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PubMed2026

Host immunogenetic variation and gut microbiome functionality in a wild vertebrate population.

BACKGROUND: The gut microbiome (GM) -important for host health and survival- is partially shaped by host immunogenetics. However, to date, no study has investigated the influence of host Major Histocompatibility Complex (MHC) genes on gut microbiome functionality in a wild population. Here we use a natural population of the Seychelles warbler (Acrocephalus sechellensis) to assess the effects of MHC genes on GM taxonomy and functionality using shotgun metagenomics. RESULTS: Our results show that taxonomic GM composition was associated with MHC-II diversity and the presence of one specific MHC-I allele (Ase-ua 7). Specifically, MHC-II diversity was associated with decreased Lactococcus lactis and increased Staphylococcus lloydii abundance, while Ase-ua 7 was linked to reduced Enterococcus casselifavus and Gordonia sp OPL2 but increased Escherichia coli and Vulcaniibacterium thermophilum. These taxonomic changes may reflect differences in MHC-mediated microbial recognition. In contrast, functional GM composition was significantly associated with increasing individual MHC-I diversity but not MHC-II diversity. In particular, increasing MHC-I diversity was associated with an increased prevalence of microbial defence genes but a reduced prevalence of microbial metabolism genes. Analysis also revealed that functional GM networks were more fragmented in high compared to low MHC-I diversity hosts. CONCLUSION: These results suggest that MHC variation (particularly at MHC-I) plays an important role in shaping both the taxonomy and function of the GM in wild vertebrates. In the Seychelles warbler, this results in trade-offs whereby there is an increase in microbial defence and a reduction in GM metabolic potential in individuals with higher MHC-I diversity. Thus, this work sheds light on the possible costs and benefits of maintaining a healthy microbiome, which is essential for understanding how the GM and immune system co-evolve. Video Abstract.

Animals↗

PubMed2025

kMermaid: Ultrafast metagenomic read assignment to protein clusters by hashing of amino acid k-mer frequencies.

Shotgun metagenomic sequencing can determine both the taxonomic and functional content of microbiomes. However, functional classification for metagenomic reads remains highly challenging as protein mapping tools require substantial computational resources and yield ambiguous classifications when short reads map to homologous proteins originating from different bacteria. Here we introduce kMermaid for the purpose of uniquely mapping bacterial short reads to taxa-agnostic clusters of homologous proteins, which can then be used for downstream analysis tasks such as read quantification and pathway or global functional analysis. Using a nested hash map containing amino acid k-mer profiles as a model for protein assignment, kMermaid achieves the sensitivity of popular existing protein mapping tools while remaining highly resource efficient. We evaluate kMermaid on simulated data and data from human fecal samples as well as demonstrate the utility of kMermaid for classifying reads originating from new, unseen proteins. kMermaid allows for highly accurate, unambiguous and ultrafast metagenomic read assignment into protein clusters, with a fixed memory usage, and can easily be employed on a typical computer.

Metagenomics↗

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

Ruminosignatures associated with methane emissions and feed efficiency across geographies and cattle breeds.

The cattle rumen microbiota represents a complex and dynamic ecosystem whose organization and relationship to host phenotypes are important for food security and environmental sustainability. We analyzed rumen microbiota profiles from 2496 cattle representing five breeds and production systems across five countries, identifying microbial co-abundance groups termed Ruminosignatures. We detected 14 distinct Ruminosignatures, including 2 observed across all populations dominated by Prevotella and UBA2810. Additional Ruminosignatures showed breed- and diet-specific patterns and collectively explained 96%-99% of variance in rumen microbial composition. Integrative cross-country analysis confirmed 10 out of 14 Ruminosignatures identified in cohort-specific analyses. Several Ruminosignatures were associated with methane emissions and feed efficiency traits and were partially under host genetic control, with heritability estimates ranging from 0.09 to 0.58. Structural equation modeling revealed consistent negative genetic and phenotypic correlations between the UBA2810-dominated Ruminosignature (RS_UBA2) and methane emissions across cohorts (rg = -0.40 to -0.65), with structural coefficients concordant in sign across all populations, supporting the expected direction of phenotypic response to selection on RS_UBA2. Meta-analysis confirmed positive associations of RS_UBA2 with average daily gain and negative associations with methane-related traits and feed conversion ratio. Functional genome-based predictions suggested RS_UBA2 may reduce methanogenesis through alternative hydrogen utilization pathways competing with methanogenic archaea. Production system type influenced both Ruminosignature occurrence and relationships with host phenotypes, emphasizing the relevance of context-specific strategies for microbiome modulation. Our findings highlight the potential of the Ruminosignatures framework for microbiome-informed breeding programs aimed at improving feed efficiency while reducing the environmental impact of cattle production.

