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24 pages, 6844 KB  
Article
Distinctive Patterns of Gut Bifidobacterium Diversity in Mongolian Adults: Regional Variation and Dairy Intake Associations
by Tuul Nyambal, Khulan Lkhamsuren, Alexander Hübner, Ser-Od Khuygaa, Sabri Bromage, Raphaela Stahl, Matthäus Rest, Björn Reichhardt, Ariunzul Battulga, Sodbileg Odonchimed, Davaalkham Dambadarjaa, Khosbayar Tulgaa, Christina Warinner and Soninkhishig Tsolmon
Nutrients 2026, 18(17), 2816; https://doi.org/10.3390/nu18172816 - 28 Aug 2026
Abstract
Background/Objectives: Despite increasing interest in the human gut microbiome, particularly in Bifidobacterium, studies focusing on traditionally living populations with high habitual dairy consumption remain limited. This study investigated species-level diversity, abundance, and regional variation of Bifidobacterium among healthy Mongolian adults and [...] Read more.
Background/Objectives: Despite increasing interest in the human gut microbiome, particularly in Bifidobacterium, studies focusing on traditionally living populations with high habitual dairy consumption remain limited. This study investigated species-level diversity, abundance, and regional variation of Bifidobacterium among healthy Mongolian adults and contextualized these findings within a global comparative framework. Methods: A total of 100 healthy adults were recruited from four Mongolian regions. Fecal samples were analyzed using species-resolved shotgun metagenomics, and dietary intake was assessed through a standardized food frequency questionnaire. Alpha- and beta-diversity metrics, differential abundance tests, and diet–microbe correlations were performed on members of the Bifidobacterium species. To assess the broader significance of the Mongolian Bifidobacterium profile, Shannon diversity was further compared against a curated global dataset comprising 1286 healthy adults from 29 countries using harmonized bioinformatic and statistical pipelines. Results: Shannon diversity within the Bifidobacterium genus was significantly higher in nomadic Mongolians, particularly those from Khuvsgul and Dundgobi, and strong geographic structuring was observed in beta-diversity analyses (PERMANOVA, p < 0.001). Nomadic populations showed higher relative abundances of B. adolescentis and B. angulatum, whereas B. pseudocatenulatum predominated in Ulaanbaatar. Although overall Bifidobacterium abundance was lowest in Bulgan, B. longum remained the dominant species in this region. Spearman correlation analysis with false discovery rate correction identified significant associations between dairy intake and specific Bifidobacterium species. Homemade yogurt and traditional dairy intake were positively associated with B. angulatum. B. catenulatum was positively associated with homemade yogurt, traditional dairy, and total fermented dairy intake, whereas factory milk intake was negatively associated with B. angulatum but positively associated with B. pseudocatenulatum. Mongolia ranked among the top eight of 30 countries for Bifidobacterium Shannon diversity though total Bifidobacterium abundance showed substantial inter-individual and regional variation. Conclusions: Mongolian adults exhibit relatively high Bifidobacterium diversity at both national and global scales. Traditional dairy consumption was associated with species-specific variation in Bifidobacterium composition, supporting the contribution of dietary practices to regional gut microbiota patterns. Full article
(This article belongs to the Section Nutrition and Public Health)
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22 pages, 2520 KB  
Article
Impact of Combined Botanical Functional Ingredients on the Canine Gut Microbiome
by Estefania Morua, Lourdes Criado-Mesas, Guillermo Chumaceiro, Maialen López Palma, Roberto Malinverni, Walter Sanseverino, Riccardo Aiese Cigliano, Laura Cuyas and Luis Matías-Hernández
Vet. Sci. 2026, 13(9), 877; https://doi.org/10.3390/vetsci13090877 - 27 Aug 2026
Abstract
The canine gut microbiome plays a key role in digestive, immune, and metabolic health and is increasingly recognized as an important indicator of overall animal well-being. Medicinal and Aromatic Plants are emerging as a promising approach to support intestinal balance through modulation of [...] Read more.
