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Bibliography on: Microbiome

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ESP: PubMed Auto Bibliography 06 Nov 2026 at 01:55 Created: 

Microbiome

It has long been known that every multicellular organism coexists with large prokaryotic ecosystems — microbiomes — that completely cover its surfaces, external and internal. Recent studies have shown that these associated microbiomes are not mere contamination, but instead have profound effects upon the function and fitness of the multicellular organism. We now know that all MCEs are actually functional composites, holobionts, composed of more prokaryotic cells than eukaryotic cells and expressing more prokaryotic genes than eukaryotic genes. A full understanding of the biology of "individual" eukaryotes will now depend on an understanding of their associated microbiomes.

Created with PubMed® Query: microbiome[tiab] NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

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RevDate: 2026-11-04

Rentzos G, Fouka E, Lazarinis N, et al (2026)

Environmental Changes and Their Effect on the Airway Microbiome: Implications for Airway Diseases.

Allergy [Epub ahead of print].

Obstructive airway diseases, including asthma and chronic obstructive pulmonary disease (COPD), represent the two major chronic airway inflammatory diseases. In both conditions, the airways are exposed to a variety of microbial and environmental stimuli. A healthy airway microbiome is characterized not only by microbial diversity but also by the absence of significant quantities of pathogens, and is signified by ecological stability, functional resilience, and balanced interactions with the host immune system. Although microbial diversity is often considered a marker of respiratory health, its association with disease depends on the anatomical site, host factors, and environmental exposures. Thus, microbial diversity alone should not be used as a universal marker of airway health-the occurrence of pathogens and the organ compartment are also factors that are important to consider. Disruption of this microbial homeostasis, known as dysbiosis, may involve reduced diversity of the commensal flora as well as increased quantity of key pathogens, and this condition is believed to stimulate inflammation that is associated with the progression of asthma and COPD, including exacerbations. Environmental changes, including air pollution, climate change, and urbanization, can disrupt microbial balance by reducing diversity and increasing the prevalence of pathogens. Several mechanisms contribute to this interaction, including damage to the airway epithelium, impaired mucociliary clearance, oxidative stress, and alterations in innate and adaptive immune responses. This review examines the interplay between external environmental factors and the airway microbiome, and how they affect airway obstructive diseases, asthma, and COPD to understand their immunopathology, and to improve disease prevention and treatment approaches. This is an area of great interest, and further research is required to elucidate these interactions so we can better help our patients.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Zhang H, Zhu L, Li D, et al (2026)

Microbiota-Derived Metabolites Mediate Immune Regulatory Networks in the Gut-Skin Axis of Psoriasis.

Frontiers in bioscience (Landmark edition), 31(10):48099.

Psoriasis is a chronic immune-mediated inflammatory disease affecting 2-3% people globally. Current biologic therapies targeting interleukin-23 and interleukin-17 pathways achieve only partial responses in most patients, highlighting the need for understanding upstream triggers. Emerging evidence implicates gut microbiome dysbiosis as a notable contributor to psoriasis pathogenesis through metabolite-mediated immune regulation. Psoriasis patients exhibit characteristic gut microbial alterations, including depletion of beneficial commensals such as Faecalibacterium prausnitzii and expansion of proinflammatory taxa. These compositional changes are associated with altered profiles of immunomodulatory metabolites, including short-chain fatty acids, tryptophan-derived indole compounds, and secondary bile acids, which promote regulatory T-cell differentiation, enhance immune tolerance through aryl hydrocarbon receptor activation, and modulate metabolic-immunological pathways. Such metabolic alterations may impair regulatory T cell function, promote T helper 17 (Th17) differentiation, compromise intestinal barrier integrity, and influence tissue-resident memory T cells that perpetuate disease chronicity. This process facilitates bacterial product translocation that amplifies inflammation, thereby amplifing relationship is bidirectional; psoriatic skin inflammation reciprocally affects gut homeostasis through circulating inflammatory mediators, systemic immune cell activation, and neuroendocrine stress pathways. Recent clinical evidence demonstrates that biologic therapies normalize gut microbiome composition and reduce trimethylamine N-oxide levels, supporting bidirectional gut-skin communication. These interactions create self-perpetuating cycles, suggesting that therapeutic strategies interrupting this feedback loop may offer novel treatment approaches. This review synthesizes current evidence on metabolite-mediated immune regulatory networks linking gut microbiome dysbiosis to psoriatic inflammation, evaluates clinical trials of microbiome-targeted interventions, and discusses methodological challenges, regulatory considerations, and future research directions for clinical translation. Understanding these mechanisms may inform the development of microbiome-targeted therapeutic approaches.

RevDate: 2026-11-04

Aghdam SA, De Souza R, AMV Brown (2026)

Metatranscriptomic profiling of active endophytic microbiome functions across diverse Musa cultivars.

Microbiology spectrum [Epub ahead of print].

Plant-endophyte symbioses play important roles in plant health and resilience, but the active functions of endophytic microbiomes remain less characterized than those of soil and rhizosphere microbiomes. We used metatranscriptomic profiling of culture-free enriched endophytic microbiomes from seven Musa cultivars grown under shared environmental conditions to characterize active microbial taxa and functional annotations across sampled tissues. Because each genotype and tissue combination had only one metatranscriptomic sample, this pilot study focuses on the microbial transcripts and functions detected in each sample rather than testing for cultivar or tissue differences. Culture-free enrichment produced metatranscriptomic profiles across samples, including 5,434 taxonomic annotations, and 32,694 gene annotations from expressed microbial transcripts. Functional annotations included pathways involved in secondary metabolism, energy production, environmental information processing, transport systems, oxidative phosphorylation, nitrogen metabolism, quorum sensing, biofilm formation, and xenobiotic biodegradation. Several taxa, including Bradyrhizobium sp., were detected across multiple samples and linked to diverse functional annotations. Approximately 30-35% of sequence reads were annotated as hypothetical proteins, showing that the functions of many detected transcripts are still unknown. Correlation analysis also showed sample-level associations among detected pathway profiles. Overall, this pilot metatranscriptomic data set provides a resource for banana endophyte research and identifies candidate microbial taxa and functional pathways for future studies of plant-microbiome interactions and microbe-microbe relationships.IMPORTANCEEndophytic microbiomes can influence plant health, but their active roles inside banana tissues remain poorly characterized. Here, we used metatranscriptomic profiling of culture-free enriched endophytic microbiomes from seven Musa cultivars to identify microbial taxa and functional pathways detected across sampled tissues. Metatranscriptomic data characterized pathways related to metabolism, transport, microbial signaling, biofilm formation, nutrient cycling, and secondary metabolism, suggesting potential variation in active microbiome profiles among sampled plants. This work provides a pilot resource for banana endophyte research and may help guide future studies on how plant-associated microbiomes interact with their hosts, how microbes function together inside plant tissues, and how these relationships could be used for microbiome-based crop improvement.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Sun GT, Du X, Zhang XT, et al (2026)

Host Fitness in Gastrointestinal Oncology: Beyond Tumor Biology.

Journal of visualized experiments : JoVE.

Patients with gastrointestinal cancers face site-specific threats to nutritional intake, muscle function, organ reserve, and recovery. This critical narrative review examines host fitness as an organizing concept for these vulnerabilities rather than as a validated composite score. A targeted PubMed update identified publications from 2022 through September 14, 2026, using gastrointestinal cancer terms combined with prehabilitation, microbiome-immunotherapy, geriatric assessment, exercise, and digital assessment terms, while retaining relevant foundational studies. The review distinguishes guideline-supported care from prognostic associations and research-stage applications. Geriatric and nutritional assessments can guide established supportive care, whereas computed tomography-derived body composition and inflammatory indices primarily provide prognostic information. Microbiome signatures, epigenetic clocks, and integrated digital models require further validation before they can guide treatment decisions. Intervention effects vary by tumor site and treatment phase: selected prehabilitation trials demonstrate short-term benefits, although findings remain inconsistent, while long-term exercise after adjuvant chemotherapy for colon cancer represents a distinct evidence base. An operational assessment protocol and multidisciplinary workflow are presented to link documented impairments with existing care pathways and repeated assessment. No host-fitness threshold is proposed for treatment escalation, de-escalation, or sequencing. Prospective studies should establish incremental predictive value and patient benefit beyond existing assessments before this integrated framework is used to support precision treatment decisions.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Wang T, Wang J, Huangfu B, et al (2026)

Allobaculum stercoricanis and Its Postbiotics Alleviate Dextran Sulfate Sodium (DSS)-Induced Colitis through the Regulation of theTLR4/NF-κB Signaling Pathway.

Journal of agricultural and food chemistry, 74(43):33790-33804.

Inflammatory bowel disease (IBD) is a chronic intestinal disorder that has become a global public health concern. Postbiotics offer advantages in biosafety and reproducibility over probiotics. Here, we demonstrated that live Allobaculum stercoricanis (A. stercoricanis) and its two postbiotic preparations─inactivated bacterial cells (POST) and cell-free fermentation supernatant (CFS)─effectively alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Integrated gut microbiome and serum metabolomics analyses indicated that these interventions may act through modulating bile acid metabolism and Toll-like receptor signaling pathways. Further investigations combining postbiotic metabolomics, network pharmacology, molecular docking, and molecular dynamics simulations identified α-muricholic acid (α-MCA) as a candidate functional metabolite, with the farnesoid X receptor (FXR) as a potential target. We hypothesize that α-MCA may contribute to ameliorating intestinal inflammation through engagement of FXR and suppression of the TLR4/NF-κB signaling pathway. These findings provide new insights into postbiotic-based therapeutic strategies for IBD.

RevDate: 2026-11-04

Osman MH, Q Wang (2026)

The role of gut microbiota on the tumor microenvironment in colorectal cancer: a systematic review and meta-analysis.

Minerva gastroenterology pii:S2724-5985.26.03961-6 [Epub ahead of print].

BACKGROUND: This meta-analysis and systematic review examined gut microbial metabolites and the tumor microenvironment (TME) in colorectal cancer (CRC), as well as the influence of microbial metabolites on cancer development and treatment. The focus was on explaining how microbial metabolites influence cancer development and treatment outcome.

METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was conducted (January 2010-December 2020) following the PRISMA 2020 guidelines.

RESULTS: Literature search yielded 765 articles, from which 22 studies were identified as meeting inclusion criteria after stringent screening. Included studies encompassed in vitro, in vivo, and patient-derived data on the role of gut microbial metabolites (e.g., short-chain fatty acids [SCFAs], bile acids, polyamines, and trimethylamine-N-oxide) in characterizing the CRC TME. Meta-analysis found that SCFAs, particularly butyrate, consistently played protective and regulatory functions, suppressing inflammation and stimulating antitumor immunity. In contrast, bile acids and certain microbial populations (e.g., Fusobacterium nucleatum) were associated with tumor-promoting pathways, including NF-κB and STAT3 activation. The overall result was moderately heterogeneous (I[2]=40%, P<0.05), reflecting variability in study design and metabolite focus. Publication bias testing with Egger's regression and funnel plots showed no indication of large small-study effects (P=0.21). Overall, 59% of studies reviewed cited a positive or modulatory function of metabolites in the TME, 27% proposed context-dependent or mixed effects, and 14% exhibited tumor-promoting activities. Moderate evidence strength, with limitations by virtue of preclinical and observational evidence, was present. Gut microbiota metabolites have context-dependent roles in CRC, SCFAs tending to be protective, and bile acids typically tumor-promoting.

CONCLUSIONS: The findings exhibit the therapeutic promise of microbiome-targeting treatments and dietary manipulation in modifying the TME. However, they remain to be confirmed by follow-up large-scale clinical trials to consolidate the evidence base.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Sohlberg E, Laitila A, Rämö S, et al (2026)

Fusarium Community Composition and Co-Occurrence with Other Fungi and Bacteria in Finnish Oat Crop.

Microbial ecology, 89(1):.

Fusarium species are major contributors to Fusarium head blight (FHB) and mycotoxin contamination in cereal production. To characterize microbial co-occurrence associated with toxin accumulation in oats, the Fusarium, fungal, and bacterial communities of 51 Finnish oat grain samples were analyzed using a multi-marker metabarcoding approach targeting Fusarium translation elongation factor 1‑alpha (EF1α), fungal ITS2, and bacterial 16S regions. Microbial profiles were compared between grains with high and low deoxynivalenol (DON) concentrations. High‑DON samples were dominated by F. graminearum, whereas F. langsethiae prevailed in low‑DON grains. Bacterial diversity was higher in high‑DON samples, while fungal diversity remained similar across groups. Several bacterial genera, including Pseudomonas, Paenibacillus, Massilia, and Curtobacterium, exhibited negative correlations with Fusarium species, indicating competition in the same niche, whereas Duganella and Xylophilus showed positive association with Fusarium abundance. Microdochium consistently co-occurred with Fusarium. Results show differences in microbial communities associated with mycotoxin levels and Fusarium community composition, identifying taxa that may influence FHB or indicate mycotoxin risk.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Gasner N, Sweeney M, Piché JV, et al (2026)

Effects of Probiotics on Migraine in Children and Adults: A Systematic Review and Meta-Analysis.

Current pain and headache reports, 30(1):.

PURPOSE OF REVIEW: Increasing evidence highlights a link between migraine, a disabling neurological disorder, and the gut microbiome. Probiotics, supplements containing colony-forming units of beneficial microbes, may influence migraine via the gut microbiome. A systematic review and meta-analysis of placebo-controlled trials was completed, and findings were synthesized narratively to evaluate probiotics for migraine prevention.

RECENT FINDINGS: Of 676 studies screened, 7 were included involving 612 participants (N = 487 females, 79.6%) consisting of 5 adult and 2 pediatric trials. Probiotics demonstrated a reduction in migraine severity on a 10-point scale (mean difference - 1.11; 95% CI - 2.26 to 0.03), monthly attack frequency (- 2.06; 95% CI - 3.6 to - 0.52), and disability (standardized mean difference - 0.86; 95% CI - 2.33 to 0.6). Certainty of evidence was graded very low. Probiotics may reduce migraine severity and frequency; however, the heterogeneity of studies limits generalizability. Despite the very low certainty of evidence, probiotics are safe and may reduce migraine as an adjunct preventative therapy.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Bhandari SA, Kumari P, M Das (2026)

Regulatory T cells in atopic dermatitis: mechanisms of dysfunction, plasticity and therapeutic reprogramming.

Inflammation research : official journal of the European Histamine Research Society ... [et al.], 75(1):.

OBJECTIVE AND DESIGN: This review focused on current evidence regarding the mechanisms underlying regulatory T cell (Treg) dysfunction in atopic dermatitis (AD), with particular emphasis on Treg instability, tissue microenvironmental reprogramming, inflammatory plasticity, and the skin-gut immune axis, and evaluated Treg-directed therapeutic strategies.

METHODS: Experimental and clinical studies investigating Treg functions, tissue microenvironment, immune regulation, microbial dysbiosis, and therapeutics in AD were critically analysed and integrated into a mechanistic framework.

RESULTS: AD is a chronic inflammatory skin disease with epidermal barrier dysfunction, pruritus, microbial dysbiosis, and immune dysregulation. Current evidence suggests that Treg abundance, phenotype, localization, and suppressive function may differ across AD endotypes and tissue compartments. Functional impairment or maladaptive plasticity might play a role in persistent inflammation within specific Treg populations. This may link to FOXP3 instability, altered IL-2/STAT5 signaling, metabolic strain, cytokine-induced destabilization, plasticity, keratinocyte-derived alarmins, inflammatory dendritic cells, Staphylococcus aureus colonization, and the skin-gut microbial axis. Novel therapeutics may restore immune tolerance beyond conventional anti-inflammatory treatment, including Treg-selective IL-2 agonists, microbiome-based therapy, and antigen-specific regulatory approaches.

CONCLUSION: Treg dysregulation may represent a major component in AD pathogenesis, but its causality for disease persistence and therapeutic reversibility is yet to be elucidated.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Yao Y, Chen X, An X, et al (2026)

From Macroenvironmental Context to Individual Proximal Exposure: Multiscale Mechanisms Linking Environmental Factors to Blood Pressure Homeostasis and Variability : Author.

Cardiovascular toxicology, 26(11):.

Hypertension is a major contributor to the global burden of cardiovascular disease. In addition to genetics, age, and lifestyle, environmental exposures can disrupt blood pressure homeostasis. Compared with air pollution and ambient temperature, evidence concerning psychosocial factors, noise, light, chemical pollutants, micro- and nanoplastics, and the individual proximal residential environment is more fragmented, and studies often conflate mean blood pressure, incident hypertension, and blood pressure variability (BPV) as equivalent outcomes. Using a continuum from macroenvironmental context to individual proximal exposure, this review integrates evidence from human studies, animal experiments, and in vitro research to compare associations of air pollution, temperature, greenspace, noise, chemical pollutants, micro- and nanoplastics, light exposure, and psychosocial stress with distinct blood pressure phenotypes. We further summarize shared pathways involving autonomic and neurohumoral regulation, oxidative stress-inflammation-endothelial injury, the renin-angiotensin-aldosterone system (RAAS), circadian rhythms, and metabolic/microbiome mechanisms. Human evidence is relatively substantial for air pollution, temperature, noise, and greenspace, whereas direct evidence linking micro- and nanoplastics and some chemical pollutants to human hypertension and BPV remains limited, with mechanistic understanding derived mainly from experimental models. Multiple exposures, genetic and epigenetic backgrounds, and socioeconomic conditions may jointly modify environmental effects. Clarifying exposure dose, level of evidence, and the relevant BPV time scale will help identify environmentally susceptible populations and provide a conceptual basis for stratified prevention and future intervention studies.

RevDate: 2026-11-04

Chen G, Du S, Li H, et al (2026)

Multi-matrix metabolome and microbiome profiling in diarrhea-predominant irritable bowel syndrome and ulcerative colitis in remission with IBS-like symptoms.

Inflammatory bowel diseases pii:9012543 [Epub ahead of print].

BACKGROUND: Irritable bowel syndrome (IBS)-like symptoms frequently persist in patients with ulcerative colitis (UC) in remission. Whether UC in remission with IBS-like symptoms (UCR-IBS) represents functional overlap with diarrhea-predominant IBS (IBS-D) or a distinct metabolic phenotype remains unclear.

METHODS: In this exploratory cross-sectional study, 39 patients with IBS-D, 21 with UCR-IBS, and 35 healthy controls were enrolled. Serum, urine, fecal, and colonic mucosal samples were collected. Untargeted metabolomics, targeted tryptophan profiling, fecal 16S ribosomal RNA gene sequencing, predicted microbial functional profiling, and microbe-metabolite association analyses were performed.

RESULTS: Tryptophan-related metabolism was altered in both patient groups, but the patterns differed across biological matrices. Compared with IBS-D, UCR-IBS showed higher serum N-formylkynurenine (NFK) concentrations, and fecal findings suggested reduced concentrations of microbiota-associated indole metabolites. Microbiome differences were modest, but predicted nicotinate/nicotinamide metabolism was enriched in UCR-IBS. Exploratory network analysis identified associations between tryptophan-related metabolites and selected bacterial genera in each group.

CONCLUSIONS: Multi-matrix profiling shows tryptophan-related metabolic differences between mesalazine-treated UCR-IBS and IBS-D, highlighting higher serum NFK concentrations in UCR-IBS. These findings provide a basis for investigating host-microbiota metabolic relationships across systemic and intestinal compartments during UC remission.This trial was registered in the Chinese Clinical Trial Registry (ChiCTR; https://www.chictr.org.cn/) under registration number ChiCTR2200060224.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Chen J, Cheng YQ, Fan LP, et al (2026)

Environmental enrichment is associated with changes in the gut microbiome and resistome of captive pythons.

PloS one, 21(11):e0360735.

Environmental enrichment is widely used to improve the welfare of captive animals, yet its effects on reptilian gut microbiota remain poorly understood. Here, we used shotgun metagenomic sequencing to investigate the gut microbiome and resistome of two captive python species: Burmese python (Python bivittatus) and reticulated python (Malayopython reticulatus), before and after environmental enrichment. We found that environmental enrichment was associated with increased α-diversity in Burmese pythons, as indicated by significantly higher ACE and observed species indices, while NMDS ordination revealed differences in the observed patterns of community composition between the two species. Pseudomonadota and Bacteroidota were dominant phyla in the gut microbiota of both python species, but their relative abundances responded differently to enrichment between hosts. Functional analyses suggested an enhanced metabolic potential in Burmese pythons, particularly in carbohydrate metabolism and environmental information processing, accompanied by increased abundance of carbohydrate-active enzymes. In addition, enrichment may influence the gut resistome, with Pseudomonadota contributing the majority of antibiotic resistance genes. Overall, our results demonstrate that environmental enrichment measures, such as dietary changes and improvements in water and air quality, are associated with changes in the gut microbiome and resistome of captive pythons in a host-dependent manner, highlighting the combined roles of diet and environmental conditions in the observed changes in the gut microbiota. These findings provide exploratory insights into the functional responses and host-microbiome evolution of reptile gut microbiota to captivity and have important implications for the management and welfare of captive animals.

RevDate: 2026-11-05
CmpDate: 2026-11-04

Mogire DB, Neondo J, Muhonja C, et al (2026)

Metagenomic analysis of tomato rhizosphere microbiomes detects Ralstonia phage sequences in Kenyan agricultural soils.

PloS one, 21(11):e0362106.

