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PubMed2026

Metagenomic insights into the global wild boar faecal microbiome reveal novel taxa and carbohydrate degraders distinguishing wild and domesticated Sus.

BACKGROUND: The inclusion of fibre in domestic pig diets is favourable from a digestive health, environmental, and socio-economic perspective. Unlike the highly optimized formulated diets of domestic pigs, wild boars feed opportunistically, consuming a broad range of foods that consist predominantly of plant materials. Consequently, the intestinal microbiota of wild boars is thought to be adapted to a versatile, fibre-rich diet and may represent a valuable source of probiotics for enhancing fibre degradation. However, comprehensive studies characterizing the wild boar gut microbiome, particularly its community structure and carbohydrate utilization potential, and comparison to that of domestic pigs are still lacking. RESULTS: We collected 89 faecal samples from wild boars across four countries and analysed them primarily using metagenomic sequencing. De novo assembly yielded 3,288 high- and medium-quality metagenome-assembled genomes (MAGs) representing 968 distinct species, of which 538 were previously unknown. Incorporating these MAGs enabled robust microbiome comparisons with 125 previously published samples largely from domestic pigs, which revealed significant structural and functional differences. These differences resolved into two community types, determined not by host species but by diet and lifestyle: C1 comprising 81% of samples from free-ranging, foraging wild boars and C2 consisting of 93% of samples from captive, fed domestic pigs. The lower alpha-diversity observed in C1 likely reflected the impact of highly fluctuating dietary resources and environmental conditions, resulting in dominance of fewer resilient or adaptable taxa. Nevertheless, both community types maintained substantial carbohydrate utilization potential: while C2 exhibited a higher relative abundance of CAZymesub genes associated with a broader range of carbohydrate substrate (CHO) classes, C1 was enriched in individual species that were generally richer in CAZymesub genes and CHO classes. To leverage this potential, we curated a catalogue of carbohydrate degraders from both community types and identified 47 highly versatile species, with several novel species amongst them. CONCLUSIONS: This study uncovered the previously untapped microbial diversity in the wild boar faecal microbiome and demonstrated that the faecal microbiome of Sus is primarily shaped by diet and lifestyle. The two community types identified, which differed both structurally and functionally, represent alternative states of microbiome homeostasis in wild versus domesticated Sus populations. The curated catalogue of carbohydrate degraders provides a valuable resource to guide tailored probiotic supplementation during dietary transitions to novel fibrous feedstocks. Video Abstract.

Animals↗

PubMed2026

Metabolic and endocrine modulation of the gut-adipose tissue axis via pro-, pre-, and postbiotics in overweight dogs: A systematic review.

Canine obesity is a complex metabolic disorder driven by luminal dysbiosis, impaired gut barrier function, and metaflammation. Following PRISMA 2020 guidelines, this systematic review evaluated the efficacy of pro-, pre-, and postbiotics in modulating the gut-adipose tissue axis in overweight dogs (BCS ≥ 6/9) or diet-induced obesity models. Searches across PubMed and Dimensions (April 2026) identified seven eligible experimental trials. Results suggest that postbiotic Bifidobacterium animalis subsp. lactis CECT 8145 reduced postprandial glucose AUC by 6 % strictly during energy restriction. Pasteurized Akkermansia muciniphila postbiotics limited diet-induced weight gain, though glucoregulatory impacts were highly strain-specific (AKK2 reduced fasting glucose and insulin resistance indexes, whereas EB-AMDK19 exerted no significant effect). Specific probiotics (including Enterococcus faecium, Bifidobacterium lactis, Lactiplantibacillus plantarum and Bifidobacterium breve) attenuated fasting hyperinsulinemia and preserved circulating adiponectin, but lipid profile improvements (triglycerides and total cholesterol) were inconsistent across trials. In dogs, increased luminal short-chain fatty acids are not consistently mirrored by endocrine responses, so the coupling between microbial metabolites and incretin signaling remains incomplete. A critical lack of standardized reporting for species-validated insulin sensitivity metrics was identified. In conclusion, microbiome-targeted therapies, particularly inanimate postbiotics, may represent useful adjunctive strategies to mitigate metabolic dysregulation in obesogenic environments. However, clinical efficacy remains strictly strain-specific and dependent on host energy balance. Given the scarcity of high-certainty evidence, future trials must integrate dynamic physiological assessments with species-validated surrogate indexes alongside standardized dietary controls.