The canine gut microbiome plays a key role in digestive, immune, and metabolic health and is increasingly recognized as an important indicator of overall animal well-being. Medicinal and Aromatic Plants are emerging as a promising approach to support intestinal balance through modulation of the gut microbiome. This pilot study evaluated the effects of Aloe vera, Artemisia annua, and Curcuma longa on the gut microbiome of healthy dogs. The study included eighteen healthy dogs, divided into an Experimental group (n = 9) and a Control group (n = 9). Dogs in the Experimental group received a daily combination of the three plants for 30 days, while Control dogs received microcrystalline cellulose as a placebo. Fecal samples were collected on Day 30 and analyzed using shotgun metagenomic sequencing. Differential abundance analysis revealed an enrichment of taxa associated with short-chain fatty acid production in the Experimental group, including Megasphaera elsdenii, Blautia, Butyricimonas, Bacteroides, and Phascolarctobacterium, together with a reduction in opportunistic and dysbiosis-associated taxa, such as Enterocloster bolteae, Anaerobiospirillum spp., and Stenotrophomonas maltophilia. Functional profiling showed a reduction in pathways related to virulence-associated mechanisms and iron siderophore systems, alongside an increase in pathways associated with GABA and putrescine metabolism and serine endopeptidase activity. Overall, these findings suggest that supplementation with these functional botanical ingredients may promote a more balanced and functionally beneficial gut microbiome in healthy dogs. Full article
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22 pages, 8654 KB  
Article
Early-Life Compound Probiotic Intervention Programs Intestinal Barrier Maturation Through Indole-3-Lactic Acid in a Porcine Model
by Mingzhi Yang, Huan He, Jie Fu, Zhixin Yu, Wentao Li, Lixia Kai, Caihong Hu, Jie Feng, Tizhong Shan, Yizhen Wang, Mingliang Jin and Zeqing Lu
Nutrients 2026, 18(17), 2776; https://doi.org/10.3390/nu18172776 - 25 Aug 2026
Viewed by 120
Abstract
Background: The early-life gut microbiota plays a critical role in programming intestinal barrier function and immune homeostasis, with profound implications for long-term host health. However, the effects of early-life compound probiotic intervention on the maturation of intestinal barrier function and the underlying [...] Read more.
Background: The early-life gut microbiota plays a critical role in programming intestinal barrier function and immune homeostasis, with profound implications for long-term host health. However, the effects of early-life compound probiotic intervention on the maturation of intestinal barrier function and the underlying molecular mechanisms remain incompletely understood, particularly in large-animal models relevant to human physiology. Methods: In this preclinical study, 3627 neonatal piglets—a well-established translational model for human infant gut development—were orally administered a novel compound probiotic formulation comprising Bifidobacterium longum subsp. infantis BZ, Lactobacillus plantarum LZ, and Pediococcus acidilactici PZ during early life. A total of 1512 fecal samples collected at seven time points from birth to day 180 were analyzed by 16S rRNA sequencing, and 525 samples from three developmental windows (days 10, 25, and 70) were subjected to LC-MS-based metabolomics. The candidate metabolite indole-3-lactic acid (ILA) was further mechanistically validated in a DSS-induced colitis mouse model and in IPEC-J2 cells. Results: Early-life probiotic intervention significantly enhanced intestinal barrier integrity, as evidenced by improved intestinal morphology and upregulated expression of tight junction proteins—zonula occludens-1 (ZO-1), occludin (OCLN), and Claudin-1 (CLDN1)—in the jejunum (p < 0.05). Notably, intervention at birth was more effective than post-weaning administration, and two administrations (birth + weaning) yielded superior outcomes compared with a single administration (p < 0.05). Microbiome analysis revealed enhanced microbial diversity and enrichment of beneficial genera during the juvenile-to-adult transition (p < 0.05). Metabolomic profiling identified ILA as a signature metabolite consistently elevated by probiotic supplementation. Conclusions: These findings provide evidence that early-life compound probiotic intervention is associated with improved intestinal barrier maturation, with ILA identified as a key candidate metabolite that may mediate this effect, as supported by functional validation in murine and cellular models. This provides a mechanistic rationale for probiotic-based strategies to support intestinal health in human infants during critical developmental windows. Full article
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25 pages, 4891 KB  
Review
Toward AI-Driven Detection of Asymptomatic Chronic Conditions from Stool Metagenomics and Dietary Data: A Multimodal Deep Learning Framework for T1DM, T2DM, MOS/PCOS, Cancer, and Autoimmune Disease
by Károly Szili, Csilla Dézsi, Viktor Gulyás-Oldal, Dániel Sallai, Gábor Patay, Ekaterine Paschali and Sándor Nagy
Microorganisms 2026, 14(9), 1880; https://doi.org/10.3390/microorganisms14091880 - 24 Aug 2026
Viewed by 457
Abstract
Chronic non-communicable conditions—type 1 and type 2 diabetes mellitus (T1DM, T2DM), metabolic obesity syndrome (MOS), polycystic ovary syndrome (PCOS), colorectal and extra-intestinal cancers, and systemic autoimmune disease—share a prolonged asymptomatic phase during which conventional screening is invasive, insensitive, or resource-intensive. This review synthesizes [...] Read more.