Bacterial wilt caused by Ralstonia solanacearum species complex is a major constraint in tomato production in Kenya, resulting in yield losses of up to 100% in heavily infested fields. This study used high-throughput shotgun metagenomic sequencing approach to characterize the rhizosphere microbiomes of tomato plants in three of the major production areas in Kenya (Kirinyaga, Kiambu, and Laikipia counties) focusing on detecting Ralstonia phage sequences. Soil samples were collected from the rhizosphere of bacterial wilt-infected tomato plants, and microbial DNA was extracted using a modified phenol-chloroform protocol and sequenced using Illumina NovaSeq platform. Taxonomic profiling revealed diverse microbial communities dominated by Actinobacteria and Proteobacteria. Four Ralstonia species were confirmed (R. insidiosa, R. pickettii, R. mannitolilytica and R. wenshanensis). Sequences similar to the R. solanacearum species complex were also detected but were too short for species-level confirmation. Metagenomic analysis detected sequences matching four previously described Ralstonia phages (RSL1, RSIBR3, Anchaing, and Cimandef). Functional annotation demonstrated abundant metabolic pathways, energy production systems, and stress response mechanisms, indicating highly adaptive microbial communities in the tomato rhizosphere. This study provides baseline data on rhizosphere microbiome composition in Kenyan tomato production systems and identifies Ralstonia phage sequences that could guide future isolation and host-range studies. If future work shows that these phages are active against Ralstonia, they could contribute to locally adapted biocontrol approaches that reduce reliance on chemical pesticides.

RevDate: 2026-11-04
CmpDate: 2026-11-04

de Souza MR, Bruce J, Cros A, et al (2026)

Stony coral symbioses show variable responses to future ocean conditions.

Science advances, 12(45):eaed4599.

Coral reefs support over a quarter of marine species and nearly a billion people worldwide but are also among the ecosystems most threatened by anthropogenic impacts. There is long-standing debate about whether coral symbioses will be disrupted or respond adaptively under future ocean conditions. Using a factorial 2.5-year future-ocean mesocosm experiment across eight coral species representing the major coral lineages, we tracked symbiont community shifts within replicate fragments from the same individual coral. Some corals exhibited stochastic divergence, whereas others showed deterministic shifts in symbiont community composition. Heat stress generally reduced symbiont diversity and promoted predictable restructuring, consistent with deterministic adaptation to moderate thermal stress but stochastic accumulation of diversity under extreme conditions. We propose that adaptive and stochastic responses represent endpoints along a continuum of host-orchestrated symbiont sorting. This study bridges coral reef ecology with broader host-microbiome theory, offering an integrated perspective on how symbiotic systems may respond to environmental change.

RevDate: 2026-11-04

Kim SG, Venzon M, JP Jacobs (2026)

Probiotics for Human Health: Mechanisms, Clinical Evidence, Risks, and Next-Generation Microbial Therapeutics.

Annual review of physiology [Epub ahead of print].

Probiotics are widely used live microbial supplements intended to promote human health, yet their clinical benefits remain inconsistent and often strain-specific. Most currently available probiotics are derived from Lactobacillus, Bifidobacterium, and Saccharomyces species originally isolated from fermented foods or human microbiota. Preclinical studies suggest that these organisms may influence host physiology through several mechanisms, including antimicrobial activity, toxin inhibition, strengthening of intestinal barrier function, modulation of immune responses, and signaling along the gut-brain axis. However, translation of these mechanisms into consistent clinical benefit has been limited by heterogeneity in probiotic strains, dosing, and study design. Emerging evidence also highlights potential unintended consequences of probiotic use, including rare infections in vulnerable patients, alterations of microbiome recovery after antibiotics, and possible interactions with host metabolism or medications. Recent advances in microbiome research have supported the development of next-generation probiotics and engineered microbial therapeutics, representing a shift toward more targeted and mechanistically informed live microbial therapies.

RevDate: 2026-11-04

Erdoğan Y, Özgen EK, Polat B, et al (2026)

Uterine microbiota across cytological severity of subclinical endometritis in Simmental cows: a full-length 16S rRNA nanopore study.

Theriogenology, 269:118301 pii:S0093-691X(26)00491-7 [Epub ahead of print].

Subclinical endometritis (SE) reduces fertility in dairy cows without clinical signs. In this cross-sectional study we compared the uterine microbiota of cows with SE and cytologically healthy cows, and examined how it varies across cytological severity, using full-length 16S rRNA nanopore sequencing. Uterine cytobrush samples were collected 48 to 62 days postpartum from Simmental cows in 24 herds and graded cytologically (score 0 to 3) using thresholds defined a priori. Of 137 cows with a valid score, 105 were included in the primary analysis after 24 cows with fewer than 1000 bacterial reads and eight cows with discordant diversity were excluded. Alpha diversity was higher in cows with SE than in cytologically healthy cows (mean Shannon 3.26 vs 3.03; p: 0.026) and was significantly correlated with the score (ρ: 0.22; p: 0.027), but did not differ among the three SE scores. Community structure differed between the groups (Bray-Curtis PERMANOVA R[2]: 0.036; p: 0.014), and pairwise comparisons showed significant differences between score 0 and scores 1 and 3, but not among the SE scores. Genera with a higher relative abundance in SE included gut-associated anaerobes such as Paeniclostridium and Mogibacterium, whereas genera with a higher relative abundance in healthy cows were environmental taxa that also dominated the negative control. The differences between healthy and SE cows were not significant when herd or sequencing library was accounted for. Herd explained 46% of the variation in community structure (p: 0.001). Classical uterine pathogens were rare, and Trueperella spp. were detected only at trace levels. Full-length 16S sequencing across four grades of cytological severity showed that diversity and community structure differed between cytologically healthy and SE cows but not among the SE scores, that this difference was not significant after adjustment for herd or sequencing library, and that herd had a significant effect on the uterine microbiota.

RevDate: 2026-11-04

McMillan R, Dria RM, Moreau GB, et al (2026)

First-Trimester Maternal Gut Microbiome and Small Vulnerable Newborns: A Prospective Cohort Study.

BJOG : an international journal of obstetrics and gynaecology [Epub ahead of print].

OBJECTIVES: To investigate the relationship between the first trimester gut microbiome and small vulnerable newborns (SVN).

SETTING: Rural low- and middle-income country: Bangladesh.

POPULATION: 213 women were enrolled during the first trimester of pregnancy as part of the NICHD Global Network for Women's and Children's Health registry, Bangladesh.

METHODS: Observational study of the maternal gut microbiome and birth outcomes. Blood and stool samples were collected at enrollment. Birth outcomes were recorded within 72 h of delivery. Random forest machine learning models trained on microbiome data were used to predict SVN or first-trimester maternal features of interest. Hold out sets were used to test model accuracy.

MAIN OUTCOME MEASURES: SVN (born preterm, low birth weight, or small for gestational age).

RESULTS: The birth outcome SVN (n = 106) was discriminated from non-SVN (n = 107) using a microbiome-trained random forest model (AUC = 0.653, 95% CI 0.518-0.789). The microbiome also predicted the inflammatory markers plasma alpha-1-acid glycoprotein and faecal calprotectin (AUC = 0.742, 95% CI: 0.616-0.868 and AUC = 0.793, 95% CI: 0.680-0.905, respectively), while micronutrient concentrations, anaemia, C-reactive protein and the presence of atypical Enteropathogenic E. coli were not reliably predicted. Higher alpha-1-acid glycoprotein was significantly associated with SVN (aOR = 1.98; 95% CI: 1.04-3.85) whereas calprotectin was not.

CONCLUSIONS: In this prospective cohort, first-trimester maternal gut microbiome composition showed modest discrimination for SVN and a marker of systemic inflammation. These findings support further investigation of early pregnancy microbiome-inflammation pathways in fetal growth restriction and preterm birth.

RevDate: 2026-11-04

Bhimavarapu K, Williams GR, Cooley M, et al (2026)

Current and emerging threats to honey bee health: a One Health perspective on antibiotic pollution.

Journal of the American Veterinary Medical Association [Epub ahead of print].

Pollinators play a critical role in global food production and ecosystem health, yet high losses of essential honey bee colonies have been reported worldwide. Climate change, habitat loss, parasites, pesticides, and poor nutrition are established pollinator threats, whereas environmental antibiotic pollution remains poorly understood. Antibiotic exposure may independently affect bees or interact with these stressors, potentially compounding adverse health effects. Synthetic antibiotic residues and resistance genes enter the environment through the fertilization of soils with antibiotic-containing animal manure, animal wastewater discharge, and airborne antibiotic contamination landing directly on flowers and crops. While the effects of direct antibiotic exposure on honey bees have been studied, the consequences of indirect environmental exposure remain largely unknown. Foraging bees may encounter antibiotic contaminants in the environment, potentially disrupting their gut microbiome, altering behavior and physiology, and increasing susceptibility to pathogens. Contamination of honey bees and their products with antibiotics serve not only as indicators of environmental antibiotic resistance but also as a practical One Health model linking human, animal, and environmental health. Studying honey bee responses to agricultural contaminants provides insight into how antibiotic resistance and environmental stressors can move across ecosystems, affecting both pollinators and the broader public. This review synthesizes current knowledge on the multifactor threats to honey bees and their mitigation strategies, emphasizing the influence of animal production and antibiotic pollution on honey bee health. We highlight knowledge gaps in understanding the transfer of antibiotic resistance from agricultural environments to honey bees to enhance pollinator health and promote long-term ecological resilience.

RevDate: 2026-11-04

Korkmaz HI, Boer DP, van der Ven F, et al (2026)

Immune function in burn patients: Pathophysiology, monitoring, and emerging therapeutic strategies.

Burns : journal of the International Society for Burn Injuries, 52(9):108260 pii:S0305-4179(26)00412-2 [Epub ahead of print].

Severe burn injury causes extensive local tissue damage and systemic immune alterations that affect infection risk, wound healing, organ function, and survival. The immune response is characterized by rapid activation of innate immune cells, including neutrophils and monocytes, with elevated pro-inflammatory cytokines (IL‑6, TNF‑α, IL‑1β) and complement activity. Simultaneously, adaptive immunity is often impaired, with reduced T and B lymphocyte function, while diminished dendritic cell activity may further compromise antigen presentation and adaptive immune responses. This combined hyperinflammatory and immunosuppressive state, known as burn-induced immune dysfunction, contributes to delayed wound healing, increased susceptibility to secondary infections, sepsis, and multiple organ dysfunction. Monitoring immune function is essential but challenging. Routine markers, including white blood cell count (WBC) and C-reactive protein (CRP), provide limited insight, whereas procalcitonin (PCT), pancreatic stone protein (PSP), and cytokine panels (IL‑6, IL‑8, IL‑10) improve early detection of infection and immune classification. Flow cytometry allows characterization of immune cell populations and functional markers such as monocyte HLA‑DR and T cell PD‑1, while functional assays assess neutrophil, monocyte, and lymphocyte responsiveness. High-resolution molecular approaches, including transcriptomics, proteomics, and single-cell profiling, reveal persistent alterations not captured by conventional assays. Therapeutic strategies to restore immune balance include targeted cytokine modulation, immune checkpoint inhibition, hemoadsorption, metabolic and nutritional interventions, and novel approaches such as nanotechnology or microbiome modulation. Early surgical excision and topical treatments, including cerium-nitrate with silver sulfadiazine, may also attenuate systemic inflammation. However, robust clinical evaluation of these interventions is limited, and their timing, dosing, and patient selection remain under investigation. This review integrates mechanistic, translational, and clinical evidence to provide a framework for understanding burn-induced immune dysfunction. Future research should aim for standardized immune phenotyping, longitudinal multi-omics integration, AI-assisted monitoring, and evaluation of mechanism-based immunomodulatory strategies to improve patient outcomes.

RevDate: 2026-11-04

Jeong M, Yeo S, Kang D, et al (2026)

Antibiotic resistance gene classes show no detectable shift despite extensive microcystin-associated river microbiome reorganization.

Water research, 309(Pt B):127235 pii:S0043-1354(26)01906-8 [Epub ahead of print].

Antibiotic resistance gene (ARG) signals can reflect increasing environmental resistance or changes in the microorganisms carrying those genes. Cyanobacterial blooms make this distinction especially important because they can reorganize entire freshwater microbial communities. We combined repeated metagenomic sampling at ten sites over eleven rounds along an 85 km Nakdong River reach with taxonomic, functional, and genome-resolved analyses and site-aware machine learning. Sampling round explained 60.9% of microbial-community variation, compared with 5.0% for site, indicating that temporal turnover dominated persistent spatial structuring. After adjusting for site, season, and water temperature, high-microcystin conditions were associated with 3,241 microbial features. None of the 18 tested ARG drug classes showed a corresponding association. The resistance-candidate inventory sums candidate annotations in representative metagenome-assembled genomes (MAGs) assigned to origin samples; drug-class profiles partition the same annotations rather than measuring sample-wide ARG abundance. Across 301 representative MAGs, candidate counts were strongly positively associated with genome size, indicating that the inventory partly reflected the microbial genomic content represented. In exploratory models, predicted resistance-candidate inventories differed between community states. High-microcystin conditions therefore coincided with extensive microbial reorganization without a detectable parallel ARG-class response. Microcystin measurements should be paired with direct ARG measurements and community profiles to track toxin hazard, resistance determinants, and microbial turnover.

RevDate: 2026-11-04

Hu J, He Y, Cui W, et al (2026)

Halophyte-derived rhizosphere microbiome transplantation improves physiological homeostasis and salt tolerance in alfalfa.

Microbiological research, 315:128801 pii:S0944-5013(26)00365-4 [Epub ahead of print].

Halophyte-associated microbiomes are promising reservoirs of stress-adapted microorganisms, yet the consequences of transferring whole rhizosphere communities to phylogenetically distinct crops have remained unclear. Here, we evaluated rhizosphere microbiome transplantation (RMT) from Suaeda salsa to alfalfa (Medicago sativa) in a 2 × 2 factorial experiment comprising control and RMT treatments at 0 and 300 mM NaCl. Plant physiological responses were integrated with metagenomic profiling, community assembly analysis, microbial association networks, and functional gene analyses. Under salinity, RMT increased plant height, leaf area, and both shoot and root biomass, reduced shoot Na[+] accumulation, and increased the shoot K[+]/Na[+] ratio. RMT also reduced H2O2, malondialdehyde, and relative electrical conductivity while increasing antioxidant enzyme activities and osmolyte concentrations, whereas gas-exchange parameters showed no significant recovery. RMT altered rhizosphere community composition and assembly and was associated with greater network connectivity and simulated robustness. Metagenomic KO profiles showed higher relative representation of functions correlated to osmoprotection, ion transport, redox protection, and cell-envelope processes. These microbial functional shifts coincided with the physiological domains most strongly improved by RMT but did not establish direct causal microbial mechanisms. Overall, halophyte-derived RMT improved alfalfa performance under salinity, with coordinated physiological recovery accompanied by substantial reorganization of the recipient rhizosphere, supporting further evaluation of whole-community microbiome transplantation for crop production in saline soils.

RevDate: 2026-11-04

Aswinanand B, Karuppiah P, Balasubramanian B, et al (2026)

Chronic exposure to sulfur species, sodium metabisulfite and methionine, causes gut microbial dysbiosis and impairs intestinal health in adult zebrafish model.

Comparative biochemistry and physiology. Toxicology & pharmacology : CBP pii:S1532-0456(26)00304-2 [Epub ahead of print].

Sulfur species (SS) are well documented for their toxicity in respiratory and dermal systems; however, their effects on the gastrointestinal (GI) microbiome remain largely unexplored. This research investigated the impact of prolonged exposure to high concentrations of sodium metabisulfite (SM) and L-methionine (MET), administered individually and in combination, on gut microbial composition and intestinal health in zebrafish. High concentrations of SM and MET, particularly in combination, significantly reduced somatic growth and intestinal weight and altered the GI microbiome, as confirmed by 16S rRNA amplicon sequencing. The highest combination group showed the greatest relative enrichment of the family Enterobacteriaceae and the genus Enterobacter compared with the control. This dysbiosis-like condition coincided with elevated intestinal sulfide levels, increased total SS accumulation, and lower relative short-chain fatty acid (SCFA) levels. High SS exposure also impaired intestinal digestive enzymatic activity and triggered oxidative stress, evidenced by reduced antioxidant defenses. Histopathological evaluation further confirmed structural injury to the intestinal mucosa, including goblet cell hyperplasia. At the transcriptional level, high SS exposure dysregulated intestinal pro-inflammatory and pro-apoptotic gene expression and upregulated ptgs2a/COX-2 protein expression. Conversely, MET at low individual doses did not show these adverse changes and was instead associated with greater relative abundance of the commensal bacterium Cetobacterium and higher relative SCFA levels. It was also associated with higher antioxidant and digestive enzyme activity, lower MDA levels, and lower baxa expression. In conclusion, these results provide evidence that prolonged exposure to excess SS drives Enterobacteriaceae-dominated gut dysbiosis, redox imbalance, and mucosal inflammation in adult zebrafish.

RevDate: 2026-11-04

Zhu W, Yu X, Niu S, et al (2026)

Context-dependent and shared responses of the zebrafish gut microbiome to KH2PO4 enrichment.

Environmental research pii:S0013-9351(26)02430-8 [Epub ahead of print].

Anthropogenic phosphorus (P) enrichment is widespread in aquatic ecosystems, yet its effects on the functional potential of fish gut microbiomes remain poorly understood. We conducted a replicated 42-day experiment with zebrafish (Danio rerio), combining shotgun metagenomics with genome-resolved analyses to examine how sustained KH2PO4 exposure reshapes the gut microbiome in water-only and sediment-associated systems. Evidence for sediment-dependent modulation of microbial diversity and community composition was primarily observed during early exposure, indicating that these effects varied over time. Despite context-specific differences in functional profiles, both environmental backgrounds showed enrichment of genes or modules associated with P acquisition and turnover, selected carbon utilization pathways, energy transduction, and biosynthesis, accompanied by reduced potential for certain aromatic compound degradation and nitrate assimilation processes. Genome-resolved analyses further identified a Mycobacterium population that exhibited positive abundance responses to KH2PO4 addition in both environmental backgrounds. Its genomic traits related to P homeostasis, substrate utilization, and cellular biosynthesis provide candidate mechanistic explanations for this shared response. These findings reveal sediment-dependent responses of the zebrafish gut microbiome to extreme KH2PO4 input and identify microbial functional shifts that warrant further investigation as potential indicators of P-associated environmental disturbance.

RevDate: 2026-11-04

Rodrigues de Paula D, Vai A, Noberini R, et al (2026)

Optimized Super-SILAC Normalization Enables Enhanced Profiling of Histone Post-Translational Modification Changes Associated with Microbiota and Acute Inflammation.

Molecular & cellular proteomics : MCP pii:S1535-9476(26)00198-2 [Epub ahead of print].

The gut microbiota produces metabolites, such as short-chain fatty acids (SCFAs) that modulate histone acylation and serve as precursors for non-acetyl acyl marks, representing a mechanism in host-microbiome epigenetic crosstalk. However, the reliable quantification of these low-abundance modifications in complex tissues remains challenging. Here, we established an optimized, non-acetyl histone acylation-focused super-SILAC strategy for profiling histone post-translational modifications (HPTM) in the gut epithelium. We generated a functionally optimized internal standard from heavy-labeled colon cancer cells (HCT-116 and Caco-2) treated with propionate, butyrate, and crotonate, thereby enriching the standard in non-canonical acylations. This custom super-SILAC mixture enabled robust normalization and improved the quantification of low-abundance histone acylations in biological tissues. Our in vitro characterization revealed that SCFAs induced distinct and overlapping acylation profiles, with propionate leading to the most pronounced changes, including increased H3K14pr and H4K16pr. Applying this method to mouse models, we found that antibiotic-induced microbiota depletion led to the loss of marks associated with active chromatin (H3K14pr and H4K16pr) and a concurrent increase in heterochromatin-associated marks (H3K9me2/3). In contrast, Dextran Sodium Sulfate (DSS)-induced early-stage intestinal inflammation caused H4 hyperacetylation, increased H3K14pr, and reduced H3K27ac. In conclusion, the super-SILAC method enables robust identification and quantification of low-abundance histone acylations in cells and tissues under both physiological and disease conditions.

RevDate: 2026-11-04

Sun L, Li J, Zhu Y, et al (2026)

Alterations of fecal microbiome and metabolome in patients with diminished ovarian reserve.

Human reproduction (Oxford, England) pii:9012814 [Epub ahead of print].

STUDY QUESTION: Are there distinct variations in the gut microbiome and metabolism among infertile women diagnosed with diminished ovarian reserve (DOR), and how might the gut microbiome influence ovarian function?

SUMMARY ANSWER: In DOR patients, Hoylesella abundance correlated with anti-Müllerian hormone (AMH)/antral follicle count (AFC), and stearic acid was identified as a key differential metabolite that was associated with activated PI3K-Akt signaling.

WHAT IS KNOWN ALREADY: Accumulating evidence underscores the presence of a 'gut-ovary axis', highlighting a substantial interplay between the intestinal microbiome and ovarian function. However, the specific microbial and metabolic profiles characterizing infertile individuals with DOR remain largely uncharacterized.

STUDY DESIGN, SIZE, DURATION: This study was a cross-sectional observational study. We enrolled participants receiving frozen embryo transfer at the First Affiliated Hospital of Zhengzhou University between 1 October 2024, and 31 December 2025. Each participant was limited to a single frozen embryo transfer within the study.

A total of 190 participants were included: 91 with DOR and 99 with normal ovarian reserve (NOR). Clinical information and stool specimens were collected from every subject. Sequencing of 16S rRNA and non-targeted metabolomics were implemented to characterize the gut microbiome and metabolome, respectively. Molecular docking analysis and network pharmacology were then implemented to screen for overlapping genetic targets among DOR-associated targets and key metabolite-targeted proteins.