Animals↗

PubMed2025

Evaluation of the gut microbiome and sex hormones in postmenopausal women with newly diagnosed hormone receptor-positive breast cancer versus healthy women: a prospective case-control study.

PURPOSE: The functional composition and diversity of the gut microbiome may affect breast cancer risk by modulation of systemic sex hormones. Gut bacteria with β-glucuronidase enzymatic activity may deconjugate estrogens, leading to increased estrogen reabsorption into the circulation thereby increasing breast cancer risk. We investigated the relationship between the gut bacterial microbiome and endogenous estrogens and related sex hormones in women with hormone receptor-positive breast cancer compared to healthy control women. The goal was to determine if the estrobolome (i.e., bacteria capable of modulating the body's circulated estrogen levels) was altered in those with breast cancer compared with controls. METHODS: In this prospective case-control study, postmenopausal women (n = 46) with newly diagnosed stage I-III estrogen and/or progesterone receptor-positive breast cancer were compared with healthy postmenopausal female controls (n = 22). Bacterial composition of the gut microbiome was analyzed by 16S rRNA gene sequencing from fecal specimens. Plasma and urine sex hormones were quantified using high-performance liquid chromatography/mass spectrometry. RESULTS: We found evidence that some β-glucuronidase positive bacteria were enriched in the breast cancer patients compared to healthy controls, whereas abundances of some β-glucuronidase negative bacteria were reduced. There was also a wide distribution of prevalence of β-glucuronidase positive taxa in both breast cancer subjects and healthy controls, as well as higher probability of breast cancer subjects having higher average β-glucuronidase levels. Significant differences were found in endogenous progesterone levels between the breast cancer patients and healthy controls. CONCLUSION: This pilot study showed differences in the gut microbiome and endogenous progesterone levels among postmenopausal women with hormone receptor-positive breast cancer compared with healthy controls. These interesting findings may have implications for breast cancer risk and prevention and warrant further exploration.

Humans↗

PubMed2025

Alterations of gut microbiome in chronic rhinosinusitis: insights from a mendelian randomization study.

OBJECTIVE: Gut microbiome dysbiosis is associated with various diseases. Causal association between Chronic Rhinosinusitis (CRS) and gut microbiome is yet unknown. This study aimed to investigate the potential causal relationship between CRS and gut microbiome dysbiosis. METHODS: We used Genome-Wide Association Study (GWAS) data from FinnGen database for CRS. The Dutch Microbiome Project study provided data on gut microbiota species. A total of 334,182 individuals were included. Two-sample bidirectional Mendelian Randomization (MR) analysis was used to investigate causal relationship between CRS and gut microbiome. The main methods of evaluation were Inverse Variance Weighting (IVW), weighted median, weighted mode, and MR-Egger regression. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. RESULTS: Forward MR analysis indicated CRS is potentially linked to decreased risk of Haemophilus parainfluenzae (OR = 0.79, 95% CI 0.66‒0.94, p = 0.009) and increased risk of Bilophila's (OR = 1.14, 95% CI 1.02-1.27, p = 0.023) within the gut. Reduced risks in gut microbiota-related pathways like UDP-N-acetyl-d-glucosamine biosynthesis I (OR = 0.85, 95% CI 0.77‒0.94, p = 0.002) and increased risk in pathway NAD biosynthesis I from aspartate (OR = 1.14, 95% CI 1.03-1.27, p = 0.010) were also linked to CRS. Reverse MR analyses, we obtained no positive results (p > 0.05/412). CONCLUSION: This study reveals CRS exerts a causal impact on shifts within the composition of the gut microbiome and also links to the changes of gut microbiota-related metabolic pathways. The risk of changes in gut microbiota should be of greater concern in patients with CRS than in the general population. LEVEL OF EVIDENCE: Mendelian Randomized (MR) studies are second only to randomized controlled trials in terms of the level of evidence.

Humans↗

PubMed2025

The Effect of Colesevelam on the Microbiome in Postoperative Crohn's Disease.