Animals↗

PubMed2025

Reduction of Bacteroides fragilis in Gut Microbiome of Chronic Hepatitis B Patients Promotes Liver Injury.

In chronic hepatitis B (CHB) patients under antiviral treatment, liver injury, as evidenced by elevated alanine transaminase (ALT), is associated with unfavorable outcomes and needs effective treatment. The interaction between gut microbiota and liver injury in CHB patients remains unclear. Using a case-control design, 28 cases with elevated ALT and 28 matched controls with normal ALT were randomly selected from CHB patients with viral control. Clinical characteristics were comparable between groups. Metagenomic sequencing revealed that Bacteroides fragilis was decreased in cases and exhibited the greatest disparity between cases and controls. Mice colonized by gut microbiota from cases exhibited more severe liver damage in both LPS-induced and MCD diet-induced liver injury models, and had a lower abundance of B. fragilis compared to mice colonized by gut microbiota from controls. Oral gavage of B. fragilis improved both LPS-induced and MCD diet-induced liver injury. Metabolomics analysis revealed that the levels of 7-Ketolithocholic acid (7-Keto-LCA) were positively correlated with B. fragilis and significantly increased in the cultural supernatant of B. fragilis. Consistently, 7-Keto-LCA exerted protective effects against both LPS-induced and MCD diet-induced liver damage. Targeting gut microbiota might be a promising therapeutic treatment for alleviation residual liver inflammation in CHB patients with viral control.

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

Two worlds beneath: Distinct microbial strategies of the rock-attached and planktonic subsurface biosphere.

BACKGROUND: Microorganisms in groundwater ecosystems exist either as planktonic cells or as attached communities on aquifer rock surfaces. Attached cells outnumber planktonic ones by at least three orders of magnitude, suggesting a critical role in aquifer ecosystem function. However, particularly in consolidated carbonate aquifers, where research has predominantly focused on planktonic microbes, the metabolic potential and ecological roles of attached communities remain poorly understood. RESULTS: To investigate the differences between attached and planktonic communities, we sampled the attached microbiome from passive samplers filled with crushed carbonate rock exposed to oxic and anoxic groundwater in the Hainich Critical Zone Exploratory and compared it to a previously published, extensive dataset of planktonic communities from the same aquifer ecosystem. Microbial lifestyle (attached vs. planktonic) explained more variance in community composition than redox conditions, prompting us to further investigate its role in shaping functional and activity profiles. Metagenomic analysis revealed a striking taxonomic and functional segregation: the 605 metagenome-assembled genomes (MAGs) from attached communities were dominated by Proteobacteria (358 MAGs) and were enriched in genes for biofilm formation, chemolithoautotrophy, and redox cycling (e.g., iron and sulfur metabolism). In contrast, the 891 MAGs from planktonic communities were dominated by Cand. Patescibacteria (464 MAGs) and Nitrospirota (60 MAGs) and showed lower functional versatility. Only a few genera were shared, and even closely related MAGs (> 90% average nucleotide identity) differed in assembly size and metabolic traits, demonstrating lifestyle-specific functional adaptation. Analysis of active replication indicated that the active fraction of the attached community was primarily represented by the most abundant MAGs. Planktonic communities featured a higher fraction of active MAGs compared to attached communities, but overall with lower relative abundances. CONCLUSIONS: The high abundance, metabolic specialization, and carbon fixation potential of attached microbes suggest that they are key drivers of subsurface biogeochemical processes. Carbonate aquifers may act as much larger inorganic carbon sinks than previously estimated based on CO2 fixation rates of the planktonic communities alone. Our findings underscore the need to incorporate attached microbial communities into models of subsurface ecosystem function. Video Abstract.