Relative to NOR controls, the DOR population exhibited significantly lower Gut Microbiota Health Index (P = 2.52 × 10-22) and higher Microbiota Dysbiosis Index (P = 8.31 × 10-10). The genus Hoylesella was significantly depleted in the DOR group (P = 0.018). Spearman analysis demonstrated that Hoylesella proportions were significantly positively correlated with AMH and AFC levels. Metabolomics analysis identified 243 differential metabolites across the study cohorts. Among these, four metabolites were associated with Hoylesella, and stearic acid exhibited high predictive performance (area under the curve = 0.89) for distinguishing DOR. Network pharmacology analysis of stearic acid and DOR identified five core targets: tumor necrosis factor, AKT serine/threonine kinase 1, SRC proto-oncogene, non-receptor tyrosine kinase (SRC), peroxisome proliferator-activated receptor gamma (PPARG), and epidermal growth factor receptor. Kyoto Encyclopedia of Genes and Genomes pathway enrichment indicated that the PI3K-Akt signaling pathway was the most significantly enriched.

LARGE SCALE DATA: Raw 16S rRNA sequencing data have been deposited in the NCBI Sequence Read Archive under BioProject accession PRJNA1444490. Untargeted metabolomics data have been deposited in MetaboLights under accession MTBLS14194.

The current investigation represents an initial effort to identify the alterations in intestinal microbes and associated metabolites in women with DOR-related infertility through 16S rRNA sequencing and untargeted metabolomics; however, experimental validation of the underlying mechanisms is still missing. Furthermore, the metabolomics analysis in this study did not further stratify by age.

Through immunological dysregulation and inflammatory reactions, aberrant alterations in key intestinal microbes and metabolic products likely participate in the underlying mechanisms of DOR. These results provide direction for further research into the causal connections between important microbial species and metabolites in patients with DOR.

FUNDING: This research was supported by grant 32271169 from the National Natural Science Foundation of China and the Henan Province Young and Middle-aged Health Science and Technology Innovation Leading Talent Project (Grant No. LJRC2024009).

DISCLOSURES: The authors have no conflicts of interest.

TRIAL REGISTRATION NUMBER: N/A.

RevDate: 2026-11-04

Passannante M, Laudisi A, Ghiso A, et al (2026)

Managing acute graft-versus-host disease after allogeneic stem cell transplantation.

Expert review of hematology [Epub ahead of print].

INTRODUCTION: Acute graft-versus-host disease (aGVHD) remains a leading cause of morbidity and non-relapse mortality after allogeneic hematopoietic cell transplantation. Despite progress in prophylactic strategies, its management remains challenging: corticosteroids are still the mainstay of first-line care, yet a substantial proportion of patients fail to achieve durable responses, underscoring the need for more effective and less toxic alternatives.

AREAS COVERED: This review outlines the current approach to aGVHD, from first-line management to steroid-refractory disease and beyond. It covers corticosteroid optimization, the established role of ruxolitinib in the steroid-refractory setting, and the use of extracorporeal photopheresis in selected patients. Cellular, microbiome-based, cytokine-directed, and regenerative strategies acting on complementary pathogenic mechanisms are also discussed. The literature was identified through a PubMed search using the terms 'acute graft-versus-host disease' and 'treatment,' including publications up to 30 June 2026, supplemented by manual screening of reference lists.

EXPERT OPINION: Ruxolitinib has reshaped the management of steroid-refractory aGVHD, although important unmet needs persist. Future progress will depend not only on new agents but on smarter use of existing options: minimizing steroid exposure, refining sequencing, and integrating combinations earlier. Biomarker-guided risk stratification may ultimately support a more individualized approach, improving disease control while limiting toxicity.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Whang SN, Wang X, Thomas-White KJ, et al (2026)

Large-scale metagenomic characterization of the vaginal microbiome and uropathogens in women with recent bacterial vaginosis and urinary tract infections.

Nature communications, 17(1):.

The vaginal microbiome (VMB) influences susceptibility to urogenital infections, yet large-scale, population-based species-level metagenomic studies are rare. We analyzed cross-sectional shotgun metagenomic profiles and linked clinical metadata from 10,003 women across the United States who self-reported recent bacterial vaginosis (BV), urinary tract infection (UTI), both, or neither. Here we show that women reporting recent BV or UTI displayed distinct community structures, including higher prevalence of VALENCIA CST-IV subtypes and significantly elevated alpha diversity compared with women who reported no prior diagnosis. Species-level Gardnerella profiling revealed that multiple Gardnerella species were enriched in the recent BV group but did not differ significantly between UTI and non-UTI groups, refining prior mechanistic hypotheses. Uropathogens such as E. coli, E. faecalis, and S. saprophyticus were detectable at higher prevalence and relative abundance in women who recently experienced UTI, including among participants who reported recent antibiotic use, consistent with the possibility of residual or recurrent vaginal colonization. These findings demonstrate that microbial signatures associated with recent BV and UTI remain detectable at population scale, provide a high-resolution reference for human vaginal metagenomics, and offer new directions for prevention strategies that consider the vaginal reservoir in recurrent urogenital infections.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Pomej K, Frick A, Scheiner B, et al (2026)

FMT combined with atezolizumab-bevacizumab in hepatocellular carcinoma refractory to immunotherapy: an open label, single-arm, phase II pilot study.

Nature communications, 17(1):.

Fecal microbiota transplantation (FMT) may help to overcome resistance to immunotherapy. In this single-center, single-arm phase II hypothesis-generating pilot study (FAB-HCC), we included 12 patients with advanced hepatocellular carcinoma (HCC) who progressed on atezolizumab plus bevacizumab. Patients received a single FMT via colonoscopy from a donor with HCC who responded to anti-PD-1 treatment or a healthy donor, combined with atezolizumab plus bevacizumab. The primary endpoint was safety as measured by incidence and severity of treatment-related adverse events (TRAEs). Secondary endpoints included radiological response and survival. Grade 3-4 TRAEs included arterial hypertension (n = 5) and proteinuria (n = 3), both related to bevacizumab, and diarrhea (n = 1), related to FMT. No serious TRAEs were observed. Objective response rate was 33% (n = 4/12) and median progression-free survival was 6.9 (95%CI, 3.0-10.8) months. Following FMT, recipient microbiome composition appeared more similar to that of the donor, and healthy donor FMT seemed to be associated with higher engraftment. FMT appeared to be associated with enrichment of response-associated and loss of deleterious gut bacteria. Circulating PD-1[+]CD8[+] T cells decreased and CD32b[+]CD14[high]CD16[low] monocytes increased following FMT plus immunotherapy. Phage-display immunoprecipitation sequencing revealed that antibody repertoire stability, rather than global diversity or composition, changed over time. Taken together, FMT combined with atezolizumab plus bevacizumab was safe and associated with a high response rate in patients with atezolizumab plus bevacizumab-refractory HCC. Given the limited sample size, these findings need cautious interpretation and confirmation in larger, adequately powered trials. ClinicalTrials.gov identifier: NCT05750030.

RevDate: 2026-11-04

Arnold J, McClure S, Glazier J, et al (2026)

Engineering commensal Lachnospiraceae for programmable therapeutic delivery in the mouse gut.

Nature microbiology [Epub ahead of print].

Engineered native gut bacteria could offer persistent, programmable therapeutic delivery in the gut, but many dominant taxa remain genetically intractable. Members of one such family of obligate anaerobic Clostridia, Lachnospiraceae, are prevalent in the human gut microbiome and produce metabolites linked to intestinal and metabolic health. Here we report a modular toolkit for engineering Lachnospiraceae, including constitutive and inducible expression, chromosomal integration and secretion systems. Applying this toolkit to gut native Coprococcus comes, we programmed the secretion of cytokine interleukin-22 (IL-22) in the mouse intestinal tract, where it induces epithelial defence transcriptional programmes. In a mouse model of metabolic dysfunction-associated steatotic liver disease, IL-22-secreting C. comes improved glucose homeostasis, reduced systemic endotoxemia and attenuated hepatic steatosis. This work demonstrates that native Lachnospiraceae can be genetically programmed to modulate host metabolic and immune physiology. The toolkit provides a foundation for the development of Lachnospiraceae-derived engineered therapeutics and for dissecting causal relationships between commensal gene programmes and host physiology.

RevDate: 2026-11-04

Nuwer R (2026)

Six highlights from Parkinson's disease research.

Nature, 659(8139):S16-S17.

RevDate: 2026-11-04

Nuwer R (2026)

How a once-controversial idea is advancing understanding of Parkinson's disease.

Nature, 659(8139):S9-S11.

RevDate: 2026-11-04

Wang D, Goumagias A, Andreu-Sánchez S, et al (2026)

Microbiome-wide PheWAS links gut microbial SNVs to health and exposures.

Nature [Epub ahead of print].

Alterations in the microbial composition of the human gut have been associated with a wide range of chronic diseases[1,2]. Yet species-level composition alone can obscure extensive within-species genetic diversity and functional variation. This has driven a shift towards strain-resolved, genetic-level analysis of the microbiome, leveraging microbial genetic variation to identify disease-relevant genes and pathways[3-6]. Here we conducted a phenome-wide association study (PheWAS) analysing 12.8 million gut microbial single-nucleotide variants (SNVs) with 244 host health phenotypes and environmental exposures in 10,781 individuals from 6 independent cohorts. We identify 940 independent associations across 69 host factors, including age, sex and cardiovascular and metabolic parameters. Structural analyses identified host-phenotype-associated SNVs in functionally important regions of proteins, findings that inform mechanistic hypotheses about how microbial genetic changes relate to environmental and host physiological factors. For example, we identified an age-associated SNV in Faecalibacterium prausnitzii that affects an amino acid within the protein pocket that binds glutathione. To support future efforts, all study summary statistics are provided in an online catalogue (https://fulab.web.rug.nl/SNV-MWAS/). Together, these results identify new biological connections between the human host and microbial genetic variants at base pair resolution and provide a resource for hypothesis generation that will aid future understanding of the strain-level functionality of the gut microbiota.

RevDate: 2026-11-04

Peixoto RS, Voolstra CR, Duarte G, et al (2026)

Global change reshapes marine microbial communities, functions and One Health outcomes.

Nature reviews. Microbiology [Epub ahead of print].

Marine microorganisms underpin primary production, biogeochemical cycling and host-associated symbioses, supporting climate regulation, coastal protection, fisheries and other ecosystem services. Rapid global change, including ocean warming and marine heatwaves, acidification, deoxygenation, eutrophication, pollution and overuse reshape microbial communities and their functions across marine habitats. These changes can alter carbon, nitrogen and sulfur cycles, promote microbialization and harmful algal blooms, disrupt host-microbiome associations and modify pathogen and antimicrobial resistance dynamics, collectively amplifying the ecological and societal impacts of global change. This Review frames marine microbiomes as cross-scale mediators that translate external pressures, including climate change, pollution, eutrophication and habitat degradation, into altered microbial metabolism, biogeochemical fluxes, host-associated health outcomes, ecosystem service consequences and broader One Health risks. We synthesize shared mechanisms and cross-habitat patterns, highlight cases in which microbiome interventions and stewardship could mitigate impacts and/or accelerate recovery, and outline management options ranging from the reduction of local stressors to emerging microbiome stewardship approaches in ecosystem restoration. Building upon this, we outline pathways for embedding marine microbiome science into globally coordinated One Health strategies, operational management protocols and financing frameworks that align economic incentives with long-term ecosystem and public health outcomes.

RevDate: 2026-11-04
CmpDate: 2026-11-05

Smoglica C, Angelucci S, Di Tana F, et al (2026)

Fecal microbiome and resistome in the long-term care of an Apennine wolf (Canis lupus italicus).

BMC veterinary research, 22(1):.

The Apennine wolf (Canis lupus italicus) increasingly inhabits human modified landscapes, where exposure to anthropogenic environments may influence microbial circulation and antimicrobial resistance. Wildlife Rehabilitation Centers provide opportunities to describe microbial and resistance gene profiles in animals at the human-wildlife interface; however, longitudinal shotgun metagenomic data from this subspecies during rehabilitation remain scarce. A juvenile male wolf admitted to a Wildlife Rehabilitation Center after traumatic injury and treated with multiple antibiotics was sampled at admission (T0) and after 11 months of rehabilitation (T1) in this case report. Fecal shotgun metagenomic sequencing was used to describe microbial communities, reads assigned to taxa of veterinary or public health interest, and antimicrobial resistance genes. Bacterial diversity increased from T0 to T1 with a shift from an Enterobacterales dominated profile to more diverse communities. Reads assigned to bacterial and viral taxa of potential health relevance were detected at both time points. The tools CARD-RGI identified 444 antibiotic resistance genes at T0 and 417 ARGs at T1, mainly associated with efflux pumps and β-lactamases. Genes related to Highest Priority Critically Important Antimicrobials-including mcr variants, van clusters, and oxazolidinone resistance determinants-were identified. This single-animal report provides baseline information on microbiome and resistome modification during wolf rehabilitation and suggests larger longitudinal studies and biosecurity awareness in Wildlife Rehabilitation Centers.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Ofordile O (2026)

Prevotella stercorea links gut microbiome ecology to respiratory infection protection through host-context-dependent, richness-independent associations.

BMC medical genomics, 19(1):.

BACKGROUND: Using a longitudinal cohort of 633 Gambian children (IHAT-GUT, NCT02941081), we investigated two ecologically distinct pathways potentially linking Prevotella stercorea abundance to infection risk: a community-mediated pathway operating through overall gut microbiome richness, and a species-specific pathway operating independently of it.

METHODS: We modelled P. stercorea abundance in relation to gut microbiome richness, adverse-event incidence (diarrhoea, acute respiratory infection [ARI], fever), inflammatory biomarkers (CRP, AGP; measured at enrolment [D1] only), and weight-for-age z-score (WAZ), using richness-mediation analysis, negative binomial and joint-species models, and WAZ-stratified interaction models, with Benjamini-Hochberg correction applied within each family of related tests.

RESULTS: P. stercorea abundance positively predicted gut microbiome richness, consistent with a role in community-level colonisation resistance for enteric outcomes. Its association with reduced ARI persisted largely unchanged after richness adjustment, consistent with a richness-independent, species-autonomous pathway. WAZ was uncorrelated with microbiome richness within strata, consistent with WAZ serving as a proxy for host immune-metabolic reserve rather than a determinant of microbiome composition. In Low-WAZ children, P. stercorea abundance at Day 1 was associated with suppressed CRP; in High-WAZ children, elevated Day 1 inflammation predicted subsequent P. stercorea abundance at Day 85. ARI and fever protection was richness-independent and concentrated in Low-WAZ children (q≤ 0.006); P. copri did not retain an independent protective association when modelled jointly with P. stercorea (q = 0.381 vs. q = 0.016).

CONCLUSIONS: These findings are consistent with a richness-independent, host-context-dependent association between P. stercorea abundance and respiratory infection risk. Given the observational design, causal and mechanistic interpretations remain hypothesis-generating; experimental validation and independent replication are needed before translational application can be considered.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Harris W, Lim YJ, Kim H, et al (2026)

The endophyte Moesziomyces antarcticus RS1 improves drought stress tolerance and yield traits in rice.

Environmental microbiome, 21(1):.

BACKGROUND: Ongoing climate change drives drought events that threaten crop yields worldwide. Traditionally, the focus has been on plant breeding to mitigate losses due to stress; however, this approach fails to leverage the resources available within the holobiont. Microbial treatments have been shown to confer drought tolerance by altering phytohormone levels, enhancing nutrient acquisition, and improving water retention in their plant hosts. However, the role of core seed-associated endophytic fungi in stress resilience remains underexplored.

RESULTS: Using Moesziomyces antarcticus RS1, which was previously identified as a core fungus in wild and domesticated rice seed microbiomes, we revealed the functional roles of a core microbe in the host plant's physiology. M. antarcticus RS1 displayed nutrient- and osmotic stress-responsive dimorphism, consistent with adaptive persistence in the seed endosphere. M. antarcticus RS1 inoculation on rice seed significantly improved yield traits by increasing grain quantity and biomass. Notably, M. antarcticus RS1 seed-inoculated rice performed better under PEG-induced osmotic stress, which was associated with increased osmoprotectant levels and growth benefits observed under PEG-treated and untreated conditions. Treatment of M. antarcticus RS1 was associated with increases in drought-related class 2 and class 3 Late Embryogenesis Abundant gene expression in rice, including a suite of RAB dehydrins.

CONCLUSIONS: These findings establish M. antarcticus RS1 as a core seed endophyte that improves rice drought tolerance and productivity, positioning it as a novel bioinoculant for sustainable agriculture, particularly in water-limited environments.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Hao Y, Li Y, Wang Y, et al (2026)

Chicken farming may influence the gut antibiotic resistome and microbiome of workers: a metagenomic analysis.

Animal microbiome, 8(1):.

In the context of the broad utilization of antibiotics in poultry breeding, an increasing number of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) are accumulating in chicken feces, which presents a latent danger to workers' health. However, few studies have explored the effect of chicken rearing on the microbial flora of workers. In this study, using metagenomic analysis techniques, a panoramic view of the intestinal microbiome and resistome across 40 chickens, 31 farm workers and 23 control villagers was obtained. The results showed that the chicken gut harbored more pathogens than the human gut. ESKAPE pathogens showed a stepwise increase from villagers to workers to chickens. The level of Streptococcus pneumoniae in workers was higher than that in villagers, indicating potential pathogen exposure risks. Chickens shared more ARGs with workers than villagers. Significantly higher abundances of 125 ARGs were detected in chicken samples compared to human samples. Among these, 22 ARGs were more abundant in worker samples than in villager samples. Metagenome-assembled genome (MAG) analysis revealed that 99 ARGs were annotated in human MAGs, predominantly in Escherichia coli (43 ARGs) and Klebsiella pneumoniae (22 ARGs). Co-occurrences of ARGs and mobile genetic elements (MGEs) were observed in E. coli and K. pneumoniae, with the transposon gene tnpA being carried by multiple bacteria. Co-localization of ARGs (APH(3'')-Ib, APH(6)-Id) and MGE (IS91) in the MAG (Parasutterella gallistercoris) of workers was detected, while these two ARGs showed increasing abundance from villager to worker to chicken samples. This study indicated that chicken guts serve as important reservoirs of ARB and ARGs, which may influence the gut bacterial health of workers. Therefore, it is necessary to strengthen the management of antibiotic use in chicken farms and the health monitoring of relevant populations.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Nofinska BA, Mizutani S, Salim F, et al (2026)

Gut microbial and metabolic biomarkers for early-onset colorectal cancer.

Microbiome, 14(1):.

BACKGROUND: Early-onset colorectal cancer (EO-CRC) is a growing global health challenge with poorly understood etiology. While gut microbiota and metabolites are implicated in colorectal carcinogenesis, EO-CRC-associated signatures remain poorly characterized. This study presents the first large-scale multi-omics analysis in Japan cohort to characterize gut microbial and metabolic features of EO-CRC, with cross-cohort validation in an independent China cohort.

RESULTS: We enrolled 510 participants (EO-CRC n = 120, late-onset CRC [LO-CRC] n = 282, young healthy controls [yHC] n = 59, old healthy controls [oHC] n = 49); after age- and sex-matching, 324 samples were analyzed using metagenomics, metabolomics, and quantitative polymerase chain reaction (qPCR). Fourteen species formed a shared CRC-associated microbiome core enriched in both EO-CRC and LO-CRC relative to age-matched controls, of which seven were reproducible across both Japan and China cohorts. Beyond this core, 34 and 21 species were enriched exclusively in EO-CRC and LO-CRC, respectively. Among EO-CRC-specific virulence findings, the bft gene of enterotoxigenic Bacteroides fragilis, fadA of Fusobacterium nucleatum, and bai operon genes were enriched in EO-CRC, with cross-cohort validation for fadA and bai operon, and stage-specific enrichement of deoxycholic acid at Stage 0 providing preliminary metabolomic support. Targeted clbP qPCR revealed enrichment of colibactin-producing Escherichia coli specifically in EO-CRC against a background of age-increasing carriage. Metabolomic profiling identified kynurenine enrichment and depletion of vitamin B-related metabolites (pyridoxine, riboflavin, and nicotinamide) as EO-CRC-specific findings; LO-CRC showed distinct enrichment of carnitine, succinate, and spermine with relative butyrate depletion. The choline degradation pathway was enriched specifically in EO-CRC based on Enteropathway analysis. Species-based random forest classifiers distinguished EO-CRC from controls (AUPRC = 0.828; SD = 0.013; 95% CI 0.739-0.909) and generalized robustly to an independent cohort (AUPRC = 0.817; 95% CI 0.717-0.894), substantially outperforming functional gene profiles in cross-cohort settings. Within the Japan cohort, adding metabolomics provided modest additional discriminative value.

CONCLUSIONS: These findings identify a shared CRC microbiome core reproducible across age groups and cohorts, alongside EO-CRC-specific signatures encompassing enrichment of virulence-associated genes (bft, fadA), colibactin-producing E. coli (clbP), secondary bile acid biosynthetic genes (bai operon), and choline degradation capacity, as well as distinct metabolic perturbations including kynurenine enrichment and vitamin B-related metabolite depletion. Species-based classifiers generalize well across age groups and cohorts, with metabolomics providing complementary discriminatory value. All findings represent cross-sectional associations; longitudinal studies are needed to establish temporal ordering and evaluate clinical utility as non-invasive biomarkers for EO-CRC. Video Abstract.

RevDate: 2026-11-05

Dickson BS, Bär AK, A Simoes-Barbosa (2026)

Microbiome-Dependent Modulation of Trichomonas vaginalis Cytotoxicity and Remodeling of the Parasite Secretome.

