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PubMed2026

Differentiating hemorrhagic shock and organophosphate poisoning through integrated skin microbiome-metabolome signatures.

Accurate determination of cause of death and estimation of postmortem interval (PMI) are critical yet challenging tasks in forensic science, particularly in cases with rapid demise and absence of obvious morphological abnormalities. We employed an integrative multi-omics approach to characterize postmortem microbial succession and metabolic alterations on facial skin in mouse models of hemorrhagic shock (HS) and organophosphorus poisoning (OP) across three decomposition stages: bloating (2 days), active decay (8 days), and advanced decay (16 days). Metagenomic profiling revealed significantly reduced α-diversity in HS compared with OP throughout all stages (p < 0.001), accompanied by stage-dependent compositional shifts, including early enrichment of Firmicutes in HS and Proteobacteria in OP. A total of 237 differential taxa were identified, with Providencia and Morganella predominating in OP, whereas Staphylococcus and Corynebacterium dominated bloating stage of HS. Untargeted metabolomics uncovered distinct cause-of-death-linked metabolites, notably elevated 2'-deoxycytidine-5'-diphosphate in early OP and persistent cholic acid/cholate accumulation in HS at later PMI. Functional analysis highlighted histidine and phosphate/phosphonate metabolism as key discriminatory pathways, exhibiting stage-specific oscillations and strong correlations with characteristic taxa. These findings demonstrate that skin-based metagenomic-metabolomic integration provides robust, mechanistically informed biomarkers for both PMI estimation and cause-of-death differentiation, offering a minimally invasive and temporally dynamic tool for forensic investigations.

Animals↗

PubMed2026

Integrated functional genomics and safety assessment of plant-growth-promoting Caryophanales from post-maize-cultivation soils.

This study aimed to evaluate six environmental bacterial strains isolated from post-maize cultivation soils as candidates for agricultural biopreparation development, using an integrated functional genomic and safety assessment framework. Building on experimental validation of plant-growth-promoting activities, the analysis included: plant-growth-promoting traits (PGPT-Pred) using PLABase; carbohydrate-active enzymes (CAZymes) relevant for lignocellulosic crop residue degradation (dbCAN3); secondary metabolite profiles (antiSMASH); and screening for virulence factors and antibiotic resistance genes (ABRicate, BTyper3).All analyzed strains possess 1,449-1,617 predicted PGPT-encoding genes (24.1-35.9% of total genes), which are strongly shaped by taxonomic relatedness, as confirmed by congruence testing against ANI-based genomic divergence. Paenibacillus amylolyticus 5mez and Priestia megaterium 7psych showed distinct functional profiles compared to Bacillus spp., while Bacillus subtilis sensu lato strains were most similar to each other. Genomic predictions suggest involvement in nutrient acquisition (N, P, K, Fe) and stress mitigation. Secondary metabolite analysis revealed high biosynthetic potential, with non-Bacillus species harbouring a large proportion of unknown gene clusters, indicating underexplored metabolite diversity. CAZyme profiling identified P. amylolyticus 5mez as the most enzyme-rich strain, while B. cereus s.s. zielonkawy showed ligninolytic potential despite low overall CAZyme abundance. The safety assessment identified B. cereus s.s. zielonkawy as toxigenic and unsuitable for use. Of the remaining strains, P. amylolyticus 5mez and Pr. megaterium 7psych demonstrated the most favourable safety profiles, exhibiting no detectable virulence factors or antibiotic resistance genes, justifying their priority use in agricultural biopreparations, pending phenotypic validation. Given the high-dimensional, low-sample-size nature of multi-trait datasets in applied microbial genomics, tailored statistical approaches, including noise-reduction-validated PCA and distance-based congruence testing, were applied; their rationale and limitations are discussed.

Soil Microbiology↗

PubMed2026

From regionalization to homogenization: Nationwide metagenomic assessment of priority pathogens and the resistome in Polish hospital wastewater.