Plankton↗

PubMed2026

Divergent microbial preludes to necrotising enterocolitis defined by gut phages and bacterial resistomes.

BACKGROUND: Translating microbiome correlations into robust predictive features for complex gut disorders remains elusive, partly due to oversimplified models of pathogenesis and neglect of the virome, a key player in microbial ecosystems. Necrotising enterocolitis (NEC), a devastating disease of preterm infants with no reliable clinical predictors, exemplifies this challenge. OBJECTIVE: To determine the predictive potential of the gut prophageome and polymicrobial aetiologies for NEC. DESIGN: We applied integrated metagenomic and metatranscriptomic analyses and machine learning to 1825 longitudinal stool samples from 43 preterm infants who later developed NEC and 86 gestational age-matched and birthweight-matched controls across three US hospitals. We characterised gut prophageome acquisitions and their association with clinical exposures, including antibiotics, diet and pharmacotherapies. To predict NEC risk, we integrated pre-onset prophageome, antibacterial resistome and bacteriome profiles with neonatal pathology, stratifying the cohort by disease onset timing (early: ≤40 days; late: >40 days) for separate analysis. RESULTS: NEC cases exhibited distinct viral diversity trajectories before disease onset. Early-onset NEC was best predicted by phage-bacterial interaction signatures (75% accuracy, 81% sensitivity). Metatranscriptomics revealed increased phage DNA abundance with low gene expression, suggesting a lysogenic lifestyle that may stabilise pathobionts. These phages encode metabolic genes potentially enhancing pathobiont resilience. Late-onset NEC was best predicted by antibacterial resistome profiles (83% accuracy). CONCLUSION: The gut prophageome serves as both a source of pre-symptomatic predictive signals and an active modulator of NEC pathogenesis, with distinct microbial mechanisms driving early-onset and late-onset disease. These polymicrobial etiologies inform strategies for early detection, risk stratification and the development of microbiome-targeted preventive and therapeutic interventions.

BIOMARKERS↗

PubMed2022

Cystic Fibrosis Airway Mucus Hyperconcentration Produces a Vicious Cycle of Mucin, Pathogen, and Inflammatory Interactions that Promotes Disease Persistence.

The dynamics describing the vicious cycle characteristic of cystic fibrosis (CF) lung disease, initiated by stagnant mucus and perpetuated by infection and inflammation, remain unclear. Here we determine the effect of the CF airway milieu, with persistent mucoobstruction, resident pathogens, and inflammation, on the mucin quantity and quality that govern lung disease pathogenesis and progression. The concentrations of MUC5AC and MUC5B were measured and characterized in sputum samples from subjects with CF (N = 44) and healthy subjects (N = 29) with respect to their macromolecular properties, degree of proteolysis, and glycomics diversity. These parameters were related to quantitative microbiome and clinical data. MUC5AC and MUC5B concentrations were elevated, 30- and 8-fold, respectively, in CF as compared with control sputum. Mucin parameters did not correlate with hypertonic saline, inhaled corticosteroids, or antibiotics use. No differences in mucin parameters were detected at baseline versus during exacerbations. Mucin concentrations significantly correlated with the age and sputum human neutrophil elastase activity. Although significantly more proteolytic cleavages were detected in CF mucins, their macromolecular properties (e.g., size and molecular weight) were not significantly different than control mucins, likely reflecting the role of S-S bonds in maintaining multimeric structures. No evidence of giant mucin macromolecule reflecting oxidative stress-induced cross-linking was found. Mucin glycomic analysis revealed significantly more sialylated glycans in CF, and the total abundance of nonsulfated O-glycans correlated with the relative abundance of pathogens. Collectively, the interaction of mucins, pathogens, epithelium, and inflammatory cells promotes proteomic and glycomic changes that reflect a persistent mucoobstructive, infectious, and inflammatory state.

Cystic Fibrosis↗

PubMed2026

Manipulation of rhizosphere microbiome by Microbacterium sp. GB16_1_BI to promote plant growth.