Molecular microbiology [Epub ahead of print].

Trichomonas vaginal is a prevalent sexually transmitted parasite whose pathogenicity is shaped by interactions with the vaginal microbiome. While previous studies have shown that host-protective lactobacilli inhibit parasite adhesion and that dysbiotic bacteria enhance pathogenic traits, the extent to which these vaginal bacteria modulate parasite-induced cytotoxicity and its underlying molecular mechanisms remain unclear. Here, we investigated the impact of Lactobacillus gasseri and Gardnerella vaginalis, as representative bacteria of the vaginal microbiome in eubiosis and dysbiosis, respectively, on parasite-induced cytotoxicity and the associated changes in the parasite secretome. Using physiologically relevant epithelial cell models, we show that vaginal L. gasseri strongly inhibits parasite-induced cytotoxicity in a strain- and an exquisite concentration-dependent manner, whereas G. vaginalis enhances cytotoxicity synergistically with the parasite. Proteomic analysis of the T. vaginalis G3 secretome revealed a conserved core set of secreted proteins, including hydrolases and candidate virulence factors, alongside strain-specific variation. Importantly, co-incubation with vaginal bacteria altered the composition and abundance of a few secreted proteins, including proteases and other enzymes implicated in host and bacteria interactions and nutrient acquisition. Together, our findings demonstrate that T. vaginalis cytotoxicity is a context-dependent phenotype shaped by microbial interactions and linked to dynamic remodeling of the parasite secretome. This work highlights the importance of bacterial interactions in modulating parasite pathogenicity and identifies parasite secreted factors as potential candidates that mediate microbiome-dependent pathogenicity.

RevDate: 2026-11-05

Patel A, P Jain (2026)

Why Gut-Brain Axis Therapies Fail in Clinical Translation: The Case for Endophenotyping and Longitudinal Trial Design.

Although there is strong preclinical evidence for the involvement of the gut-brain axis in neuroimmune, metabolic and behavioural regulation, translation of gut-centric therapies to consistent clinical outcomes is challenging. Although probiotics, postbiotics, faecal microbiota transplants and mucosal anti-inflammatory treatments show therapeutic promise in animal studies, clinical trials often provide inconsistent or unclear results. One major reason for this translational gap is the biological heterogeneity hidden behind broad diagnostic categories. Individuals with the same clinical features can vary considerably in gut barrier function, mucosal immune responses, microbial community composition, microbial metabolite production, and systemic inflammatory pathways. Therapies targeting specific gut-brain pathways might, therefore, be tested in groups that include individuals without the relevant biological abnormality, potentially decreasing measurable therapeutic effects. There is a shift away from diagnosis-based recruitment toward mechanism-based endophenotyping. The integration of standardised composite inflammatory and metabolic endophenotypes with longitudinal host and microbial biomarkers could help to define physiologically meaningful therapeutic cohorts and differentiate between target engagement and clinical outcomes. Future studies should include initial stratification, ongoing biological sampling, and prospective validation of biomarkers that predict treatment response. Such an approach may turn seemingly ineffective therapies into mechanistic findings to identify patients most likely to benefit from changes in microbial, metabolic, or mucosal factors. Therefore, accurate endophenotyping may represent an important tool to bridge the translational gap from promising gut-brain studies to practical therapeutic interventions.

RevDate: 2026-11-05

Chen J, Zhang S, Zhu Y, et al (2026)

Engineered Chiral Probiotics Ameliorate MASH via Gut-Liver Axis.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Epub ahead of print].

The global epidemic of metabolic dysfunction-associated steatohepatitis (MASH) is escalating without effective therapies. This study identified a significant depletion of the gut commensal bacterium Faecalibacterium duncaniae (F. duncaniae) as a core feature of MASH. To overcome the poor colonization by traditional probiotics in inflammatory environments, we engineered a living microbial therapeutic by incorporating chiral gold nanozymes onto F. duncaniae. We discovered that biological performance is enantiomer-dependent: the right-handed nanozyme (D-Au) serves as a superior ROS-scavenging shield, protecting the probiotic from oxidative assault and enhancing its colonization in the inflamed gut. In mouse models of MASH, this engineered probiotic (F@D-Au) reversed disease progression, ameliorating steatosis, inflammation, and fibrosis. It further restored systemic homeostasis, rectifying dysbiosis, metabolic disturbances, and-notably-MASH-associated cognitive impairment. Metabolomic analyses revealed that this multi-organ benefit was linked to the restoration of key microbial metabolites, including kynurenic acid and linoleic acid. Our work establishes a new class of chirality-enhanced living therapeutics that precisely remodel the gut-liver axis, offering a transformative strategy for treating MASH and its complications.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Blumstein DM, Patel A, Schiro G, et al (2026)

Biogeographic Barriers and Gut Microbiome Turnover Across the Peromyscus maniculatus Species Complex.

Molecular ecology, 35(21):.

Biogeographic barriers are fundamental in shaping the distribution of animals and plants, yet the role of discrete landscape features in constraining microbial dispersal remains poorly understood. Identifying the barriers that partition gut microbial communities is essential for modelling the distribution of hosts and their symbionts across physical space and evolutionary time. The deer mouse (Peromyscus maniculatus species complex), which inhabits nearly all terrestrial environments in North America, provides an ideal model for testing these biogeographic drivers of the mammalian gut microbiome. Using NSF NEON biorepository samples, we characterized the gut microbiomes of 13 populations across the contiguous United States using full-length 16S rRNA long-read sequencing. The presence or absence of microbial taxa was best explained by eastern versus western regions compared to habitat or climate, suggesting a role of large fluvial systems as discrete barriers to microbial transmission, likely due to restricted host dispersal. Although we observed a consistent distance-decay relationship across the continent, our results suggest that the Mississippi River is associated with increased microbial species turnover, with dissimilarity across the river exceeding levels predicted by geographic distance alone. Furthermore, we identified specific microbial lineages that exhibit varying patterns of isolation by distance across the continent, suggesting a gradient in microbial transmission patterns ranging from lineages that are freely shared across space to those that are dispersal limited. Together, these findings suggest that the gut microbiome may act as a bioindicator of landscape-level ecological connectivity, revealing discontinuities in microbial transmission associated with large-scale landscape barriers even among closely related host populations that lack reproductive barriers.

RevDate: 2026-11-05

Zhai J, Liu BH, Guo LY, et al (2026)

GutBiomeDB: an integrated human gut microbiome database of 168 464 samples.

Nucleic acids research pii:9013047 [Epub ahead of print].

The gut microbiome plays an important role in maintaining human health. Despite the rapid growth of literature and publicly accessible data on the gut microbiome, a large-scale, well-curated database integrating a unified matrix with multiple analytical tools is still lacking. Here, we introduced GutBiomeDB, a comprehensive database and analysis platform for the human gut microbiome. GutBiomeDB contains 168 464 samples from 482 BioProjects, spanning 72 countries, 224 disease conditions, and seven life stages. To improve the reusability and accessibility of data, the uniformly processed taxonomic profiles generated by Abdill et al. were reused without reprocessing to construct a matrix of 4680 taxa and 3142 genera, and disease, life-stage, sex, and geographic metadata were manually curated by our team. Additionally, GutBiomeDB offers four tools for in-depth analysis: "Differential Analysis" for comparing diversity and abundance of user-selected cohorts and performing random-effects meta-analysis across projects; "Interaction Network" for comparing disease and healthy-control co-occurrence networks; "Lifecycle Atlas" for visualizing genus trajectories across seven life stages; and "Health Index" for searching similar samples and scoring uploaded genus profiles. GutBiomeDB serves as a versatile and valuable resource for advancing a broad spectrum of gut microbiome research and clinical relevance. GutBiomeDB is freely accessed at https://gutbiomedb.online.

RevDate: 2026-11-05

Nieciecki V, Edwards E, Seitz VA, et al (2026)

Forensically significant microbial community responses to aboveground cadaver decomposition in Southeast Texas soils.

Journal of forensic sciences [Epub ahead of print].

During vertebrate decomposition, a purge of nutrient-rich fluids enters the surrounding soil producing a localized nutrient hotspot. The composition of microbial communities at the soil surface is known to predictably change in response to this influx of decomposition fluids over time. However, the depth to which these compositional changes permeate the soil near a decomposing human cadaver and whether specific microbial members exhibit spatial responses to aboveground decomposition both represent significant knowledge gaps. In this study, we longitudinally sampled forest soils adjacent to decomposing human cadavers and from nearby control sites in 2 cm increments to a depth of 10 cm. Soil samples were collected during purge, post purge, and the dry remains stage of decomposition over three seasons at Sam Houston State University's Southeast Texas Applied Forensic Science facility. We detected season-dependent microbial community responses in the upper 0-4 cm of soils adjacent to decomposition fluids. On average, microbial community diversity decreased and community composition became increasingly different in comparison to nearby control soils. Cadaver soils remained impacted for the duration of the 4.5-month spring trial and 1.5-month summer trial. Terriglobus, Acidisoma, Ignatzschineria, and Pandoraea may represent forensically informative biological markers, as they significantly increased in response to decomposition. We observed a more limited, yet still detectable response in the lower 6-10 cm of soil. In addition to improving our understanding of decomposition ecology, we anticipate that incorporating these findings into forensic investigations could help strengthen postmortem interval model estimation and better inform investigative sampling practices.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Rocchetti A, Gotta F, Bottino P, et al (2026)

Development and expert appraisal of a lifestyle questionnaire for microbiome host metadata.

Frontiers in cellular and infection microbiology, 16:1932122.

INTRODUCTION: Lifestyle information can help contextualize variation in the human gut microbiome, but its collection and operational definitions differ across studies. We developed a candidate questionnaire combining diet, physical activity and sleep for microbiome host metadata and undertook an initial appraisal by Italian experts. Candidate content was informed by a focused narrative literature appraisal and established lifestyle-assessment frameworks.

METHODS: Seventeen experts were invited and nine responded (53%). In a single anonymous rating round, experts assessed the relevance of 37 candidate items on a five-point scale. The prespecified agreement criterion was at least 70% of respondents assigning a rating of 4 or 5, corresponding to at least seven of nine experts.

RESULTS: Twenty-five items (67.6%) met this criterion: 18 of 23 dietary items (78.3%), six of eight physicalactivity items (75.0%), and one of six sleep items (16.7%). Twelve items remained exploratory.

DISCUSSION: These findings provide an initial prioritization of candidate lifestyle metadata within an Italian specialist network. They do not establish a stable iterative Delphi consensus, instrument reliability, construct validity, or associations between questionnaire responses and microbiome outcomes. Participant testing, operational refinement and empirical evaluation are required before research deployment or potential use in fecal microbiota transplantation donor characterization.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Ge M, Chen Q, Wang Y, et al (2026)

Plant physiological control of root microbiome assembly and feedback under environmental stress.

Frontiers in microbiology, 17:1974097.

Root-associated microbiomes contribute to plant nutrition, defense and stress tolerance, but their variable responses across hosts and environments limit the predictability of microbiome-based interventions. This review examines plant physiological regulation of root microbiome assembly and feedback under environmental stress. Evidence from plant and microbial genetics, defined-metabolite assays, synthetic communities and physiological analyses links changes in carbon allocation, nutrient status, hydraulics, redox balance and hormone-immune signaling to root-derived outputs and microbial responses. These outputs influence microbial sensing and resource use, while host immune and metabolic conditions help regulate colonization and persistence. Flavonoid-NodD signaling, strigolactone-induced mycorrhizal fungal responses and coumarin-mediated selection illustrate comparatively well-resolved transitions; the roles of stress-associated purines, nucleotides and compatible solutes remain more context dependent. However, microbial enrichment and metabolite associations alone do not establish plant-controlled recruitment or benefit. Stronger evidence connects plant regulation, microbial response mechanisms and physiological outcomes through causal perturbations. Microbial activity can modify host physiology, although evidence that the altered host state subsequently redirects community assembly remains limited. We integrate these illustrative findings into a framework linking physiological regulation, root outputs, microbial responses, establishment and feedback. This synthesis identifies testable connections for improving microbiome interventions under stress. Translation requires attention to plant carbon and immune costs, competition within resident communities, and validation across host genotypes and environments.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Rawat A, Prasad N, Rawat P, et al (2026)

Beyond solute clearance: the kidney-gut-immune-nutrition axis in hemodialysis and peritoneal dialysis and a proposed framework for integrated risk stratification.

Frontiers in nutrition, 13:1931760.

Kidney disease affects approximately ~850 million people globally, with millions dependent on dialysis as life-sustaining renal replacement therapy. While dialysis corrects solute accumulation and fluid overload, it incompletely replicates normal renal physiology and introduces its own biological stressors, perpetuating a cycle of systemic dysfunction that extends well beyond the kidney. Central to this dysfunction is the kidney-gut-immune-nutrition (KGIN) axis: a bidirectional network linking renal clearance, intestinal microbial homeostasis, immune regulation, and nutritional metabolism. In end-stage renal disease, each component of this axis is simultaneously disrupted and becomes a driver of further deterioration. Uremic toxin accumulation remodels the gut microbiome toward a dysbiotic state, characterized by depletion of short-chain fatty acid-producing organisms and expansion of pathobionts. The resulting compromise of intestinal barrier integrity permits systemic translocation of lipopolysaccharide and other microbial products, sustaining chronic low-grade inflammation and a paradoxical state of immune dysfunction marked by heightened inflammatory signaling alongside impaired pathogen defense. These perturbations converge on nutritional status, driving protein-energy wasting through catabolic cytokine signaling, anorexia, and suppression of anabolic pathways, with sarcopenia reported in several dialysis cohorts to progress at two to three fold faster than age related muscle loss. Hemodialysis and peritoneal dialysis produce distinct patterns of axis disruption: hemodialysis is characterized by intermittent toxin peaks, bioincompatible membrane-driven complement activation, and more severe dysbiosis, whereas peritoneal dialysis introduces continuous peritoneal glucose exposure and a unique local immune microenvironment, with generally slower decline in residual kidney function. These modality-specific differences translate into divergent cardiovascular, infectious, and nutritional risk profiles that are incompletely explained by traditional clinical variables. Emerging multi-omics approaches, including metagenomics, metabolomics, and high-throughput immune profiling, are beginning to characterize axis disruption with unprecedented resolution, enabling in-depth characterization of host-microbiome-immune identification of patient subgroups with distinct mechanistic signatures that cannot be captured by single domain analysis alone. To bridge this analytical capability with clinical practice, we propose the Microbiome-Immune-Nutrition (MIN) Index, a conceptual, hypothesis generating composite biomarker framework designed to synthesize data across all three axis domains and stratify patients by the severity of disruption to guide targeted, personalized interventions, which remain to be demonstrated through prospective validation studies. Therapeutic strategies targeting the axis, including dietary fiber and plant-based approaches, synbiotics, fecal microbiota transplantation, advanced dialysis modalities, and omega-3 and polyphenol supplementation, show mechanistic promise but require larger, better-designed trials with hard clinical endpoints before routine clinical adoption. Standardization of microbiome research methodology, investment in longitudinal multi-omics cohorts, and development of international collaborative consortia are research priorities that will be essential to translate mechanistic insights into improvements in survival and quality of life for patients on maintenance dialysis.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Hartvigsson O, Ross AB, Moesta A, et al (2026)

Metabolomic and lipidomic signatures of aging in cats reveal shifts in energy metabolism and inflammation: an 11-year longitudinal study.

Frontiers in veterinary science, 13:1953163.

BACKGROUND: Aging encompasses multiple biochemical changes, some of which may be associated with the development of age-related diseases. The dynamics of aging in relation to metabolism in cats has not been established and understanding this could identify targets for early intervention.

OBJECTIVES: The aim of this longitudinal study was to identify changes in the plasma and fecal metabolome and lipidome of cats from 1 to 11 years of age.

METHODS: Twenty-one cats from a research colony had plasma and fecal samples collected yearly between one and 11 years of age. Clinical biomarkers were measured in serum, while plasma and fecal metabolomics and lipidomics were measured using mass spectrometry. Data were analyzed using repeated measures-ANOVA Simultaneous Component Analysis.

RESULTS: Two metabolic trajectories were observed: one linear, suggestive of progressive accumulation of metabolic alterations with aging, and a U-shape, suggestive of more complex metabolic changes over time. Three themes emerged: inflammaging (linear decrease of plasma albumin:globulin ratio, increase in fecal inflammatory mediators), mitochondrial dysfunction (linear increase of plasma long-chain phosphatidylcholines, U-shape for plasma hydroxy-butyric acids and lactic acid, inverse U-shape for fecal coenzyme Q), and a possible link to an aging gut microbiome (tryptophan pathway with linear increase of plasma kynurenine versus decrease of fecal anthranilic acids).

CONCLUSION: Metabolic changes in plasma and feces support the inflammaging hypothesis for cats, alongside mitochondrial dysfunction, and possible changes to gut microbial metabolism. Clear metabolic shifts between 6 and 8 years of age suggest that early intervention could help to support a healthy aging trajectory in cats.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Furuta S (2026)

Editorial: Roles of metabolism, immunity, and microbiome in the pathophysiology of the breast cancer microenvironment.

Frontiers in oncology, 16:2014425.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Dash D, Rajak M, Manothiya P, et al (2026)

Microbiome-mitochondria crosstalk in neuro-oncology: molecular mechanisms, immunometabolic reprogramming, and therapeutic opportunities.

Frontiers in microbiomes, 5:1983174.

Although the gut microbiome is increasingly recognized as an important regulator of metabolic, immune, and neurophysiological functions, and mitochondrial dysfunction is considered a hallmark of metabolic flexibility, oxidative stress, and resistance to therapy in cancers, the role of microbiome-derived cues and mitochondrial processes in brain tumors remains poorly understood. The Microbiome-Gut-Brain-Mitochondria Axis in Neuro-Oncology provides a framework for understanding metabolism and immunity in neuro-oncology by highlighting this axis and emphasizing its role in glioblastoma. Metabolites produced by the microbiome, including short-chain fatty acids, bile acid metabolites, tryptophan metabolites, and other microbial compounds, have been shown to affect the immune system, barrier function, cellular metabolism, and neural signaling. Mitochondria are capable of functioning as intracellular communication mechanisms that will help to decipher those signals in order to create energy, ROS, calcium communication, biogenesis of mitochondria, quality control, and apoptosis. These processes may contribute to metabolic plasticity in glioblastomas, including glycolytic, oxidative phosphorylation, and amino- and lipid-metabolic adaptations, mitochondrial transfer, adaptation to hypoxia, tumor cell stemness, and immune suppression in the tumor microenvironment. The article also discusses the relationships between microbiome-derived cues, mitochondria, and tumor-associated immune populations. Microbiome-derived and mitochondrial biomarkers, combined with multi-omics approaches, single-cell technologies, spatial biology, artificial intelligence, and new experimental models, may help to identify relevant microbiome-mitochondria signatures. Modulating the microbiome, mitochondria, and combination therapies appears promising for glioblastomas. However, the causative link between microbiome-derived mitochondrial mechanisms and human brain tumors remains unproven. The necessity of prospective and mechanistic studies of the microbiome, mitochondria, metabolism, immunity, and clinical aspects arises.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Du X, Zhang H, Tian W, et al (2026)

Precision nutrition in companion animals: a response-based framework linking dietary strategies, metabolic function, and measurable clinical outcomes.

Frontiers in veterinary science, 13:1914947.

Population-level nutrient recommendations provide the foundation for complete and balanced diets in dogs and cats, but they do not fully account for inter-individual variation in nutritional requirements, metabolic phenotypes, and dietary responses. Precision nutrition provides a response-guided framework that integrates individual characteristics with monitored dietary responses to refine nutritional management through repeated reassessment. This review examines the conceptual framework, host determinants, clinical applications, and translational challenges of precision nutrition in companion animals. Obesity, chronic enteropathy, chronic kidney disease, and urolithiasis are discussed as representative clinical models in which dietary interventions can be linked to measurable outcomes and adjusted according to individual response. Current clinical implementation is informed primarily by phenotypic assessment, dietary history, routine clinical and biochemical measures, and longitudinal monitoring, with biomarkers such as serum phosphate providing direct guidance in specific clinical contexts. Microbiome and metabolomic profiles, selected molecular biomarkers, and digital monitoring tools, such as smart feeders and activity monitors, may provide complementary information, whereas multi-omics integration and AI-assisted prediction remain largely exploratory. Further progress will require standardized species-specific datasets, prospective validation of predictive biomarkers, reliable digital measurements, and externally validated, interpretable models that demonstrate added value beyond established clinical assessment. Overall, precision nutrition represents an iterative, response-guided framework in which individual characteristics and monitored outcomes inform dietary selection and adjustment over time.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Cheng C, Xiao XP, Zhang L, et al (2026)

Severe pneumonia-associated lung injury: gut-lung-immune-metabolic connections in the critically ill host environment-microecology, barrier function, and mechanical ventilation.

Frontiers in immunology, 17:1914644.