Hospital wastewater (HWW) is a critical hotspot for the dissemination of antibiotic resistance genes (ARGs) and pathogens. This study provides the first comprehensive metagenomic characterization of HWW across Poland, analyzing 64 medical facilities across two seasons via Nanopore long-read sequencing (total of 128 HWW samples). The HWW microbiome was mostly dominated by Proteobacteria, Bacteroidota, and Firmicutes. Multivariate analysis confirmed a significant seasonal shift in the resistome. Winter samples exhibited geographic regionalization, with localized hotspots of specific ARGs, including vancomycin resistance (operon van) and carbapenemase genes (blaOXA, blaNDM). Conversely, summer samples showed a significant trend toward nationwide homogenization, characterized by a uniform distribution of ESBL genes (blaTEM, blaCTX-M) and multidrug resistance (MDR) determinants, alongside the persistence of localized clinical hotspots. Klebsiella pneumoniae emerged as a central network hub, particularly in summer, showing strong correlations with ESBLs. Quantitative genomic co-occurrence analysis revealed a functional division within dominant taxa: while environmental species like Acinetobacter johnsonii comprised the general background microbiome, clinical pathogens such as Acinetobacter baumannii served as primary vectors, showing frequent associations with high-risk ARGs. Environmental and opportunistic bacteria, such as Aeromonas spp. and Citrobacter spp., were identified as putative 'bridge hosts' associated with mobile resistance determinants and potentially contributing to HGT. The findings indicate that seasonal factors, such as increased temperature and sub-inhibitory antibiotic concentrations, may contribute to the transition from regionalized to homogenized resistance profiles, demonstrating that background resistome convergence can coexist with point-source clinical outbreaks. This seasonal "blurring" of regional boundaries positions HWW as an active vector for large-scale antimicrobial resistance (AMR) dissemination. These results underscore the urgent need for nationwide metagenomic surveillance and advanced wastewater treatment strategies within the "One Health" framework to mitigate the environmental spread of WHO priority pathogens.

Acinetobacter baumannii↗

PubMed2025

Concurrent stimulation of diflufenican biodegradation and changes in the active microbiome in gravel revealed by Total RNA.

The use of slowly degraded pesticides poses a particular problem when these are applied to urban areas such as gravel paths. The urban gravel provides an environment very different from agricultural soils; i.e., it is both lower in carbon and microbial activity. We, therefore, endeavored to stimulate the degradation of the pesticide diflufenican added to urban gravel microcosms amended with dry alfalfa to increase microbial activity. In the present study, alfalfa addition significantly increased the formation of diflufenican's primary metabolite, 2-[3-(trifluoromethyl)phenoxy]nicotinic acid (AE-B), indicating stimulated biotransformation. The concurrent changes of the active microbial communities within the gravel were explored using shotgun metatranscriptomic sequencing of ribosomal RNA and messenger RNA. Although bacterial taxa remained dominant (87.0%-98.5% relative abundance), the alfalfa treatment led to a 4-5-fold increase in eukaryotic groups, including fungi and microbial grazers. Several microbial taxa potentially involved in the degradation of complex carbon compounds and aromatic pollutants-including Bacteroidetes, Verrucomicrobia, Sordariomycetes, Mortierellales, Tremellales, Sphingopyxis, and Phenylobacterium-increased in relative abundance following alfalfa amendment. Functional gene profiling revealed elevated expression of genes related to microbial activity and biomass production. Genes with potential roles in the breakdown of complex carbon structures (e.g., xylanases/chitin deacetylases) and in the transformation of aromatic compounds (e.g., ring-cleaving dioxygenases) were revealed. We conclude that complex carbon amendments can enhance the microbial activity, promoting the biotransformation of diflufenican in urban gravel environments. These findings provide new insights into the interactions between microbial community dynamics, gene expression profiles, and pesticide biotransformation in non-agricultural matrices.IMPORTANCEPesticides used on urban areas, e.g., gravel paths, are likely to have different effects and fates than when these are used on agricultural soils. Hence, studies into the degradation of pesticides applied to urban matrices are needed. We have previously shown that metabolites of the persistent pesticide diflufenican are even more persistent in urban soils, and it has also previously been shown that these metabolites leach from gravel surfaces. The reasons behind this are that the urban gravel provides an environment very different from agricultural soils; i.e., it is both lower in carbon and microbial activity. In the present study, we, therefore, endeavored to stimulate the degradation of the pesticide diflufenican added to urban gravel microcosms amended with dry alfalfa to increase microbial activity, concurrently studying the changes in the active microbiome by Total RNA-metatranscriptomics.

Biodegradation, Environmental↗

PubMed2022

Characterizing the metabolic effects of the selective inhibition of gut microbial β-glucuronidases in mice.

