scale was used to assess study quality. Predominantly, the studies focused on disparities in urine microbiota between IC/BPS patients and normal controls, with one study examining gut microbiota differences between the groups, and two studies exploring vaginal microbiota distinctions. Unfortunately, analyses of discrepancies in other microbiota were limited. Our findings revealed evidence of distinct bacterial abundance variations, particularly involving Lactobacillus, alongside variations in specific metabolites among IC/BPS patients compared to controls.

CONCLUSIONS: Currently, there is evidence suggesting significant variations in the diversity and species composition of the urinary microbiota between individuals diagnosed with IC/BPS and control groups. In the foreseeable future, urologists should consider urine microbiota dysbiosis as a potential aetiology for IC, with potential clinical implications for diagnosis and treatment.},
}

@article {pmid38884446,
year = {2024},
author = {Moussa, AY},
title = {Streptomyces endophytes in edible plants: chemistry and medicinal significance.},
journal = {Chemistry & biodiversity},
volume = {},
number = {},
pages = {e202400888},
doi = {10.1002/cbdv.202400888},
pmid = {38884446},
issn = {1612-1880},
abstract = {Streptomyces is the largest source of microbial antibiotics with about 50% of marketed antimicrobial drugs originating from this genus. Endophytic streptomyces are the link between medicinal plants and the microbial world. Edible plants endophytic streptomyces were not targeted before despite their uniqueness and importance. In this review, we analyzed the chemical diversity of more than 150 compounds belonging to endophytic Streptomyces chemical classes such as alkaloids, polyketides, peptides, macrolides and terpenes and their biological activities. This analysis showed a dominant antimicrobial effect for most of the isolated compounds and highlighted an underestimated diversity to be studied or repurposed for other biological activities. Return to edible plants use and conducting toxicity studies to rationalize their nutraceutical potential based on their beneficial endophytes is urged. Although there are many studies for non-vertebrates, the nutraceutical potential of these plants is expected to improve the gut microbiota since they are enriched with bioactive compounds from streptomyces species. This is the first review to discuss edible plants associated streptomyces, and we prospect that many studies will follow to unravel the mysterious health benefits of streptomyces in the human microbiome and encourage the revival of a correct lifestyle for the sack of a healthier microbiome.},
}

@article {pmid38882496,
year = {2024},
author = {Zhang, Z and Zhang, HL and Yang, DH and Hao, Q and Yang, HW and Meng, DL and Meindert de Vos, W and Guan, LL and Liu, SB and Teame, T and Gao, CC and Ran, C and Yang, YL and Yao, YY and Ding, QW and Zhou, ZG},
title = {Lactobacillus rhamnosus GG triggers intestinal epithelium injury in zebrafish revealing host dependent beneficial effects.},
journal = {iMeta},
volume = {3},
number = {2},
pages = {e181},
pmid = {38882496},
issn = {2770-596X},
abstract = {Lactobacillus rhamnosus GG (LGG), the well-characterized human-derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase-3-GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)-producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2-GSDMEb pyroptosis pathway. Further analysis reveals the Caspase-3-GSDMEa pyroptosis is initiated by the species-specific recognition of SpaC by TLR4ba, which accounts for the species-specificity of the SpaC-inducing intestinal pyroptosis in zebrafish. The observed pyroptosis-driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host-specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.},
}

@article {pmid38882486,
year = {2024},
author = {Wu, D and Guan, YX and Li, CH and Zheng, Q and Yin, ZJ and Wang, H and Liu, NN},
title = {"Nutrient-fungi-host" tripartite interaction in cancer progression.},
journal = {iMeta},
volume = {3},
number = {2},
pages = {e170},
pmid = {38882486},
issn = {2770-596X},
abstract = {The human microbiome exhibits a profound connection with the cancer development, progression, and therapeutic response, with particular emphasis on its components of the mycobiome, which are still in the early stages of research. In this review, we comprehensively summarize cancer-related symbiotic and pathogenic fungal genera. The intricate mechanisms through which fungi impact cancer as an integral member of both gut and tissue-resident microbiomes are further discussed. In addition, we shed light on the pivotal physiological roles of various nutrients, including cholesterol, carbohydrates, proteins and minerals, in facilitating the growth, reproduction, and invasive pathogenesis of the fungi. While our exploration of the interplay between nutrients and cancer, mediated by the mycobiome, is ongoing, the current findings have yet to yield conclusive results. Thus, delving into the relationship between nutrients and fungal pathogenesis in cancer development and progression would provide valuable insights into anticancer therapy and foster precision nutrition and individualized treatments that target fungi from bench to bedside.},
}

@article {pmid38878076,
year = {2024},
author = {Jawanda, IK and Soni, T and Kumari, S and Prabha, V},
title = {The evolving facets of vaginal microbiota transplantation: reinvigorating the unexplored frontier amid complex challenges.},
journal = {Archives of microbiology},
volume = {206},
number = {7},
pages = {306},
pmid = {38878076},
issn = {1432-072X},
mesh = {Humans ; *Vagina/microbiology ; Female ; *Microbiota ; *Probiotics/administration & dosage ; *Dysbiosis/microbiology/therapy ; Animals ; Anti-Bacterial Agents/therapeutic use ; Fecal Microbiota Transplantation ; Lactobacillus ; },
abstract = {In an age of cutting-edge sequencing methods and worldwide endeavors such as The Human Microbiome Project and MetaHIT, the human microbiome stands as a complex and diverse community of microorganisms. A central theme in current scientific inquiry revolves around reinstating a balanced microbial composition, referred to as "eubiosis," as a targeted approach for treating vast array of diseases. Vaginal Microbiota Transplantation (VMT), inspired by the success of fecal microbiota transplantation, emerges as an innovative therapy addressing vaginal dysbacteriosis by transferring the complete microbiota from a healthy donor. Antibiotics, while effective, pose challenges with adverse effects, high recurrence rates, and potential harm to beneficial Lactobacillus strains. Continued antibiotic usage also sparks worries regarding the development of resistant strains. Probiotics, though showing promise, exhibit inconsistency in treating multifactorial diseases, and concerns linger about their suitability for diverse genetic backgrounds. Given the recurrent challenges associated with antibiotic and probiotic treatments, VMT emerges as an imperative alternative, offering a unique and promising avenue for efficiently and reliably managing vaginal dysbiosis among a majority of women. This review critically evaluates findings from both animal and human studies, offering nuanced insights into the efficacy and challenges of VMT. An extensive analysis of clinical trials, provides a current overview of ongoing and completed trials, shedding light on the evolving clinical landscape and therapeutic potential of VMT. Delving into the origins, mechanisms, and optimized protocols of VMT, the review underscores the imperative for sustained research efforts to advance this groundbreaking gynecological therapy.},
}

Humans
*Vagina/microbiology
Female
*Microbiota
*Probiotics/administration & dosage
*Dysbiosis/microbiology/therapy
Animals
Anti-Bacterial Agents/therapeutic use
Fecal Microbiota Transplantation
Lactobacillus

@article {pmid38874821,
year = {2024},
author = {Wu, K and Chen, J and Lin, J and Zhu, E and Xu, X and Yan, X and Ju, L and Huang, M and Zhang, Y},
title = {The role of ferroptosis in DM-induced liver injury.},
journal = {Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine},
volume = {},
number = {},
pages = {},
pmid = {38874821},
issn = {1572-8773},
abstract = {The liver damage caused by Diabetes Mellitus (DM) has attracted increasing attention in recent years. Liver injury in DM can be caused by ferroptosis, a form of cell death caused by iron overload. However, the role of iron transporters in this context is still not clear. Herein, we attempted to shed light on the pathophysiological mechanism of ferroptosis. DM was induced in 8-week-old male rats by streptozotocin (STZ) before assessment of the degree of liver injury. Together with histopathological changes, variations in glutathione peroxidase 4 (GPX4), glutathione (GSH), superoxide dismutase (SOD), transferrin receptor 1 (TFR1), ferritin heavy chain (FTH), ferritin light chain (FTL), ferroportin and Prussian blue staining, were monitored in rat livers before and after treatment with Fer-1. In the liver of STZ-treated rats, GSH and SOD levels decreased, whereas those of malondialdehyde (MDA) increased. Expression of TFR1, FTH and FTL increased whereas that of glutathione peroxidase 4 (GPX4) and ferroportin did not change significantly. Prussian blue staining showed that iron levels increased. Histopathology showed liver fibrosis and decreased glycogen content. Fer-1 treatment reduced iron and MDA levels but GSH and SOD levels were unchanged. Expression of FTH and FTL was reduced whereas that of ferroportin showed a mild decrease. Fer-1 treatment alleviated liver fibrosis, increased glycogen content and mildly improved liver function. Our study demonstrates that ferroptosis is involved in DM-induced liver injury. Regulating the levels of iron transporters may become a new therapeutic strategy in ferroptosis-induced liver injury.},
}

@article {pmid38873568,
year = {2024},
author = {Shang, Z and Pai, L and Patil, S},
title = {Unveiling the dynamics of gut microbial interactions: a review of dietary impact and precision nutrition in gastrointestinal health.},
journal = {Frontiers in nutrition},
volume = {11},
number = {},
pages = {1395664},
pmid = {38873568},
issn = {2296-861X},
abstract = {The human microbiome, a dynamic ecosystem within the gastrointestinal tract, plays a pivotal role in shaping overall health. This review delves into six interconnected sections, unraveling the intricate relationship between diet, gut microbiota, and their profound impact on human health. The dance of nutrients in the gut orchestrates a complex symphony, influencing digestive processes and susceptibility to gastrointestinal disorders. Emphasizing the bidirectional communication between the gut and the brain, the Brain-Gut Axis section highlights the crucial role of dietary choices in physical, mental, and emotional well-being. Autoimmune diseases, particularly those manifesting in the gastrointestinal tract, reveal the delicate balance disrupted by gut microbiome imbalances. Strategies for reconciling gut microbes through diets, precision nutrition, and clinical indications showcase promising avenues for managing gastrointestinal distress and revolutionizing healthcare. From the Low-FODMAP diet to neuro-gut interventions, these strategies provide a holistic understanding of the gut's dynamic world. Precision nutrition, as a groundbreaking discipline, holds transformative potential by tailoring dietary recommendations to individual gut microbiota compositions, reshaping the landscape of gastrointestinal health. Recent advancements in clinical indications, including exact probiotics, fecal microbiota transplantation, and neuro-gut interventions, signify a new era where the gut microbiome actively participates in therapeutic strategies. As the microbiome takes center stage in healthcare, a paradigm shift toward personalized and effective treatments for gastrointestinal disorders emerges, reflecting the symbiotic relationship between the human body and its microbial companions.},
}

@article {pmid38873138,
year = {2024},
author = {Chi, J and Ye, J and Zhou, Y},
title = {A GLM-based zero-inflated generalized Poisson factor model for analyzing microbiome data.},
journal = {Frontiers in microbiology},
volume = {15},
number = {},
pages = {1394204},
pmid = {38873138},
issn = {1664-302X},
abstract = {MOTIVATION: High-throughput sequencing technology facilitates the quantitative analysis of microbial communities, improving the capacity to investigate the associations between the human microbiome and diseases. Our primary motivating application is to explore the association between gut microbes and obesity. The complex characteristics of microbiome data, including high dimensionality, zero inflation, and over-dispersion, pose new statistical challenges for downstream analysis.