Chronic non-communicable conditions—type 1 and type 2 diabetes mellitus (T1DM, T2DM), metabolic obesity syndrome (MOS), polycystic ovary syndrome (PCOS), colorectal and extra-intestinal cancers, and systemic autoimmune disease—share a prolonged asymptomatic phase during which conventional screening is invasive, insensitive, or resource-intensive. This review synthesizes the 2021–2026 literature on fecal microbiome-based artificial intelligence (AI) diagnostics across these conditions, extracting reported discrimination, validation strategy, microbial and short-chain fatty acid (SCFA) biomarkers, and cross-cohort reproducibility. Across the primary classifier studies tabulated here, reported areas under the curve (AUCs) span 0.76–0.99 under internal validation but 0.69–0.91 under external or cross-population validation; in the four studies reporting both, the median AUC falls from 0.875 to 0.810. Verified external-validation values include 0.82 for colorectal cancer, 0.79 for T2DM and 0.792 for discrimination of systemic lupus erythematosus from rheumatoid arthritis and controls. Clinical readiness turns on this internal-to-external gap more than on the headline AUC. We propose a multimodal deep learning architecture coupled with explainable AI; no component has been implemented or evaluated on data, and it is presented as a design proposal. Fecal-microbiome-based multimodal AI is technically feasible but clinically unvalidated, pending prospective, harmonized cross-cohort trials. Full article
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32 pages, 2122 KB  
Review
Microbiome–Immune Interactions as Determinants of Checkpoint Inhibitor Efficacy in Hepatocellular Carcinoma
by Madalina Raluca Ostafe, Simona Ruxandra Volovat, Ana Clement, Cezara Ioana Litcanu, Smaranda Iuliana Tabarcea, Cristian Constantin Volovat, Diana-Ioana Panaite, Iolanda Georgiana Augustin and Constantin Volovat
Int. J. Mol. Sci. 2026, 27(17), 7543; https://doi.org/10.3390/ijms27177543 - 23 Aug 2026
Viewed by 748
Abstract
Hepatocellular carcinoma (HCC) remains a major global health challenge and one of the leading causes of cancer-related mortality, with advanced disease continuing to be associated with limited therapeutic options and substantial heterogeneity in response to systemic treatment. Recent evidence has established the gut [...] Read more.
Hepatocellular carcinoma (HCC) remains a major global health challenge and one of the leading causes of cancer-related mortality, with advanced disease continuing to be associated with limited therapeutic options and substantial heterogeneity in response to systemic treatment. Recent evidence has established the gut microbiota, through the gut–liver axis, as a critical determinant of immunotherapy efficacy, while also influencing antitumor immunity and liver carcinogenesis. Microbial dysbiosis may promote chronic inflammation, intestinal barrier disruption, bacterial translocation, and immune dysfunction, thereby contributing to hepatocarcinogenesis. Moreover, gut microbial composition and microbial-derived metabolites, including bile acids, short-chain fatty acids (SCFAs), and inosine, have been associated with modulation of antitumor immune responses and differential outcomes to immune checkpoint inhibitors (ICIs). Emerging clinical evidence in HCC has identified distinct gut microbial signatures associated with response to nivolumab, pembrolizumab, and atezolizumab-based regimens, including enrichment of Akkermansia muciniphila and SCFA-producing taxa such as Ruminococcaceae, Roseburia, and Prevotella in responders. However, these findings remain inconsistent across studies, with no reproducible microbial signature identified because of small cohort sizes, heterogeneous patient populations, geographic variation, cirrhosis-related confounding factors, and methodological differences in microbiome analysis. This review summarizes the current understanding of microbiome–immune interactions in HCC, examines mechanistic pathways linking the microbiota to immunotherapy response, critically evaluates available clinical evidence, and discusses current limitations and future therapeutic strategies, including fecal microbiota transplantation, probiotics, dietary modulation, and engineered bacterial platforms. Collectively, microbiome-based approaches may contribute to the development of personalized immunotherapeutic strategies in HCC, although larger standardized prospective studies are required before microbiome-derived biomarkers can be implemented in routine clinical practice. Full article
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21 pages, 7432 KB  
Article
Exercise Training Transiently Increases Gut Microbiota Diversity and Short-Chain Fatty Acid Production in a Diet-Dependent Manner in Healthy Adults
by Seonhong Hwang, Xuangao Wu, Jang-Won Yoon, In-Cheol Jeon, Young-In Hwang, Ki-Song Kim and Sunmin Park
Microorganisms 2026, 14(9), 1867; https://doi.org/10.3390/microorganisms14091867 - 22 Aug 2026
Viewed by 227
Abstract
Exercise alters gut microbiome composition, but the temporal dynamics and diet-dependent metabolic interactions remain unclear. We investigated longitudinal changes in gut microbiota, functional pathways, and metabolite profiles during and after an exercise intervention. Twenty-four healthy adults completed a sequential three-phase protocol: an 8-week [...] Read more.