The hydrolysis of xenobiotic glucuronides by gut bacterial glucuronidases reactivates previously detoxified compounds resulting in severe gut toxicity for the host. Selective bacterial β-glucuronidase inhibitors can mitigate this toxicity but their impact on wider host metabolic processes has not been studied. To investigate this the inhibitor 4-(8-(piperazin-1-yl)-1,2,3,4-tetrahydro-[1,2,3]triazino[4',5':4,5]thieno[2,3-c]isoquinolin-5-yl)morpholine (UNC10201652, Inh 9) was administered to mice to selectively inhibit a narrow range of bacterial β-glucuronidases in the gut. The metabolomic profiles of the intestinal contents, biofluids, and several tissues involved in the enterohepatic circulation were measured and compared to control animals. No biochemical perturbations were observed in the plasma, liver or gall bladder. In contrast, the metabolite profiles of urine, colon contents, feces and gut wall were altered compared to the controls. Changes were largely restricted to compounds derived from gut microbial metabolism. This work establishes that inhibitors targeted towards bacterial β-glucuronidases modulate the functionality of the intestinal microbiota without adversely impacting the host metabolic system.

Mice↗

PubMed2026

Metagenomic analysis of the midgut microbiome in Dermacentor abaensis ticks at different feeding states.

Ticks are blood-sucking ectoparasites of humans and animals, ranking second only to mosquitoes as vectors of diseases. Dermacentor abaensis is distributed in Sichuan, Qinghai, and Gansu, China. Because D. abaensis harbors several pathogens, it poses a threat to public health and livestock production. However, the midgut microbiota of D. abaensis at distinct feeding states remains poorly characterized. Adult D. abaensis ticks at various feeding states were collected from yaks in Gansu Province, China. Genomic DNA was extracted from midguts and midgut contents of unfed, partially fed, and fully engorged female D. abaensis. A metagenomic sequencing approach was employed to profile the midgut microflora among three groups. A total of 83 phyla, 908 genera, and 1857 species were annotated across the three groups. At the phylum level, Pseudomonadota, Mucoromycota, and Ascomycota were the most abundant. At the species level, common bacterial species such as Klebsiella pneumoniae and Anaplasma phagocytophilum, alongside viruses and eukaryotes, were detected in all three groups. Unique microorganisms were also observed in each group: unfed (n = 305), partially fed (n = 59), and fully engorged (n = 20). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that the D. abaensis microbiome contains a relatively high abundance of functional genes involved in lipid and amino acid metabolism across the three different feeding states. These findings indicate that while core microbial taxa are shared in the midgut of female D. abaensis, observable trends suggest variations in microbial diversity and composition as blood-feeding progresses. The present study provides a descriptive baseline of the midgut microbial composition of D. abaensis, which may inform future studies on tick biology and the ecology of tick-borne pathogens.

Animals↗

PubMed2026

Gut microbiome composition and predicted functions relate to growth and behavior in a Japanese preschool cohort.

Early childhood is a period of rapid brain maturation and gut microbiome assembly, when emerging behavioral difficulties can shape later mental health and learning trajectories. Microbiota-gut-brain communication has been implicated in neurodevelopment through microbial metabolites and immune signaling. However, most pediatric evidence comes from high-risk or clinically referred cohorts, and gut microbiome-related correlates of typical behavioral variation in community-based preschool children remain poorly defined. In a cross-sectional sample of typically developing Japanese preschool children, we observed exploratory nominal associations between behavioral variation within normative ranges and gut microbiome composition and predicted functions. Internalizing domains showed candidate links with taxa and predicted pathways related to inflammatory potential and nucleotide biosynthesis, whereas somatic complaints and withdrawn behavior showed nominal associations with lower predicted respiratory and fermentative activity. Sleep-related difficulties showed multiple representative nominal pathway-level associations, including pathways related to methyl-donor and heme biosynthesis, while externalizing domains showed candidate links with predicted cell-envelope and carbohydrate-remodeling pathways. In contrast, age, height, and weight tracked expected maturation-related microbiome features, indicating that behavioral associations were not simple proxies of growth. Together, these findings provide an exploratory profile of microbiome-behavior correlations in a low-risk Japanese preschool cohort and highlight pathway-level candidates that may interface with neurodevelopment.

Humans↗

PubMed2026

Airway microbiome diversity, intramucosal bacteria, and spatial immunity in asthmatic adults and controls.