RESULTS: We propose a GLM-based zero-inflated generalized Poisson factor analysis (GZIGPFA) model to analyze microbiome data with complex characteristics. The GZIGPFA model is based on a zero-inflated generalized Poisson (ZIGP) distribution for modeling microbiome count data. A link function between the generalized Poisson rate and the probability of excess zeros is established within the generalized linear model (GLM) framework. The latent parameters of the GZIGPFA model constitute a low-rank matrix comprising a low-dimensional score matrix and a loading matrix. An alternating maximum likelihood algorithm is employed to estimate the unknown parameters, and cross-validation is utilized to determine the rank of the model in this study. The proposed GZIGPFA model demonstrates superior performance and advantages through comprehensive simulation studies and real data applications.},
}

@article {pmid38868076,
year = {2024},
author = {Takallu, S and Aiyelabegan, HT and Zomorodi, AR and Alexandrovna, KV and Aflakian, F and Asvar, Z and Moradi, F and Behbahani, MR and Mirzaei, E and Sarhadi, F and Vakili-Ghartavol, R},
title = {Nanotechnology improves the detection of bacteria: Recent advances and future perspectives.},
journal = {Heliyon},
volume = {10},
number = {11},
pages = {e32020},
pmid = {38868076},
issn = {2405-8440},
abstract = {Nanotechnology has advanced significantly, particularly in biomedicine, showing promise for nanomaterial applications. Bacterial infections pose persistent public health challenges due to the lack of rapid pathogen detection methods, resulting in antibiotic overuse and bacterial resistance, threatening the human microbiome. Nanotechnology offers a solution through nanoparticle-based materials facilitating early bacterial detection and combating resistance. This study explores recent research on nanoparticle development for controlling microbial infections using various nanotechnology-driven detection methods. These approaches include Surface Plasmon Resonance (SPR) Sensors, Surface-Enhanced Raman Scattering (SERS) Sensors, Optoelectronic-based sensors, Bacteriophage-Based Sensors, and nanotechnology-based aptasensors. These technologies provide precise bacteria detection, enabling targeted treatment and infection prevention. Integrating nanoparticles into detection approaches holds promise for enhancing patient outcomes and mitigating harmful bacteria spread in healthcare settings.},
}

@article {pmid38866914,
year = {2024},
author = {Heinzel, S and Jureczek, J and Kainulainen, V and Nieminen, AI and Suenkel, U and von Thaler, AK and Kaleta, C and Eschweiler, GW and Brockmann, K and Aho, VTE and Auvinen, P and Maetzler, W and Berg, D and Scheperjans, F},
title = {Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {13513},
pmid = {38866914},
issn = {2045-2322},
support = {675915//Germany Research Society/ ; 310835//Research Council of Finland/ ; },
mesh = {Humans ; *Leukocyte L1 Antigen Complex/analysis/metabolism ; *Feces/microbiology/chemistry ; *Dysbiosis/diagnosis ; *Gastrointestinal Microbiome ; Aged ; Female ; Male ; *Biomarkers/blood/analysis ; Middle Aged ; Cohort Studies ; Inflammatory Bowel Diseases/blood/metabolism/microbiology ; },
abstract = {Fecal calprotectin is an established marker of gut inflammation in inflammatory bowel disease (IBD). Elevated levels of fecal calprotectin as well as gut microbial dysbiosis have also been observed in other clinical conditions. However, systemic and multi-omics alterations linked to elevated fecal calprotectin in older individuals remain unclear. This study comprehensively investigated the relationship between fecal calprotectin levels, gut microbiome composition, serum inflammation and targeted metabolomics markers, and relevant lifestyle and medical data in a large sample of older individuals (n = 735; mean age ± SD: 68.7 ± 6.3) from the TREND cohort study. Low (0-50 μg/g; n = 602), moderate (> 50-100 μg/g; n = 64) and high (> 100 μg/g; n = 62) fecal calprotectin groups were stratified. Several pro-inflammatory gut microbial genera were significantly increased and short-chain fatty acid producing genera were decreased in high vs. low calprotectin groups. In serum, IL-17C, CCL19 and the toxic metabolite indoxyl sulfate were increased in high vs. low fecal calprotectin groups. These changes were partially mediated by the gut microbiota. Moreover, the high fecal calprotectin group showed increased BMI and a higher disease prevalence of heart attack and obesity. Our findings contribute to the understanding of fecal calprotectin as a marker of gut dysbiosis and its broader systemic and clinical implications in older individuals.},
}

Humans
*Leukocyte L1 Antigen Complex/analysis/metabolism
*Feces/microbiology/chemistry
*Dysbiosis/diagnosis
*Gastrointestinal Microbiome
Aged
Female
Male
*Biomarkers/blood/analysis
Middle Aged
Cohort Studies
Inflammatory Bowel Diseases/blood/metabolism/microbiology

@article {pmid38862605,
year = {2024},
author = {},
title = {The human microbiome and immune response shift during spaceflight.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
pmid = {38862605},
issn = {2058-5276},
}

@article {pmid38867907,
year = {2022},
author = {Ma, Y and Ke, D and Li, D and Zhang, Q},
title = {Donors' experiences and attitudes of fecal microbiota transplantation: An empirical bioethics study from China.},
journal = {iMeta},
volume = {1},
number = {4},
pages = {e62},
pmid = {38867907},
issn = {2770-596X},
abstract = {Donor participation is a critical part of ensuring the development of human microbiome research and the clinical application of fecal microbiota transplantation (FMT). Most FMT donors are still not sufficiently aware of the risks associated with the act of donating gut microbiota, especially the risk of data privacy disclosure. Enhanced awareness of the moral responsibility of the researchers and ethical oversight by ethics committees are needed.},
}

@article {pmid38862604,
year = {2024},
author = {Tierney, BT and Kim, J and Overbey, EG and Ryon, KA and Foox, J and Sierra, MA and Bhattacharya, C and Damle, N and Najjar, D and Park, J and Garcia Medina, JS and Houerbi, N and Meydan, C and Wain Hirschberg, J and Qiu, J and Kleinman, AS and Al-Ghalith, GA and MacKay, M and Afshin, EE and Dhir, R and Borg, J and Gatt, C and Brereton, N and Readhead, BP and Beyaz, S and Venkateswaran, KJ and Wiseman, K and Moreno, J and Boddicker, AM and Zhao, J and Lajoie, BR and Scott, RT and Altomare, A and Kruglyak, S and Levy, S and Church, GM and Mason, CE},
title = {Longitudinal multi-omics analysis of host microbiome architecture and immune responses during short-term spaceflight.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
pmid = {38862604},
issn = {2058-5276},
support = {NNX14AH50G//NASA | Johnson Space Center (JSC)/ ; NNX16AO69A//NASA | Johnson Space Center (JSC)/ ; R01MH117406//U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)/ ; },
abstract = {Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes. However, documenting microbial shifts during spaceflight has been difficult due to mission constraints that lead to limited sampling and profiling. Here we executed a six-month longitudinal study to quantify the high-resolution human microbiome response to three days in orbit for four individuals. Using paired metagenomics and metatranscriptomics alongside single-nuclei immune cell profiling, we characterized time-dependent, multikingdom microbiome changes across 750 samples and 10 body sites before, during and after spaceflight at eight timepoints. We found that most alterations were transient across body sites; for example, viruses increased in skin sites mostly during flight. However, longer-term shifts were observed in the oral microbiome, including increased plaque-associated bacteria (for example, Fusobacteriota), which correlated with immune cell gene expression. Further, microbial genes associated with phage activity, toxin-antitoxin systems and stress response were enriched across multiple body sites. In total, this study reveals in-depth characterization of microbiome and immune response shifts experienced by astronauts during short-term spaceflight and the associated changes to the living environment, which can help guide future missions, spacecraft design and space habitat planning.},
}

@article {pmid38862602,
year = {2024},
author = {Osbelt, L and Almási, ÉDH and Wende, M and Kienesberger, S and Voltz, A and Lesker, TR and Muthukumarasamy, U and Knischewski, N and Nordmann, E and Bielecka, AA and Giralt-Zúñiga, M and Kaganovitch, E and Kühne, C and Baier, C and Pietsch, M and Müsken, M and Greweling-Pils, MC and Breinbauer, R and Flieger, A and Schlüter, D and Müller, R and Erhardt, M and Zechner, EL and Strowig, T},
title = {Klebsiella oxytoca inhibits Salmonella infection through multiple microbiota-context-dependent mechanisms.},
journal = {Nature microbiology},
volume = {},
number = {},
pages = {},
pmid = {38862602},
issn = {2058-5276},
support = {01KI1824//Joint Programming Initiative on Antimicrobial Resistance (Joint Programming Initiative for Antimicrobial Resistance)/ ; },
abstract = {The Klebsiella oxytoca species complex is part of the human microbiome, especially during infancy and childhood. K. oxytoca species complex strains can produce enterotoxins, namely, tilimycin and tilivalline, while also contributing to colonization resistance (CR). The relationship between these seemingly contradictory roles is not well understood. Here, by coupling ex vivo assays with CRISPR-mutagenesis and various mouse models, we show that K. oxytoca provides CR against Salmonella Typhimurium. In vitro, the antimicrobial activity against various Salmonella strains depended on tilimycin production and was induced by various simple carbohydrates. In vivo, CR against Salmonella depended on toxin production in germ-free mice, while it was largely toxin-independent in mice with residual microbiota. This was linked to the relative levels of toxin-inducing carbohydrates in vivo. Finally, dulcitol utilization was essential for toxin-independent CR in gnotobiotic mice. Together, this demonstrates that nutrient availability is key to both toxin-dependent and substrate-driven competition between K. oxytoca and Salmonella.},
}

@article {pmid38855423,
year = {2024},
author = {Zhang, L and Wu, R and Ma, T and Fu, W and Chen, J and Li, L and He, Q},
title = {Investigation on the Therapeutic Mechanism of Danbie Capsules for Endometriosis: A Network Pharmacology Approach.},
journal = {International journal of general medicine},
volume = {17},
number = {},
pages = {2557-2574},
pmid = {38855423},
issn = {1178-7074},
abstract = {OBJECTIVE: To explore the active substances and targets of Danbie Capsules in Endometriosis therapy.

METHODS: This study was conducted through TCMSP and published literature screened and obtained 183 active substances of Danbie Capsules, combined and intersected with Endometriosis target genes collected and screened in the GEO database, obtained 24 target genes for Endometriosis treatment, and mapped the target network map of Danbie Capsules active substances against Endometriosis. The network was analyzed with the aid of Cytoscape version 3.9.1. With the aid of the platform of the STRING data analysis, PPI network analysis was conducted on 24 anti-Endometriosis targets of the Danbie Capsules.

RESULTS: The research results obtained three critical active substances, namely, Quercetin, β-sitosterol, and Luteolin. Seven critical targets were identified, and two representative genes (TP53 and AKT1) have been verified in Macromolecular docking and immunohistochemical verification.