Severe pneumonia-associated lung injury is a major cause of acute respiratory failure, acute respiratory distress syndrome (ARDS), and death in critically ill patients. Its course is shaped within the critically ill host environment by pulmonary infection and tissue injury, systemic inflammation, circulatory and organ dysfunction, host reserve, and ICU treatment exposures, and may be accompanied by changes in gut microbiota, barrier integrity, and cellular immune metabolism. Thus, pulmonary, intestinal, circulatory, and metabolic changes should be viewed as interrelated processes occurring at different physiological levels rather than as a predefined linear pathway. Emerging studies suggest links among gut microbiota remodeling, barrier disruption, microbial or host-derived circulating signals, altered microbial metabolites, and immune-cell metabolic reprogramming. However, their biological significance varies. Some may represent parallel responses to severe infection and critical illness, whereas others may arise secondary to lung injury, hypoxia, hypoperfusion, or treatment exposure. Longitudinal human evidence remains insufficient to establish whether gut-derived signals achieve physiologically effective remote exposure and independently modify lung injury. Mechanical ventilation is essential for severe respiratory failure, and its direct mechanical contribution to ventilator-induced lung injury has a relatively clear physiological basis. In contrast, sedation, hemodynamic and splanchnic perfusion changes, oxygenation and ventilation status, antibiotics, and nutritional support are distinct concomitant exposures that may independently influence gastrointestinal function, microbiota, barrier integrity, and immune metabolism. Using the critically ill host response as the overarching framework, this review evaluates the temporality, directionality, and functional support of relationships among gut microbiota, barrier function, candidate remote signals, cellular immune metabolism, and ventilation-related exposures, and assesses whether current evidence supports biologically and clinically meaningful gut-lung-immune-metabolic interactions. It also discusses lung-protective ventilation, nutritional support, microbiota modulation, anti-inflammatory therapy, and barrier protection. Current evidence derives mainly from limited studies in severe pneumonia or pneumonia-associated ARDS, clinical evidence from other critically ill populations, and preclinical studies. Evidence that pulmonary and systemic critical illness responses affect the gut is stronger than evidence for an independent gut-to-lung effect. Future longitudinal multi-compartment studies, source tracing, multi-omics integration, and mechanism-oriented interventions are needed to clarify functional cross-compartment relationships and their incremental clinical value for risk stratification and targeted treatment.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Qiu C, She P, L Wu (2026)

Cross-Cohort Transcriptomic and Oral Microbiome Analyses Identify Ferroptosis-Associated Signatures in Periodontitis and Oral Squamous Cell Carcinoma.

International journal of genomics, 2026:7538825.

BACKGROUND: Periodontitis (PD) and oral squamous cell carcinoma (OSCC) have been investigated in relation to inflammation, oral microbial alterations, and iron/redox biology. Whether ferroptosis-associated expression patterns overlap across independently sampled periodontal and cancer cohorts remains uncertain. We characterized these patterns without presuming that the available datasets represent matched individuals or a temporal disease sequence.

METHODS: We analyzed gingival single-cell RNA-sequencing data (GSE171213), an OSCC discovery expression cohort (GSE30784), and an independent oral tongue squamous cell carcinoma validation cohort (GSE13601). Periodontal microbial functional gene profiles (GSE54290) and a cross-study OSCC 16S abundance resource were examined separately. Analyses included cell annotation, KEGG ferroptosis gene-set scoring, sample- and cell type-level comparisons, differential expression, external transcriptomic signature validation, microbial diversity and abundance analyses, and LPS-stimulated cell-line RT-qPCR and ELISA measurements. The transcriptomic and microbial cohorts were not linked at the individual-patient level.

RESULTS: Quality control retained 34,342 cells from 12 gingival samples (four healthy controls [HCs], five PD, and three treated periodontitis [PDT]), assigned to 11 annotated cell populations. Mean sample-level ferroptosis gene-set scores were 0.081 in HC, 0.114 in PD, and 0.076 in PDT; these descriptive scores do not measure ferroptotic cell death. SAT1 showed a positive PD-versus-HC association in cell type pseudobulk analysis (log2 fold change, 0.546; false discovery rate [FDR], 0.012) and positive effects across all three transcriptomic cohorts. A discovery-derived ferroptosis-associated OSCC signature achieved an area under the receiver operating characteristic curve of 0.933 in GSE13601. Periodontal functional profiling identified 25 advanced PD-associated annotations (FDR < 0.05), including lower ferrochelatase signals. Cross-study OSCC microbiome analysis found 293 diagnosis-associated features after project adjustment; project-held-out classification yielded an AUC of 0.674. Following lipopolysaccharide stimulation, GPX4, SLC7A11, and FTH1 increased and ACSL4 decreased at the measured mRNA and protein levels in gingival fibroblasts and THP-1-derived macrophages.

CONCLUSIONS: Independently sampled periodontal and OSCC cohorts show ferroptosis-associated transcriptomic changes, with SAT1 emerging as a cross-cohort candidate. Parallel microbial datasets identify disease-associated functional gene and taxonomic differences but do not demonstrate within-patient host-microbe interactions or causal mediation. LPS-exposed cell-line measurements show expression changes in selected ferroptosis-associated markers, not ferroptotic cell death or functional resistance. The results are exploratory associations; in the absence of direct ferroptosis assays, paired longitudinal cohorts, and prospective clinical validation, they cannot establish a disease-progression mechanism, clinically deployable biomarker or therapeutic efficacy.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Zhang B, Bao J, Zhang Z, et al (2026)

Rhizophagus clarus and phosphorus co-regulate oat rhizosphere metabolome-microbiome under drought: a candidate hub metabolite perspective.

Frontiers in plant science, 17:1984943.

The interaction between arbuscular mycorrhizal fungi (AMF) and phosphorus (P) availability could enhance plant drought tolerance. Yet whether this interaction modulates nutrient uptake and grain yield in oat by reshaping rhizosphere metabolite and microbial networks remains unresolved. A pot experiment was conducted across three relative water contents (75%, 55%, and 35% relative water content, designated WW, MDS, and SDS), two AMF treatments, and three P levels (0, 40, and 80 mg kg[-][1] soil, designated P0, P1, and P2). Untargeted metabolomics and metagenomics were applied to characterize rhizosphere metabolite profiles and bacterial community structure, and to assess their relationships with nitrogen (N) and P status in the plant-soil system, grain yield and β-glucan. Drought significantly reduced grain yield, whereas moderate drought increased β-glucan accumulation; the beneficial effects of AMF on both traits were strongly modulated by soil P level. Under drought, AMF inoculation and P addition synergistically promoted N and P accumulation across oat organs; relative to P0AMF, P2AMF significantly elevated total N and P concentrations in roots, stems, leaves, panicles, and grains. Water availability was the dominant driver of rhizosphere metabolome and bacterial community variation. Under drought, AMF-P interaction further enriched rhizosphere metabolites, including amino acids and derivatives, organic acids, and benzene and substituted derivatives, while shifting the signature bacterial taxa toward Pseudomonadota (P1AMF) and Myxococcota and Gemmatimonadota (P2AMF). Network analysis identified isopentenyl pyrophosphate (IPP) as a highly connected hub metabolite, exhibiting the strongest associations with N and P nutrition, grain yield, β-glucan, and bacterial community composition. Exogenous IPP application significantly increased oat plant height, stem dry weight, and average root diameter under drought and markedly elevated the relative abundances of several rhizosphere bacterial taxa. Collectively, these findings indicate that AMF inoculation combined with P addition is associated with restructuring of the rhizosphere metabolite-microbe network under drought, and that IPP represents a candidate metabolite that warrants further investigation in these plant-microbe-soil interactions. This study provides a correlative framework linking this dual strategy to shifts in rhizosphere microbial communities and crop yield and functional quality under water-limited conditions, although mechanistic validation will require future experimental work.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Dener B, Gülal Sİ, Bulut M, et al (2026)

Nutritional modulation of microbiome proteomics in insulin resistance.

Frontiers in nutrition, 13:1913314.

RevDate: 2026-11-05
CmpDate: 2026-11-05

Xu Z, Chen W, F Lu (2026)

Microbial control of mucosal wound immunity in colorectal anastomotic healing: from barrier repair to matrix failure.

Frontiers in immunology, 17:1928237.

Colorectal anastomotic leakage is commonly framed as a technical complication or a consequence of intestinal dysbiosis. Neither view fully explains how a contaminated mucosal wound restores epithelial continuity while preserving a load-bearing submucosal matrix. We define anastomotic healing as a spatially organized mucosal immune process: luminal microbes and metabolites, the epithelial wound edge, recruited immune cells, fibroblasts, collagen, and vascular support occupy distinct but interacting compartments. The most compelling available anastomosis-specific evidence supports a destructive pathway in which expressed microbial virulence, host plasminogen activation, epithelial inflammatory signaling, sustained neutrophil recruitment, and MMP9 converge on collagen loss. A complementary repair pathway is supported by human-to-mouse microbiota-transfer and metabolite-rescue experiments, but this evidence is less direct and more heterogeneous. It links commensal function and AhR-dependent IL-22 signaling to epithelial restitution, myeloid resolution, and matrix repair. NLRP3, NLRP6, and NLRC4 remain candidate threshold regulators rather than demonstrated mediators of colorectal anastomotic healing. Human macrophage atlases refine cell-state definitions, but prospective evidence linking anastomotic macrophage states or efferocytosis to leakage remains limited. We propose an evidence-weighted framework that separates human association, direct microbial-function measurements, experimental causation, and human intervention evidence. Translation will require paired spatial sampling and functional microbial assays, together with immune, matrix, mechanical, target-engagement, and ecological-safety endpoints. This framework extends beyond taxonomic dysbiosis toward testable wound-immune endotypes and mechanism-matched prevention.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Nahar N, Kumar A, Grossman AS, et al (2026)

A domesticated prophage enzyme links bacterial metabolism, episymbiosis and phage fitness.

bioRxiv : the preprint server for biology.

Prophages are increasingly recognized as drivers of bacterial adaptation, yet how domesticated prophage genes shape microbial symbiosis remains poorly understood. Here, we identify GDPDXhp1, a glycerophosphodiester phosphodiesterase encoded by prophage Xhp1 of Schaalia odontolytica XH001, as a metabolic regulator linking bacterial physiology, episymbiosis and phage fitness. Association with the epibiotic bacterium Nanosynbacter lyticus TM7x strongly induced gdpd Xhp1 expression and triggered GDPDXhp1-dependent lipid droplet accumulation in XH001. GDPDXhp1 orchestrated glycerophospholipid remodeling, membrane biophysical properties, respiration and cell-surface glycan composition in XH001, thereby promoting TM7x episymbiosis. Remarkably, GDPDXhp1 was also required for productive Xhp1 infection by remodeling susceptible bacterial host envelope structures to facilitate phage-host interactions. Together, our findings reveal a domesticated prophage enzyme that contributes to bacterial metabolism, interspecies symbiosis and viral reproduction, highlighting prophage as an overlooked source of metabolic innovation in microbial symbiosis.

RevDate: 2026-11-03

Mari PV, Macerola N, Carriera L, et al (2026)

Gut dysbiosis and intestinal permeability in relation to liver stiffness assessed by elastography: a systematic review.

Journal of ultrasound [Epub ahead of print].

BACKGROUND: The gut-liver axis represents a pivotal bidirectional pathway in chronic liver disease. Gut dysbiosis, intestinal barrier dysfunction, microbial translocation and downstream immune activation have been associated with liver disease severity; however, their relationship with liver stiffness measured by elastography has not been systematically synthesised.

AIM: To systematically review the association between gut dysbiosis and gut-related biomarkers and liver stiffness assessed by elastography in adults.

METHODS: A systematic literature search was conducted across PubMed/MEDLINE, Embase, CENTRAL and Web of Science from inception through 31 March 2026. Original studies reporting both a gut-related exposure, including microbiome profiling or circulating, faecal or functional gut-related biomarkers, and liver stiffness measurement by a validated elastographic modality were eligible. Findings were classified according to the hepatic outcome actually evaluated as direct liver stiffness measurements, histologically defined fibrosis, or steatosis/other indirect liver-related outcomes. Study selection, data extraction and risk-of-bias assessment were performed independently by two reviewers.

RESULTS: 13 studies comprising 2,912 participants met the inclusion criteria. Nine assessed gut microbiota composition, six evaluated circulating or faecal gut-related biomarkers, and two assessed both domains. Direct positive associations with liver stiffness were reported for the kynurenine-to-tryptophan ratio in two studies and for soluble CD14 and soluble CD163 in one study; a separate study provided supportive histological evidence linking higher soluble CD14 and soluble CD163 levels to fibrosis. Evidence for lipopolysaccharide-binding protein and intestinal fatty acid-binding protein was null or limited, whilst faecal calprotectin was associated with steatosis rather than liver stiffness. Microbiome findings were heterogeneous, with no reproducible taxonomic signature across populations. Overall risk of bias was low in five studies, raised some concerns in six, and was high in two.

CONCLUSIONS: Selected gut-related biomarkers, particularly markers of monocyte-macrophage activation and tryptophan catabolism, are associated with higher liver stiffness although direct elastographic evidence remains limited and heterogeneous. Liver stiffness should not be considered synonymous with histological fibrosis, and findings based on fibrosis histology, steatosis or indirect liver-related outcomes should be interpreted separately. Further prospective studies using standardised gut-barrier assessment and rigorously reported elastography protocols are warranted.

RevDate: 2026-11-03
CmpDate: 2026-11-03

Menasria T, Zaatout N, M Benhadj (2026)

Genomic insights into Agathobaculum and Butyricicoccus highlight taxonomic refinements and synonymization with proposal of a new genus within the family Oscillospiraceae, Parabutyricicoccus gen. nov.

International journal of systematic and evolutionary microbiology, 76(11):.

Members of the family Oscillospiraceae are prominent anaerobic bacteria of the gut microbiota, with numerous taxa capable of butyrate production and other metabolically important activities. Despite their growing importance in microbiome research, the taxonomy of several Oscillospiraceae lineages remains unresolved. In particular, the genera Agathobaculum and Butyricicoccus were established largely on the basis of 16S rRNA gene phylogeny, yet accumulating genomic evidence indicates inconsistencies in their current classification. In this study, we performed a comprehensive genome-scale reassessment of all validly published species assigned to these genera using an integrated approach combining core-genome phylogenomic analysis and genome relatedness indices, including average nucleotide identity, average amino acid identity, digital DNA-DNA hybridization and percentage of conserved proteins, complemented by phenotypic and chemotaxonomic comparisons. Genomic similarity metrics revealed that Agathobaculum faecis Liu et al. 2022 and Agathobaculum ammoniilyticum Hitch et al. 2022 exceeded established species delineation thresholds, supporting their synonymization. In addition, Butyricicoccus faecihominis Takada et al. 2016 showed high genomic relatedness to members of Agathobaculum, justifying its transfer to this genus. Conversely, Butyricicoccus porcorum Trachsel et al. 2018 and Butyricicoccus intestinisimiae Li et al. 2022 formed a coherent and well-separated lineage distinct from both genera, warranting recognition of a novel genus within the family Oscillospiraceae, for which the name Parabutyricicoccus gen. nov. is proposed. These taxonomic revisions provide a robust phylogenomic framework for resolving relationships within Oscillospiraceae and improve the accuracy of bacterial classification in gut microbiome studies.

RevDate: 2026-11-03

You X, Paik J, Meeker S, et al (2026)

Gut microbiota are required for reduced IGF-1 and bone growth in postnatal cystic fibrosis mice.

JCI insight pii:207933 [Epub ahead of print].

Children with cystic fibrosis (CwCF) have impaired linear growth that correlates with poor clinical outcomes. Growth-stunted CwCF also exhibit a marked fecal dysbiosis, and lower serum levels of the gut microbiome-regulated growth factor IGF-1, relative to those without stunting. We hypothesized that the CF gut microbiome negatively impacts IGF-1 and skeletal growth in CwCF. To test this hypothesis, we compared bone phenotypes, IGF-1 and linear growth trajectories of C57BL/6 Cftrtm1Unc mutant mice (CF) to their wild-type littermates (WT) either colonized with (specific pathogen free, SPF) or without (germ-free, GF) normal microbiota. At 4 weeks of age, CF mice had reduced femur length and diminished serum IGF-1 compared to WT mice under SPF, but not GF, conditions. In contrast, by 14 weeks femur lengths and IGF-1 were similar in CF mice raised under both SPF and GF conditions. Accordingly, we observed significantly slower growth in CF mice under SPF, but not GF, conditions only from 1 to 4 weeks. CF mice also exhibited more pronounced relative taxonomic and functional dysbiosis at 4 compared with 14 weeks. These results suggest that gut microbiota play a critical role in early postnatal CF skeletal growth impairment, while microbe-independent mechanisms likely predominate in later life.

RevDate: 2026-11-03

Xu A, WB Ludington (2026)

The enemy of my friend is … my friend? Host phage-microbiome symbiosis: An unexpected story of mutualism and betrayal.

Cell reports, 45(11):118194 pii:S2211-1247(26)01273-8 [Epub ahead of print].

How does a host turn a beneficial symbiont into a nutrient source? In this issue of Cell Reports, Zhu et al. describe a novel symbiotic mechanism where an animal hijacks a prophage in its symbiont, which triggers lysis and nutrient release.

RevDate: 2026-11-03
CmpDate: 2026-11-03

López-Gutiérrez S, Espinosa-Barrera LA, Soto-Hernández A, et al (2026)

A Baltic Sea microbiome-derived Type III polyketide synthase produces host-protective alkylresorcinols in E. coli.

PloS one, 21(11):e0361965.

Marine microorganisms are a prolific source of novel polyketide synthases (PKSs) that generate structurally diverse and functional polyketides. Here, we identify a novel type III PKS, ArsMB, from Pontimonas sp. via metagenomic mining of a Baltic Sea microbiome. Heterologous expression of arsMB synthetic gene in an Escherichia coli host that lacks a native type III PKS, combined with a two-step strategy to boost acyl-CoA precursor availability in a glucose-mineral medium, enabled the in vivo synthesis of two cell-associated alkylresorcinols, identified by GC-MS as 5-pentadecyl-1,3-benzenediol (ars1) and 5-tridecyl-1,3-benzenediol (ars2). The product profile is consistent with a tetraketide alkylresorcinol biosynthetic pathway utilizing C16 and C14 acyl starter units, drawn from the host acyl-CoA pool. In agreement, AlphaFold2-based structural modeling predicts a Cys139/His275/Asn308 catalytic triad and a long hydrophobic substrate tunnel compatible with long-chain acyl starter units. E. coli producing the amphipathic cell-associated alkylresorcinols ars1/ars2 exhibited increased resistance to muralytic digestion by endolysins and to hydrogen peroxide. These findings expand the known repertoire of marine-derived type III PKSs and highlight the biotechnological potential of ArsMB-derived alkylresorcinols.

RevDate: 2026-11-03

Rendeiro J, Santos VH, P Silva-Vaz (2026)

Psychobiotic modulation of the microbiome-gut-brain axis: A systematic review of the literature.

Psychoneuroendocrinology, 195:108064 pii:S0306-4530(26)00324-0 [Epub ahead of print].

BACKGROUND: Major depressive disorder (MDD) is incompletely explained by the monoaminergic model. The microbiome-gut-brain (MGB) axis may link gut microbial ecology to immune, metabolic, neuroendocrine and neural signalling relevant to mood and antidepressant response.

OBJECTIVES: To synthesise recent evidence on (I) microbiota-targeted (psychobiotic) interventions; (II) the gut microbiome as a diagnostic and treatment-response biomarker; and (III) biopsychosocial and immunometabolic correlates of depression.

METHODS: PubMed, Scopus and PubPsych were searched (January 2022 to February 2025) following PRISMA 2020. Risk of bias was assessed with RoB 2, ROBINS-I and the Newcastle-Ottawa Scale. Findings were synthesised narratively, stratified by population, intervention type and study design.

RESULTS: Sixty-six studies were included: 36 in diagnosed depressive disorders, 10 in non-clinical samples, 15 in other medical conditions and 5 genetic or biobank analyses; most were of low or very low methodological quality. Depression was associated with lower abundance of short-chain fatty acid-producing taxa and with altered tryptophan, bile acid, inflammatory and barrier-related markers, largely in cross-sectional designs. In MDD, some strain-specific add-on probiotics were associated with greater symptom reduction than placebo, whereas others showed no benefit; prebiotic, dietary and faecal microbiota transplantation data were sparse or derived from non-MDD populations. Diagnostic and treatment-response models came from small samples and were rarely externally validated.

CONCLUSIONS: The gut microbiome is a plausible contributor to depressive pathophysiology and treatment variability, but current evidence is heterogeneous, predominantly associative and of low certainty. Psychobiotic interventions and microbiome-based biomarkers remain investigational; adequately powered, strain- and dose-specific trials and independently validated models are required before clinical application.

RevDate: 2026-11-03

Sikdar D, Panda SK, S Das (2026)

Rhizoplastisphere in mangrove ecosystems: A nexus of plastic pollution and microbial ecology.

Microbiological research, 315:128802 pii:S0944-5013(26)00366-6 [Epub ahead of print].

Plastic pollution is an increasing threat to coastal ecosystems, particularly mangrove forests, where complex root structures and sediment characteristics promote the retention and persistence of plastic debris. Microplastics (MPs) and nanoplastics (NPs) can alter sediment properties, microbial communities, nutrient cycling, plant physiology, and interactions across trophic levels, with potential consequences for ecosystem functioning and human health. This review presents the "rhizoplastisphere" as an integrative framework that describes the overlap between root-influenced soil or sediment (rhizosphere) and plastic-associated microbial habitats (plastisphere) under demonstrable living root influence. Although potentially applicable across rooted soils and sediments, the framework is examined primarily in mangrove ecosystems. The rhizoplastisphere provides a conceptual basis for examining the combined effects of root-derived inputs, plastic properties, and microbial processes. Particular emphasis is placed on the microbiome as both a potential target of plastic-associated stress and a functional component that influences nutrient cycling, plant-microbe interactions, biofilm development, and plastic transformation. Further, this review evaluates evidence for microbial contributions to plastic biodegradation and bioremediation while considering potential risks, including altered community structure, horizontal gene transfer, pathogen enrichment, and other forms of microbial dysbiosis. By integrating current evidence from mangrove, coastal, and relevant non-mangrove systems, this review identifies key knowledge gaps and methodological priorities for experimentally validating the rhizoplastisphere concept. Understanding these root-plastic-microbe interactions is essential for assessing the ecological consequences of plastic contamination and developing evidence-based strategies for managing plastics in mangrove ecosystems.