BACKGROUND: While surgery plays a pivotal role in the management of ileal Crohn's disease, the risk of endoscopic recurrence following an ileocaecal resection can be greater than 65% within 12 months of surgery. More than 90% of patients with Crohn's disease have a concomitant diagnosis of bile acid diarrhea following an ileal resection. This pilot study aimed to assess whether the use of bile acid sequestrants in patients with Crohn's disease who have undergone a primary terminal ileal resection with concomitant bile acid diarrhea can alter the microbiome and prevent disease recurrence. METHODS: Patients with Crohn's disease who underwent a primary terminal ileal resection and had symptoms of diarrhea within 1-3 months of surgery underwent 75SeHCAT testing for bile acid diarrhea. If positive (75SeHCAT ≤ 15%), patients were treated with colesevelam and stool samples were collected at 4 weeks, 8 weeks, and 6-12 months posttreatment. If negative (75SeHCAT > 15%), treatment was not given and were reviewed in the clinic as per local guidelines. All patients underwent a 6-12 month postoperative colonoscopy where further stool samples and mucosal biopsies were taken. Disease activity was established using the endoscopic Rutgeert's score, with disease remission defined as Rutgeert's score <i2 and disease recurrence ≥i2. 16S ribosomal RNA gene analysis was undertaken for the collected fecal and mucosal samples to assess α/β-diversity and microbial composition. RESULTS: A total of 14 patients who completed the study, 10 of whom had a 75SeHCAT positive diagnosis of bile acid diarrhea and were started on treatment with colesevelam. Four patients did not require treatment as 3 were asymptomatic and 1 had a negative 75SeHCAT scan. Three of the fourteen patients had disease recurrence at their 6-12 month postoperative colonoscopy assessment, of which 1 patient was taking colesevelam and 2 patients were not taking colesevelam. A total of 44 fecal samples and 44 mucosal biopsies underwent 16S ribosomal RNA gene analysis to assess α/β-diversity and microbial composition. In the colesevelam treated patients there was no significant difference in α/β-diversity pre- and posttreatment. Pretreatment, the 3 most abundant bacterial classes in all patients were Bacteroidia, Clostridia, and Gammaproteobacteria. Following 6-12 months of treatment, out of the 9 patients on colesevelam, 5/9 (55.6%) had a reduction in Bacteroidia, 9/9 (100%) had an increase in Clostridia, and 7/9 (77.8%) had a reduction in Gammaproteobacteria. Of the 2 patients not given colesevelam, one showed a reduction in Bacteroidia, increase in Clostridia and a reduction in Gammaproteobacteria. CONCLUSIONS: This small pilot study demonstrated that patients who were given colesevelam, were more likely to be in disease remission at their 6-12 months colonoscopy review compared with those not treated. Furthermore, treatment with colesevelam may have a role in altering the microbiome to help maintain remission states in postoperative Crohn's disease. Larger mechanistic studies are now needed to confirm these findings and demonstrate statistical significance as well as investigate whether this benefit may be present even in those patients with 75SeHCAT negative disease.

Humans↗

PubMed2026

Genome-resolved multi-omics provide new insights into microbial nitrogen utilization by the rumen microbiota.

BACKGROUND: Optimizing nitrogen (N) utilization in ruminant production systems holds both economic and environmental significance. However, traditional paradigms of N metabolism, derived primarily from well-studied model rumen bacteria, do not fully reflect the diverse and complex N metabolism in the rumen ecosystem. RESULTS: To address this gap, we utilized comparative genomics and genome-resolved multi-omics analyses using a curated set of microbial genomes to investigate N assimilation and regulation in rumen microbes. We discovered that well-established mechanisms of ammonia assimilation and regulation, such as the glutamine synthetase (GS)/glutamate synthase (GOGAT) pathways and their regulatory proteins, are absent in many of the predominant rumen microbes, which likely utilize alternative pathways for ammonia assimilation. These findings challenge the applicability of E. coli-based N regulation models to rumen bacteria in response to ammonia availability. We further linked polysaccharide utilization and ammonia assimilation across hundreds of rumen microbial species. Furthermore, we identified specific microbial species involved in ureolysis and denitrification, as well as phages carrying auxiliary metabolic genes involved in N assimilation. Using an animal trial involving 11 pairs of lamb twins in a crossover design, we demonstrated that dietary crude protein (CP) at 10% and 13% had minimal impact on rumen microbiome composition and expression of N assimilation genes. Instead, changes in concentrate levels altered N assimilation, notably increasing expression of amino acid biosynthesis pathways. CONCLUSION: These findings indicate a nuanced, species-specific microbial response to dietary interventions, highlighting the limitations of traditional N metabolism models applied to rumen microbes and the need for more granular studies of rumen microbial ecosystems.