AIM: The bioinoculant properties of a newly identified ammonium-releasing novel strain of Actinomycetota-Microbacterium bengalense sp. nov. GB16_1_BI (Accession number: SRX9280401) on the microbiome structure of rice rhizosphere were assessed. METHODS AND RESULT: GB16_1_BI may inhibit most bacteria present in the rice rhizosphere as well as encouraged the growth of rare bacteria specific to the waterlogged rice rhizosphere. The genome sequence as well as untargeted metabolome analyses of GB16_1_BI showed abundance of secondary metabolites with probable antimicrobial activity. Amplicon sequencing of the 16S rRNA V3-V4 region from the rhizosphere of the black rice showed inhibition of most bacteria by GB16_1_BI. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) analysis showed increased abundance in the marker genes for nitrogen cycling (nifH, nrfA, and nrt) but not for nifD or nifK, which was also reflected in the ANOSIM analysis in the OTUs of the N-fixing bacteria. Higher abundance of the nitrogen-fixing methanotrophs, Methylosinus and Methylocystis in inoculated plants also led to study of the marker genes for methane metabolism. CONCLUSION: Microbes present in the rhizosphere contribute to the biogeochemical cycle by transforming unavailable minerals and by retaining nutrients for their growth, which get released after death for plant adsorption. However, not all microbes contribute positively to plant growth. Microbes compete with plants for nutrients, cause disease, or produce harmful greenhouse gases. Hence, GB16_1_BI could influence plant growth predominantly by suppressing microbes and encouraged niche-specific microbes specifically involved in nitrogen cycling.

Rhizosphere↗

PubMed2026

Microbiome and resistome successions in pig carcasses and fresh pork meat throughout slaughtering, processing and shelf-life.

BACKGROUND: Slaughterhouses and meat cutting plants represent potential hotspots for the spread and transfer of spoilage and pathogenic, including antimicrobial resistant, bacteria to meat and meat products. Here, we characterise the progression of the microbiome and resistome of two pork cuts (loin and sirloin) at different stages of processing, from the slaughter line to the end of shelf-life. To this end, we analysed samples from facility surfaces, carcasses, and meat cuts using whole metagenome sequencing. RESULTS: The taxonomic and antimicrobial resistance gene (ARG) profiles of carcasses and meat cuts were significantly influenced by the point of sampling and the processing room. The facility surfaces were found to be the main source of some abundant genera, such as Anoxybacillus, Acinetobacter, Pseudomonas, and Brochothrix, in carcasses and meat cuts. A total of 1,291 metagenome-assembled genomes were reconstructed, corresponding to the most prevalent species identified in the taxonomic analysis at the read level. A reduction in bacterial and ARGs richness and diversity was observed for carcasses and meat cuts along the production chain, which suggests that processing procedures are effective in reducing bacterial and ARGs loads. Nonetheless, an increase in the ARGs load was observed at two sampling points: the carcass after evisceration and the sirloin at the end of its shelf-life (in this case linked to the increase of a single gene, tet(L)). The ARGs most frequently detected were those associated with resistance to tetracyclines, aminoglycosides, and lincosamides. Acinetobacter (in processing environments and carcass/meat samples) and Staphylococcus (in carcasses and meat) were identified as the main genera associated with the ARGs found. CONCLUSIONS: Overall, our results provide the most detailed metagenomics-based perspective on the microbial successions of pig carcasses and fresh meat cuts during slaughtering, processing, and commercialisation. The observations made suggest that selection pressures imposed by processing steps and contact with facility surfaces contribute to shaping the microbiome and resistome of the two pork products throughout their production line and shelf-life. Video Abstract.

Animals↗

PubMed2026

Virome metatranscriptomic profiling of birch pollen reveals a diverse viral community.