RevDate: 2026-11-03

Yue Y, Yuan M, Fan Z, et al (2026)

A synthetic microbial community derived from the roots of Kalidium gracile enhances its salt tolerance by modulating gene transcription and reshaping the rhizosphere soil microbiota.

Microbiological research, 315:128805 pii:S0944-5013(26)00369-1 [Epub ahead of print].

Soil salinization and alkalinization are severe environmental problems in the desert-oasis transition zone of the Hexi Corridor, China. Rhizosphere microbial communities are key regulators of plant adaptation to saline-alkali environments. However, the functional microbial resources and ecological mechanisms underlying the contribution of the rhizosphere microbiome associated with Kalidium gracile to its saline adaptation remain poorly understood. In this study, we characterized the rhizosphere microbiome of K. gracile inhabiting severely saline-alkali soil and isolated two Bacillus strains with strong plant growth-promoting potential, which were subsequently used to construct a synthetic microbial community (SynCom). Inoculation experiments under salt stress demonstrated that SynCom increased plant biomass and chlorophyll content and modulated host transcriptional responses associated with the "growth-defense trade-off." Shortly after inoculation, plant growth-related pathways were suppressed, while CAT and POD activities surged by 45% and 213%, respectively. At later stages after inoculation, the expression of growth-related pathways was significantly upregulated. Metagenomic sequencing revealed that SynCom reshaped the rhizosphere microbial community, with the relative abundances of the halophilic bacteria Halomonas and Marinobacter increasing by 317% and 1162%, respectively. The abundances of functional genes involved in soil carbon, nitrogen, phosphorus, and sulfur nutrient cycling were all significantly increased. Collectively, these findings indicate that SynCom enhances plant salt tolerance through a multi-layered regulatory mechanism by coordinating host physiological responses and rhizosphere microbial functions. Collectively, these findings reveal a multi-level regulatory mechanism through which SynCom enhances plant salt tolerance by coordinating host physiological responses and rhizosphere microbiome functions.

RevDate: 2026-11-03

Zhang B, Li Y, Du C, et al (2026)

Environmental constraints reveal condition-dependent advantages of a defined benzene-degrading consortium.

Journal of hazardous materials, 518:144093 pii:S0304-3894(26)03074-8 [Epub ahead of print].

Benzene-contaminated soils remain difficult to remediate because bioaugmentation strategies often rely on selecting individual strains with high degradation activity, while their long-term performance under environmental constraints is uncertain. Here, we show that a defined three-member consortium sustained benzene removal more effectively than the strongest degrader alone under environmental constraints. By integrating field microbiome analysis, [13]C-benzene DNA stable isotope probing, genome-resolved metagenomics, cultivation, defined consortia, isotope labeling, and long-term soil incubation, we identified and reconstructed a functional benzene-degrading consortium. Field profiling identified a limited set of taxa associated with benzene contamination. DNA-SIP, genome-resolved metagenomics, and isolate assays further differentiated the roles of the focal lineages. Stutzerimonas showed the strongest benzene degradation, Rhodococcus encoded additional aromatic-catabolic potential, and Rhizobium exhibited nitrogenase activity. Although Stutzerimonas showed the highest degradation efficiency in monoculture (approximately 78%), the three-member consortium displayed a stronger advantage under environmental constraints. When the exogenous nitrogen source was omitted, corrected degradation reached approximately 73% in the three-member consortium, compared with approximately 38% in the Stutzerimonas-Rhodococcus consortium. At 700 mg L[-1] benzene, the three-member consortium retained approximately 86% corrected degradation, whereas Stutzerimonas alone declined to approximately 44%. During 6 months of repeated benzene amendment in soil, the consortium maintained rapid benzene removal together with continued detection of all three focal bacterial lineages. These findings show that the benefit of the consortium depended on environmental context and provide a basis for evaluating candidate inocula for benzene remediation.

RevDate: 2026-11-03

Xu X, Wang S, Xue Y, et al (2026)

Effects of heat wave combined with sublethal doses of thiamethoxam on oviposition performance and gut microbial community of Bombus terrestris.

Ecotoxicology and environmental safety, 326:121013 pii:S0147-6513(26)01343-6 [Epub ahead of print].

Climate warming has increased the frequency and intensity of extreme heat events, while neonicotinoid insecticides such as thiamethoxam are widely applied in agroecosystems. These two stressors frequently co-occur, yet their combined effects on pollinator health remain poorly understood. Here, we aimed to investigate the individual and interactive impacts of sublethal thiamethoxam and heat stress on bumblebee microcolonies. We examined the median lethal concentration (LC50), food intake, survival rate, oviposition performance, biochemical activity, gene expression, and gut microbiota in Bombus terrestris microcolonies. The findings revealed that thiamethoxam and heat stress, alone and in combination, exerted effects on bumblebees across different dimensions. Heat stress markedly weakened worker tolerance to thiamethoxam: the LC50 at 32 °C was 0.69 times and 0.52 times that at 26 °C at the 24 h and 48 h time points, respectively. Food intake declined significantly under all three exposure scenarios, whereas survival remained unaffected. The combined treatment significantly altered egg size and VgR expression. Heat stress offset the thiamethoxam-induced decline in SOD and GSH, but MDA remained elevated, indicating that maintained antioxidant markers did not restore protection against lipid peroxidation. Neither thiamethoxam nor heat stress, whether applied singly or in combination, significantly changed the alpha diversity indices of the gut microbiota; however, the microbial community composition underwent marked restructuring. The heat stress alone group yielded the highest number of unique ASVs. Thiamethoxam treatment noticeably shifted the gut microbial community profile, and the combined treatment produced a shift similar to that of thiamethoxam alone but with additional synergistic modulation. LEfSe analysis identified distinct sets of differentially abundant bacterial taxa across the treatment groups, confirming substantial community restructuring; the heat stress alone group harbored the largest number of significantly discriminant taxa. Overall, heat stress synergistically amplifies the sublethal toxicity of thiamethoxam in bumblebees, altering egg traits and reproductive gene expression and reshaping the gut microbiota, which underscores the urgency of incorporating temperature scenarios into pesticide risk assessment and pollinator conservation strategies.

RevDate: 2026-11-03

Liang C, Chen Y, Li P, et al (2026)

Chronic exposure to diclofenac and meloxicam from early development elicits endpoint-specific adult responses in marine medaka (Oryzias melastigma).

Aquatic toxicology (Amsterdam, Netherlands), 302:108057 pii:S0166-445X(26)00353-X [Epub ahead of print].

Adult responses to prolonged exposure to diclofenac (DCF) and meloxicam (MEX) remain insufficiently characterized in marine fish. Marine medaka (Oryzias melastigma) were exposed to nominal concentrations of DCF (0.01-10 μg/L) or MEX (0.1-10 μg/L) from 3 to 4 h post-fertilization to 6 months post-fertilization, with exploratory equimass co-exposures at 0.1 + 0.1 and 10 + 10 μg/L. Adult assessments used three replicate tanks per treatment and included organismal and somatic endpoints, with intestinal 16S rRNA gene profiling and cardiac data-independent acquisition proteomics in selected treatments. No somatic endpoint differed significantly from the solvent control in either sex after multiple-comparison adjustment. Intestinal community composition differed overall among treatments. DCF at 10 μg/L reduced Chao1 richness and Shannon diversity, whereas MEX at 0.1 or 10 μg/L did not differ significantly from the control in either index. Direct DCF-MEX comparisons at 10 μg/L detected no significant differences in sex-specific somatic endpoints or alpha-diversity indices after Holm correction. Cardiac proteomics compared DCF (0.01 and 10 μg/L) and MEX (10 μg/L) treatments with the solvent control. Over-representation analysis identified Lysosome enrichment in all three treatment-control comparisons after pathway-level Benjamini-Hochberg correction. Gene set enrichment analysis identified positive enrichment of Lysosome, Other glycan degradation, and Sphingolipid metabolism in all three comparisons (false discovery rate < 0.05). These findings identify a shared cardiac proteomic signature associated with lysosomal substrate processing, although its implications for intracellular turnover and cardiac performance remain unresolved. The study supports comparative assessment of chronic pharmaceutical responses across biological endpoints.

RevDate: 2026-11-03
CmpDate: 2026-11-03

Guo C, C Jiang (2026)

Metformin-supportive nutrition: When gut microbes eat drugs.

Cell metabolism, 38(11):2165-2166.

Metformin is a first-line treatment for type 2 diabetes in adults and children, but its efficacy varies significantly among patients. Zhao et al. identify microbial AdhE as a metformin-degrading enzyme in metformin low-responders and propose enzyme-based microbiome intervention as a strategy to rescue therapy.

RevDate: 2026-11-03
CmpDate: 2026-11-03

McGrath S, ML Benton (2025)

From Foundations to Frontiers: Best Papers in Bioinformatics and Translational Informatics 2024.

Yearbook of medical informatics, 34(1):124-128.

OBJECTIVES: To identify and summarize the top bioinformatics and translational informatics (BTI) papers published in 2024, we focus on advancements in disease prediction, foundation models for single-cell biology, and antimicrobial discovery.

METHODS: We conducted a comprehensive literature search using PubMed and BlueSky crowdsourcing to identify candidate BTI papers. The 620 resulting articles were systematically reviewed by section editors using three primary criteria: novelty, significance, and quality. A final list of 15 candidate papers was then evaluated by external reviewers to select the top three papers for this year.

RESULTS: Three outstanding BTI papers demonstrated significant contributions to the field. These papers showcase innovative approaches to leverage machine learning for disease prediction using multi-omics data, develop foundation models for single-cell biology, and apply computational methods to identify novel antimicrobial peptides from the global microbiome. In addition, our honorable mention paper provides a framework for building a virtual cell using artificial intelligence (AI).

CONCLUSIONS: This year's top BTI papers reflect several important trends, including the integration of multi-omics data for improved disease prediction, the application of foundation models to biological data, and the use of machine learning to address critical healthcare challenges such as antimicrobial resistance. These papers highlight how computational approaches continue to drive innovation in precision medicine and biological research.

RevDate: 2026-11-03
CmpDate: 2026-11-03

Yang S, Jin L, Deng W, et al (2026)

An integrated gut phage catalogue of nonhuman primates reveals functional adaptation to host ecology and evolutionary link to humans.

Proceedings. Biological sciences, 293(2082):.

Nonhuman primates (NHPs), the closest evolutionary relatives of humans, are pivotal models for biomedical and ecological research. Gut phage are recognized as critical modulators of gut microbial communities; however, comprehensive insight into gut phage of NHPs is lacking. We used gut metagenomes spanning 25 NHP species and constructed an integrated gut phage catalogue (IGPC) comprising 11 389 nonredundant phage genomes. Our results revealed that the composition and function of NHP gut phage were significantly influenced by host clade, dietary niche and lifestyle. Host clade exerted a stronger influence than dietary niche on gut phage diversity. The lifestyle of NHPs influenced gut phage diversity and altered auxiliary metabolic gene profiles for different NHP species. Comparatively, 78.5% of IGPC phages were detected in human guts, with higher prevalence in nonindustrialized human guts. crAss-like phage-the most prevalent human-associated phage-were abundant in NHP guts, while exhibiting distinct evolutionary differences from crAss-like phage of humans. These findings comprehensively characterize the gut phageome of NHPs, revealing NHP host-driven and environment-driven functional adaptations, and provide an evolutionary understanding of the gut phageome between NHPs and humans.

RevDate: 2026-11-04

Asemoloye MD (2026)

Engineering rhizosphere microbial consortia for soil bioremediation: Mechanisms, field constraints, and evidence-based design.

Plant science : an international journal of experimental plant biology, 375:113566 pii:S0168-9452(26)00594-7 [Epub ahead of print].

Soil contamination continues to threaten ecosystem health and agricultural productivity worldwide. However, rhizosphere-mediated bioremediation has emerged as a nature-inspired, sustainable approach for mitigating these impacts. This review advocates field-scale implementation of rhizosphere microbiome engineering by exploiting interactions among plants, microorganisms, and soil. Unlike previous reviews that primarily summarize rhizosphere-mediated remediation processes, it integrates mechanistic, ecological, and engineering perspectives to identify critical barriers limiting field performance. This review synthesizes recent advances in rhizosphere microbiome engineering, with an emphasis on root-exudate manipulation, synthetic microbial communities (SynComs), biochar-assisted remediation, and multi-omics technologies. The evidence reviewed indicates that root exudates are key regulators of microbial recruitment, biofilm formation, and expression of contaminant-degrading genes, while engineered microbial consortia enhance functional complementarity and pollutant transformation. A comparative analysis of laboratory and field studies reveals substantial performance gaps, with highly efficient degradation observed under controlled conditions often declining following field deployment because of microbial competition, environmental variability, and contaminant sorption dynamics. The review further shows that integration of SynComs with biochar carriers and precision root-exudate engineering can improve microbial establishment and remediation efficiency. Advances in metagenomics, metabolomics, and systems biology are enabling more predictive design and monitoring of rhizosphere processes. Collectively, this review provides a mechanistic synthesis, identifies key translational bottlenecks, and outlines practical directions for developing scalable rhizosphere-based remediation technologies.

RevDate: 2026-11-03

Plunk EC, Hazzard H, Bordt E, et al (2026)

Immune-Microbiome Crosstalk in the Developmental Origins of Neurodevelopmental Disorders.

Biological psychiatry pii:S0006-3223(26)01659-8 [Epub ahead of print].

Neurodevelopmental disorders (NDDs) arise from genetic and environmental factors converging across development, from embryogenesis through adulthood. Two systems central to brain development, the immune system and the microbiome, are incompletely formed at birth. Development of these immune and microbiome systems is shaped by factors transferred across prenatal and postnatal maternal-offspring interfaces including the placenta, birth canal, and breast. Despite literature linking each system independently to NDD risk, these fields have largely proceeded in parallel, rarely interrogating their interactions. This siloed approach constrains mechanistic understanding and progress. Here, we present evidence that the immune system and microbiome are interacting, not independent, influences on neurodevelopmental programming. Preclinical evidence from germ-free, antibiotic depletion, and maternal immune activation models demonstrates that perturbation of either system alters the other; human cohort evidence remains largely associational. Across each maternal-offspring interface, immune and microbial signals converge on the developing brain, acting on peripheral and neuroimmune populations. Microglia emerge as a recurring cellular mediator. Resolving mechanisms of NDD risk requires experimental designs that treat immune and microbial variables as interactive and that span prenatal through postnatal development. The field must move beyond disciplinary silos to integrate these systems across the full neurodevelopmental time course they jointly shape.

RevDate: 2026-11-03

El-Sherbiny GM (2026)

Reprogramming the tumor microbiome: Opportunities for cancer prevention, diagnosis, and precision therapy.

Biochimica et biophysica acta. Reviews on cancer pii:S0304-419X(26)00220-9 [Epub ahead of print].

Microbiota-cancer interactions operate across distinct anatomical compartments, including the gut microbiota, the distal gut-tumor axis, and intratumoral microbiota residing within tumor tissues. These microbial communities and their metabolites can influence carcinogenesis, tumor progression, immune surveillance, and therapeutic responses through inflammation, genotoxicity, metabolic remodeling, epithelial and tumor-barrier dysfunction, and immune regulation. However, the magnitude and direction of these effects are highly context dependent, varying with cancer type, tumor site, microbial composition, host factors, treatment exposure, and methodological approaches. Importantly, associations between microbial signatures and clinical outcomes do not necessarily establish causality, and findings from gut microbiome studies should not be extrapolated directly to local intratumoral communities. This review critically synthesizes current evidence linking gut and intratumoral microbiota to tumor biology and treatment response, distinguishing compartment-specific mechanisms and evaluating the strength and limitations of available evidence. We examine how microbial metabolites, microbe-host interactions, and microbiota-driven immune and metabolic pathways shape the tumor microenvironment and may modify responses to immunotherapy, chemotherapy, radiotherapy, and targeted therapies. We further assess multi-omics and spatial approaches for resolving microbial heterogeneity and identifying clinically relevant biomarkers, alongside emerging microbiome-directed interventions, including probiotics, fecal microbiota transplantation, engineered microorganisms, and nanotechnology-based strategies. Particular emphasis is placed on discrepancies between preclinical and clinical findings, causal inference, reproducibility, interindividual variability, contamination and sampling challenges, and the barriers to clinical translation. Collectively, the evidence supports a context-specific role for microbiota in cancer biology while underscoring the need for standardized methodologies, longitudinal and mechanistic studies, and well-controlled clinical trials before microbiome-based strategies can be reliably incorporated into precision oncology.

RevDate: 2026-11-03

Yang J, Wang R, Hu N, et al (2026)

Polyethylene microplastics reduce aluminum uptake but obstruct nodulation in broad bean under acidic aluminum stress.

Environmental pollution (Barking, Essex : 1987) pii:S0269-7491(26)01841-5 [Epub ahead of print].

Soil acidification and microplastic pollution increasingly threaten agricultural systems worldwide, yet their combined effects on crops remain largely unexplored. In this study, we subjected broad bean (Vicia faba L.) to polyethylene (PE) microplastics, aluminum (Al) stress, or their combination, and integrated physiological assays, root metabolomics, and rhizosphere metagenomics to dissect their interactive effects. PE microplastics unexpectedly lowered root Al accumulation by 41.7% compared to Al alone, which was associated with reduced exchangeable Al in the rhizosphere. Despite this reduction, the combined PE and Al treatment still significantly suppressed root (by 50.1%) and shoot (by 42.0%) biomasses and severely compromised nodulation and nitrogen (N) acquisition, with effects similar to or even stronger than those of the mono Al treatment. Metabolomic profiling revealed that combined stress extensively downregulated ten flavonoids and fundamentally rewired flavonoid-rhizobia correlation networks, shifting potential symbiotic signaling away from compatible interactions. Metagenomic analysis further showed that while combined stress increased microbial co-occurrence network connectivity by 54.8%, it simultaneously suppressed the abundance of functional genes related to metal resistance and N cycling, pointing to a systemic metabolic burden rather than a targeted stress response. These results demonstrate that PE microplastics modulate Al bioavailability but do not mitigate phytotoxicity; instead, they exacerbate symbiotic disruption through flavonoid signaling interference and microbiome functional decline. These findings highlight the vulnerability of legume-rhizobia symbiosis to multi-stressor environments and call for a reassessment of soil management practices in regions where acidification and microplastic contamination co-occur.

RevDate: 2026-11-03

Kommineni N, Sainaga Jyothi VGS, Katta C, et al (2026)

Translational resilience in intravaginal HIV prevention and multipurpose prevention technologies: formulation, exposure, and implementation barriers.

Journal of controlled release : official journal of the Controlled Release Society pii:S0168-3659(26)00928-4 [Epub ahead of print].

Intravaginal HIV prevention has progressed from early nonspecific microbicides to antiretroviral gels, films, inserts, and intravaginal rings, alongside emerging biologic agents and multipurpose prevention technologies (MPTs). Despite substantial advances in antiviral potency and formulation technology, translation from pharmaceutical development to consistent clinical protection has remained uneven, indicating that API activity or dosage-form performance alone is insufficient to explain clinical outcomes. This review critically examines the development of intravaginal HIV prevention and MPT products through a mechanistic pharmaceutical perspective, focusing on the relationships between controllable product attributes, drug release and transport, the cervicovaginal environment, compartment-specific pharmacokinetics/pharmacodynamics (PK/PD), and product use. Historical microbicide and antiretroviral programs are examined as translational case studies to identify how mucosal safety, local exposure and use-dependent drug delivery contributed to divergent clinical outcomes. The review further evaluates how cervicovaginal fluid, semen, mucus, epithelial barriers, hormonal state, microbiome composition, and inflammation can modify formulation behavior and drug transport; how API physicochemistry, solid state, drug loading, drug-polymer partitioning, and diffusivity constrain formulation architecture and release; and how these relationships differ among gels, films, inserts, sustained-release devices, MPTs, and biologic delivery systems. Particular attention is given to the distinction between drug incorporation, release, tissue transport, and pharmacologically relevant exposure, and to the additional challenges created when multiple APIs require different release rates, biological compartments, or durations of action. Platform characteristics are further considered in relation to the exposure patterns and product-use conditions they are intended to support. By integrating formulation science with cervicovaginal physiology, PK/PD, and clinical experience, this review provides a mechanistic basis for identifying where intravaginal prevention systems lose translational performance and which formulation-transport-exposure relationships require stronger evidence to support more reproducible clinical protection.

RevDate: 2026-11-03
CmpDate: 2026-11-03

Hasija T, P Khare (2026)

The Oral Microbiota-Taste Axis: Microbial Influences on Gustatory Perception and Food Sensory Experience.

Journal of texture studies, 57(6):.

Taste is a key determinant of food choice and dietary behavior, yet differences in taste perception are often attributed mainly to genetic variation, taste receptor expression, and neural processing. Emerging evidence suggests that the oral microbiota may represent an additional, and largely overlooked, factor influencing gustatory perception. This review examines the potential role of oral microorganisms in shaping taste by bringing together current evidence from oral microbiology, taste physiology, and nutritional science. Particular attention is given to the close association between tongue-associated microbial communities and taste buds, and to the potential effects of microbial biofilms, local pH changes, and microbial metabolites on the chemical environment surrounding taste receptors. The review further considers how these interactions may influence taste sensitivity, food preferences, dietary patterns, and, ultimately, metabolic health. Importantly, current evidence remains largely associative, and direct mechanistic links between specific microorganisms, microbial metabolites, and taste receptor function are still poorly defined. We therefore highlight key methodological and knowledge gaps and discuss emerging opportunities for dietary modulation, oral probiotics, and microbiome-informed approaches. Understanding this oral microbiota-taste axis may provide a new perspective on taste variability and its nutritional consequences.