CONCLUSION: The active substances of Danbie Capsules in the treatment of Endometriosis are Quercetin, β-sitosterol and Luteolin, and the main targets are TP53 and AKT1.},
}

@article {pmid38854053,
year = {2024},
author = {Byrne, SR and DeMott, MS and Yuan, Y and Ghanegolmohammadi, F and Kaiser, S and Fox, JG and Alm, EJ and Dedon, PC},
title = {Temporal dynamics and metagenomics of phosphorothioate epigenomes in the human gut microbiome.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.05.29.596306},
pmid = {38854053},
abstract = {BACKGROUND: Epigenetic regulation of gene expression and host defense is well established in microbial communities, with dozens of DNA modifications comprising the epigenomes of prokaryotes and bacteriophage. Phosphorothioation (PT) of DNA, in which a chemically-reactive sulfur atom replaces a non-bridging oxygen in the sugar-phosphate backbone, is catalyzed by dnd and ssp gene families widespread in bacteria and archaea. However, little is known about the role of PTs or other microbial epigenetic modifications in the human microbiome. Here we optimized and applied fecal DNA extraction, mass spectrometric, and metagenomics technologies to characterize the landscape and temporal dynamics of gut microbes possessing PT modifications.

RESULTS: Exploiting the nuclease-resistance of PTs, mass spectrometric analysis of limit digests of PT-containing DNA reveals PT dinucleotides as part of genomic consensus sequences, with 16 possible dinucleotide combinations. Analysis of mouse fecal DNA revealed a highly uniform spectrum of 11 PT dinucleotides in all littermates, with PTs estimated to occur in 5-10% of gut microbes. Though at similar levels, PT dinucleotides in fecal DNA from 11 healthy humans possessed signature combinations and levels of individual PTs. Comparison with a widely distributed microbial epigenetic mark, m [6] dA, suggested temporal dynamics consistent with expectations for gut microbial communities based on Taylor's Power Law. Application of PT-seq for site-specific metagenomic analysis of PT-containing bacteria in one fecal donor revealed the larger consensus sequences for the PT dinucleotides in Bacteroidota, Firmicutes, Actinobacteria, and Proteobacteria, which differed from unbiased metagenomics and suggested that the abundance of PT-containing bacteria did not simply mirror the spectrum of gut bacteria. PT-seq further revealed low abundance PT sites not detected as dinucleotides by mass spectrometry, attesting to the complementarity of the technologies.

CONCLUSIONS: The results of our studies provide a benchmark for understanding the behavior of an abundant and chemically-reactive epigenetic mark in the human gut microbiome, with implications for inflammatory conditions of the gut.},
}

@article {pmid38850297,
year = {2024},
author = {Hoisington, AJ and Stamper, CE and Ellis, JC and Lowry, CA and Brenner, LA},
title = {Quantifying variation across 16S rRNA gene sequencing runs in human microbiome studies.},
journal = {Applied microbiology and biotechnology},
volume = {108},
number = {1},
pages = {367},
pmid = {38850297},
issn = {1432-0614},
support = {U.S. Department of Veterans Affairs//U.S. Department of Veterans Affairs/ ; 140755//Mindsource Brain Injury Network/ ; },
mesh = {Humans ; *RNA, Ribosomal, 16S/genetics ; *Feces/microbiology ; *Microbiota/genetics ; *Sequence Analysis, DNA/methods ; *DNA, Bacterial/genetics ; Bacteria/genetics/classification/isolation & purification ; Reproducibility of Results ; Mouth/microbiology ; High-Throughput Nucleotide Sequencing/methods ; },
abstract = {Recent microbiome research has incorporated a higher number of samples through more participants in a study, longitudinal studies, and metanalysis between studies. Physical limitations in a sequencing machine can result in samples spread across sequencing runs. Here we present the results of sequencing nearly 1000 16S rRNA gene sequences in fecal (stabilized and swab) and oral (swab) samples from multiple human microbiome studies and positive controls that were conducted with identical standard operating procedures. Sequencing was performed in the same center across 18 different runs. The simplified mock community showed limitations in accuracy, while precision (e.g., technical variation) was robust for the mock community and actual human positive control samples. Technical variation was the lowest for stabilized fecal samples, followed by fecal swab samples, and then oral swab samples. The order of technical variation stability was inverse of DNA concentrations (e.g., highest in stabilized fecal samples), highlighting the importance of DNA concentration in reproducibility and urging caution when analyzing low biomass samples. Coefficients of variation at the genus level also followed the same trend for lower variation with higher DNA concentrations. Technical variation across both sample types and the two human sampling locations was significantly less than the observed biological variation. Overall, this research providing comparisons between technical and biological variation, highlights the importance of using positive controls, and provides semi-quantified data to better understand variation introduced by sequencing runs. KEY POINTS: • Mock community and positive control accuracy were lower than precision. • Samples with lower DNA concentration had increased technical variation across sequencing runs. • Biological variation was significantly higher than technical variation due to sequencing runs.},
}

Humans
*RNA, Ribosomal, 16S/genetics
*Feces/microbiology
*Microbiota/genetics
*Sequence Analysis, DNA/methods
*DNA, Bacterial/genetics
Bacteria/genetics/classification/isolation & purification
Reproducibility of Results
Mouth/microbiology
High-Throughput Nucleotide Sequencing/methods

@article {pmid38849871,
year = {2024},
author = {Lu, W and Aihaiti, A and Abudukeranmu, P and Liu, Y and Gao, H},
title = {Unravelling the role of intratumoral bacteria in digestive system cancers: current insights and future perspectives.},
journal = {Journal of translational medicine},
volume = {22},
number = {1},
pages = {545},
pmid = {38849871},
issn = {1479-5876},
mesh = {Humans ; *Digestive System Neoplasms/microbiology/therapy ; *Bacteria/metabolism ; Gastrointestinal Microbiome ; Animals ; },
abstract = {Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.},
}

Humans
*Digestive System Neoplasms/microbiology/therapy
*Bacteria/metabolism
Gastrointestinal Microbiome
Animals

@article {pmid38849503,
year = {2024},
author = {Kingsley, SF and Seo, Y and Wood, A and Wani, KA and Gonzalez, X and Irazoqui, J and Finkel, SE and Tissenbaum, HA},
title = {Glucose-fed microbiota alters C. elegans intestinal epithelium and increases susceptibility to multiple bacterial pathogens.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {13177},
pmid = {38849503},
issn = {2045-2322},
support = {W911NF1210321//U.S. Army Research Office/ ; 5R21AG067317//National Institutes of Aging,United States/ ; },
mesh = {*Caenorhabditis elegans/microbiology ; Animals ; *Glucose/metabolism ; *Intestinal Mucosa/microbiology/metabolism ; *Gastrointestinal Microbiome ; *Escherichia coli ; Reactive Oxygen Species/metabolism ; Longevity ; Disease Susceptibility ; },
abstract = {Overconsumption of dietary sugar can lead to many negative health effects including the development of Type 2 diabetes, metabolic syndrome, cardiovascular disease, and neurodegenerative disorders. Recently, the human intestinal microbiota, strongly associated with our overall health, has also been known to be affected by diet. However, mechanistic insight into the importance of the human intestinal microbiota and the effects of chronic sugar ingestion has not been possible largely due to the complexity of the human microbiome which contains hundreds of types of organisms. Here, we use an interspecies C. elegans/E. coli system, where E. coli are subjected to high sugar, then consumed by the bacterivore host C. elegans to become the microbiota. This glucose-fed microbiota results in a significant lifespan reduction accompanied by reduced healthspan (locomotion), reduced stress resistance, and changes in behavior and feeding. Lifespan reduction is also accompanied by two potential major contributors: increased intestinal bacterial density and increased concentration of reactive oxygen species. The glucose-fed microbiota accelerated the age-related development of intestinal cell permeability, intestinal distention, and dysregulation of immune effectors. Ultimately, the changes in the intestinal epithelium due to aging with the glucose-fed microbiota results in increased susceptibility to multiple bacterial pathogens. Taken together, our data reveal that chronic ingestion of sugar, such as a Western diet, has profound health effects on the host due to changes in the microbiota and may contribute to the current increased incidence of ailments including inflammatory bowel diseases as well as multiple age-related diseases.},
}

*Caenorhabditis elegans/microbiology
Animals
*Glucose/metabolism
*Intestinal Mucosa/microbiology/metabolism
*Gastrointestinal Microbiome
*Escherichia coli
Reactive Oxygen Species/metabolism
Longevity
Disease Susceptibility

@article {pmid38846023,
year = {2024},
author = {Jones, J and Murphy, CP and Sleator, RD and Culligan, EP},
title = {An exploratory in silico analysis of bacteriocin gene clusters in the urobiome.},
journal = {Microbiome research reports},
volume = {3},
number = {2},
pages = {24},
pmid = {38846023},
issn = {2771-5965},
abstract = {Background: The role of the urobiome in health and disease remains an understudied area compared to the rest of the human microbiome. Enhanced culturing techniques and next-generation sequencing technologies have identified the urobiome as an untapped source of potentially novel antimicrobials. The aim of this study was to screen the urobiome for genes encoding bacteriocin production. Methods: The genomes of 181 bacterial urobiome isolates were screened in silico for the presence of bacteriocin gene clusters using the bacteriocin mining tool BAGEL4 and secondary metabolite screening tool antiSMASH7. Results: From these isolates, an initial 263 areas of interest were identified, manually annotated, and evaluated for potential bacteriocin gene clusters. This resulted in 32 isolates containing 80 potential bacteriocin gene clusters, of which 72% were identified as class II, 13.75% as class III, 8.75% as class I, and 5% as unclassified bacteriocins. Conclusion: Overall, 53 novel variants were discovered, including nisin, gassericin, ubericin, and colicins.},
}

@article {pmid38843312,
year = {2024},
author = {Davison, C and Tallman, S and de Ste-Croix, M and Antonio, M and Oggioni, MR and Kwambana-Adams, B and Freund, F and Beleza, S},
title = {Long-term evolution of Streptococcus mitis and Streptococcus pneumoniae leads to higher genetic diversity within rather than between human populations.},
journal = {PLoS genetics},
volume = {20},
number = {6},
pages = {e1011317},
doi = {10.1371/journal.pgen.1011317},
pmid = {38843312},
issn = {1553-7404},
abstract = {Evaluation of the apportionment of genetic diversity of human bacterial commensals within and between human populations is an important step in the characterization of their evolutionary potential. Recent studies showed a correlation between the genomic diversity of human commensal strains and that of their host, but the strength of this correlation and of the geographic structure among human populations is a matter of debate. Here, we studied the genomic diversity and evolution of the phylogenetically related oro-nasopharyngeal healthy-carriage Streptococcus mitis and Streptococcus pneumoniae, whose lifestyles range from stricter commensalism to high pathogenic potential. A total of 119 S. mitis genomes showed higher within- and among-host variation than 810 S. pneumoniae genomes in European, East Asian and African populations. Summary statistics of the site-frequency spectrum for synonymous and non-synonymous variation and ABC modelling showed this difference to be due to higher ancestral bacterial population effective size (Ne) in S. mitis, whose genomic variation has been maintained close to mutation-drift equilibrium across (at least many) generations, whereas S. pneumoniae has been expanding from a smaller ancestral bacterial population. Strikingly, both species show limited differentiation among human populations. As genetic differentiation is inversely proportional to the product of effective population size and migration rate (Nem), we argue that large Ne have led to similar differentiation patterns, even if m is very low for S. mitis. We conclude that more diversity within than among human populations and limited population differentiation must be common features of the human microbiome due to large Ne.},
}