INTRODUCTION: Viruses are increasingly recognized as integral components of plant-associated biological systems. However, their occurrence and diversity in the reproductive tissues of woody plants remain poorly understood. Birch (Betula spp.) produces large quantities of wind-dispersed pollen that can travel over long distances and may harbour viruses or virus-derived nucleic acids originating from the host plant and/or its associated microbiota. METHODS: We investigated the virome of birch pollen collected from trees growing in central and suburban Berlin, Germany. Metatranscriptomic analyses were performed on pooled pollen samples collected in 2020. These analyses were complemented by RT-PCR screening of individually processed pollen samples collected in 2025 from resampled trees. Primer walking was additionally used to recover an extended genome sequence of a pollen-associated birch toti-like virus. RESULTS: Multiple virus-associated contigs were identified in both pooled metatranscriptomic datasets. These included sequences corresponding to the cherry leaf roll virus (CLRV), the birch idaeovirus (BIV) and the birch toti-like virus (BTLV), as well as additional virus-like contigs provisionally assigned to lineages related to the Orthototiviridae, Botourmiaviridae, Endornaviridae, and Chrysoviridae families. RT-PCR analysis of individually processed pollen samples confirmed the continued detection of CLRV, BIV, and BTLV within the Berlin sampling framework. A near-complete genome sequence was recovered from a pollen-derived BTLV isolate from Berlin, showing high amino acid sequence identity to a recently described leaf-derived BTLV isolate from the United States. DISCUSSION: These findings demonstrate that birch pollen harbours a diverse assemblage of plant- and/or microbiome-associated viruses and expand the known tissue distribution and geographic range of BTLV. More broadly, they establish pollen as an underexplored ecological niche for virome research and provide a foundation for future studies on the ecology, transmission dynamics, and epidemiological significance of pollen-associated and pollen-transmitted viruses.

Betula↗

PubMed2026

Association Between the Root Canal Microbiome and Apical Lesion Size: An Observational Shotgun Metagenomic Study.

AIM: The aim was to characterize the taxonomic and functional composition of the microbiome involved in primary endodontic infections and to evaluate their association with the periapical lesion size using shotgun metagenomic sequencing. METHODOLOGY: Samples from primary root canal infections diagnosed with apical periodontitis were analysed with shotgun sequencing. Samples were classified according to the lesion size as small (< 3 mm) or large (> 7 mm). The bacterial DNA copies in each group were quantified by qPCR. Taxonomic and functional annotations were made using Bracken/Kraken2 and HUMAnN3 software. Species richness, Shannon, Simpson and Pielou indices were used to measure alpha diversity. The similarity of the bacterial communities between study groups was evaluated by Principal Coordinate Analysis based on Bray-Curtis distances. The ALDEx2 package was used to infer the differences between species, and the edgeR package for KEGG pathways. For all statistical analyses, p < 0.05 was considered as significant. RESULTS: A total of 49 samples were analysed, 27 with small lesions and 22 with large lesions. Species richness and Shannon indices showed differences between both groups, whereas no differences were seen according to Simpson and Pielou indices. A different community composition (PERMANOVA, p = 0.0019) was observed between the two groups. Three species were significantly enriched in the large lesion samples, Filifactor alocis, Lachnospiraceae bacterium oral taxon 500 and Olsenella uli, while three others were enriched in small lesion samples, Acinetobacter baumannii, Acinetobacter pittii and Cutibacterium acnes. Functionally, benzoate, flavonoid and steroid degradation, the sphingolipid signalling pathway and proteasome function were enriched in samples with large lesions. Monoterpenoid biosynthesis, phospholipase D signalling, the sulphur relay system and staurosporine biosynthesis were enriched in small lesions. CONCLUSIONS: Teeth with large periapical lesions harbour greater bacterial loads and exhibit a more diverse microbial community than those with small lesions. Differences in species-level taxonomic composition were observed between both groups. Functionally, large lesions are enriched in pathways associated with immune evasion and pro-inflammatory activity, whereas small lesions are characterized by pathways related to apoptosis, metabolic adaptation and anti-inflammatory processes. These findings suggest that lesion severity is also shaped by the functional potential of the microbiome to modulate host inflammation.

Humans↗

PubMed2026

Divergent responses of the rhizosphere microbiome to organic amendments sustain cadmium immobilization and low crop Cd accumulation after remediation.