Multiomics↗

PubMed2026

Prevalence and chronology of colibactin-associated mutational processes and their microbiome spectra in Japanese colorectal cancer.

The incidence of colorectal cancer (CRC) has risen in recent decades, with a disproportionate increase observed among younger individuals in Japan and other countries. The etiological contribution of the gut microbiota to CRC pathogenesis is recognized, yet the mechanisms involved remain to be fully clarified. Here we integrated whole-genome sequencing (WGS) and transcriptome profiling of CRC with whole-genome metagenomic sequencing of fecal samples to interrogate host-microbiome interactions at high resolution. Application of interpretable artificial intelligence enabled the stratification of CRC into four distinct microbiome-informed subtypes. WGS analysis identified mutational signatures SBS88 and ID18, linked to colibactin exposure, as early clonal events detected in 44.8% of non-hypermutated patients. Notably, these signatures were significantly more frequent among patients born after the 1960s. Microbiome-based subclassification revealed subtype-specific clinical and molecular features. Collectively, our findings indicate that colibactin exposure constitutes a prevalent and potentially modifiable risk factor for CRC in the Japanese population.

Humans↗

PubMed2024

Interactions between microbiota and uterine corpus endometrial cancer: A bioinformatic investigation of potential immunotherapy.

Microorganisms in the gut and other niches may contribute to carcinogenesis while also altering cancer immune surveillance and therapeutic response. However, determining the impact of genetic variations and interplay with intestinal microbes' environment is difficult and unanswered. Here, we examined the frequency of thirteen mutant genes that caused aberrant gut in thirty different types of cancer using The Cancer Genomic Atlas (TCGA) database. Substantially, our findings show that all these mutated genes are quite frequent in uterine corpus endometrial cancer (UCEC). Further, these mutant genes are implicated in the infiltration of different subset of immune cells within the Tumor Microenvironment (TME) of UCEC patients. The top-ranking mutant genes that promote immune cell invasion into the TME of UCEC patients were PGLYRP2, OLFM4, and TLR5. In this regard, we used the same deconvolution of the TCGA database to analyze the microbiome that have a strong association with immune cells invasion with TME of UCEC patients. Several bacteria and viruses have been linked to the invasion of immune cells, such as B cell memory and T cell regulatory (Tregs), into the TME of UCEC patients. As a result, our findings pave the way for future research into generating novel immunizations against bacteria or viruses as immunotherapy for UCEC patients.

Humans↗

PubMed2026

The antimicrobial gut resistome of the Wayampi reveals a shared background of antibiotic and metal resistance genes with industrialized populations, underscoring the "robust-yet-fragile" architecture of human gut microbiomes.