@article {pmid38841413,
year = {2024},
author = {Manrique, P and Montero, I and Fernandez-Gosende, M and Martinez, N and Cantabrana, CH and Rios-Covian, D},
title = {Past, present, and future of microbiome-based therapies.},
journal = {Microbiome research reports},
volume = {3},
number = {2},
pages = {23},
pmid = {38841413},
issn = {2771-5965},
abstract = {Technological advances in studying the human microbiome in depth have enabled the identification of microbial signatures associated with health and disease. This confirms the crucial role of microbiota in maintaining homeostasis and the host health status. Nowadays, there are several ways to modulate the microbiota composition to effectively improve host health; therefore, the development of therapeutic treatments based on the gut microbiota is experiencing rapid growth. In this review, we summarize the influence of the gut microbiota on the development of infectious disease and cancer, which are two of the main targets of microbiome-based therapies currently being developed. We analyze the two-way interaction between the gut microbiota and traditional drugs in order to emphasize the influence of gut microbial composition on drug effectivity and treatment response. We explore the different strategies currently available for modulating this ecosystem to our benefit, ranging from 1st generation intervention strategies to more complex 2nd generation microbiome-based therapies and their regulatory framework. Lastly, we finish with a quick overview of what we believe is the future of these strategies, that is 3rd generation microbiome-based therapies developed with the use of artificial intelligence (AI) algorithms.},
}

@article {pmid38838470,
year = {2024},
author = {Matharu, D and Ponsero, AJ and Lengyel, M and Meszaros-Matwiejuk, A and Kolho, KL and de Vos, WM and Molnar-Gabor, D and Salonen, A},
title = {Human milk oligosaccharide composition is affected by season and parity and associates with infant gut microbiota in a birth mode dependent manner in a Finnish birth cohort.},
journal = {EBioMedicine},
volume = {104},
number = {},
pages = {105182},
doi = {10.1016/j.ebiom.2024.105182},
pmid = {38838470},
issn = {2352-3964},
abstract = {BACKGROUND: Human milk oligosaccharides (HMOs), their determinants, infant gut microbiota and health are under extensive research; however, seldom jointly addressed. Leveraging data from the HELMi birth cohort, we investigated them collectively, considering maternal and infant secretor status.

METHODS: HMO composition in breastmilk collected 3 months postpartum (n = 350 mothers) was profiled using high-performance liquid chromatography. Infant gut microbiota taxonomic and functional development was studied at 3, 6, and 12 months (n = 823 stool samples) via shotgun metagenomic sequencing, focusing on HMO metabolism via glycoside hydrolase (GH) analysis. Maternal and infant secretor statuses were identified through phenotyping and genotyping, respectively. Child health, emphasizing allergies and antibiotics as proxies for infectious diseases, was recorded until 2 years.

FINDINGS: Mother's parity, irritable bowel syndrome, gestational diabetes, and season of milk collection associated with HMO composition. Neither maternal nor infant secretor status associated with infant gut microbiota, except for a few taxa linked to individual HMOs. Analysis stratified for birth mode revealed distinct patterns between the infant gut microbiota and HMOs. Child health parameters were not associated to infant or maternal secretor status.

INTERPRETATION: This comprehensive exploration unveils intricate links between secretor genotype, maternal factors, HMO composition, infant microbiota, and child health. Understanding these nuanced relationships is paramount for refining strategies to optimize early life nutrition and its enduring impact on long-term health.

FUNDING: Sweet Crosstalk EU H2020 MSCA ITN, Academy of Finland, Mary and Georg C. Ehrnrooth Foundation, Päivikki and Sakari Sohlberg Foundation, and Tekes.},
}

@article {pmid38830891,
year = {2024},
author = {Lopes, W and Amor, DR and Gore, J},
title = {Cooperative growth in microbial communities is a driver of multistability.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4709},
pmid = {38830891},
issn = {2041-1723},
mesh = {*Microbiota/physiology ; Humans ; *Microbial Interactions ; Bacteria/genetics/classification/metabolism/growth & development ; Glutamic Acid/metabolism ; Models, Biological ; Coculture Techniques ; },
abstract = {Microbial communities often exhibit more than one possible stable composition for the same set of external conditions. In the human microbiome, these persistent changes in species composition and abundance are associated with health and disease states, but the drivers of these alternative stable states remain unclear. Here we experimentally demonstrate that a cross-kingdom community, composed of six species relevant to the respiratory tract, displays four alternative stable states each dominated by a different species. In pairwise coculture, we observe widespread bistability among species pairs, providing a natural origin for the multistability of the full community. In contrast with the common association between bistability and antagonism, experiments reveal many positive interactions within and between community members. We find that multiple species display cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A biochemical screening reveals that glutamate either reduces or eliminates cooperativity in the growth of several species, and we confirm that such supplementation reduces the extent of bistability across pairs and reduces multistability in the full community. Our findings provide a mechanistic explanation of how cooperative growth rather than competitive interactions can underlie multistability in microbial communities.},
}

*Microbiota/physiology
Humans
*Microbial Interactions
Bacteria/genetics/classification/metabolism/growth & development
Glutamic Acid/metabolism
Models, Biological
Coculture Techniques

@article {pmid38830853,
year = {2024},
author = {Kitsios, GD and Sayed, K and Fitch, A and Yang, H and Britton, N and Shah, F and Bain, W and Evankovich, JW and Qin, S and Wang, X and Li, K and Patel, A and Zhang, Y and Radder, J and Dela Cruz, C and Okin, DA and Huang, CY and Van Tyne, D and Benos, PV and Methé, B and Lai, P and Morris, A and McVerry, BJ},
title = {Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4708},
pmid = {38830853},
issn = {2041-1723},
support = {R03 HL162655/HL/NHLBI NIH HHS/United States ; P01 HL114453/HL/NHLBI NIH HHS/United States ; COVID-19 Respiratory Virus Research//American Lung Association (Lung Association)/ ; IK2BX004886//U.S. Department of Veterans Affairs (Department of Veterans Affairs)/ ; },
mesh = {Humans ; Female ; Male ; *Dysbiosis/microbiology ; Middle Aged ; *Lung/microbiology ; *COVID-19/microbiology/virology ; Aged ; *Microbiota/genetics ; *Gastrointestinal Microbiome/genetics ; Host Microbial Interactions/genetics ; Longitudinal Studies ; RNA, Ribosomal, 16S/genetics ; Respiratory Insufficiency/microbiology ; SARS-CoV-2/genetics/isolation & purification ; Adult ; Respiration, Artificial ; Bacteria/genetics/classification/isolation & purification ; Critical Illness ; Metagenomics/methods ; },
abstract = {Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.},
}

Humans
Female
Male
*Dysbiosis/microbiology
Middle Aged
*Lung/microbiology
*COVID-19/microbiology/virology
Aged
*Microbiota/genetics
*Gastrointestinal Microbiome/genetics
Host Microbial Interactions/genetics
Longitudinal Studies
RNA, Ribosomal, 16S/genetics
Respiratory Insufficiency/microbiology
SARS-CoV-2/genetics/isolation & purification
Adult
Respiration, Artificial
Bacteria/genetics/classification/isolation & purification
Critical Illness
Metagenomics/methods

@article {pmid38828147,
year = {2024},
author = {Tan, J and Zhang, J and Hu, C and Wang, G and Ren, Q and Wang, C and Dan, J and Zeng, Z and Hu, J and Zhu, W and Liang, J and Cai, J and Liu, Y and Yan, G and Lin, Y},
title = {Pharmacokinetic enhancement of oncolytic virus M1 by inhibiting JAK‒STAT pathway.},
journal = {Acta pharmaceutica Sinica. B},
volume = {14},
number = {6},
pages = {2554-2566},
pmid = {38828147},
issn = {2211-3835},
abstract = {Oncolytic viruses (OVs), a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact, are emerging as promising living anticancer agents. Unlike traditional drugs composed of non-replicating compounds or biomolecules, the replicative nature of viruses confer unique pharmacokinetic properties that require further studies. Despite some pharmacokinetics studies of OVs, mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague. Here, we characterized the pharmacokinetic profile of oncolytic virus M1 (OVM) in immunocompetent mouse tumor models and identified the JAK‒STAT pathway as a key modulator of OVM pharmacokinetics. By suppressing the JAK‒STAT pathway, early OVM pharmacokinetics are ameliorated, leading to enhanced tumor-specific viral accumulation, increased AUC and Cmax, and improved antitumor efficacy. Rather than compromising antitumor immunity after JAK‒STAT inhibition, the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment, providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade, such as anti-PD-L1. Taken together, this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.},
}

@article {pmid38826830,
year = {2024},
author = {Sahle, Z and Engidaye, G and Shenkute Gebreyes, D and Adenew, B and Abebe, TA},
title = {Fecal microbiota transplantation and next-generation therapies: A review on targeting dysbiosis in metabolic disorders and beyond.},
journal = {SAGE open medicine},
volume = {12},
number = {},
pages = {20503121241257486},
pmid = {38826830},
issn = {2050-3121},
abstract = {The human microbiome, particularly the gut microbiome, has emerged as a central determinant of health and disease. Dysbiosis, an imbalance in the microbial composition of the gut, is associated with a variety of metabolic and other diseases, highlighting the potential for microbiota-targeted treatments. Fecal microbiota transplantation has received considerable attention as a promising therapy to modulate the gut microbiome and restore microbial homeostasis. However, challenges remain, including standardization, safety, and long-term efficacy. This review summarizes current knowledge on fecal microbiota transplantation and describes the next generation therapies targeting microbiome. This review looked at the mechanistic understanding of fecal microbiota transplantation and alternative strategies, elucidating their potential role in improving dysbiosis-associated metabolic disorders, such as obesity, and type 2 diabetes and others. Additionally, this review discussed the growing application of therapies targeting the gut microbiome. Insights from clinical trials, preclinical studies, and emerging technologies provide a comprehensive overview of the evolving landscape of microbiome-based interventions. Through a critical assessment of current advances and prospects, this review aims to highlight the therapeutic potential of targeting gut microbiome and pave the way for innovative approaches in precision medicine and personalized treatments.},
}