RATIONALE: Asthma is characterized by disruption of the thoracic airway mucosae and loss of microbial diversity. Spatial profiling of the mucosal transcriptome may systematically discover mechanisms for microbial influences on immunity. OBJECTIVES: We investigated relationships between clinical measures, microbial communities, and the host mucosal transcriptome within different strata of bronchial biopsies in subjects with and without asthma. METHODS: We performed bronchoscopy in 65 asthmatic adults and 44 healthy controls, quantifying bacterial operational taxonomic units (OTUs) in bronchial brushings by 16S ribosomal RNA (rRNA) gene amplicon sequences. Biopsy histologic features were scored blind to diagnosis. Following 16S rRNA in situ hybridization of 44 biopsies, bacterial foci were scored in epithelium, basement membrane, and stroma. Global human gene expression was quantified in epithelial and stromal compartments using digital spatial profiling. MEASUREMENTS AND MAIN RESULTS: Clinical asthma was independently predicted by basement membrane abnormalities (BaseMA), endobronchial bacterial diversity, and circulating eosinophil counts, but not by specific OTU abundances. 16S rRNA staining revealed bacteria within epithelium and mucosa of all biopsies. Intramucosal bacteria counts correlated negatively with spatially organized coexpression networks encoding antigen-specific immunity, neutrophil functions, and matrix activation, whereas BaseMA correlated positively with the adaptive immunity module. Eosinophil counts correlated with epithelial bacterial counts and senescence pathways. Clinical asthma was accompanied by upregulation of a regulatory T-cell network. CONCLUSIONS: Asthma and its related phenotypes are accompanied by complex mucosal events that extend beyond eosinophilic pathways. Components of diverse airway microbiota may modify immunity by beneficial interactions within the mucosa.

Humans↗

PubMed2026

Metagenomic profiling of blood-associated microbial DNA signatures in leukemia-associated febrile neutropenia.

Febrile neutropenia (FN) is a life-threatening complication of chemotherapy, but the low microbial biomass of blood makes shotgun metagenomic profiles highly sensitive to technical background. We reanalyzed 47 publicly available patient sequencing runs representing 43 unique patient-timepoint samples from 19 SRA-labeled patients, together with 23 no-template-control (NTC) runs spanning 21 sequencing batches. To distinguish reference-catalogue content from progressively stronger evidence of patient-associated signal, we applied batch-matched NTC correction together with nested abundance thresholds and a feature-specific global NTC envelope. CheckM2 evaluated 1,013 bins; 13 met completeness ≥50% and contamination <10%, and dereplication yielded 11 draft MAG representatives. Ten representatives showed positive patient-to-control abundance excess, but only four showed recurrent support above both threefold matched-control abundance and the global NTC envelope. Functional annotations were therefore interpreted as reference-genome homologs rather than evidence of expression, phenotype, viability or bloodstream origin. Matched-control correction retained 19 read-level ARG types, but only seven subjects contributed complete longitudinal ARG-profile contrasts, limiting reliable temporal inference. The resulting run-resolved, nested evidence framework identified a subset of microbial DNA and ARG signals that remained detectable under increasingly stringent control criteria while distinguishing them from catalogue-level or background-sensitive signals. These findings support cautious reporting of patient-enriched microbial DNA and ARG signals rather than inference of a resident blood microbiome or clinical resistance phenotype.

antimicrobial resistance genes↗

PubMed2026

Characterization of age-related changes in the gut microbiome and metabolome of Kunming dogs and their associations with police performance.