BACKGROUND: Metagenomics enables detailed profiling of genes encoding antimicrobial resistance. However, most studies focus exclusively on antibiotic resistance genes (ARGs), excluding those associated with non-antibiotic antimicrobials (metals, biocides), and often rely on methods with low-sensitivity and low-specificity. Furthermore, they rarely examine populations exposed to minimal anthropogenic pollution. We analyzed fecal resistomes of 95 Wayampi individuals, an Indigenous community in remote French Guiana, using a targeted metagenomic capture platform covering 8667 genes, including ARGs, metal resistance genes (MRGs) and biocide resistance genes (BRGs) (PMID: 29335005). Resistome profiles were compared with those of Europeans to assess population-level differences. RESULTS: ARG richness was similar between groups (259 in Wayampi vs. 264 in Europeans, 159 shared), but MRGs + BRGs gene richness was significantly higher in Wayampi (11,930 vs. 7419). Most genes appeared in a minority of individuals (mean 5% for ARGs, 2% for MRGs + BRGs), but several ARGs for tetracyclines [tet(32), tet(40), tet(O), tet(Q), tet(W), tet(X), tetAB(P)], aminoglycosides (ant6'-I, aph3-III), macrolides (ermB, ermF, mefA), and sulfonamides (sul2) were present in all individuals. Tetracycline resistance genes predominated overall, while beta-lactam resistance genes were more common in Wayampi, and genes conferring resistance to aminoglycosides, amphenicols, and folate inhibitors were more frequent in Europeans. Among MRGs, copper and arsenic resistance genes prevailed in both groups, followed by those for zinc, iron, cobalt, and nickel. Up to 76% of Wayampiis carried acquired MRGs for copper (pcoABCDRS and tcrB), silver (silACFPRS), arsenic (ars), and mercury (mer) detoxification. Shannon diversity indices were similar for ARGs, MRGs, and BRGs, but composition and evenness differed significantly. UMAP and ADONIS analyses distinguished cohorts based on ARG profiles (p < 0.001), but not on MRGs or BRGs. Correlation analysis revealed conserved gene-sharing networks and introgression of acquired ARGs and MRGs within both gut microbiomes. CONCLUSIONS: The diverse and balanced Wayampi resistome reflects a less perturbed microbiome compared to industrialized populations, and reveals a background of "core" and "shell" acquired ARGs and MRGs, consistent with the "robust-yet-fragile" architecture of scale-free networks. The patchy yet resilient gene distribution suggests varying levels of conserved gene sharing highways among populations, likely shaped by long-term microbial-human evolution, and supports a broader view on acquired antimicrobial resistance. Video Abstract.

Humans↗

PubMed2026

Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host-microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p = 0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p = 0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host-microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.

Humans↗

PubMed2024

Major depletion of insulin sensitivity-associated taxa in the gut microbiome of persons living with HIV controlled by antiretroviral drugs.

BACKGROUND: Persons living with HIV (PWH) harbor an altered gut microbiome (higher abundance of Prevotella and lower abundance of Bacillota and Ruminococcus lineages) compared to non-infected individuals. Some of these alterations are linked to sexual preference and others to the HIV infection. The relationship between these lineages and metabolic alterations, often present in aging PWH, has been poorly investigated. METHODS: In this study, we compared fecal metagenomes of 25 antiretroviral-treatment (ART)-controlled PWH to three independent control groups of 25 non-infected matched individuals by means of univariate analyses and machine learning methods. Moreover, we used two external datasets to validate predictive models of PWH classification. Next, we searched for associations between clinical and biological metabolic parameters with taxonomic and functional microbiome profiles. Finally, we compare the gut microbiome in 7 PWH after a 17-week ART switch to raltegravir/maraviroc. RESULTS: Three major enterotypes (Prevotella, Bacteroides and Ruminococcaceae) were present in all groups. The first Prevotella enterotype was enriched in PWH, with several of characteristic lineages associated with poor metabolic profiles (low HDL and adiponectin, high insulin resistance (HOMA-IR)). Conversely butyrate-producing lineages were markedly depleted in PWH independently of sexual preference and were associated with a better metabolic profile (higher HDL and adiponectin and lower HOMA-IR). Accordingly with the worst metabolic status of PWH, butyrate production and amino-acid degradation modules were associated with high HDL and adiponectin and low HOMA-IR. Random Forest models trained to classify PWH vs. control on taxonomic abundances displayed high generalization performance on two external holdout datasets (ROC AUC of 80-82%). Finally, no significant alterations in microbiome composition were observed after switching to raltegravir/maraviroc. CONCLUSION: High resolution metagenomic analyses revealed major differences in the gut microbiome of ART-controlled PWH when compared with three independent matched cohorts of controls. The observed marked insulin resistance could result both from enrichment in Prevotella lineages, and from the depletion in species producing butyrate and involved into amino-acid degradation, which depletion is linked with the HIV infection.

Humans↗

PubMed2026

Enhancing the fiber degradation efficiency in dairy cattle rumen through engineered bacterial communities.