@article {pmid38823201,
year = {2024},
author = {Kasperek, MC and Velasquez Galeas, A and Caetano-Silva, ME and Xie, Z and Ulanov, A and La Frano, M and Devkota, S and Miller, MJ and Allen, JM},
title = {Microbial aromatic amino acid metabolism is modifiable in fermented food matrices to promote bioactivity.},
journal = {Food chemistry},
volume = {454},
number = {},
pages = {139798},
doi = {10.1016/j.foodchem.2024.139798},
pmid = {38823201},
issn = {1873-7072},
abstract = {Ingestion of fermented foods impacts human immune function, yet the bioactive food components underlying these effects are not understood. Here, we interrogated whether fermented food bioactivity relates to microbial metabolites derived from aromatic amino acids, termed aryl-lactates. Using targeted metabolomics, we established the presence of aryl-lactates in commercially available fermented foods. After pinpointing fermented food-associated lactic acid bacteria that produce high levels of aryl-lactates, we identified fermentation conditions to increase aryl-lactate production in food matrices up to 5 × 10[3] fold vs. standard fermentation conditions. Using ex vivo reporter assays, we found that food matrix conditions optimized for aryl-lactate production exhibited enhanced agonist activity for the human aryl-hydrocarbon receptor (AhR) as compared to standard fermentation conditions and commercial products. Reduced microbial-induced AhR activity has emerged as a hallmark of many chronic inflammatory diseases, thus we envision strategies to enhance AhR bioactivity of fermented foods to be leveraged to improve human health.},
}

@article {pmid38820745,
year = {2024},
author = {Haange, SB and Riesbeck, S and Aldehoff, AS and Engelmann, B and Jensen Pedersen, K and Castaneda-Monsalve, V and Rolle-Kampczyk, U and von Bergen, M and Jehmlich, N},
title = {Chemical mixture effects on the simplified human intestinal microbiota: Assessing xenobiotics at environmentally realistic concentrations.},
journal = {Journal of hazardous materials},
volume = {474},
number = {},
pages = {134683},
doi = {10.1016/j.jhazmat.2024.134683},
pmid = {38820745},
issn = {1873-3336},
abstract = {The microbial community present in our intestines is pivotal for converting indigestible substances into vital nutrients and signaling molecules such as short-chain fatty acids (SCFAs). These compounds have considerable influence over our immune system and the development of diverse human diseases. However, ingested environmental contaminants, known as xenobiotics, can upset the delicate balance of the microbial gut community and enzymatic processes, consequently affecting the host organism. In our study, we employed an in vitro bioreactor model system based on the simplified human microbiome model (SIHUMIx) to investigate the direct effects of specific xenobiotics, such as perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA) and perfluorobutanoic acid (PFBA) or bisphenol S (BPS) and bisphenol F (BPF), either individually or in combination, on the microbiota. We observed increased SCFA production, particularly acetate and butyrate, with PFAS exposure. Metaproteomics revealed pathway alterations across treatments, including changes in vitamin synthesis and fatty acid metabolism with BPX. This study underscores the necessity of assessing the combined effects of xenobiotics to better safeguard public health. It emphasizes the significance of considering adverse effects on the microbiome in the risk assessment of environmental chemicals.},
}

@article {pmid38819500,
year = {2024},
author = {Solasaari, T and Korpela, K and Lommi, S and Hyvönen, S and Gardemeister, S and Merras-Salmio, L and Salonen, A and de Vos, WM and Kolho, KL},
title = {Bowel function in a prospective cohort of 1052 healthy term infants up to 4 months of age.},
journal = {European journal of pediatrics},
volume = {},
number = {},
pages = {},
pmid = {38819500},
issn = {1432-1076},
support = {32510//the Academy of Finland/ ; 32510//the Academy of Finland/ ; 5851//the Finnish Medical Foundation/ ; 5044//Signe and Ane Gyllenberg Foundation/ ; 329/31/2015//Tekes/ ; 329/31/2015//Tekes/ ; },
abstract = {The purpose of this study is to describe the defecation pattern of healthy infants up to 17 weeks of age. We included 1052 healthy term infants from the prospective HELMi cohort (NCT03996304). Parents filled in recurring online questionnaires on feeding, gastrointestinal function, and crying weekly for the first 17 weeks of life. Defecation frequency was highest at the age of 3 weeks (a median of 4 times/day, interquartile range (IQR) 2.9-5). At each time point, the median defecation frequency of breastfed infants was higher than that of infants receiving formula (e.g., at week 17 a median of 2 times/day, IQR 0.9-3.6, and a median of 1.1, IQR 0.6-1.4, respectively). The dominant color of the stool was most often yellow or light brown. Nearly black stools were reported in the first week of life in 3.4%. Nearly half (47.4%) of the infants had green stool color dominating for at least 1 week, with comparable frequency among breastfed (47.7%) and formula-fed (45.2%) infants. Green stools were associated with a higher defecation frequency (linear mixed-effect model p < 0.0001). Occasional blood in stool was reported in 9.3% and recurrent blood in 5.2% of the infants with no difference in stool consistency. Hard stools were rare (≤ 1%). Conclusion: This study enlightens the spectrum of defecation patterns in healthy term infants during the first 17 weeks of life. A better understanding of bowel function helps healthcare professionals distinguish normal from abnormal when addressing defecation, the color of stools, and the type of feeding. What is Known: • Breastfed infants have more frequent and more yellow-colored stools than formula-fed infants. • Stools with green color are often suggested by the parents or even by medical professionals to indicate disease or discomfort in early life. What is New: • Nearly half of the healthy term infants had green stool dominating for at least one week during the first 17 weeks and occasional blood was reported in almost 10% of the infants during this period. • Data on normal variation in bowel function and stool may serve primary health care professionals when educating the families and caretakers of infants.},
}

@article {pmid38818295,
year = {2024},
author = {Efremova, I and Maslennikov, R and Poluektova, E and Medvedev, O and Kudryavtseva, A and Krasnov, G and Fedorova, M and Romanikhin, F and Zharkova, M and Zolnikova, O and Bagieva, G and Ivashkin, V},
title = {Presepsin as a biomarker of bacterial translocation and an indicator for the prescription of probiotics in cirrhosis.},
journal = {World journal of hepatology},
volume = {16},
number = {5},
pages = {822-831},
pmid = {38818295},
issn = {1948-5182},
abstract = {BACKGROUND: The gut-liver axis and bacterial translocation are important in cirrhosis, but there is no available universal biomarker of cellular bacterial translocation, for which presepsin may be a candidate.

AIM: To evaluate the relationship of the blood presepsin levels with the state of the gut microbiota in cirrhosis in the absence of obvious infection.

METHODS: This study included 48 patients with Child-Pugh cirrhosis classes B and C and 15 healthy controls. The fecal microbiome was assessed using 16S rRNA gene sequencing. Plasma levels of presepsin were measured. A total of 22 patients received a probiotic (Saccharomyces boulardii) for 3 months.

RESULTS: Presepsin levels were higher in patients with cirrhosis than in healthy individuals [342 (91-2875) vs 120 (102-141) pg/mL; P = 0.048]. Patients with elevated presepsin levels accounted for 56.3% of all included patients. They had lower levels of serum albumin and higher levels of serum total bilirubin and overall severity of cirrhosis as assessed using the Child-Pugh scale. Patients with elevated presepsin levels had an increased abundance of the main taxa responsible for bacterial translocation, namely Bacilli and Proteobacteria (including the main class Gammaproteobacteria and the minor taxa Xanthobacteraceae and Stenotrophomonas), and a low abundance of bacteria from the family Lachnospiraceae (including the minor genus Fusicatenibacter), which produce short-chain fatty acids that have a positive effect on intestinal barrier function. The presepsin level directly correlated with the relative abundance of Bacilli, Proteobacteria, and inversely correlated with the abundance of Lachnospiraceae and Propionibacteriaceae. After 3 months of taking the probiotic, the severity of cirrhosis on the Child-Pugh scale decreased significantly only in the group with elevated presepsin levels [from 9 (8-11) to 7 (6-9); P = 0.004], while there were no significant changes in the group with normal presepsin levels [from 8 (7-8) to 7 (6-8); P = 0.123]. A high level of presepsin before the prescription of the probiotic was an independent predictor of a greater decrease in Child-Pugh scores (P = 0.046), as well as a higher level of the Child-Pugh scale (P = 0.042), but not the C-reactive protein level (P = 0.679) according to multivariate linear regression analysis.

CONCLUSION: The level of presepsin directly correlates with the abundance in the gut microbiota of the main taxa that are substrates of bacterial translocation in cirrhosis. This biomarker, in the absence of obvious infection, seems important for assessing the state of the gut-liver axis in cirrhosis and deciding on therapy targeted at the gut microbiota in this disease.},
}

@article {pmid38817603,
year = {2024},
author = {Warren, A and Nyavor, Y and Zarabian, N and Mahoney, A and Frame, LA},
title = {The microbiota-gut-brain-immune interface in the pathogenesis of neuroinflammatory diseases: a narrative review of the emerging literature.},
journal = {Frontiers in immunology},
volume = {15},
number = {},
pages = {1365673},
pmid = {38817603},
issn = {1664-3224},
mesh = {Humans ; *Gastrointestinal Microbiome/immunology ; Animals ; *Brain-Gut Axis/immunology ; *Neuroinflammatory Diseases/immunology/microbiology/etiology ; *Brain/immunology/microbiology ; },
abstract = {IMPORTANCE: Research is beginning to elucidate the sophisticated mechanisms underlying the microbiota-gut-brain-immune interface, moving from primarily animal models to human studies. Findings support the dynamic relationships between the gut microbiota as an ecosystem (microbiome) within an ecosystem (host) and its intersection with the host immune and nervous systems. Adding this to the effects on epigenetic regulation of gene expression further complicates and strengthens the response. At the heart is inflammation, which manifests in a variety of pathologies including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Multiple Sclerosis (MS).

OBSERVATIONS: Generally, the research to date is limited and has focused on bacteria, likely due to the simplicity and cost-effectiveness of 16s rRNA sequencing, despite its lower resolution and inability to determine functional ability/alterations. However, this omits all other microbiota including fungi, viruses, and phages, which are emerging as key members of the human microbiome. Much of the research has been done in pre-clinical models and/or in small human studies in more developed parts of the world. The relationships observed are promising but cannot be considered reliable or generalizable at this time. Specifically, causal relationships cannot be determined currently. More research has been done in Alzheimer's disease, followed by Parkinson's disease, and then little in MS. The data for MS is encouraging despite this.