Exercise alters gut microbiome composition, but the temporal dynamics and diet-dependent metabolic interactions remain unclear. We investigated longitudinal changes in gut microbiota, functional pathways, and metabolite profiles during and after an exercise intervention. Twenty-four healthy adults completed a sequential three-phase protocol: an 8-week self-directed exercise intervention, an 8-week washout, and an 8-week no-exercise control period. Fecal samples were collected at T1 (baseline), T2 (post-exercise), T3 (post-washout), and T4 (post-control). Microbiota composition was assessed by 16S rRNA sequencing, functional pathways predicted using PICRUSt2, metabolites predicted using COBRA Toolbox, and fecal SCFAs and bile acids quantified by GC and HPLC. Temporal causal relationships were examined using Tigramite analysis with dietary pattern stratification, and microbiota-environment associations were assessed by redundancy analysis (RDA). Alpha diversity was significantly higher at T2 than at T4 (p < 0.05). Beta diversity differed significantly between T2 and both T3 and T4, with no difference between T1 and T4, indicating reversibility. Ruminococcus gnavus was significantly higher at T2 than at T4 (p < 0.001), with several additional taxa higher at T2 at a less stringent threshold. Propionate and butyrate were elevated at T2, while total bile acids were lower. Bacteroides thetaiotaomicron was positively associated with body weight in the total cohort and specifically under a balanced dietary pattern (BD), with no significant time-lagged associations detected under a Western-style diet (WSD). In RDA, taxa associated with body weight substantially overlapped with taxa found to increase during exercise, whereas physical performance measures showed no direct temporal association with microbiota composition in causal analysis. In conclusion, exercise-induced changes in the gut microbiome were not sustained after structured exercise ended, suggesting that continuous exercise may be required. Diet further shaped whether microbiota–host associations were detectable, underscoring dietary pattern as a factor for future microbiome-targeted exercise interventions. Full article
(This article belongs to the Special Issue Effects of Diet and Nutrition on Gut Microbiota)
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25 pages, 9696 KB  
Article
Distinct Inflammation-Associated Microbiome Signatures in Pediatric Non-IgE-Mediated Food Allergy
by Maria-Teodora Coșoreanu, Gratiela Gradisteanu Pircalabioru, Irina-Oana Lixandru-Petre, Mara-Ioana Ionescu, Andreea Ioan, Eliza-Elena Cinteză and Felicia Galoș
Int. J. Mol. Sci. 2026, 27(16), 7482; https://doi.org/10.3390/ijms27167482 - 21 Aug 2026
Viewed by 152
Abstract
Non-IgE-mediated food allergy is characterized by delayed gastrointestinal manifestations and the absence of reliable non-invasive biomarkers. Increasing evidence suggests that gut microbiota may contribute to this disease pathogenesis. The aim of this study was to characterize the gut microbiome composition in thirty pediatric [...] Read more.
Non-IgE-mediated food allergy is characterized by delayed gastrointestinal manifestations and the absence of reliable non-invasive biomarkers. Increasing evidence suggests that gut microbiota may contribute to this disease pathogenesis. The aim of this study was to characterize the gut microbiome composition in thirty pediatric patients diagnosed with non-IgE-mediated food allergy, in comparison to fifteen healthy controls children, and to investigate its association with fecal calprotectin, eosinophil-derived neurotoxin (EDN) and IgA. Gut microbiota profiling was performed by 16S rRNA gene sequencing targeting the V3–V4 region. Compared with healthy controls, higher mean relative abundances of Bacteroides, Faecalibacterium, Alistipes, Parabacteroides, and Sutterella were observed in patients. Conversely, healthy children showed higher mean relative abundances of Pseudobutyrivibrio, Roseburia, Bifidobacterium, Collinsella, Clostridium, Eubacterium, Streptococcus, and Barnesiella. Several genera (Escherichia–Shigella, Agathobacter, and Enterococcus/Streptococcus) were detected only in the allergy cohort. Shannon diversity was higher in patients compared to controls and in the subgroups of patients with elevated fecal calprotectin (p = 0.028), previous antibiotic exposure (p = 0.015), and atopic dermatitis (p = 0.021). Stratification according to inflammatory biomarkers identified a distinct inflammatory microbiome endotype characterized by increased fecal calprotectin and EDN together with enrichment of Veillonellaceae and depletion of Bifidobacteriaceae and Lachnospiraceae. Correlation analyses further revealed positive associations between Veillonella abundance and both fecal calprotectin and EDN. These findings suggest that pediatric non-IgE-mediated food allergy is characterized by distinct microbiome–inflammation relationships rather than a single dysbiotic signature. Full article
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29 pages, 736 KB  
Review
The Importance of the Gut–Muscle Axis: From Mechanistic Insights in Cell Culture and Rodent Models to Descriptive and Associative Evidence in Livestock
by Robert Ringseis, Klaus Eder and Denise K. Gessner
Animals 2026, 16(16), 2594; https://doi.org/10.3390/ani16162594 - 19 Aug 2026
Viewed by 275
Abstract
The gut microbiota is a metabolically active ecosystem that influences host physiology through bioactive metabolites and interactions with host signaling pathways. Recent research has established a bidirectional gut–muscle axis in which microbial metabolites and muscle-derived factors (myokines) regulate muscle protein synthesis, degradation, regeneration, [...] Read more.