BACKGROUND: The rumen functions as an anaerobic fermentation chamber, housing microorganisms with cellulolytic and proteolytic capabilities that facilitate feed utilization. Fiber-degrading bacteria possess the capability to enhance the productivity of cellulolytic feed. The application of omics technologies has greatly improved our understanding of the rumen microbiome. Determining microbial composition and functional patterns in the rumen does not equate to a comprehensive exploration of rumen microbial resources and their mechanisms of action. This study seeks to integrate high throughput 16S rRNA data with information on culturomics, cellulolytic activities, nutrition, and synthetic microbial communities (SynCom) engineering. The objective is to evaluate the relationship between rumen microbial activity and fiber utilization efficiency in cattle, ultimately aiming to develop a more powerful intervention strategy for the ruminant industry. RESULTS: The enrichment culture with various carbon sources led to significant alterations in the composition and structure of rumen microbiota, particularly enhancing those associated with carbohydrate metabolism. Employing the culturomics methodology, 896 strains from 78 species (including 8 novel species) were isolated, resulting in a 10.1% isolation rate relative to the rumen bacterial community. Among them, 35 strains demonstrated boosted cellulose-degrading capability on plates, while 25 exhibited the ability to degrade hemicellulose as well. SynComs of these candidates were prepared based on the ratio observed in rumen microbiota exhibiting high cellulolytic performance. SynCom 3 improved the neutral detergent fiber degradation (NDFD) by 20.39% averagely. Additionally, both in vitro and in situ assessments indicated that the optimization of dose/strain in SynCom 3 significantly improved the in vitro NDFD by 20.56% and increased the in situ NDFD by 7.81%, along with the acidic detergent fiber (ADF, + 11.47%). Genomic analysis revealed that the SynCom 3 functioned well in fiber degradation through the synergistic action of key carbohydrate-active enzymes. CONCLUSIONS: This study strengthens rumen microbiome research by integrating omics and SynCom engineering within a microbiota-bacteria-enzymes-genes framework, revealing the significance of enzymatic synergy in carbohydrate metabolism. The findings establish a framework for utilizing low-abundance microbes and engineering functional consortia, which are crucial for improving ruminant feed utilization and biomass conversion. Future research should investigate the transcriptomic profiles and the metabolic cross-feeding mechanisms of fiber-degrading strains in the rumen. Video Abstract.

Animals↗

PubMed2026

The mechanism by which long-term exposure to TDCIPP promotes cognitive impairment in 3 ×Tg-AD mice: Insights from multi-omics studies.

Tri(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a commonly used organophosphate ester that has the potential to adversely affect human health. Although previous studies have closely associated TDCIPP with cognitive impairment, the underlying mechanisms remain unclear. To elucidate the neurotoxic effects of TDCIPP and its mechanistic contribution to cognitive impairment in 3 ×Tg-AD mice, a multi-omics approach incorporating proteomics, untargeted metabolomics, and 16S ribosomal RNA (rRNA) gene sequencing was employed to evaluate the impact of TDCIPP exposure on neurobehavioral function. TDCIPP exposure promoted cognitive impairment in 3 ×Tg-AD mice. Proteomic analyses revealed that this promotion is associated with disturbances in the hippocampal mitochondrial autophagy pathway. Furthermore, TDCIPP may interfere with the PINK1/Parkin-mediated mitophagy pathway at the functional level, without altering PINK1 protein abundance. Untargeted metabolomic analysis of urine samples demonstrated that TDCIPP exposure altered the metabolic profile of 3 ×Tg-AD mice, with 58 metabolites upregulated and 11 downregulated. Additionally, 16S rRNA sequencing revealed substantial modifications in gut microbiome composition following exposure to TDCIPP. Notably, significant correlations were identified between the perturbed bacterial genera and the differential metabolites. In conclusion, exposure to TDCIPP promotes cognitive impairment in 3 ×Tg-AD mice, which is associated with the interference with the PINK1/Parkin-mediated mitophagy pathway, as well as alterations in the urinary metabolome and gut microbiota. These findings suggest the potential to mitigate such cognitive impairment by targeting the microbiota-gut-brain axis.

Animals↗

PubMed2025

Leveraging chemical synthesis to discover metabolites from the gut microbiome.