BACKGROUND: Gut microbiota plays a pivotal role in regulating the host's central nervous system (CNS) activity and behavior. However, its influence on the police performance of Kunming dogs and the underlying mechanisms remain largely unexplored. This study was the first to apply multi-omics technologies to investigate the dynamic variations in gut microbiota and their metabolic profiles across different ages of Kunming dogs. Furthermore, we systematically examined the associations between these microbial alterations and police performance metrics, providing a theoretical foundation for enhancing the working capabilities of Kunming dogs through targeted modulation of intestinal microecology. RESULTS: The study showed that puppies, young dogs and adult dogs had significantly better police performance than elderly dogs, with young dogs exhibiting the highest scores. Analysis of 16S rRNA sequencing demonstrated that gut microbial diversity and stability were highest during the young dog stage, gradually declining with age. Metagenomic analysis revealed that the abundance of Lactobacillus acidophilus, Lactobacillus johnsonii, Limosilactobacillus reuteri, Ligilactobacillus animalis and Muribaculum gordoncarteri were strongly correlated with police performance. The results of metagenome-assembled genomes (MAGs) indicated that the above species have functional genes involved in GABAergic and glutamatergic synapse pathways. Furthermore, metabolomic analysis showed that differential metabolites were enriched in the neuroactive ligand-receptor interaction pathway, in which GABA (γ-aminobutyric acid), histamine and tyramine metabolites were positively correlated with the above species and police performance. CONCLUSION: The species L. acidophilus, L. johnsonii, L. reuteri, L. animalis, and M. gordoncarteri, which were enriched in the gut of puppies and young Kunming dogs, may potentially influence the nervous system through the production of neurotransmitters and neuromodulators, suggesting a possible association with police performance. Video Abstract.

Animals↗

PubMed2026

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1α axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

Humans↗

PubMed2026

Multi-omics approaches in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic targets and precision medicine.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options and marked molecular heterogeneity. Despite available antifibrotic therapies, disease progression remains poorly predictable, highlighting the need for improved mechanistic understanding and therapeutic targeting. This review summarizes recent advances in multi-omics research to elucidate the molecular mechanisms underlying IPF and to identify potential biomarkers and pharmacological targets. Multi-omics studies, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiome profiling, and single-cell sequencing, have revealed key pathogenic mechanisms in IPF. Genetic susceptibility factors such as MUC5B promoter variants and telomere-related genes contribute to disease risk. Epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNAs, plays a central role in fibrotic remodeling. Transcriptomic and proteomic analyses have identified dysregulated signaling pathways, including TGF-β, mTOR, cellular senescence, and extracellular matrix remodeling. Metabolomic alterations indicate disrupted lipid and amino acid metabolism. Importantly, integration of multi-omics datasets enables the identification of molecular endotypes, candidate biomarkers, and potential therapeutic targets. However, challenges including data integration, tissue heterogeneity, limited cohort size, and the need for functional validation remain important barriers to clinical translation. Continued development of multi-omics approaches may facilitate more accurate disease classification and support the development of personalized therapeutic strategies for IPF.

biomarkers↗

PubMed2024

Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on the oropharyngeal metagenome in adolescents with cystic fibrosis.

BACKGROUND: Triple modulator therapy elexacaftor/tezacaftor/ivacaftor (ETI) improves lung function and impacts upon the respiratory microbiome in people with Cystic fibrosis (pwCF) with advanced lung disease. However, adolescents with cystic fibrosis (CF) are less colonized with bacterial pathogens than adult pwCF but their microbiota already differs from healthy individuals. The aim of this study was to longitudinally analyze the impact of ETI on the respiratory metagenome in adolescents with predominantly mild CF lung disease. METHODS: In this prospective observational study, we included pwCF aged 12-20 years with at least one F508del mutation, who collected oropharyngeal swabs before and after initiation of ETI therapy twice per week to biweekly over three months. We performed whole metagenome shotgun sequencing, followed by host DNA filtering and taxonomic profiling. We used linear and additive mixed effects models adjusted for known confounders and corrected for multiple testing to study longitudinal development of the microbiome. We analyzed bacterial diversity, abundance, and strain-level phylogeny. RESULTS: We analyzed the metagenomic data of 297 swabs of 20 pwCF. Microbiome composition changed after initiation of ETI therapy. We observed a slight diversification of the microbiome over time (Inv Simpson, Coef 0.085, 95 %CI 0.003, 0.17, p = 0.04). Strain-level analysis and clustering showed that strain retention of the most frequent bacterial species is predominant even during ETI therapy. CONCLUSIONS: During three months of ETI therapy, commensal bacteria increased, which may help to prevent overgrowth of bacterial pathogens.

Humans↗

PubMed2025

ITIH4 alleviates OVA-induced asthma by regulating lung-gut microbiota.