The gut microbiota is a metabolically active ecosystem that influences host physiology through bioactive metabolites and interactions with host signaling pathways. Recent research has established a bidirectional gut–muscle axis in which microbial metabolites and muscle-derived factors (myokines) regulate muscle protein synthesis, degradation, regeneration, fiber-type specification, and overall muscle performance. Studies using germ-free, antibiotic-treated, probiotic-supplemented, and fecal microbiota transplantation models demonstrate that the gut microbiota is a critical determinant of skeletal muscle mass and function. Key mediators include short-chain fatty acids, bile acids, aromatic amino acid metabolites, microbial-associated molecular patterns, and methylamine metabolites. This review summarizes current mechanistic knowledge of gut–muscle communication and its relevance to livestock production. In monogastric livestock, particularly pigs and poultry, microbiota transplantation experiments and targeted probiotic interventions provide causal evidence that gut microbial communities influence muscle growth, muscle fiber composition, intramuscular fat deposition, carcass traits, and meat quality, including tenderness, marbling, water-holding capacity, and flavor. Several studies have also identified specific microbial taxa and metabolites capable of transferring desirable production phenotypes. In contrast, evidence in ruminants remains largely associative and originates mainly from multi-omics and dietary intervention studies. Future research should validate causal mechanisms, identify robust microbial biomarkers, and develop species-specific microbiome-based strategies for precision livestock production. Full article
(This article belongs to the Section Animal Physiology)
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14 pages, 692 KB  
Review
Microbiome Disturbance, Nutritional Vulnerability, and Treatment Tolerance in Pancreatic Ductal Adenocarcinoma: Mechanistic Links and Clinical Readiness
by Naotake Funamizu, Yasutaka Ihara, Kei Tamura, Yoshiaki Kamei and Yuzo Umeda
Cancers 2026, 18(16), 2658; https://doi.org/10.3390/cancers18162658 - 17 Aug 2026
Viewed by 271
Abstract
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive tumor biology and profound host vulnerability, including pancreatic exocrine insufficiency (PEI), maldigestion, malnutrition, cachexia, sarcopenia, frailty, systemic inflammation, and poor tolerance to multimodal therapy. Gut and intratumoral microbiota have been implicated in pancreatic carcinogenesis, [...] Read more.
Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive tumor biology and profound host vulnerability, including pancreatic exocrine insufficiency (PEI), maldigestion, malnutrition, cachexia, sarcopenia, frailty, systemic inflammation, and poor tolerance to multimodal therapy. Gut and intratumoral microbiota have been implicated in pancreatic carcinogenesis, tumor immunity, chemotherapy response, and postoperative outcomes. However, the clinical readiness of microbiome-informed supportive care in PDAC remains uncertain. Results: Current evidence supports plausible mechanistic links among PEI, maldigestion, dysbiosis, microbial metabolites, barrier dysfunction, systemic inflammation, cachexia, sarcopenia, and treatment intolerance. Nevertheless, PDAC microbiome research is limited by major heterogeneity in sampling sites, sequencing platforms, antibiotic exposure, biliary drainage, diet, treatment timing, tumor stage, and analytic pipelines. Evidence is also discordant, particularly regarding alpha diversity and reproducible microbial signatures. Low-biomass tissue contamination and incomplete consideration of fungal and multi-kingdom microbiota further limit interpretation. Conclusions: Microbiome disturbance should currently be viewed as an investigational modifier of nutritional vulnerability and treatment tolerance rather than as a validated clinical biomarker or therapeutic target in PDAC. A clinically responsible framework should distinguish what is actionable now—nutrition screening, PEI management, inflammation and frailty assessment, body-composition evaluation, and treatment-exposure monitoring—from what remains investigational, including microbiome profiling, microbial signatures, probiotics, prebiotics, fecal microbiota transplantation, and metabolite-guided intervention. Full article
(This article belongs to the Section Clinical Research in Cancer)
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23 pages, 14484 KB  
Article
Gut Microbiota Signatures and Ecological Network Alterations Associated with Hemodialysis
by Nisrine Souai, Oumaima Zidi, Panagiota Stathopoulou, Anis Bafoun, Oussama Souiai, Mariem Hanachi, Elias Asimakis, Ameur Cherif, Amor Mosbah, George Tsiamis and Soumaya Kouidhi
Microorganisms 2026, 14(8), 1791; https://doi.org/10.3390/microorganisms14081791 - 14 Aug 2026
Viewed by 277
Abstract
Hemodialysis (HD) is the most widely used renal replacement therapy for patients with end-stage renal disease (ESRD) and is frequently accompanied by long-term complications that impair quality of life, including metabolic and inflammatory disturbances. Growing evidence suggests that these complications may be linked [...] Read more.
Hemodialysis (HD) is the most widely used renal replacement therapy for patients with end-stage renal disease (ESRD) and is frequently accompanied by long-term complications that impair quality of life, including metabolic and inflammatory disturbances. Growing evidence suggests that these complications may be linked to alterations in the gut microbiota; however, microbial composition and interaction patterns in HD patients remain incompletely characterized. In this exploratory, cross-sectional study, high throughput 16S rRNA gene sequencing was used to profile the fecal microbiota of patients undergoing hemodialysis and of healthy controls. The objective was to characterize associations between hemodialysis and gut microbial composition, ecological network organization, and predicted functional potential. Comparative analyses revealed significant differences in bacterial community structure and microbial networks in the HD cohort. Both gender and dialysis vintage were associated with variation in specific taxa, including increased detection of the Synergistetes phylum, particularly among male patients and those undergoing long-term HD. Associations were also observed between clinical and demographic factors and the relative abundance of several short-chain fatty acid-associated taxa, including members of the Lachnospiraceae and Ruminococcaceae families and the genus Bifidobacterium. Predicted functional potential (PICRUSt2) indicated distinct microbial metabolic profiles in HD patients compared with controls, particularly in pathways related to carbohydrate, nucleotide, and amino acid metabolism, with additional variation according to dialysis vintage. Overall, these findings provide an exploratory characterization of structural, compositional, and predicted functional alterations of the gut microbiota associated with hemodialysis. Although the modest cohort size precludes definitive conclusions, the results support the rationale for larger, longitudinal studies investigating microbiota-derived biomarkers and host–microbiome interactions in ESRD. Full article
(This article belongs to the Section Environmental Microbiology)
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19 pages, 6092 KB  
Article
Chronic Intermittent Hypoxia Disrupts Intestinal Homeostasis Through Gut Microbiota Remodeling and Microbiota-Metabolite Interactions
by Yuying He, Jun Gao, Qiang Li, Chuxi Zhang, Mingrui Zhai and Yuehua Liu
Biomolecules 2026, 16(8), 1186; https://doi.org/10.3390/biom16081186 - 14 Aug 2026
Viewed by 248
Abstract
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which contributes to systemic metabolic disorders. However, the mechanisms underlying CIH-induced intestinal dysfunction remain unclear. In this study, we investigated the effects of CIH on intestinal barrier integrity, gut microbiota, and host [...] Read more.