The gut microbiome has the biosynthetic potential to make a variety of secondary metabolites or natural products, which serve as molecular messages between cells and organisms. These chemical signals are capable of affecting physiology and behavior in real time, and are, therefore, bioactive and can exhibit medicinal properties including anticancer, antimicrobial, or immunomodulating activities. It is clearly important to identify signaling molecules in the human gut, but elucidating their chemical structures can be challenging since traditional isolation methods are typically not available. The discovery of microbiome-related metabolites requires multidisciplinary collaboration, where chemical synthesis often plays an essential role. This review highlights examples where synthetic chemistry was used to study novel metabolites produced by the gut microbiota. In the first part, we describe examples where organic synthesis was utilized in traditional contexts, as a last step for validating structures and sourcing material for biological testing. The final section of this review discusses next-generation applications for chemical synthesis, where integration with metabolomic or genomic analysis simultaneously uncovers both structural and biological information about small molecules from the gut.

Gastrointestinal Microbiome↗

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↗

PubMed2025

Coarse-grained model of serial dilution dynamics in synthetic human gut microbiome.

Many microbial communities in nature are complex, with hundreds of coexisting strains and the resources they consume. We currently lack the ability to assemble and manipulate such communities in a predictable manner in the lab. Here, we take a first step in this direction by introducing and studying a simplified consumer resource model of such complex communities in serial dilution experiments. The main assumption of our model is that during the growth phase of the cycle, strains share resources and produce metabolic byproducts in proportion to their average abundances and strain-specific consumption/production fluxes. We fit the model to describe serial dilution experiments in hCom2, a defined synthetic human gut microbiome with a steady-state diversity of 63 species growing on a rich media, using consumption and production fluxes inferred from metabolomics experiments. The model predicts serial dilution dynamics reasonably well, with a correlation coefficient between predicted and observed strain abundances as high as 0.8. We applied our model to: (i) calculate steady-state abundances of leave-one-out communities and use these results to infer the interaction network between strains; (ii) explore direct and indirect interactions between strains and resources by increasing concentrations of individual resources and monitoring changes in strain abundances; (iii) construct a resource supplementation protocol to maximally equalize steady-state strain abundances.

Gastrointestinal Microbiome↗

PubMed2025

Bone Adhered Sediments as a Source of Target and Environmental DNA and Proteins.

In recent years, sediments from cave environments have provided invaluable insights into ancient hominids, as well as past fauna and flora. Unfortunately, however, sediments are not always collected during excavation. In this study, we analyzed an overlooked but abundant resource in archaeological collections - sediments adhered to bone. We performed metagenomics and metaproteomics analysis on sediment from several human skeletal elements, originating from Neolithic to Medieval sites in England. We were able to reconstruct a partial human genome, the genetic profile of which matches that recovered from the original skeletal element. Additionally, aDNA sequences matching the genomes of endogenous gut microbiome bacteria were identified. We also found the presence of genetic sequences corresponding to animals and plants. In particular, we managed to retrieve the partial genome and proteome of a Black Rat (Rattus rattus), sharing close genetic affinities to other medieval Rattus rattus. Our results demonstrate that material that is usually ignored or discarded, can be used to reveal information about the individual and the environmental conditions at the time of their death.

Animals↗

PubMed2025

AI-driven multi-omics modeling of myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic illness with a multifactorial etiology and heterogeneous symptomatology, posing major challenges for diagnosis and treatment. Here we present BioMapAI, a supervised deep neural network trained on a 4-year, longitudinal, multi-omics dataset from 249 participants, which integrates gut metagenomics, plasma metabolomics, immune cell profiling, blood laboratory data and detailed clinical symptoms. By simultaneously modeling these diverse data types to predict clinical severity, BioMapAI identifies disease- and symptom-specific biomarkers and classifies ME/CFS in both held-out and independent external cohorts. Using an explainable AI approach, we construct a unique connectivity map spanning the microbiome, immune system and plasma metabolome in health and ME/CFS adjusted for age, gender and additional clinical factors. This map uncovers altered associations between microbial metabolism (for example, short-chain fatty acids, branched-chain amino acids, tryptophan, benzoate), plasma lipids and bile acids, and heightened inflammatory responses in mucosal and inflammatory T cell subsets (MAIT, γδT) secreting IFN-γ and GzA. Overall, BioMapAI provides unprecedented systems-level insights into ME/CFS, refining existing hypotheses and hypothesizing unique mechanisms-specifically, how multi-omics dynamics are associated to the disease's heterogeneous symptoms.

Humans↗