This study integrated a two-stage immobilization-cultivation experiment to evaluate the effects of three immobilization strategies (inorganic, organic, and organo-mineral amendments) and two fertilization modes (mineral fertilizer alone and partial substitution with organic fertilizer) on soil cadmium (Cd) immobilization and plant Cd accumulation. During the immobilization phase, the organo-mineral strategy achieved the highest Cd immobilization efficiency of 69.5%. In the cultivation phase, the use of mineral fertilizer alone led to Cd remobilization, whereas organic substitution maintained or even enhanced immobilization, reducing shoot Cd accumulation in pak choi by up to 58.3%. Notably, the combined organic immobilization and organic substitution treatment (OP) was particularly effective: despite not having the lowest soil available Cd, it achieved the lowest plant Cd accumulation (2.83 mg·kg-1). Genomic analysis indicated that the OP treatment enriched core metagenome-assembled genomes (MAGs), including MAG8/Pelagerythrobacter, MAG13/Sphingomicrobium, and MAG30/VAYN01, which contained the highest abundances of genes related to extracellular polymeric substance (EPS) synthesis, phosphorus mobilization, and complexation-precipitation, suggesting the potential of these microbes to enhance EPS secretion and phosphate precipitation for rhizospheric Cd interception. This functional potential, along with the measured high EPS content (259.88 mg·kg-1) and low plant Cd accumulation in the OP group, provides coherent correlative evidence supporting the hypothesis that an "EPS barrier-chemical precipitation" mechanism synergistically reduces Cd migration to root surfaces. Collectively, continuous organic management can maintain soil fertility, enhance Cd immobilization, and promote low-Cd crop production, offering an efficient strategy for the safe utilization of remediated farmland.

Cadmium contamination↗

PubMed2026

Gut microbiome in advanced non-small cell lung cancer: effect of chemotherapy and impact on efficacy.

BACKGROUND: While evidence linking the gut microbiome (GM) to cancer immunotherapy is growing, data regarding its role in chemotherapy remains limited. This study aims to investigate the effect of chemotherapy on GM composition and its potential as a predictive biomarker for treatment outcomes in advanced non-small cell lung cancer (NSCLC). METHODS: Advanced NSCLC patients treated with chemotherapy at Ramathibodi Hospital were prospectively enrolled. Clinical data and stool samples were collected at three time points: baseline, post-evaluation, and at progression of disease (PD). Fecal bacterial DNA was extracted, followed by PacBio Sequel II sequencing and comprehensive bioinformatic analysis. Clinical data were summarized using descriptive statistics. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and predictive factors were identified using Cox-regression analysis. RESULTS: This study analyzed 54 stool samples from 27 NSCLC patients treated with platinum-doublet chemotherapy. The median PFS and OS were 5.3 months [95% confidence interval (CI): 2.4-8.4] and 13.8 months (95% CI: 5.2-not reached), respectively. Post-chemotherapy changes (n=20 paired samples) showed a significant decrease in microbial richness, as evidenced by reduced abundance-based coverage estimator (ACE) (P=0.02) and Chao1 (P=0.03) alpha diversity indices. Taxonomically, the relative abundance of Enterobacter was significantly decreased post-chemotherapy (P=0.03). Regarding treatment response (n=26 evaluable patients; 13 PD, 13 clinical benefit), baseline alpha diversity was not predictive of outcome. However, the relative abundance of Akkermansia was notably higher in the clinical benefit group, approaching statistical significance (P=0.07). CONCLUSIONS: Chemotherapy significantly reduced GM by decreasing species richness (as measured by the ACE and Chao1 index), while species diversity (as measured by the Shannon and Simpson index) remained unchanged. Therefore, confirming the definitive role of the GM as a predictive biomarker in chemotherapy-treated NSCLC patients necessitates further investigation in a larger, more robustly powered cohort.

Gut microbiome (GM)↗

PubMed2025

Gut fungi are associated with human genetic variation and disease risk.

Human genetic determinants of the gut mycobiome remain uninvestigated despite decades of research highlighting tripartite relationships between gut bacteria, genetic background, and disease. Here, we present the first genome-wide association study on the number and types of human genetic loci influencing gut fungi relative abundance. We detect 148 fungi-associated variants (FAVs) across 7 chromosomes that statistically associate with 9 fungal taxa. Of these FAVs, several occur in the protein-coding genes PTPRC, ANAPC10, NAV2, and CDH13. Additional FAVs link to tissue-specific gene expression as fungi-associated expression quantitative trait loci. Notably, the relative abundance of gut yeast Kazachstania associates with genetic variation in CDH13 encoding T-cadherin, a protein linked to cardiovascular disease. Kazachstania forms a causal relationship with cardiovascular disease risk in a mendelian two-sample randomization analysis. These findings establish previously unrecognized connections between human genetics, gut fungi, and chronic disease, broadening the paradigm of human-microbe interactions in the gut to the mycobiome.