BACKGROUND: Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), a Type 2 acute phase protein, is critical for resolving inflammation and promoting tissue repair. While its role in chronic respiratory diseases is recognized, its effects on asthma remain unclear. This study investigated the effects of ITIH4 on the modulation of lung and gut microbiota, the attenuation of allergic inflammation, and the improvement of respiratory outcomes in an asthma mouse model. METHODS: Six-week-old male Balb/c mice were divided into five groups: control, ITIH4, ovalbumin (OVA), and two OVA + ITIH4 treatment groups at different doses. Lung function and oxygen saturation were measured, and bronchoalveolar lavage fluid (BALF) was analyzed for white blood cell counts and cytokines. Lung and gut microbiota were profiled using 16 S rRNA gene sequencing, and short-chain fatty acids (SCFAs) were measured using gas chromatography-mass spectrometry (GC-MS). Proteomic profiling of intestinal tissues was conducted to identify ITIH4-associated signaling pathways. RESULTS: ITIH4 administration significantly mitigated OVA-induced asthma symptoms by reducing weight loss, airway resistance, and tissue damping (p < 0.05). Histological analysis showed decreased airway wall thickening and lung injury scores (p < 0.05). ITIH4 also lowered BALF eosinophils and lymphocytes, IgE, and Th2 cytokines (IL-4, IL-5, and IL-13) (p < 0.05). ITIH4 treatment modulated microbiome composition, enriching Gram-positive taxa (Nocardioidaceae and Acholeplasmataceae) and depleting Gram-negative Helicobacteraceae (p < 0.05). SCFAs correlated with microbiome alterations, notably reduced 4-methylpentanoic acid levels (p < 0.05). Proteomic analysis revealed a dose-dependent activation of granzyme A signaling and suppression of metabolic and solute transport pathways. CONCLUSIONS: ITIH4 ameliorates asthma symptoms by modulating lung and gut microbiota, dampening Th2-driven inflammation, and restoring mucosal immune balance. These findings support ITIH4 as a potential candidate for microbiome-targeted asthma therapy.

Animals↗

PubMed2026

Impacts of host genetics on gut microbiome composition in Alzheimer's disease.

BACKGROUND: Host-microbiome interactions play essential roles in the development of Alzheimer's disease (AD), yet the host genetic impacts on gut microbial alterations in AD remain poorly understood. RESULTS: Here, we simultaneously profiled host genotype and gut microbiome in 252 Chinese individuals with varying degrees of cognitive disability. Using the latent Dirichlet allocation topic model, we identified the Anaerostipes-enriched enterosignature (ES-Ana) at the microbial subgroup level as significantly negatively associated with cognitive disability, which could be recapitulated in external cohorts. With the whole-genome sequencing data, we performed microbiome genome-wide association studies for the ES-Ana relative abundance. We prioritized 41 lead genetic variants and confirmed that the high ES-Ana relative abundance showed a negative correlation with the polygenic risk score of AD, indicating its protective effect against AD. Furthermore, we identified 174 ES-Ana-associated genes, which are enriched in AD-related biological functions and phenotypes, and exhibite pervasive underexpression in glial cells during brain aging. CONCLUSIONS: In summary, our study reveals the complex genetic effects on the gut microbiota in AD, and provides novel evidence for the roles of the gut-brain axis in AD. Video Abstract.

Alzheimer Disease↗

PubMed2026

Oral bacteriome in pediatric patients with malignancies prior to chemotherapy: a pilot study using full-length 16S rRNA sequencing.

OBJECTIVE: To characterize the composition, diversity, and ecological features of the oral bacteriome in pediatric patients with malignancies prior to chemotherapy initiation. METHODS: In this prospective pilot study,supragingival plaque samples were collected from 10 pediatric cancer patients prior to the initiation of chemotherapy. Bacterial genomic DNA was extracted from each sample, and the full-length 16S rRNA gene was amplified and sequenced on the PacBio Sequel II platform using circular consensus sequencing (CCS). Raw CCS reads were quality-filtered and denoised into amplicon sequence variants (ASVs) using DADA2, and taxonomic assignment was performed against the SILVA 138 reference database. Alpha diversity was assessed using the Chao1, Shannon, Simpson, and Faith's phylogenetic diversity (PD whole tree) indices, while beta diversity was evaluated through principal coordinate analysis (PCoA), and non-metric multidimensional scaling (NMDS). Microbial co-occurrence networks were constructed to characterize bacterial interactions, and functional potential was predicted using PICRUSt2, and BugBase. RESULTS: A total of 614,473 high-quality CCS reads were generated, yielding 1,697 ASVs. Alpha diversity analysis revealed substantial inter-individual variation in microbial richness and diversity among the pediatric cancer patients. The bacterial community was dominated by the phyla Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota. At the genus level, Streptococcus, Prevotella, Neisseria, and Haemophilus were the most abundant taxa. Beta diversity analysis revealed distinct clustering patterns, indicating highly individualized microbial profiles. Co-occurrence network analysis identified several keystone taxa and potential pathogenic associations within the supragingival plaque community. Functional prediction indicated that the dominant metabolic pathways were related to amino acid metabolism, carbohydrate metabolism, and membrane transport. CONCLUSION: These preliminary findings reveal a taxonomically diverse, highly individualized pre-chemotherapy oral bacteriome, providing foundational baseline profiles to guide future longitudinal investigations of chemotherapy-induced dysbiosis and personalized interventions.