CONCLUSIONS AND RELEVANCE: While the research is still nascent, the microbiota-gut-brain-immune interface may be a missing link, which has hampered our progress on understanding, let alone preventing, managing, or putting into remission neurodegenerative diseases. Relationships must first be established in humans, as animal models have been shown to poorly translate to complex human physiology and environments, especially when investigating the human gut microbiome and its relationships where animal models are often overly simplistic. Only then can robust research be conducted in humans and using mechanistic model systems.},
}

Humans
*Gastrointestinal Microbiome/immunology
Animals
*Brain-Gut Axis/immunology
*Neuroinflammatory Diseases/immunology/microbiology/etiology
*Brain/immunology/microbiology

@article {pmid38814902,
year = {2024},
author = {Ezra, S and Bashan, A},
title = {Network impact of a single-time-point microbial sample.},
journal = {PloS one},
volume = {19},
number = {5},
pages = {e0301683},
pmid = {38814902},
issn = {1932-6203},
mesh = {Humans ; *Microbiota ; Female ; Pregnancy ; Diabetes, Gestational/microbiology ; },
abstract = {The human microbiome plays a crucial role in determining our well-being and can significantly influence human health. The individualized nature of the microbiome may reveal host-specific information about the health state of the subject. In particular, the microbiome is an ecosystem shaped by a tangled network of species-species and host-species interactions. Thus, analysis of the ecological balance of microbial communities can provide insights into these underlying interrelations. However, traditional methods for network analysis require many samples, while in practice only a single-time-point microbial sample is available in clinical screening. Recently, a method for the analysis of a single-time-point sample, which evaluates its 'network impact' with respect to a reference cohort, has been applied to analyze microbial samples from women with Gestational Diabetes Mellitus. Here, we introduce different variations of the network impact approach and systematically study their performance using simulated 'samples' fabricated via the Generalized Lotka-Volttera model of ecological dynamics. We show that the network impact of a single sample captures the effect of the interactions between the species, and thus can be applied to anomaly detection of shuffled samples, which are 'normal' in terms of species abundance but 'abnormal' in terms of species-species interrelations. In addition, we demonstrate the use of the network impact in binary and multiclass classifications, where the reference cohorts have similar abundance profiles but different species-species interactions. Individualized analysis of the human microbiome has the potential to improve diagnosis and personalized treatments.},
}

Humans
*Microbiota
Female
Pregnancy
Diabetes, Gestational/microbiology

@article {pmid38811534,
year = {2024},
author = {Elzinga, J and Narimatsu, Y and de Haan, N and Clausen, H and de Vos, WM and Tytgat, HLP},
title = {Binding of Akkermansia muciniphila to mucin is O-glycan specific.},
journal = {Nature communications},
volume = {15},
number = {1},
pages = {4582},
pmid = {38811534},
issn = {2041-1723},
support = {737.016.003//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; 024.002.002//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; Spinoza Grant Willem M de Vos//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research)/ ; FEMS-GO-2021-069//Federation of European Microbiological Societies (FEMS)/ ; 0071658//Novo Nordisk Fonden (Novo Nordisk Foundation)/ ; NA//Lundbeckfonden (Lundbeck Foundation)/ ; GlycoSkin H2020-ERC; 772735//EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)/ ; },
mesh = {*Akkermansia/metabolism ; Humans ; *Mucins/metabolism ; *Polysaccharides/metabolism ; Neuraminidase/metabolism ; Protein Binding ; Glycosylation ; Disaccharides/metabolism ; Verrucomicrobia/metabolism ; Epitopes/metabolism ; Bacterial Adhesion ; },
abstract = {The intestinal anaerobic bacterium Akkermansia muciniphila is specialized in the degradation of mucins, which are heavily O-glycosylated proteins that constitute the major components of the mucus lining the intestine. Despite that adhesion to mucins is considered critical for the persistence of A. muciniphila in the human intestinal tract, our knowledge of how this intestinal symbiont recognizes and binds to mucins is still limited. Here, we first show that the mucin-binding properties of A. muciniphila are independent of environmental oxygen concentrations and not abolished by pasteurization. We then dissected the mucin-binding properties of pasteurized A. muciniphila by use of a recently developed cell-based mucin array that enables display of the tandem repeats of human mucins with distinct O-glycan patterns and structures. We found that A. muciniphila recognizes the unsialylated LacNAc (Galβ1-4GlcNAcβ1-R) disaccharide selectively on core2 and core3 O-glycans. This disaccharide epitope is abundantly found on human colonic mucins capped by sialic acids, and we demonstrated that endogenous A. muciniphila neuraminidase activity can uncover the epitope and promote binding. In summary, our study provides insights into the mucin-binding properties important for colonization of a key mucin-foraging bacterium.},
}

*Akkermansia/metabolism
Humans
*Mucins/metabolism
*Polysaccharides/metabolism
Neuraminidase/metabolism
Protein Binding
Glycosylation
Disaccharides/metabolism
Verrucomicrobia/metabolism
Epitopes/metabolism
Bacterial Adhesion

@article {pmid38809163,
year = {2024},
author = {Chang, CJ and Liu, B and Liebmann, JM and Cioffi, GA and Winn, BJ},
title = {Glaucoma and the Human Microbiome.},
journal = {Journal of glaucoma},
volume = {},
number = {},
pages = {},
doi = {10.1097/IJG.0000000000002448},
pmid = {38809163},
issn = {1536-481X},
abstract = {PURPOSE OF REVIEW: To explore a view of the human microbiome as an interconnected, functional, dynamic system that may be linked to the pathogenesis and progression of glaucoma.

METHOD: A literature review was undertaken that included publications from 1966 to 2023.

RESULTS: Bacterial lipopolysaccharides (LPS) activate toll-like receptors (TLR) and mediate the human immune response. The LPS-TLR4 pathway is a potential avenue for the ocular, gut, and oral microbiomes to interface and/or influence ocular disease. Studies of gut dysbiosis have shown that alterations on the healthy microbiota can predispose the host to immune-mediated inflammatory and neurodegenerative conditions, while oral and ocular surface dysbiosis have been correlated with glaucoma. While developmental exposure to commensal microflora has shown to be necessary for the autoimmune and neurodegenerative responses to elevated intraocular pressure to take place, commensal bacterial products like short chain fatty acids have regulatory effects protective against glaucoma.

SUMMARY: Alterations to human microbiotas have been associated with changes in intestinal permeability, gene regulation, immune cell differentiation, and neural functioning, which may predispose the host to glaucoma. Select microbes have been highlighted for their potential contributions to glaucoma disease progression or protection, raising the potential for microbiota-based treatment modalities. Current topical glaucoma treatments may disrupt the ocular surface microbiota, potentially having ramifications on host health. Further study of the relationships between human microbiome and glaucoma is needed.},
}

@article {pmid38809053,
year = {2024},
author = {Selma-Royo, M and Ricci, L and Golzato, D and Servais, C and Nabinejad, A and Armanini, F and Asnicar, F and Pinto, F and Tamburini, S and Segata, N},
title = {Draft genome sequences of multiple bacterial strains isolated from human feces.},
journal = {Microbiology resource announcements},
volume = {},
number = {},
pages = {e0030724},
doi = {10.1128/mra.00307-24},
pmid = {38809053},
issn = {2576-098X},
abstract = {Bacterial isolation is necessary for functional and mechanistic analyses, and the increased human microbiome diversity revealed by metagenomic sequencing is expanding the relevant cultivation targets. Here, we report 46 draft genome sequences of bacterial isolates obtained from fecal samples of healthy adults in Trento and Milan (Italy), including strains from seven taxonomically uncharacterized species.},
}

@article {pmid38808120,
year = {2024},
author = {Wang, T and Li, L and Figeys, D and Liu, YY},
title = {Pairing metagenomics and metaproteomics to characterize ecological niches and metabolic essentiality of gut microbiomes.},
journal = {ISME communications},
volume = {4},
number = {1},
pages = {ycae063},
pmid = {38808120},
issn = {2730-6151},
abstract = {The genome of a microorganism encodes its potential functions that can be implemented through expressed proteins. It remains elusive how a protein's selective expression depends on its metabolic essentiality to microbial growth or its ability to claim resources as ecological niches. To reveal a protein's metabolic or ecological role, we developed a computational pipeline, which pairs metagenomics and metaproteomics data to quantify each protein's gene-level and protein-level functional redundancy simultaneously. We first illustrated the idea behind the pipeline using simulated data of a consumer-resource model. We then validated it using real data from human and mouse gut microbiome samples. In particular, we analyzed ABC-type transporters and ribosomal proteins, confirming that the metabolic and ecological roles predicted by our pipeline agree well with prior knowledge. Finally, we performed in vitro cultures of a human gut microbiome sample and investigated how oversupplying various sugars involved in ecological niches influences the community structure and protein abundance. The presented results demonstrate the performance of our pipeline in identifying proteins' metabolic and ecological roles, as well as its potential to help us design nutrient interventions to modulate the human microbiome.},
}

@article {pmid37975292,
year = {2024},
author = {Chmiel, JA and Stuivenberg, GA and Wong, JFW and Nott, L and Burton, JP and Razvi, H and Bjazevic, J},
title = {Predictive Modeling of Urinary Stone Composition Using Machine Learning and Clinical Data: Implications for Treatment Strategies and Pathophysiological Insights.},
journal = {Journal of endourology},
volume = {},
number = {},
pages = {},
doi = {10.1089/end.2023.0446},
pmid = {37975292},
issn = {1557-900X},
abstract = {Purpose: Preventative strategies and surgical treatments for urolithiasis depend on stone composition. However, stone composition is often unknown until the stone is passed or surgically managed. Given that stone composition likely reflects the physiological parameters during its formation, we used clinical data from stone formers to predict stone composition. Materials and Methods: Data on stone composition, 24-hour urine, serum biochemistry, patient demographics, and medical history were prospectively collected from 777 kidney stone patients. Data were used to train gradient boosted machine and logistic regression models to distinguish calcium vs noncalcium, calcium oxalate monohydrate vs dihydrate, and calcium oxalate vs calcium phosphate vs uric acid stone types. Model performance was evaluated using the kappa score, and the influence of each predictor variable was assessed. Results: The calcium vs noncalcium model differentiated stone types with a kappa of 0.5231. The most influential predictors were 24-hour urine calcium, blood urate, and phosphate. The calcium oxalate monohydrate vs dihydrate model is the first of its kind and could discriminate stone types with a kappa of 0.2042. The key predictors were 24-hour urine urea, calcium, and oxalate. The multiclass model had a kappa of 0.3023 and the top predictors were age and 24-hour urine calcium and creatinine. Conclusions: Clinical data can be leveraged with machine learning algorithms to predict stone composition, which may help urologists determine stone type and guide their management plan before stone treatment. Investigating the most influential predictors of each classifier may improve the understanding of key clinical features of urolithiasis and shed light on pathophysiology.},
}

@article {pmid38806600,
year = {2024},
author = {Kwon, KM and Kim, EH and Sim, KH and Lee, YJ and Kang, EJ and Han, KH and Jin, JS and Kim, DK and Ahn, JH and Hwang, IH},
title = {Phenylacetic acid, an anti-vaginitis metabolite produced by the vaginal symbiotic bacterium Chryseobacterium gleum.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {12226},
pmid = {38806600},
issn = {2045-2322},
support = {2017R1D1A3B06035312//National Research Foundation of Korea/ ; 2020R1I1A3073660//National Research Foundation of Korea/ ; 2017R1C1B5073761//National Research Foundation of Korea/ ; },
mesh = {Female ; Animals ; *Phenylacetates/metabolism/pharmacology ; *Vagina/microbiology ; Mice ; Humans ; *Chryseobacterium/metabolism ; Candida albicans/metabolism/drug effects ; Symbiosis ; Hydrogen-Ion Concentration ; Gardnerella vaginalis/metabolism/drug effects ; Disease Models, Animal ; Vaginitis/microbiology/metabolism/drug therapy ; },
abstract = {The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.},
}

Female
Animals
*Phenylacetates/metabolism/pharmacology
*Vagina/microbiology
Mice
Humans
*Chryseobacterium/metabolism
Candida albicans/metabolism/drug effects
Symbiosis
Hydrogen-Ion Concentration
Gardnerella vaginalis/metabolism/drug effects
Disease Models, Animal
Vaginitis/microbiology/metabolism/drug therapy