Humans↗

PubMed2025

Specificities of chemosensory receptors in the human gut microbiota.

The human gut is rich in metabolites and harbors a complex microbial community, yet surprisingly little is known about the spectrum of chemical signals detected by the large variety of sensory receptors present in the gut microbiome. Here, we systematically mapped the ligand specificities of selected extracytoplasmic sensory domains from twenty members of the human gut microbiota, with a primary focus on the abundant and physiologically important class of Clostridia. Twenty-five metabolites from different chemical classes-including amino acids, nucleobase derivatives, amines, indole, and carboxylates-were identified as specific ligands for fifteen sensory domains from nine bacterial species, which represent all three major functional classes of transmembrane receptors: chemotaxis receptors, histidine kinases, and enzymatic sensors. We have further characterized the specificity and evolution of ligand binding to Cache superfamily sensors specific for lactate, dicarboxylic acids, and for uracil and short-chain fatty acids (SCFAs). Structural and biochemical analysis of the dCache sensor of uracil and SCFAs revealed that its two different ligand types bind at distinct sensory modules. Overall, combining experimental identification with computational analyses, we were able to assign ligands to approximately half of the Cache-type chemotaxis receptors found in the eleven gut commensal genomes from our set, with carboxylic acids representing the largest ligand class. Among these, the most commonly found ligand specificities were for lactate and formate, indicating a particular importance of these metabolites in the human gut microbiota and consistent with their observed growth-promoting effects on selected bacterial commensals.

Humans↗

PubMed2026

The Safety, Efficacy, and Feasibility of Fecal Microbiota Transplantation in a Population With Bipolar Disorder During Depressive Episodes: A Pilot Parallel Arm Randomized Controlled Trial: Sécurité, efficacité et faisabilité de la transplantation de microbiote fécal chez une population atteinte de troubles bipolaires, au cours d'épisodes dépressifs : essai pilote contrôlé à répartition aléatoire et à groupes parallèles.

BackgroundThe gut microbiome has been proposed as a potential modifiable target to treat mental illness. This double-blind randomized control trial investigated fecal microbiota transplant (FMT) in bipolar disorder (BD) to assess efficacy, safety, and feasibility. The primary outcome evaluated the effectiveness of standard approved therapy for BD depression + FMT in individuals not responding to standard treatment, measured by change in the Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to week 24. Secondary outcomes included FMT's impact on anxiety, global function, side-effects, and safety. The feasibility of this novel intervention was also assessed. Microbial analysis utilized whole-genome shotgun metagenomic sequencing, comparing outcomes between allogenic (donor) and autologous (participants own) FMT.MethodsA total of 35 participants (28 women and 7 men) with at least moderate depressive-phase BD (MADRS) were randomized to receive either allogenic FMT (n = 17) or autologous FMT (n = 18) via colonoscopy and were followed for 24 weeks.ResultsMADRS scores significantly improved from baseline to the last visit in both treatment arms. There was no significant difference between allogenic FMT (16.74-point improvement) and autologous FMT (15.4-point improvement) regarding clinical efficacy (t = -0.47, p-value = .64, 95% confidence interval [CI] = -7.3-4.6). Microbiota analysis showed that allogenic FMT let to a bacterial profile similar to the healthy donor and increased bacterial diversity at the 6-month mark, whereas those receiving autologous FMT did not. The intervention was well tolerated with no significant adverse events. Recruitment, randomization, and retention metrics support feasibility of a larger trial.ConclusionFeasibility and tolerability data indicate further investigation into microbial manipulation in BD is warranted. The absence of efficacy differences between the two types of FMT, despite microbial change, highlights the importance of a true placebo in future studies, as well as the importance of understanding exactly what bacteria are linked to improvements. ClinicalTrials.gov, NCT0327922Plain Language Summary TitleResults of a Double-Blind Randomized Control Trial Investigating Fecal Microbiota Transplant (FMT) as an Add-on Treatment for Depression in Bipolar Disorder and Analyzing Microbial Diversity Changes Over 24 Weeks.

Humans↗