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which contributes to systemic metabolic disorders. However, the mechanisms underlying CIH-induced intestinal dysfunction remain unclear. In this study, we investigated the effects of CIH on intestinal barrier integrity, gut microbiota, and host metabolism using a multi-omics approach. Male C57BL/6J mice were exposed to six weeks of CIH or normoxia. Colonic barrier integrity was assessed by histological and molecular analyses. Gut microbiota was profiled by full-length 16S rRNA gene sequencing. Untargeted metabolomics was performed on fecal and serum samples, followed by integrated microbiome–metabolome analysis. CIH markedly impaired colonic barrier integrity, as evidenced by disrupted crypt architecture, reduced goblet cell abundance, and decreased expression of ZO-1, Occludin, and Claudin-5. CIH also induced gut microbial dysbiosis, characterized by depletion of the beneficial mucin-associated bacterium Akkermansia muciniphila and enrichment of several anaerobic taxa. Metabolomic analysis revealed opposite alterations of PC (20:2/0:0) and LysoPE (20:5/0:0) between feces and serum, whereas melatonin was consistently decreased in both compartments. Integrated multi-omics analysis further revealed close associations between microbial dysbiosis and metabolic remodeling. Collectively, these findings demonstrate that CIH disrupts intestinal homeostasis through coordinated alterations in barrier integrity, gut microbiota composition, and host metabolism, providing new insights into the intestinal mechanisms underlying OSA-associated systemic dysfunction. Full article
(This article belongs to the Special Issue Gut Microbiome and Related Diseases in Animals)
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24 pages, 12804 KB  
Review
Beyond the Lungs: ICU Oral Care and Gut Resilience—A Hypothesis-Generating Narrative Review
by Tingting Jin, Xueqiang Sun, Xing Zhao and Jiancheng Zhang
Microorganisms 2026, 14(8), 1772; https://doi.org/10.3390/microorganisms14081772 - 12 Aug 2026
Viewed by 482
Abstract
The oral and gut microbiomes form an interconnected ecosystem that may influence host defense. In the intensive care unit (ICU), endotracheal intubation, broad-spectrum antibiotics, and proton pump inhibitors can disrupt physiological barriers and may facilitate ectopic gut colonization by oral pathobionts. Such translocation [...] Read more.
The oral and gut microbiomes form an interconnected ecosystem that may influence host defense. In the intensive care unit (ICU), endotracheal intubation, broad-spectrum antibiotics, and proton pump inhibitors can disrupt physiological barriers and may facilitate ectopic gut colonization by oral pathobionts. Such translocation could contribute to intestinal inflammation, barrier dysfunction, and systemic immune dysregulation; however, direct clinical evidence in critically ill patients remains limited and largely associative, and much of the mechanistic evidence derives from animal models or non-ICU populations. This hypothesis-generating narrative review synthesizes evidence across oral microbiology, gastroenterology, immunology, and critical care, while explicitly distinguishing clinically observed associations from preclinical mechanisms and proposed ICU pathways. Current evidence supports mechanical toothbrushing as a core component of oral care, whereas routine non-selective chlorhexidine use warrants caution. Saline irrigation and selective oropharyngeal decontamination may be considered in context, but evidence for protecting the gut through oral care remains insufficient for definitive practice recommendations. We also examine probiotics, prebiotics, postbiotics, and fecal microbiota transplantation as investigational approaches and propose standardized prospective multicenter studies to test the oral–gut axis framework. Full article
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31 pages, 12782 KB  
Article
Gut Microbiome and Metabolome Responses to Fermented Fish Paste (Kapi-pla) in a Simulated Colonic Model of Alzheimer’s Disease
by Nisa Alfilasari, Nattha Tampanna, Nualpun Sirinupong and Santad Wichienchot
Fermentation 2026, 12(8), 380; https://doi.org/10.3390/fermentation12080380 - 11 Aug 2026
Viewed by 278
Abstract
Bioactive peptides (BPs) are increasingly recognized for modulating the gut microbiome, metabolome, and brain function via the gut–brain axis. Kapi-pla, a traditional Thai fermented freshwater fish paste rich in proteins and peptides, is widely consumed in Southern Thailand. This study profiled the peptides [...] Read more.
Bioactive peptides (BPs) are increasingly recognized for modulating the gut microbiome, metabolome, and brain function via the gut–brain axis. Kapi-pla, a traditional Thai fermented freshwater fish paste rich in proteins and peptides, is widely consumed in Southern Thailand. This study profiled the peptides of Phatthalung Kapi-pla (PK) and Songkhla Kapi-pla (SK) and investigated their impacts on gut microbiota and metabolome using a simulated colonic fermentation model with fecal samples from patients with Alzheimer’s disease (AD). Microbial composition and metabolites were assessed by 16S rRNA sequencing and LC–MS/MS, respectively. After 24 h fermentation, PK modestly increased Shannon diversity relative to the unsupplemented control, with richness indices unchanged, reduced Proteobacteria abundance and opportunistic pathogens such as Escherichia–Shigella and Klebsiella, and selectively increased short- and branched-chain fatty acids, including acetate, propionate, butyrate, and iso-valerate. PK further enhanced neuroactive metabolites relevant to AD pathology, underscoring its potential as a functional food ingredient to ameliorate AD-associated dysbiosis and support gut–brain axis health. Full article
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22 pages, 11834 KB  
Article
Microbiome Responses of Beef Steers to Rotational Grazing of Toxic Endophyte-Infected Tall Fescue Under Fall Conditions
by Ignacio M. Llada, Jeferson M. Lourenco, Mikayla M. Dycus, Utsav Lamichhane, Matthew K. Ross, Garret Suen, Dean P. Jones, Nicholas S. Hill and Nikolay M. Filipov
Animals 2026, 16(16), 2497; https://doi.org/10.3390/ani16162497 - 11 Aug 2026
Viewed by 225
Abstract
Fescue toxicosis results from ingestion of tall fescue infected with the ergot alkaloid (EA)-producing endophyte Epichloë coenophiala. The gastrointestinal microbiota is the first point of interaction with EAs and may be modulated by them. To investigate this, rumen and fecal samples were [...] Read more.