Humans↗

PubMed2026

Probiotic Lacticaseibacillus casei 2S-1 Attenuates Escherichia coli-Induced Enteritis via Gut Microbiota Modulation and Host Gene Regulation.

Maintaining gut microbial homeostasis is crucial for host health, whereas infection with Escherichia coli (E. coli) is a major contributor to intestinal inflammation and microbial dysbiosis. Recent research has focused on probiotic strategies for managing enteric inflammatory disorders. Previous studies have shown that beneficial microorganisms show protection through modulating host immune responses, enhancing intestinal epithelial barrier integrity, and inhibiting pathogenic bacteria. To evaluate the prophylactic effectiveness of a recently isolated strain, Lacticaseibacillus casei 2S-1, in a murine model of E. coli-induced enteritis, this study focuses on interactions within the microbiota-intestinal-immune axis, together with host transcriptional responses and pathway enrichment associated with oxidative stress and mitochondrial function. In vitro analysis of probiotic features, including growth dynamics, acidogenic capacity, and tolerance to acidic and bile salt environments, as well as genetic safety profiling, followed the methodical isolation and taxonomic identification of L. casei 2S-1. A preventive intervention protocol was established, and a murine model of enteritis was induced by exposure to E. coli. Histopathological analyses were performed to observe in vivo safety and protective efficacy. Changes in gut microbial structure were characterized by 16S rRNA gene sequencing, while host responses were identified by intestinal immunohistochemistry and transcriptome profiling. L. casei 2S-1 showed probiotic properties. In vitro analyses showed that the strain exhibited tolerance to acidic and bile salt conditions, and its untreated culture supernatant showed antimicrobial activity against pathogenic bacteria. Its safety profile was supported by genomic analysis, which verified the lack of virulence-associated genes and antibiotic resistance factors. In vivo, L. casei 2S-1 pretreatment reduced mortality and intestinal inflammation, modulated gut microbial composition, and preserved intestinal barrier-associated protein expression in infected mice. This study provides experimental evidence supporting the prophylactic effects of L. casei 2S-1 and its associations with gut microbiota modulation and host transcriptional responses, providing a foundation for further investigation of probiotic-based preventive strategies against intestinal infections.

Animals↗

PubMed2026

An oral tyrosine challenge test for functional phenotyping of microbiota-derived phenyl sulfate production.

Phenyl sulfate (PS), a gut microbiota-derived metabolite implicated in the pathogenesis of diabetic kidney disease, is generated through microbial conversion of dietary tyrosine to phenol, followed by hepatic sulfation via SULT1A1. We developed an oral tyrosine challenge test (OTyCT) to phenotype individual PS-producing capacity. Forty-eight healthy adults underwent a standardized tyrosine load with serial plasma PS levels measured over 48 h using LC-MS. OTyCT revealed substantial interindividual variability of PS production independent of baseline PS levels, highlighting marked heterogeneity in host-microbiome metabolic interactions. Sixteen participants in the highest tertile of the incremental area under the curve of PS were defined as high-PS producers. High PS producers exhibited distinct gut microbial signatures despite comparable abundances of known phenol-biosynthetic genes and host SULT1A1 genotypes. These findings suggest that susceptibility to PS-related complications may vary according to gut microbial profiles, supporting OTyCT as a practical tool for metabolic phenotyping and microbiome-informed precision nutrition. Clinical Trial registry name and registration number: Identification of P-Cresyl Sulfate Producer Phenotype by Oral Tyrosine Challenge Test: Interactions Among Diet, Gut Microbiota, and Host Genome, NCT04204174.

Journal Article↗