RevDate: 2026-11-03
CmpDate: 2026-11-03

Fan S, Wang X, Zhang Z, et al (2026)

Integrating microbiome source tracking, machine learning, and precision intervention for data-driven control of microbial contamination in food processing.

Food research international (Ottawa, Ont.), 245(Pt 5):120937.

The microbial contamination in food processing environments is jointly influenced by complex interactions among raw materials, equipment, water, air, personnel, microbial communities, and processing conditions. Consequently, routine monitoring and fixed-frequency sanitation programs may be insufficient for managing persistent or intermittent contamination. This review synthesizes recent evidence on microbiome-based source tracking, predictive microbiology and machine learning, and targeted decontamination technologies, with a focus on potential pathways for their integration into data-driven food safety management. A literature search was conducted in Scopus, Web of Science, and PubMed for peer-reviewed studies published between 2020 and 2026, and a narrative synthesis approach was adopted to integrate the findings due to considerable heterogeneity in study designs, data types, and outcome measures. The reviewed evidence indicates that microbiome analysis and multi-omics approaches can improve the characterization of contamination reservoirs, while predictive models can integrate environmental, process, and microbiological data to support risk prioritization. However, the reliability of source attribution remains constrained by sequencing biases, incomplete reference databases, contamination interference, and limited taxonomic resolution. Machine learning applications are further limited by small and highly heterogeneous dataset sizes, information leakage, overfitting, distribution shifts, and insufficient external validation. Precision decontamination technologies show promise but face challenges in cost, scale-up, process integration, and regulatory validation. Based on these findings, this review proposes a conceptual "Sense-Trace-Predict-Act-Learn" framework for linking environmental monitoring, source investigation, risk prediction, targeted intervention, and post-intervention evaluation. This framework is intended as a decision-support roadmap rather than a validated autonomous industrial system. Future advances will depend on standardized data infrastructure, prospective industrial validation, uncertainty-aware modeling approaches, and integration with existing food safety management systems.

RevDate: 2026-11-03
CmpDate: 2026-11-03

Li X, Hu H, Li X, et al (2026)

Multi-omics insights into the effects of NFT and MAP-B on metabolite and microbiome dynamics in fresh Ophiocordyceps sinensis during storage.

Food research international (Ottawa, Ont.), 245(Pt 5):120946.

To investigate the effects of optimal modified atmosphere packaging (MAP) at near freezing-point temperature (NFT) on the quality of fresh Ophiocordyceps sinensis and its multi-omics profiles, three MAP conditions (MAP-A: 3% O2 + 5% CO2 + 92% N2; MAP-B: 5% O2 + 10% CO2 + 85% N2; MAP-C: 7% O2 + 18% CO2 + 75% N2) were first compared at 4 °C, with air packaging (CK1) as the control. The MAP-B treatment was selected as optimal based on sensory and texture properties. Subsequently, samples were stored at -3.9 °C under MAP-B and CK2 for 60 d, and physicochemical indices, volatile organic compounds (VOCs), untargeted metabolome, and microbial community dynamics were analyzed every 10 d. Results showed that MAP-B treatment effectively maintained the storage quality of fresh O. sinensis for up to 30 d, with weight loss consistently remaining below 5%, protein content staying stable, and texture deterioration being significantly delayed. A total of 113 VOCs were identified by HS-SPME-GC-TQ/MS, mainly aldehydes, alcohols, and ketones, with 15 key VOCs determined by relative odor activity values (ROAVs) analysis. UPLC-Q-Exactive-MS/MS detected 58 metabolites, primarily organic acids and their derivatives, lipids and lipid-like molecules. High-throughput sequencing of 16S rRNA and ITS revealed 38 bacterial phyla (693 genera) and 7 fungal phyla (223 genera); the core bacterial genera were Ralstonia, Serratia, and uncultured__MSB-4B10, while the core fungal genera were uncultured__Sordariales, Aspergillus, and Thermomyces. KEGG pathway analysis indicated that lipid, carbohydrate, and amino acid metabolisms were the most active. Correlation analysis demonstrated that weight loss rate was significantly negatively correlated with protein content and texture properties. The variation in 1-octen-3-ol content was closely associated with quality deterioration indicators, suggesting its potential as a candidate indicator for monitoring quality deterioration. This study provides data support based on multi-omics correlation analysis for the preservation of O. sinensis under NFT with MAP-B treatment; however, the current conclusions are limited to multi-omics characterization, and the direct molecular mechanisms and biomarker functions remain to be independently validated.

RevDate: 2026-11-03
CmpDate: 2026-11-03

de Oliveira TS, Iamanaka BT, de Lemos OF, et al (2026)

From soil to market: Microbiome dynamics and food safety implications along Brazilian black pepper production chain.

Food research international (Ottawa, Ont.), 245(Pt 5):120948.

Understanding how the microbiome is influenced throughout food production chains is crucial for advancing microbial ecology and food safety. However, integrative studies tracking microbiome dynamics from field to consumer remain scarce. In this study, we investigated the structure of the bacterial microbiome along the production chain of black pepper (Piper nigrum L.) produced in Brazil, using 16S rRNA gene metabarcoding combined with culture-dependent and conventional molecular methods (BAX® system and Sanger sequencing). We analyzed 180 samples collected along the production chain in the states of Pará and Espírito Santo, as well as from retail outlets in São Paulo. Enterobacterales counts ranged from <10 to 7.7 × 10[8] CFU/g, with the highest levels observed during storage (intermediary collectors) and persistent detection throughout the entire production chain. Microbiome analysis revealed a clear ecological succession: soil exhibited the highest alpha diversity (Chao1 > 4300; Shannon >10), followed by a progressive reduction in diversity during drying and storage stages, and a partial recovery in retail samples. The stages displayed distinct microbial profiles, with a predominance of oligotrophic taxa in soil, fermentative genera in field samples, and desiccation-tolerant taxa, particularly Bacillus and Enterobacteriaceae, becoming more prevalent in dried and retail samples. Salmonella spp. was detected in only 3.9% of samples, appearing in fresh, dried, and retail pepper, indicating both pre- and post-harvest contamination pathways. Molecular characterization identified Salmonella enterica subsp. salamae and subsp. diarizonae, representing the first report of these subspecies in black pepper. These results provide new insights into microbiome succession and Salmonella ecology along the black pepper supply chain, aiding in the identification of critical control points to improve the quality and safety of this foodstuff.

RevDate: 2026-11-03
CmpDate: 2026-11-03

Peng Y, Chang H, Kang L, et al (2026)

Multi-omics analysis of aroma differences in chili oil from different geographical origins using flavoromics and microbiomics.

Food research international (Ottawa, Ont.), 245(Pt 5):120987.

Chili peppers grown in different production regions often exhibit distinct aroma profiles. However, the soil-microbiome mechanisms underlying such origin-associated aroma variation remain poorly understood. Using a single cultivar and a fully standardized processing protocol, we compared two adjacent sites (PTG and ZJH) in Togtoh County with contrasting perceived chili oil aroma to elucidate the cascade from soil to fruit to oil. No climatic differences were found, yet soil N, P, S, and organic matter differed significantly and correlated with fruit traits (capsaicin, vitamin C, soluble solids, color). A consumer survey (n = 117) provided exploratory evidence of perceived aroma: >86% perceived aroma differences, with PTG receiving 89% mention for "more aromatic". Flavoromics clearly separated volatile profiles (R[2]Y = 0.987, Q[2] = 0.971; 200 permutation tests, P < 0.01), identifying 13 differential volatile markers, of which four (bornyl acetate, 6-undecanol, 5-methyl-2-furanmethanethiol, and (E,Z)-2,4-decadienal) showed relative odor activity values >1 and are candidate aroma-active compounds. These differential volatile markers were also associated with fruit quality traits. Microbiomics showed site-enriched bacterial taxa, enriched in Bacillus, Desulfitibacter, and Paenibacillus, with FAPROTAX-predicted enrichment of functions related to sulfur oxidation and lignin decomposition. Mantel analyses revealed a significant association between bacterial community structure and predicted functional profiles (R = 0.667, P = 0.001). Procrustes analysis showed that both soil physicochemical properties (M[2] = 0.345, P = 0.001) and bacterial community composition (M[2] = 0.608, P = 0.012) were significantly associated with the overall structure of fruit quality and aroma metabolites, with soil physicochemical properties showing a closer fit. Network analysis identified Desulfitibacter and Bacillus as potential hub taxa that were positively correlated with key differential volatiles (P < 0.001), suggesting potential associations with aroma-related metabolic processes. Collectively, these results support an integrated association framework linking soil properties, microbial communities, fruit quality, and chili oil aroma differences, providing a basis for future targeted microecological regulation studies.

RevDate: 2026-11-03
CmpDate: 2026-11-03

Li Z, Li B, Sun X, et al (2026)

Metagenomics reveals potential risks of antibiotic and metal resistance genes in agricultural production systems.

Food research international (Ottawa, Ont.), 245(Pt 5):120990.

Agricultural environments harbor diverse microbiomes and serve as key reservoirs of resistance genes, yet their influence on fresh produce remains unclear. In this study, metagenomics was employed to reveal the microbiome and resistome in soil, irrigation water, and fresh produce surfaces in production settings. The results revealed that soil harbored the greatest microbial diversity along with the highest abundance and diversity of antibiotic resistance genes (ARGs). Fresh produce harbored diverse ARGs of potential relevance to food-chain resistance surveillance. Among the 528 bacterial metagenome-assembled genomes (MAGs) retained for genome-resolved analysis, Pseudomonadota were the predominant carriers of ARGs, including those conferring resistance to tetracyclines, aminoglycosides, and β-lactams. Interestingly, similar contigs containing rep22_1b and tet(L) were found in MAGs obtained from irrigation water and vegetable samples, indicating a high level of conservation in the genetic environment. In addition, irrigation water harbored the most abundant mobile genetic elements (MGEs), found to be significantly associated with ARG profiles. Copper (Cu) resistance genes were predominant among the detected metal resistance genes (MRGs), indicating widespread genetic potential for copper resistance across the sampled agricultural environments. Overall, these findings reveal distinct but interconnected resistome profiles across soil, irrigation water, and fresh produce and identify resistance-associated genetic features of potential relevance to food safety surveillance.

RevDate: 2026-11-03

Chen C, Hao L, Xie W, et al (2026)

Heterogeneity of microbiome responses to menopausal hormone therapy among perimenopausal women.

Nature medicine [Epub ahead of print].

Menopausal hormone therapy (MHT) alleviates climacteric symptoms, yet its microbiome-wide effects and efficacy determinants remain unclear. Here we show that oral estradiol/dydrogesterone, given for 6 months to 356 perimenopausal women, improved neuroendocrine, metabolic and symptom outcomes and induced site-specific microbial remodeling. Vaginocervical and urinary niches showed the most pronounced restructuring, with moderate oral and minimal gut changes. MHT increased vaginocervical Lactobacillus crispatus and reduced Gardnerella vaginalis. Higher baseline vaginocervical L. crispatus predicted greater postintervention vaginocervical and urinary colonization and superior Female Sexual Function Index improvement. Baseline vaginocervical community types determined differential outcomes: G. vaginalis-dominated individuals shifted most toward healthier communities, whereas diversified individuals improved least. MHT efficacy also varied according to baseline gut community type: Phocaeicola vulgatus-dominated women exhibited greater hormonal responsiveness, superior clinical outcomes and were more likely to achieve 4-week rapid clinical remission than Prevotella copri-dominated women. These findings support a precision MHT framework integrating gut and vaginocervical community typing for personalized care. Chictr.org.cn ID: ChiCTR2100049768 .

RevDate: 2026-11-03

Ponce DM, DeFilipp Z, Ford CB, et al (2026)

A live biotherapeutic product for adult allogeneic hematopoietic cell transplantation recipients: a partially randomized, placebo-controlled phase 1b trial.

Nature medicine [Epub ahead of print].

Gastrointestinal (GI) microbiome disruption and impaired GI barrier integrity increase the risk of bloodstream infection (BSI) following allogeneic hematopoietic cell transplant. Here we report results from a two-cohort (open-label, n = 15; randomized, placebo-controlled, n = 45) phase 1b study of SER-155, an investigational, cultivated, multi-strain, oral live biotherapeutic designed to address GI microbiome disruption GI epithelial barrier integrity in allogeneic hematopoietic cell transplant recipients. In cohort 2, 34 of 45 participants received either SER-155 treatment (n = 20, SER-155 following microbiome conditioning with oral vancomycin), or placebo (n = 14), and subsequently received transplant. For the primary safety endpoint, SER-155 was well tolerated, with a safety profile comparable to placebo, no treatment-related serious adverse events and no infections with SER-155 species; the most common adverse events were diarrhea and nausea. Four participants in cohort 1 and four participants in cohort 2 (two participants in the SER-155 arm and two in the placebo arm) died during the study; none was attributable to SER-155. For the primary pharmacokinetic endpoint, engraftment was detected for 16 of 16 SER-155 strains, with a median of 11.5 strains detected after the first treatment course. The key secondary efficacy endpoint revealed a significantly lower incidence of BSI with SER-155 versus placebo (10.0% versus 43%; OR 0.15; 95% CI 0.01-1.13; P = 0.0423; 77% relative risk reduction). Other secondary efficacy endpoints (GI infection, acute graft-versus-host disease ≥grade 2, febrile neutropenia and a composite endpoint of BSI, GI infection or acute graft-versus-host disease) were not statistically significant. The secondary pharmacodynamic endpoint of GI domination by Enterococcus and Enterobacteriaceae spp. was not achieved. ClinicalTrials.gov identifier: NCT04995653 .

RevDate: 2026-11-03
CmpDate: 2026-11-03

Shaji V R, Mishra RK, Shukla D, et al (2026)

Role of gut microbiota dysbiosis on the functional outcomes in ischemic and haemorrhagic stroke patients: a systematic review.

BMC neurology, 26(1):.

BACKGROUND: Stroke is a leading cause of death and long-term disability worldwide, yet the biological determinants of post-stroke recovery remain incompletely understood. Recent evidence implicates the gut microbiome as a key regulator of neuroinflammation, metabolic signalling, and immune response through microbiota-gut brain axis. However, the extent to which gut microbial dysbiosis influences neurological severity and functional recovery across ischemic and haemorrhagic stroke remains unclear.

METHODS: This systematic review examined the relationship between gut dysbiosis and functional outcomes following stroke. A comprehensive search of PubMed, Scopus, Web of Science, ScienceDirect, and the Cochrane Library identified eligible studies published up to July 2025. Twenty-three clinical studies comprising 2,951 participants were included. Microbiome diversity indices, microbial taxa, and microbiota-derived metabolites were evaluated in relation to standardized stroke outcomes, including acute neurological severity (NIHSS) and functional outcomes (mRS, Barthel Index. The study quality was assessed using the Newcastle-Ottawa Scale and the Cochrane risk-of-bias framework.

RESULTS: Across the included cohorts, stroke patients exhibited consistent alterations in gut microbial ecology compared with healthy controls. Alpha diversity analyses demonstrated a significant reduction in microbial richness and evenness in several cohorts, while beta diversity metrics revealed pronounced restructuring and clear separation between stroke and control microbiomes. Differential abundance analysis consistently identified depletion of short-chain fatty acid (SCFA)-producing commensals, including Roseburia, Faecalibacterium, and Coprococcus, alongside enrichment of opportunistic and pro-inflammatory taxa such as Enterobacteriaceae, Enterococcus, and Escherichia/Shigella. Metabolomic analysis further revealed a convergent disruption of key microbial metabolic pathways, including reduced SCFA production, increased endotoxin-associated signalling and trimethylamine-N-oxide (TMAO) metabolism. These microbial and metabolic perturbations were significantly associated with greater neurological severity, higher disability scores, increased infection risk, and poorer functional outcomes following stroke.

CONCLUSION: This systematic synthesis demonstrates that stroke is accompanied by a reproducible pattern of gut microbial dysbiosis characterized by ecological contraction, expansion of inflammatory pathobionts, and disruption of microbial metabolic signalling. These findings support the existence of a conserved gut-brain-metabolic axis influencing stroke severity and recovery trajectories. Integrating microbiome-derived biomarkers with clinical prognostic models may enable earlier risk stratification and the development of microbiota-targeted therapeutic strategies to improve post-stroke outcomes.

PROSPERO (Identifier: CRD420251106958).

RevDate: 2026-11-03
CmpDate: 2026-11-04

Tičinović Kurir T, Pavlović N, Šantić R, et al (2026)

Diet-stress interactions in gut barrier dysfunction and metabolic inflammation.

Molecular medicine (Cambridge, Mass.), 32(1):.

BACKGROUND: The intestinal barrier is a dynamic host-microbe interface that contributes to metabolic homeostasis. Chronic psychological stress and adverse dietary patterns can each disturb microbiota, mucus, junctional, and inflammatory processes. This review evaluates the evidence for convergence of diet- and stress-responsive pathways at the intestinal barrier and their possible relevance to metabolic inflammation.

MAIN BODY: Activation of the hypothalamic-pituitary-adrenal (HPA) and sympatho-adrenomedullary axes, together with adverse dietary exposures, converges on the gut microbiota and epithelial barrier. Stress-related corticotropin-releasing hormone/mast-cell signalling, glucocorticoids, and catecholamines can remodel mucus and tight junctions, while high-fat, Western-style, ultra-processed, or prolonged substrate-restricted diets reduce butyrogenic support and may shift bile-acid metabolism toward barrier-disruptive secondary bile acids. The resulting mucus erosion and tight-junction remodelling, including reduced occludin/ZO-1 and increased pore-forming claudin-2, increase permeability and facilitate lipopolysaccharide translocation. LPS-TLR4-NF-κB signalling provides inflammatory priming and can converge with diet- and stress-related danger signals on the NLRP3 inflammasome, promoting IL-1β, TNF-α, and IL-6 release. These pathways plausibly contribute to obesity, insulin resistance, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease, although direct human evidence for a true diet × stress barrier interaction remains limited.

CONCLUSION: Preclinical studies provide mechanistic support for overlapping diet- and stress-responsive barrier pathways, and acute human stress studies provide functional permeability evidence. Human dietary evidence is more often indirect, and direct factorial studies of diet × stress effects on barrier function are largely absent. The proposed framework should therefore be treated as a testable synthesis rather than an established causal model.

RevDate: 2026-11-03
CmpDate: 2026-11-03

Zhang Z, Yang F, Zhang Z, et al (2026)

Metagenomics reveals biogeography and functional potential of phage communities in bee gut.

Animal microbiome, 8(1):.

BACKGROUND: Bacteriophages (phages) are pivotal regulators of microbiome ecology and function, yet their distribution, diversity and ecological roles within the bee gut remain largely unexplored, particularly across diverse bee species and geographic regions. Here, we used a large-scale metagenomic dataset to investigate phage communities associated with seven bee species across China.

RESULTS: We recovered 121 viral operational taxonomic units (vOTUs) from 132 bee gut metagenomes, revealing that bee gut phages are dominated by the class Caudoviricetes and include numerous previously uncharacterized viral lineages. Biogeographic analyses revealed spatial structuring of phage communities such as latitudinal diversity gradient, distance-decay relationship. Variation partitioning analysis (VPA) indicated that bee host identity explained a substantially larger proportion of community variation than environmental factors. More, functional annotation further revealed that bee gut phages encode diverse carbohydrate-active enzymes (CAZymes) potentially involved in polysaccharide metabolism, as well as multiple anti-defense systems targeting bacterial antiviral mechanisms.

CONCLUSIONS: Our study demonstrates that bee gut phages exhibit biogeographic structuring and host specificity. In addition, phages carry diverse functional genes that may influence bacterial metabolism and host-microbe interactions. These findings provide a comprehensive framework for understanding the ecological roles of phages in the bee gut and highlight their importance in shaping tripartite interactions among phages, bacteria, and bee hosts.

RevDate: 2026-11-03
CmpDate: 2026-11-03

Wen J, Yao Y, Hu X, et al (2026)

The microbiome bottleneck in seahorse aquaculture: a conceptual framework linking biofilm ecology, probiotics and larval survival.

Animal microbiome, 8(1):.

Extremely high mortality during early juvenile development remains the primary constraint to establishing sustainable aquaculture protocols for threatened seahorse species (Hippocampus spp.). Despite sustained efforts focused on nutritional optimisation, water quality control and pathogen suppression, survival rates have improved only marginally, suggesting that key underlying drivers remain insufficiently addressed. This conceptual review posits that juvenile mortality fundamentally constitutes a microbial ecological challenge, in which conventional rearing environments generate dysbiotic states that selectively favour opportunistic pathogens while failing to support protective microbial communities. Here we propose a microbiome-centric conceptual framework that reconceptualises the larval rearing unit as a dynamic microbial ecosystem, in which biofilm formation, microbial succession and host-microbe interactions collectively shape disease risk and larval survival. By integrating insight from biofilm ecology, probiotic research and biofloc technology, we synthesise dispersed findings to interpret larval mortality as an emergent outcome of disbiotic rearing environments, rather than isolated pathogenetic events. Emphasis is placed on ecological mechanisms, such as niche preemption, competitive exclusion and quorum quenching, rather than on taxonomic inventories of candidate probiotics. Finally, we translate this framework into a structured research agenda by identifying key knowledge gapes, testable hypothesis and operational implications for hatchery practices. By shifting the focus from pathogen eradication to microbial ecosystem engineering, this conceptual synthesis provides a foundation for more resilient and predictable seahorse aquaculture systems, offering a perspective applicable to other sensitive marine larval cultures.