@article {pmid38805126,
year = {2024},
author = {Mahoney, D},
title = {The Role of the Human Microbiome in Epithelial Ovarian Cancer.},
journal = {Advances in experimental medicine and biology},
volume = {1452},
number = {},
pages = {97-105},
pmid = {38805126},
issn = {0065-2598},
mesh = {Humans ; Female ; *Ovarian Neoplasms/microbiology ; *Carcinoma, Ovarian Epithelial/microbiology/pathology ; *Microbiota/physiology ; },
abstract = {Ovarian cancer is the fifth-leading cause of cancer deaths among women due to the absence of available screening methods to identify early disease. Thus, prevention and early disease detection investigations are of high priority, surrounding a critical window of opportunity to better understand important pathogenic mechanisms of disease progression. Microorganisms modulate molecular interactions in humans that can influence states of health and disease, including ovarian cancer. While the mechanisms of infectious microbial invasion that trigger the immune-inflammatory axis are well studied in cancer research, the complex interactions that promote the transition of noninfectious healthy microbes to pathobiont expansion are less understood. As traditional research has focused on the influences of infectious pathogens on ovarian cancer development and progression, the impact of noninfectious microbes has gained scientific attention. The objective of this chapter is to summarize current evidence on the role of microbiota in epithelial ovarian cancer throughout disease.},
}

Humans
Female
*Ovarian Neoplasms/microbiology
*Carcinoma, Ovarian Epithelial/microbiology/pathology
*Microbiota/physiology

@article {pmid38795687,
year = {2024},
author = {Quesada, S and Rosso, AD and Mascardi, F and Soler-Rivero, V and Aguilera, P and Mascuka, SN and Boiro, A and Arenielo, E and Vijoditz, G and Ferreyra-Mufarregue, LR and Caputo, MF and Cimolai, MC and Coluccio Leskow, F and Penas-Steinhardt, A and Belforte, FS},
title = {Integrative analysis of systemic lupus erythematosus biomarkers: Role of fecal hsa-mir-223-3p and gut microbiota in transkingdom dynamics.},
journal = {Molecular immunology},
volume = {171},
number = {},
pages = {77-92},
doi = {10.1016/j.molimm.2024.05.004},
pmid = {38795687},
issn = {1872-9142},
abstract = {Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223-3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, Collinsella, Bifidobacterium, Streptococcus genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223-3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.},
}

@article {pmid38792733,
year = {2024},
author = {Putrino, A and Marinelli, E and Galeotti, A and Ferrazzano, GF and Ciribè, M and Zaami, S},
title = {A Journey into the Evolution of Human Host-Oral Microbiome Relationship through Ancient Dental Calculus: A Scoping Review.},
journal = {Microorganisms},
volume = {12},
number = {5},
pages = {},
pmid = {38792733},
issn = {2076-2607},
abstract = {One of the most promising areas of research in palaeomicrobiology is the study of the human microbiome. In particular, ancient dental calculus helps to reconstruct a substantial share of oral microbiome composition by mapping together human evolution with its state of health/oral disease. This review aims to trace microbial characteristics in ancient dental calculus to describe the evolution of the human host-oral microbiome relationship in oral health or disease in children and adults. Following the PRISMA-Extension for Scoping Reviews guidelines, the main scientific databases (PubMed, Scopus, Lilacs, Cochrane Library) have been drawn upon. Eligibility criteria were established, and all the data collected on a purpose-oriented collection form were analysed descriptively. From the initial 340 records, only 19 studies were deemed comprehensive enough for the purpose of this review. The knowledge of the composition of ancient oral microbiomes has broadened over the past few years thanks to increasingly well-performing decontamination protocols and additional analytical avenues. Above all, metagenomic sequencing, also implemented by state-of-the-art bioinformatics tools, allows for the determination of the qualitative-quantitative composition of microbial species associated with health status and caries/periodontal disease. Some microbial species, especially periodontal pathogens, do not appear to have changed in history, while others that support caries disease or oral health could be connected to human evolution through lifestyle and environmental contributing factors.},
}

@article {pmid38792577,
year = {2024},
author = {Koo, H and Morrow, CD},
title = {Bacteroidales-Specific Antimicrobial Genes Can Influence the Selection of the Dominant Fecal Strain of Bacteroides vulgatus and Bacteroides uniformis from the Gastrointestinal Tract Microbial Community.},
journal = {Life (Basel, Switzerland)},
volume = {14},
number = {5},
pages = {},
pmid = {38792577},
issn = {2075-1729},
abstract = {Bacteroides vulgatus and Bacteroides uniformis are known to be abundant in the human fecal microbial community. Although these strains typically remain stable over time in humans, disruption of this microbial community following antibiotics resulted in the transient change to new strains suggesting that a complex, dynamic strain community exists in humans. To further study the selection of dominant fecal microbial strains from the gastrointestinal tract (GIT) community, we analyzed three longitudinal metagenomic sequencing data sets using BLAST+ to identify genes encoding Bacteroidales-specific antimicrobial proteins (BSAP) that have known functions to restrict species-specific replication of B. uniformis (BSAP-2) or B. vulgatus (BSAP-3) and have been postulated to provide a competitive advantage in microbial communities. In the HMP (Human Microbiome Project) data set, we found fecal samples from individuals had B. vulgatus or B. uniformis with either complete or deleted BSAP genes that did not change over time. We also examined fecal samples from two separate longitudinal data sets of individuals who had been given either single or multiple antibiotics. The BSAP gene pattern from most individuals given either single or multiple antibiotics recovered to be the same as the pre-antibiotic strain. However, in a few individuals, we found incomplete BSAP-3 genes at early times during the recovery that were replaced by B. vulgatus with the complete BSAP-3 gene, consistent with the function of the BSAP to specifically restrict Bacteroides spp. The results of these studies provide insights into the fluxes that occur in the Bacteroides spp. GIT community following perturbation and the dynamics of the selection of a dominant fecal strain of Bacteroides spp.},
}

@article {pmid38791599,
year = {2024},
author = {Olteanu, G and Ciucă-Pană, MA and Busnatu, ȘS and Lupuliasa, D and Neacșu, SM and Mititelu, M and Musuc, AM and Ioniță-Mîndrican, CB and Boroghină, SC},
title = {Unraveling the Microbiome-Human Body Axis: A Comprehensive Examination of Therapeutic Strategies, Interactions and Implications.},
journal = {International journal of molecular sciences},
volume = {25},
number = {10},
pages = {},
pmid = {38791599},
issn = {1422-0067},
mesh = {Humans ; *Dysbiosis/microbiology/therapy ; *Gastrointestinal Microbiome ; *Fecal Microbiota Transplantation ; Microbiota ; Animals ; Human Body ; Host Microbial Interactions/physiology ; },
abstract = {This review scrutinizes the intricate interplay between the microbiome and the human body, exploring its multifaceted dimensions and far-reaching implications. The human microbiome, comprising diverse microbial communities inhabiting various anatomical niches, is increasingly recognized as a critical determinant of human health and disease. Through an extensive examination of current research, this review elucidates the dynamic interactions between the microbiome and host physiology across multiple organ systems. Key topics include the establishment and maintenance of microbiota diversity, the influence of host factors on microbial composition, and the bidirectional communication pathways between microbiota and host cells. Furthermore, we delve into the functional implications of microbiome dysbiosis in disease states, emphasizing its role in shaping immune responses, metabolic processes, and neurological functions. Additionally, this review discusses emerging therapeutic strategies aimed at modulating the microbiome to restore host-microbe homeostasis and promote health. Microbiota fecal transplantation represents a groundbreaking therapeutic approach in the management of dysbiosis-related diseases, offering a promising avenue for restoring microbial balance within the gut ecosystem. This innovative therapy involves the transfer of fecal microbiota from a healthy donor to an individual suffering from dysbiosis, aiming to replenish beneficial microbial populations and mitigate pathological imbalances. By synthesizing findings from diverse fields, this review offers valuable insights into the complex relationship between the microbiome and the human body, highlighting avenues for future research and clinical interventions.},
}

Humans
*Dysbiosis/microbiology/therapy
*Gastrointestinal Microbiome
*Fecal Microbiota Transplantation
Microbiota
Animals
Human Body
Host Microbial Interactions/physiology

@article {pmid38791230,
year = {2024},
author = {Pérez-Pérez, ME and Nieto-Torres, E and Bollain-Y-Goytia, JJ and Delgadillo-Ruíz, L},
title = {Protein Citrullination by Peptidyl Arginine Deiminase/Arginine Deiminase Homologs in Members of the Human Microbiota and Its Recognition by Anti-Citrullinated Protein Antibodies.},
journal = {International journal of molecular sciences},
volume = {25},
number = {10},
pages = {},
doi = {10.3390/ijms25105192},
pmid = {38791230},
issn = {1422-0067},
support = {the F002 Support for scientific, technological and innovation activities//This work was supported by the F002 Support for scientific, technological and innovation activities. Zacatecas Council of Science./ ; },
mesh = {Humans ; *Citrullination ; *Anti-Citrullinated Protein Antibodies/immunology/metabolism ; *Protein-Arginine Deiminases/metabolism/genetics ; *Arthritis, Rheumatoid/immunology/microbiology ; *Microbiota ; *Protein-Arginine Deiminase Type 2/metabolism ; *Protein-Arginine Deiminase Type 4/metabolism ; Female ; Citrulline/metabolism ; Case-Control Studies ; Male ; Cross-Sectional Studies ; Adult ; Middle Aged ; Hydrolases/metabolism ; },
abstract = {The human microbiome exists throughout the body, and it is essential for maintaining various physiological processes, including immunity, and dysbiotic events, which are associated with autoimmunity. Peptidylarginine deiminase (PAD) enzymes can citrullinate self-proteins related to rheumatoid arthritis (RA) that induce the production of anti-citrullinated protein antibodies (ACPAs) and lead to inflammation and joint damage. The present investigation was carried out to demonstrate the expression of homologs of PADs or arginine deiminases (ADs) and citrullinated proteins in members of the human microbiota. To achieve the objective, we used 17 microbial strains and specific polyclonal antibodies (pAbs) of the synthetic peptide derived from residues 100-200 of human PAD2 (anti-PAD2 pAb), and the recombinant fragment of amino acids 326 and 611 of human PAD4 (anti-PAD4 pAb), a human anti-citrulline pAb, and affinity ACPAs of an RA patient. Western blot (WB), enzyme-linked immunosorbent assay (ELISA), elution, and a test with Griess reagent were used. This is a cross-sectional case-control study on patients diagnosed with RA and control subjects. Inferential statistics were applied using the non-parametric Kruskal-Wallis test and Mann-Whitney U test generated in the SPSS program. Some members of phyla Firmicutes and Proteobacteria harbor homologs of PADs/ADs and citrullinated antigens that are reactive to the ACPAs of RA patients. Microbial citrullinome and homolog enzymes of PADs/ADs are extensive in the human microbiome and are involved in the production of ACPAs. Our findings suggest a molecular link between microorganisms of a dysbiotic microbiota and RA pathogenesis.},
}

Humans
*Citrullination
*Anti-Citrullinated Protein Antibodies/immunology/metabolism
*Protein-Arginine Deiminases/metabolism/genetics
*Arthritis, Rheumatoid/immunology/microbiology
*Microbiota
*Protein-Arginine Deiminase Type 2/metabolism
*Protein-Arginine Deiminase Type 4/metabolism
Female
Citrulline/metabolism
Case-Control Studies
Male
Cross-Sectional Studies
Adult
Middle Aged
Hydrolases/metabolism