Fescue toxicosis results from ingestion of tall fescue infected with the ergot alkaloid (EA)-producing endophyte Epichloë coenophiala. The gastrointestinal microbiota is the first point of interaction with EAs and may be modulated by them. To investigate this, rumen and fecal samples were collected from steers grazing toxic (E+) or non-toxic fescue for 14 days, followed by a pasture switch. Microbial communities were characterized using 16S rRNA amplicon sequencing (bacterial V4, archaeal V6-V8 regions). Short-term E+ grazing did not affect alpha diversity in either matrix, but beta diversity differences were significant, though of small magnitude (rumen: R2 < 0.07; feces: R2 < 0.06), consistent with the overlap of communities between treatments. Relative abundance (RA) of dominant taxa remained unchanged, but low-abundance taxa were enriched in E+. In the rumen, these included proteolytic, amino acid decarboxylating, and methyl-compound forming microbes (e.g., Clostridia, Prevotellaceae, Lachnospiraceae (Butyrivibrio, Eubacterium), Streptococcaceae, and Gamma/Alphaproteobacteria), while fibrolytic taxa (e.g., Ruminococcus flavefaciens) declined. Hydrogenotrophic methanogens (Methanobrevibacter_A) decreased, while methylotrophic methanogens and hydrogen-utilizing bacteria (e.g., Selenomonadaceae) increased, indicating altered hydrogen flow in the rumen. Similar subtle but significant shifts were observed in fecal communities, including members of Lachnospiraceae (Eubacterium) and Rikenellaceae (Mucinivorans). Comparable RA of core (dominant) rumen and fecal microbiomes in steers previously exposed and never exposed to E+ fescue suggests no lasting effects on the dominant community. Short-term exposure to E+ tall fescue was associated with enrichment of low-abundance taxa whose previously described metabolic functions may contribute to maintaining rumen homeostasis under E+-induced dietary stress. Full article
(This article belongs to the Collection Cattle Diseases)
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Review
Gut Microbiota in Type 2 Diabetes and Metabolic Disorders: Sources of Heterogeneity and Ways to Resolve Contradictions in Research
by Ekaterina Nesterova, Maria Gladkikh, Inna Burakova, Olga Korneeva, Polina Morozova and Mikhail Syromyatnikov
Diabetology 2026, 7(8), 153; https://doi.org/10.3390/diabetology7080153 - 11 Aug 2026
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Abstract
Metabolic diseases, including obesity and type 2 diabetes mellitus, represent a major global health burden and are closely linked to the composition and function of the gut microbiota. Advances in molecular methods have enabled detailed characterization of microbial communities and their interactions with [...] Read more.
Metabolic diseases, including obesity and type 2 diabetes mellitus, represent a major global health burden and are closely linked to the composition and function of the gut microbiota. Advances in molecular methods have enabled detailed characterization of microbial communities and their interactions with diet, medications, and host physiology, positioning the microbiome as an active metabolic organ. However, the field faces persistent challenges in distinguishing causal relationships from associations, largely owing to substantial biological, exposure-related, and methodological heterogeneity. This review systematizes the principal lines of evidence connecting the gut microbiome to metabolic disorders and critically examines the sources of variability that limit reproducibility and cross-cohort transferability of these findings. We discuss the taxonomic, functional, and metabolite-based levels of microbiome analysis, evaluate the strengths and limitations of cross-sectional, case–control, cohort, and interventional study designs, and consider approaches for establishing causality, including fecal microbiota transplantation, Mendelian randomization, mediation analysis, causal diagrams, and triangulation of evidence. We conclude that only a comprehensive, standardized, and causally informed approach will allow reliable discrimination between true microbiota-driven effects and methodological artifacts, thereby advancing the integration of microbiome science into the management of metabolic diseases and diabetes. Full article
(This article belongs to the Section Prevention and Public Health Management of Diabetes)
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