RevDate: 2026-11-04

Elashkar OI, Kasparian KV, McCurdy CR, et al (2026)

A Quantitative Framework for Characterizing Oral pH Dynamics.

Journal of dental research [Epub ahead of print].

Dental caries is a polymicrobial biofilm-based disease whereby acidogenic and aciduric microorganisms within dental plaque generate an acidic milieu resulting in dissolution of enamel and dentin below their critical pH. The relationship of pH over time following exposure to a cariogenic substrate, coined the "Stephan curve," continues to be a critical determinant in whether a substance is deemed cariogenic. Several caries-associated parameters can be extracted from the data, including minimum pH, time corresponding to the minimum pH, recovery time, time below the critical pH, and area below the critical pH. While wire telemetry devices were developed for continuous recording of plaque pH in vivo, most clinical datasets use the indirect method or strip method due to patient compliance issues, ease of use, and cost limitations. Most of the time, this results in sparse sampling time points. In this work, we demonstrate how sparse datasets lead to underestimation of critical parameters associated with caries risk and can therefore alter the interpretation of the data and conclusions drawn, potentially leading to inaccurate claims. To mitigate this issue, we developed a quantitative framework that harnesses nonlinear mixed effects and fixed effects modeling to better predict these caries-associated pH parameters and show superiority as compared with traditional methods used in prior literature. We conclude by introducing a web-based and publicly available interface (GatorpH) that utilizes our mathematical models. This interface can be readily applied to plaque and saliva pH profiles that are routinely collected in clinical studies 1) assessing the potential relative cariogenicity of dietary items, 2) establishing the efficacy of novel cariostatic agents or biomaterials, or 3) characterizing changes in acidogenicity among patient populations or microbiome studies. Translational researchers, clinicians, and regulatory agencies can therefore utilize GatorpH for the study of oral pH dynamics and for rapid and reliable quantification of critical parameters associated with dental caries.

RevDate: 2026-11-04

Imai C, Ohsugi Y, Lin P, et al (2026)

Effects of Maternal Ligature-Induced Periodontitis on Brain in Offspring.

Journal of dental research [Epub ahead of print].

The combined effects of chronic maternal periodontitis on offspring gut microbiome and brain outcomes remain unclear. This study aimed to evaluate the effects of maternal oral microbiome disruption on brain function and gut microbiome in offspring. Periodontitis was induced in 11- to 12-wk-old parous C57BL/6J mice by maintaining ligatures around both sides of the maxillary second molars for 4 wk, followed by breeding with naïve male mice. Maternal oral and gut microbiome, as well as the offspring gut microbiome, was analyzed by 16S rRNA gene sequencing. Male offspring were evaluated at 7 to 8 wk of age via a set of analyses, including behavioral tests, microbiome profiling, RNA sequencing, immunohistochemistry for glial cell populations, and in vivo calcium imaging. Cerebellar DNA methylation was assessed at embryonic day 18.5 to examine early epigenetic alterations. Maternal periodontitis significantly reduced microbial diversity in the maternal oral microbiome and altered the composition of the maternal gut microbiome. In offspring, α-diversity was reduced in the gut microbiome. Behavioral analyses revealed impaired social interaction and reduced spontaneous locomotion, while motor coordination and memory-related behaviors were preserved. RNA sequencing identified region-specific changes in gene expression, particularly in the cerebellum, highlighting its vulnerability to maternal inflammatory conditions. DNA methylation analysis revealed epigenetic alterations during the fetal stage, suggesting early programming effects. Immunohistochemical analysis demonstrated a significant increase in astrocyte density in the cerebellum and frontal cortex, whereas oligodendrocytes and microglia were unaffected. Furthermore, calcium imaging revealed disrupted neuronal synchrony among Purkinje cells without significant changes in individual neuronal activity parameters. Maternal oral microbiome disruption induces coordinated alterations in maternal and offspring microbiomes and leads to persistent neurobehavioral, molecular, and cellular changes in offspring. These findings provide new insights into the link between maternal oral health and offspring neurodevelopment, highlighting the potential role of microbiome-mediated mechanisms in shaping brain function.

RevDate: 2026-11-04

Sun Y, Li B, K Ye (2026)

Gut-Induced Synuclein Propagation: A New Mechanism in Neurodegenerative Disease.

The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry [Epub ahead of print].

Gut-induced synuclein propagation has emerged as a potential mechanism linking gastrointestinal disturbances with the development and progression of Parkinson disease and related synucleinopathies. These disorders are characterized by progressive accumulation and spreading of misfolded α-synuclein (α-Syn), leading to selective neuronal dysfunction and degeneration. Although traditionally considered brain-centered diseases, increasing evidence indicates that gastrointestinal abnormalities, peripheral α-Syn pathology, and gut-associated immune alterations may precede neurological manifestations, suggesting that peripheral processes can influence disease evolution. Here, we review clinical, pathological, and experimental evidence supporting the role of intestinal environmental stress, microbial dysregulation, barrier dysfunction, and immune activation in promoting α-Syn misfolding, aggregation, and transmission through interconnected pathways. However, peripheral α-Syn abnormalities alone are unlikely to be sufficient to initiate neurodegeneration, indicating the presence of additional biological constraints. We propose a cumulative-threshold and biological-gates framework in which α-Syn induction, seed formation, propagation efficiency, anatomical connectivity, and neuronal vulnerability collectively determine whether gut-associated pathology progresses into a self-sustaining neurodegenerative cascade. Understanding the determinants that enable gut-induced synuclein propagation may provide new insights into disease heterogeneity and guide biomarker development and mechanism-based therapeutic strategies for synucleinopathies.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Sheng Y, Dai X, Lu J, et al (2026)

The Potential Role of Gut Microbiome Dysbiosis and Functional Reprogramming in Colorectal Liver Metastasis via the Gut-Liver Axis.

Cancer reports (Hoboken, N.J.), 9(11):.

BACKGROUND: Colorectal liver metastasis (CRLM) is a leading cause of mortality in colorectal cancer (CRC), yet current surveillance often misses occult micrometastases, underscoring an urgent need for early non-invasive biomarkers and mechanistic insights.

AIMS: This study aimed to investigate gut microbiota dysbiosis and functional alterations associated with CRLM and explore potential non-invasive biomarkers.

METHODS AND RESULTS: Fecal metagenomic sequencing was performed in 60 participants, comprising healthy controls, patients with non-metastatic CRC, and patients with synchronous CRLM (n = 20 per group). Microbial composition, functional pathways, co-occurrence networks, and clinical associations were systematically analyzed, and a random forest model was constructed to identify potential diagnostic biomarkers. Results showed that gut microbiota dysbiosis intensified as CRC progressed toward CRLM, characterized by the depletion of commensal flora and significant enrichment of specific genera, such as Eikenella and Porphyromonas. Functionally, the gut microbiome displayed stage-specific remodeling, shifting from infection- and virulence-related pathways in CRC to functions associated with microbial secondary metabolism and stress adaptation in CRLM. Furthermore, SPIEC-EASI-based network analysis revealed a sparser and more compartmentalized microbial ecological structure in CRLM, with [Clostridium] symbiosum, Campylobacter concisus, and Coprococcus eutactus emerging as module hubs. A random forest model integrating nine core taxa and one virulence factor (VF0160 FeoAB) achieved an overall 97.5% classification accuracy in discriminating CRLM from non-metastatic CRC, indicating the potential of fecal metagenomic biomarkers for future risk stratification. However, prospective validation in larger multicenter cohorts is required before clinical translational utility.

CONCLUSION: Collectively, our findings suggest that gut microbiota dysbiosis and functional reprogramming are strongly associated with CRLM progression, potentially through remodeling the hepatic pre-metastatic niche via the gut-liver axis.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Bai X, Yang L, Zhou Z, et al (2026)

A study on differences in the structure and function of the oral microbiome in 3- to 5-year-old children from plateau and plain regions'.

Frontiers in oral health, 7:1983860.

BACKGROUND: The oral microbiome critically influences childhood caries and periodontal disease, yet how altitude and ethnicity shape it in preschool children remains unclear. This study aimed to investigate the associations of altitude and ethnicity on the composition, diversity, and metabolic pathways of the oral microbiome; analyze the potential associations between microbiome characteristics and dental caries and periodontal mucosal inflammation; and provide a microbiome-based theoretical foundation for the precise prevention and control of oral diseases in young children in high-altitude regions.

METHODS: This study included 87 children aged 3-5 years who were divided into three groups: low-altitude Han Chinese (n = 27), high-altitude Han Chinese (n = 30), and high-altitude Tibetan (n = 30). Demographic, dietary, oral hygiene, and family socioeconomic data were collected via questionnaires. Unstimulated saliva samples were collected for high-throughput 16S rRNA gene sequencing, and microbial community potential function was predicted using PICRUSt2 and the KEGG database. A multiple linear regression model was used to adjust for confounding variables and false discovery rate (FDR) correction was applied to assess the associations of altitude and ethnicity on oral microbial diversity, microbial abundance, and metabolic pathways.

RESULTS: High-altitude children had greater oral microbial alpha diversity, with all four indices remaining significant after FDR correction (all q < 0.01); ethnicity showed no independent effect. Altitude showed independent positive associations with Bacteroidetes, Prevotella melaninogenica, Haemophilus parainfluenzae, Veillonella parvula, and Veillonella atypica (q < 0.01); None of the six species-level associations with ethnicity remained significant after FDR correction (all q > 0.05). Functional prediction analysis revealed that the microbial communities of low-altitude children presented higher predicted enrichment of glycolysis and fatty acid metabolism pathways, whereas high-altitude children predicted enrichment of NOD-like receptor signaling and protein digestion and absorption pathways.

CONCLUSION: Altitude shows strong statistical associations with oral microbial diversity and community structure in 3-5-year-old children, and the magnitude of these associations exceeded those for ethnicity-associated factors ethnicity-associated factors. Based on the association patterns between the microbiota and oral diseases, this study provides foundational data to support differentiated management and microbiome-based interventions for oral health in children living at different altitudes.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Hoffmann K, Pucek WF, Skrzypek W, et al (2026)

Diabesity: an old term, a modern challenge - multi-omics and precision anti-obesity pharmacotherapy in type 2 diabetes.

Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques, 29:17560.

Type 2 diabetes mellitus (T2DM) and obesity are closely interconnected but heterogeneous conditions in which treatment response, safety, body weight, glycemic control, and long-term clinical outcomes vary substantially between individuals. This narrative review evaluates emerging anti-obesity pharmacotherapy in patients with coexisting T2DM and obesity and examines the translational role of multi-omics in future precision treatment selection. Distinct from reviews focused primarily on obesity pharmacotherapy or omics-based disease stratification, the present review emphasizes the interface between contemporary drug mechanisms, T2DM-associated metabolic heterogeneity, candidate molecular signatures, and the level of evidence required for clinically actionable prescribing. We summarize evidence for approved and investigational oral incretin therapies, dual and triple receptor agonists, amylin-based strategies, established antidiabetic drugs, and adjunctive approaches targeting body composition. Throughout the review, we distinguish established clinical evidence from mechanistic rationale, candidate biomarkers, exploratory associations, and hypothetical future precision applications. We also separate metabolic efficacy endpoints, such as body weight and HbA1c, from intermediate cardiometabolic risk markers and from cardiovascular or kidney outcomes demonstrated in dedicated outcome trials. At present, no genomic, metabolomic, lipidomic, proteomic, microbiome, or integrated multi-omics signature has been clinically validated to select a specific anti-obesity medication for patients with T2DM and obesity. Major unresolved issues include the need for prospective biomarker validation, direct comparative trials, standardized assays, externally validated and calibrated prediction models, preservation of skeletal muscle health and physical function, long-term safety, treatment durability, affordability, and equitable implementation. Multi-omics should therefore be viewed as an investigational framework for generating and testing precision-treatment hypotheses rather than as a basis for routine prescribing.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Hashimoto Y, Yasuda K, Okada S, et al (2026)

Short-term clinical observations following local L8020 application in peri-implantitis with suppuration: a pilot study.

Frontiers in oral health, 7:1967259.

OBJECTIVES: To evaluate feasibility, short-term safety, and preliminary clinical observations following local application of Lactobacillus rhamnosus KO3 (L8020) after standardized saline irrigation in patients with peri-implantitis presenting with suppuration.

MATERIALS AND METHODS: This prospective, single-arm, open-label pilot clinical study enrolled ten patients with peri-implantitis presenting with suppuration. After standardized irrigation of the peri-implant sulcus, L8020 was topically applied. Clinical examinations and submucosal microbiological sampling were performed at baseline and Day 7. The primary outcome was disappearance of suppuration at Day 7. The prespecified secondary outcome was change in the peri-implant microbial community; PPD was exploratory, and adverse events were monitored. Microbiome analyses included 16S rRNA V3-V4 sequencing, paired alpha-diversity analysis, Bray-Curtis beta-diversity analysis, taxonomic composition profiling, and exploratory paired differential-abundance testing.

RESULTS: Suppuration was absent in 7 of 10 implants (70%) at Day 7, whereas mean PPD remained unchanged (7.1 ± 1.9 mm at both time points). No significant changes were detected in five alpha-diversity indices. Bray-Curtis PCoA showed no distinct separation between baseline and Day 7, and a paired PERMANOVA using all 2^10 within-participant label permutations showed no difference in overall community structure (pseudo-F = 0.158; exact p = 0.883). Genus- and species-level taxonomic profiles showed no consistent community-wide shift, and no genus or species remained significant after paired Wilcoxon testing with Benjamini-Hochberg correction. No intervention-related adverse events were observed.

CONCLUSIONS: The combined local procedure was feasible and well tolerated over 7 days. The disappearance of suppuration is a preliminary short-term observation and should not be interpreted as resolution of peri-implantitis or evidence of an L8020-specific therapeutic effect. The clinical observation occurred without a detectable major compositional shift in the peri-implant microbiota. Controlled studies with an irrigation-only comparator, larger samples, and longer follow-up are required.

CLINICAL TRIAL REGISTRATION: https://jrct.mhlw.go.jp/latest-detail/jRCTs061230059, Japan Registry of Clinical Trials (jRCT) jRCTs061230059.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Tamasgen N, B Asefa (2026)

Nutrigenomics in Dairy Cattle: Causes and Implications.

Veterinary medicine international, 2026:3660248.

Nutrigenomics is a rapidly developing interdisciplinary field that investigates the interactions between nutrients and the genome, with particular emphasis on how dietary components regulate gene expression and metabolic pathways. In dairy cattle, nutrigenomics has gained increasing attention due to its potential to improve milk production, metabolic efficiency, health, reproduction, and overall animal performance. Nutrients and bioactive dietary compounds can influence gene activity directly through transcriptional regulation or indirectly through epigenetic mechanisms such as DNA methylation, histone modification, and noncoding RNA-mediated gene regulation. These nutrigenomic interactions affect important biological processes including lipid metabolism, adipogenesis, immune response, mammary gland development, and milk synthesis. Advances in omics technologies including transcriptomics, proteomics, metabolomics, and next-generation sequencing have enhanced understanding of the molecular responses of dairy cows to nutritional interventions. Dietary fatty acids, vitamins, methyl donors, and short-chain fatty acids such as butyrate have been shown to regulate key transcription factors including peroxisome proliferator-activated receptors (PPARs), sterol regulatory element binding proteins (SREBPs), and liver X receptors (LXRs), thereby modulating metabolic and physiological functions. Nutritional interventions, feed restriction, and supplementation produce tissue-specific molecular responses in the liver, adipose tissue, mammary gland, and immune system, demonstrating interaction between diet, physiological state, and metabolic regulation. Despite these advances, challenges with genetic and physiological variability, tissue-specific responses, integration of multi-omics data, and translation of molecular findings into practical feeding strategies remain unresolved. Future integration of nutrigenomics with microbiome research, multi-omics, artificial intelligence, and precision livestock technologies may facilitate nutritional strategies to improve dairy cattle health, productivity, feed efficiency, and product quality.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Candela E, Zucchini S, F Baronio (2026)

Editorial: Growth and pubertal development in paediatric endocrinology: from physiological pathways to clinical challenges.

Frontiers in pediatrics, 14:2020433.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Yan P, Cai S, J Xia (2026)

Gut microbiota and treatment response heterogeneity across pharmacological therapies for MASH.

Frontiers in pharmacology, 17:1968956.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease with increasing global prevalence. However, substantial inter-individual variability in therapeutic response remains a major challenge for effective disease management. Although the gut microbiota is well recognized as a key contributor to MASH pathogenesis, its role in shaping pharmacological treatment response remains insufficiently understood and underexplored in clinical contexts. In this Review, we summarize evidence suggesting that gut microbiota-associated metabolites, including bile acids, short-chain fatty acids, sphingolipids, and other microbial products, may contribute to variability in therapeutic response across major pharmacological classes for MASH, including FXR agonists, PPAR agonists, FGF19/FGF21 analogues, thyroid hormone receptor-β agonists, and incretin-based therapies. However, for most therapeutic classes, direct clinical evidence linking microbiota features to inter-individual treatment response remains limited, and much of the mechanistic evidence is derived from preclinical studies. We integrate current evidence into a response-oriented conceptual framework linking microbiome composition and metabolic activity to biological processes relevant to drug efficacy. This framework identifies priorities for the prospective validation of microbiome-derived biomarkers and microbiome-informed patient stratification in MASH.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Zhang N, Jin Y, Ren W, et al (2026)

Illuminating the microbial 'dark matter' in obesity: integrated multi-omics approaches to characterize uncultured taxa and their potential metabolic crosstalk with host pathways.

Frontiers in microbiology, 17:1940402.

BACKGROUND: Obesity is a global health challenge shaped by interactions among host genetics, diet, lifestyle, and gut microbial ecology. Although reference genome catalogues and cultivation approaches have expanded knowledge of the human gut microbiome, many intestinal microorganisms remain uncultured, poorly characterized, or functionally unresolved. These microorganisms are collectively referred to as microbial "dark matter," a conceptual category rather than a defined taxonomic group encompassing diverse lineages, including members of Patescibacteriota, historically referred to collectively as the Candidate Phyla Radiation (CPR), with Saccharibacteria representing a historically used designation for a lineage within this broader group.

OBJECTIVE: This review examines the potential relevance of uncultured and poorly characterized gut microorganisms-collectively referred to here as microbial "dark matter"-to obesity-associated microbial ecology and metabolism. We focus on how integrated multi-omics approaches can identify candidate microbial functions, metabolic interactions, and host-associated pathways, while distinguishing genomic prediction and ecological association from demonstrated activity and causal effects. Particular attention is given to the evidence gaps surrounding microbial metabolite production or transformation by poorly characterized taxa and to experimental strategies required for functional and causal validation.

DESIGN: We summarize evidence on the ecological characteristics, genome reduction, metabolic dependencies, and potential host-microbe interactions of uncultured microorganisms. We discuss microbial metabolites, including short-chain fatty acids and bile acid derivatives, while distinguishing established microbiome-host mechanisms from functions specifically attributed to uncultured taxa. We also evaluate cultivation, gnotobiotic models, organoids, and microbial engineering for experimental validation.

RESULTS: Uncultured microorganisms represent an important but incompletely characterized component of the gut ecosystem. Genome-resolved and single-cell approaches have revealed substantial metabolic diversity and ecological dependencies. Some uncultured lineages may participate in carbohydrate metabolism, metabolite exchange, and bile acid transformation. However, direct evidence linking specific uncultured taxa to obesity phenotypes remains limited, with many proposed mechanisms based on genomic prediction, multi-omics associations, or extrapolation from better-characterized microorganisms. Their roles in antibiotic resistance and environmental-stressor responses also remain emerging rather than established mechanisms of obesity.

CONCLUSION: Microbial dark matter represents an unresolved dimension of obesity-associated microbiome research. Integrated multi-omics can generate functional hypotheses, but causal attribution requires complementary experimental validation. A function-oriented framework distinguishing established evidence, mechanistic inference, and future hypotheses may provide a rigorous foundation for understanding uncultured components of the gut microbiome.

RevDate: 2026-11-04
CmpDate: 2026-11-04

Riccardo F, Conti L, Defilippi P, et al (2026)

Closing the adaptive window: immune-metabolic strategies to constrain melanoma therapy resistance.

Frontiers in immunology, 17:1954638.

Melanoma cells respond to therapy not only through selection of pre-existing resistant clones, but also by rapidly engaging reversible adaptive programs that preserve viability under treatment. These programs connect signaling rewiring, metabolic plasticity, inflammatory responses, cell-state transitions and remodeling of the tumor microenvironment. We propose that this early adaptive phase creates a temporal and biological window in which melanoma cells acquire sufficient fitness to persist and subsequently evolve more stable epigenetic and genetic resistance. We first examine the rapid signaling responses elicited by MAPK pathway inhibition and the adaptive programs induced by immune-mediated pressure, emphasizing multifunctional hubs that integrate growth, stress, metabolic and inflammatory cues. We then discuss the metabolic flexibility of melanoma cells, including mitochondrial respiration, glutamine and lipid utilization, redox control and NAD/NAMPT-dependent immunometabolic regulation. Finally, we consider therapeutic vaccination and microbiome modulation as complementary strategies that may broaden anti-tumor immunity and reshape treatment responsiveness. Thus, this review focuses primarily on convergent adaptive processes that define this biological window and explores whether their experimental characterization may reveal opportunities to therapeutically constrain adaptive capacity through rationally timed combinations or sequential interventions. Closing the adaptive window may reduce the evolutionary opportunities available to melanoma cells before heterogeneous, fixed resistance mechanisms become established.

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