@article {pmid38788999,
year = {2024},
author = {Filippo, D and Guardone, L and Listorti, V and Elisabetta, R},
title = {Microbiome in cancer: A comparative analysis between humans and dogs.},
journal = {Veterinary journal (London, England : 1997)},
volume = {},
number = {},
pages = {106145},
doi = {10.1016/j.tvjl.2024.106145},
pmid = {38788999},
issn = {1532-2971},
abstract = {Cancer is a major cause of death in humans and animals worldwide. While cancer survival rates have increased over recent decades, further research to identify risk factors for the onset and progression of disease, and safe and highly efficacious treatments, is needed. Spontaneous tumours in pets represent an excellent model for neoplastic disease in humans. In this regard, dogs are an interesting species, as the divergence between the dog and human genome is low, humans and dogs have important similarities in the development and functioning of the immune system, and both species often share the same physical environment. There is also a higher homology between the canine and human microbiome than murine model. This review aims to describe and organize recently published information on canine microbiome assemblages and their relationship with the onset and progression of colorectal cancer, breast cancer and lymphoma, and to compare this with human disease. In both species, dysbiosis can induce variations in the gut microbiota that strongly influence shifts in status between health and disease. This can produce an inflammatory state, potentially leading to neoplasia, especially in the intestine, thus supporting canine studies in comparative oncology. Intestinal dysbiosis can also alter the efficacy and side effects of cancer treatments. Fewer published studies are available on changes in the relevant microbiomes in canine lymphoma and mammary cancer, and further research in this area could improve our understanding of the role of microbiota in the development of these cancers.},
}

@article {pmid38788190,
year = {2024},
author = {Mishra, AK and Mahmud, I and Lorenzi, PL and Jenq, RR and Wargo, JA and Ajami, NJ and Peterson, CB},
title = {TARO: tree-aggregated factor regression for microbiome data integration.},
journal = {Bioinformatics (Oxford, England)},
volume = {},
number = {},
pages = {},
doi = {10.1093/bioinformatics/btae321},
pmid = {38788190},
issn = {1367-4811},
abstract = {MOTIVATION: Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. However, this remains challenging to the high dimensionality, compositionality, and rare features found in microbiome profiling data. These challenges necessitate the use of methods that can achieve structured sparsity in learning cross-platform association patterns.

RESULTS: We propose Tree-Aggregated factor RegressiOn (TARO) for the integration of microbiome and metabolomic data. We leverage information on the taxonomic tree structure to flexibly aggregate rare features. We demonstrate through simulation studies that TARO accurately recovers a low-rank coefficient matrix and identifies relevant features. We applied TARO to microbiome and metabolomic profiles gathered from subjects being screened for colorectal cancer to understand how gut microrganisms shape intestinal metabolite abundances.

The R package TARO implementing the proposed methods is available online at https://github.com/amishra-stats/taro-package.},
}

@article {pmid38782975,
year = {2024},
author = {McKee, K and Bassis, CM and Golob, J and Palazzolo, B and Sen, A and Comstock, SS and Rosas-Salazar, C and Stanford, JB and O'Connor, T and Gern, JE and Paneth, N and Dunlop, AL and , },
title = {Host factors are associated with vaginal microbiome structure in pregnancy in the ECHO Cohort Consortium.},
journal = {Scientific reports},
volume = {14},
number = {1},
pages = {11798},
pmid = {38782975},
issn = {2045-2322},
support = {U2COD023375//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3OD023285//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3OD023318//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3OD023249//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3OD023282//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; U24OD023382//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; U24OD023319//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; UH3OD023251//Environmental influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health/ ; },
mesh = {Humans ; Female ; Pregnancy ; *Vagina/microbiology ; *Microbiota/genetics ; Adult ; *RNA, Ribosomal, 16S/genetics ; Cohort Studies ; Young Adult ; },
abstract = {Using pooled vaginal microbiota data from pregnancy cohorts (N = 683 participants) in the Environmental influences on Child Health Outcomes (ECHO) Program, we analyzed 16S rRNA gene amplicon sequences to identify clinical and demographic host factors that associate with vaginal microbiota structure in pregnancy both within and across diverse cohorts. Using PERMANOVA models, we assessed factors associated with vaginal community structure in pregnancy, examined whether host factors were conserved across populations, and tested the independent and combined effects of host factors on vaginal community state types (CSTs) using multinomial logistic regression models. Demographic and social factors explained a larger amount of variation in the vaginal microbiome in pregnancy than clinical factors. After adjustment, lower education, rather than self-identified race, remained a robust predictor of L. iners dominant (CST III) and diverse (CST IV) (OR = 8.44, 95% CI = 4.06-17.6 and OR = 4.18, 95% CI = 1.88-9.26, respectively). In random forest models, we identified specific taxonomic features of host factors, particularly urogenital pathogens associated with pregnancy complications (Aerococcus christensenii and Gardnerella spp.) among other facultative anaerobes and key markers of community instability (L. iners). Sociodemographic factors were robustly associated with vaginal microbiota structure in pregnancy and should be considered as sources of variation in human microbiome studies.},
}

Humans
Female
Pregnancy
*Vagina/microbiology
*Microbiota/genetics
Adult
*RNA, Ribosomal, 16S/genetics
Cohort Studies
Young Adult

@article {pmid38781679,
year = {2024},
author = {Mangalea, MR and Halpin, AL and Haile, M and Elkins, CA and McDonald, LC},
title = {Decolonization and Pathogen Reduction Approaches to Prevent Antimicrobial Resistance and Healthcare-Associated Infections.},
journal = {Emerging infectious diseases},
volume = {30},
number = {6},
pages = {1069-1076},
doi = {10.3201/eid3006.231338},
pmid = {38781679},
issn = {1080-6059},
mesh = {Humans ; *Cross Infection/prevention & control/microbiology ; *Drug Resistance, Bacterial ; *Anti-Bacterial Agents/pharmacology/therapeutic use ; Microbiota/drug effects ; Bacterial Infections/prevention & control/microbiology ; Infection Control/methods ; Bacteria/drug effects ; },
abstract = {Antimicrobial resistance in healthcare-associated bacterial pathogens and the infections they cause are major public health threats affecting nearly all healthcare facilities. Antimicrobial-resistant bacterial infections can occur when colonizing pathogenic bacteria that normally make up a small fraction of the human microbiota increase in number in response to clinical perturbations. Such infections are especially likely when pathogens are resistant to the collateral effects of antimicrobial agents that disrupt the human microbiome, resulting in loss of colonization resistance, a key host defense. Pathogen reduction is an emerging strategy to prevent transmission of, and infection with, antimicrobial-resistant healthcare-associated pathogens. We describe the basis for pathogen reduction as an overall prevention strategy, the evidence for its effectiveness, and the role of the human microbiome in colonization resistance that also reduces the risk for infection once colonized. In addition, we explore ideal attributes of current and future pathogen-reducing approaches.},
}

Humans
*Cross Infection/prevention & control/microbiology
*Drug Resistance, Bacterial
*Anti-Bacterial Agents/pharmacology/therapeutic use
Microbiota/drug effects
Bacterial Infections/prevention & control/microbiology
Infection Control/methods
Bacteria/drug effects

@article {pmid38779566,
year = {2024},
author = {Scanu, M and Toto, F and Petito, V and Masi, L and Fidaleo, M and Puca, P and Baldelli, V and Reddel, S and Vernocchi, P and Pani, G and Putignani, L and Scaldaferri, F and Del Chierico, F},
title = {An integrative multi-omic analysis defines gut microbiota, mycobiota, and metabolic fingerprints in ulcerative colitis patients.},
journal = {Frontiers in cellular and infection microbiology},
volume = {14},
number = {},
pages = {1366192},
pmid = {38779566},
issn = {2235-2988},
mesh = {Humans ; *Colitis, Ulcerative/microbiology/metabolism ; *Gastrointestinal Microbiome ; Male ; Adult ; Female ; *Bacteria/classification/isolation & purification/metabolism/genetics ; Middle Aged ; *Metabolomics/methods ; *RNA, Ribosomal, 16S/genetics ; *Gas Chromatography-Mass Spectrometry ; *Feces/microbiology ; *Fungi/classification/isolation & purification/metabolism ; Dysbiosis/microbiology ; Metabolome ; Aged ; Young Adult ; Solid Phase Microextraction ; Mycobiome ; Multiomics ; },
abstract = {BACKGROUND: Ulcerative colitis (UC) is a multifactorial chronic inflammatory bowel disease (IBD) that affects the large intestine with superficial mucosal inflammation. A dysbiotic gut microbial profile has been associated with UC. Our study aimed to characterize the UC gut bacterial, fungal, and metabolic fingerprints by omic approaches.

METHODS: The 16S rRNA- and ITS2-based metataxonomics and gas chromatography-mass spectrometry/solid phase microextraction (GC-MS/SPME) metabolomic analysis were performed on stool samples of 53 UC patients and 37 healthy subjects (CTRL). Univariate and multivariate approaches were applied to separated and integrated omic data, to define microbiota, mycobiota, and metabolic signatures in UC. The interaction between gut bacteria and fungi was investigated by network analysis.

RESULTS: In the UC cohort, we reported the increase of Streptococcus, Bifidobacterium, Enterobacteriaceae, TM7-3, Granulicatella, Peptostreptococcus, Lactobacillus, Veillonella, Enterococcus, Peptoniphilus, Gemellaceae, and phenylethyl alcohol; and we also reported the decrease of Akkermansia; Ruminococcaceae; Ruminococcus; Gemmiger; Methanobrevibacter; Oscillospira; Coprococus; Christensenellaceae; Clavispora; Vishniacozyma; Quambalaria; hexadecane; cyclopentadecane; 5-hepten-2-ol, 6 methyl; 3-carene; caryophyllene; p-Cresol; 2-butenal; indole, 3-methyl-; 6-methyl-3,5-heptadiene-2-one; 5-octadecene; and 5-hepten-2-one, 6 methyl. The integration of the multi-omic data confirmed the presence of a distinctive bacterial, fungal, and metabolic fingerprint in UC gut microbiota. Moreover, the network analysis highlighted bacterial and fungal synergistic and/or divergent interkingdom interactions.

CONCLUSION: In this study, we identified intestinal bacterial, fungal, and metabolic UC-associated biomarkers. Furthermore, evidence on the relationships between bacterial and fungal ecosystems provides a comprehensive perspective on intestinal dysbiosis and ecological interactions between microorganisms in the framework of UC.},
}

Humans
*Colitis, Ulcerative/microbiology/metabolism
*Gastrointestinal Microbiome
Male
Adult
Female
*Bacteria/classification/isolation & purification/metabolism/genetics
Middle Aged
*Metabolomics/methods
*RNA, Ribosomal, 16S/genetics
*Gas Chromatography-Mass Spectrometry
*Feces/microbiology
*Fungi/classification/isolation & purification/metabolism
Dysbiosis/microbiology
Metabolome
Aged
Young Adult
Solid Phase Microextraction
Mycobiome
Multiomics