Microbiome最新文献

{"title":"Metagenomics and culturomics reveal the dual role of the gut microbiome in the development of immune-related toxicities and the efficacy of immune checkpoint inhibitors in cancer.","authors":"Khoudia Diop, Myriam Benlaïfaoui, Sébastien Hunter, Eder Orlando Méndez-Salazar, Taiki Hakozaki, Corentin Richard, Diogjena Katerina Prifti, Sylva Kourtian, Francis Proulx-Rocray, Sabrine Naimi, Mayra Ponce, Meriem Messaoudene, Florent Cauchois, Wiam Belkaid, Veronique Bataille, Karla Lee, Catalin Mihalcioiu, Ian Robert Watson, Arielle Elkrief, Bertrand Routy","doi":"10.1186/s40168-026-02419-4","DOIUrl":"https://doi.org/10.1186/s40168-026-02419-4","url":null,"abstract":"<p><strong>Background: </strong>Despite their major impact on cancer treatment, immune checkpoint inhibitors (ICI) are frequently associated with immune-related adverse events (irAE). Growing evidence suggests that the occurrence of irAE may be correlated with enhanced ICI efficacy, although the underlying mechanisms remain unknown. Most studies investigating the role of the gut microbiome in oncology have relied on sequencing approaches, particularly shotgun metagenomics. Although microbiome profiling revealed strong associations between specific bacterial taxa and clinical outcomes, it has limitations, including an inability to detect low-abundance bacteria and to recover live cultivable bacteria. To overcome these limitations, we combined shotgun metagenomics and culturomics on fecal samples collected from patients with melanoma and non-small cell lung cancer (NSCLC), at baseline and at the onset of immune related (ir)-colitis.</p><p><strong>Results: </strong>We first validated across three independent cohorts of 589 patients with melanoma or NSCLC treated with ICI that grade ≥ 2 irAE were associated with significantly longer overall survival (OS) and progression-free survival (PFS). Complementary analysis using shotgun metagenomics and culturomics revealed that patients who developed grade ≥ 2 irAE had a lower alpha diversity compared to those who did not develop grade ≥ 2 irAE. Metagenomics results showed enrichment of Ruminococcus gnavus and Streptococcus vestibularis at baseline in grade ≥ 2 irAE patients, while Clostridium paraputrificum and Streptococcus spp. were isolated by culturomics from baseline stool samples from ir-colitis patients. Longitudinal analysis of paired stool samples revealed a shift in microbiome composition with enrichment of Paraclostridium bifermentans and Clostridium paraputrificum, lower lipopolysaccharide and higher flagellin concentrations at baseline compared with the time of ir-colitis. Fecal microbiome transplantation from a patient with ir-colitis into mice induced surrogate markers of colonic inflammation and enhanced the anti-tumor activity of combined anti-PD-1/CTLA-4. P. bifermentans isolated from this patient sample demonstrated direct epithelial barrier disruption in Caco-2 monolayers, characterized by decreased ZO-1 and Occludin immunofluorescence signal and increased TNF-α and IL-1β expression. Moreover, in the dextran sodium sulfate (DSS) colitis model, P. bifermentans worsened weight loss. In a separate tumor model, it amplified the anti-tumor effect of dual ICI. This beneficial effect was also maintained after treatment with P. bifermentans < 3 kDa filtered supernatant.</p><p><strong>Conclusion: </strong>Altogether, our results suggest that P. bifermentans promotes subclinical colitis while increasing the efficacy of dual ICI. This provides a potential microbiome-derived link between irAE and improved anti-tumor responses. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":12.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Precisely designed keystone metabolites boost shrimp disease resistance by recruiting symbionts via the lipoxin A4-AP-1 pathway.","authors":"Haonan Sha, Jiong Chen, Jianguo He, Bin He, Jie Huang, Jizhong Zhou, Xuan Dong, Jinbo Xiong","doi":"10.1186/s40168-026-02418-5","DOIUrl":"https://doi.org/10.1186/s40168-026-02418-5","url":null,"abstract":"<p><strong>Background: </strong>Gut metabolites and symbionts are indispensable for host health, yet the precise identification of keystone metabolites and construction of synthetic microbial communities (SynComs) to enhance disease resistance remains limited.</p><p><strong>Results: </strong>Using Litopenaeus vannamei as a model, we identified pyruvic acid and DL-glutamine (1:2) as keystone metabolites by borrowing the microbial ecology principles of bio-indicators and driver taxa. Dietary supplementation with these metabolites sufficiently protected shrimp from white feces syndrome (WFS). Multi-omics analyses demonstrated that keystone metabolites exerted positive effects by enriching beneficial Ruegeria lacuscaerulensis, Bacillus subtilis and Nioella nitratireducens, strengthening the gut network stability, and enhancing shrimp immunity, which collectively potentiated WFS resistance. The recruited three strains were consumers and producers of the two keystone metabolites, and discriminative strains between healthy and diseased shrimp across global datasets. A SynCom constructed from the three strains (4:3:2) replicated the efficacy of keystone metabolites. Both keystone metabolites and SynCom elevated shrimp gut and hepatopancreas lipoxin A4 (LXA4) levels, which suppressed the pro-inflammatory transcription factor AP-1, as validated by in vivo inhibition assay.</p><p><strong>Conclusions: </strong>Our findings demonstrate that precisely designed keystone metabolites enhance shrimp disease resistance through the recruitment of key symbionts-LXA4-AP-1 axis. The rationally designed keystone metabolites and SynCom are compelling biocontrol solutions in improving host disease resistance. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":12.7,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-seq sheds light on \"who is doing what\" in the coral Porites lutea.","authors":"Kshitij Tandon, Juntong Hu, Francesco Ricci, Linda Louise Blackall, Mónica Medina, Michael Kühl, Heroen Verbruggen","doi":"10.1186/s40168-026-02414-9","DOIUrl":"https://doi.org/10.1186/s40168-026-02414-9","url":null,"abstract":"<p><strong>Background: </strong>The coral holobiont functions as a complex biogeochemical system, sustained by intricate metabolic exchanges between the host and its associated microbiome. While the taxonomic diversity of these communities is well documented, the specific metabolic roles and biogeochemical contributions of microorganisms across distinct coral compartments, particularly within the endolithic habitats, remain poorly understood. Using RNA-seq, we investigated the active microbiome of healthy stony coral Porites lutea, focusing on the coral tissue, the green endolithic algal layer (Ostreobium layer), and the deeper coral skeleton.</p><p><strong>Results: </strong>We identified distinct, metabolically active communities within these compartments and highlight substantial metabolic redundancy across carbon, nitrogen, and sulfur pathways. Our study provides the first transcriptomic evidence of Ostreobium's ability to transfer fixed carbon to other holobiont members and the coral host. We highlight the critical roles of diverse coral holobiont members in nutrient cycling and maintaining homeostasis through scavenging of reactive oxygen and nitrogen species.</p><p><strong>Conclusions: </strong>This study provides a novel molecular-level understanding of the functional roles played by diverse coral holobiont members in their respective compartments and underscores that corals harbor distinct microbiomes with wide-ranging functions. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":12.7,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Streptomyces-induced Glycerol-3-Phosphate enriches beneficial microbiota to enhance resistance against banana Fusarium wilt.","authors":"Bingyu Cai, Lu Zhang, Zekai Wu, Jie Wang, Yongzan Wei, Raza Waseem, Miaoyi Zhang, Dengfeng Qi, Dengbo Zhou, Yankun Zhao, Kai Li, Huigang Hu, Jianghui Xie, Wei Wang","doi":"10.1186/s40168-026-02409-6","DOIUrl":"https://doi.org/10.1186/s40168-026-02409-6","url":null,"abstract":"<p><strong>Background: </strong>Fusarium oxysporum f. sp. cubense Tropical Race 4 (Foc TR4) is the causal agent of banana Fusarium wilt, a destructive soil-borne disease. Using antagonistic microorganisms, such as Streptomyces species, offers a promising strategy for controlling fungal diseases. However, their field application is limited by an incomplete understanding of microbe-plant-pathogen interactions.</p><p><strong>Results: </strong>This study shows that the marine-derived Streptomyces malaysiensis WHL7 exhibits strong antagonistic activity against multiple phytopathogenic fungi in vitro, particularly Foc TR4. In pot experiments using natural soil, WHL7 treatment significantly reduced the incidence of Fusarium wilt from 55% in the Foc TR4-inoculated control to 15%. No protective effect was observed in sterilized soil, indicating that its biocontrol efficacy depends on the indigenous microbial community. Integrated metabolomic analysis reveals that WHL7 stimulates the key root secretion of glycerol-3-phosphate (G3P). The compound enriches beneficial Bacillus and Pseudomonas species in the rhizosphere. Compared to the Foc TR4-treated group, exogenous application of G3P reduced Foc TR4 abundance by 73%, inhibited pathogenic infection, and consistently increased the populations of Bacillus and Pseudomonas. These enriched microbes were directly linked with reduced disease severity by inducing systemic ACQUIRED RESISTANCE OF plant.</p><p><strong>Conclusions: </strong>While S. malaysiensis WHL7 directly suppresses Foc TR4 via antagonistic compounds in vitro, it controls disease in pot experiments indirectly by reshaping the rhizosphere microbiome. This restructuring induces host resistance through a g3p-mediated signaling pathway. the study highlights g3p-mediated priming as a sustainable strategy for managing soil-borne diseases. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":12.7,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Convergent evolution of intestinal lineages in the phylum Methanobacteriota.","authors":"Evgenii Protasov, Undine S Mies, Cathrin Spröer, Boyke Bunk, Sebastian Cristian Treitli, Katja Platt, Andreas Brune","doi":"10.1186/s40168-026-02434-5","DOIUrl":"10.1186/s40168-026-02434-5","url":null,"abstract":"<p><strong>Background: </strong>Representatives of the phylum Methanobacteriota occur in various anoxic environments, but only members of the genera Methanosphaera and Methanobrevibacter exclusively colonize the digestive tract of animals. Recent phylogenomic analyses revealed that the genus Methanobrevibacter, which harbors the majority of the intestinal species, is severely underclassified and represents a family-level taxon, \"Methanobrevibacteraceae\", that evolved entirely in the digestive tract of animals.</p><p><strong>Results: </strong>Comparative genome analysis of 158 species of Methanobacteriota, including uncultured representatives in the Genome Taxonomy Database (GTDB), demonstrated that the intestinal lineages are clearly separated from the remaining members of the phylum. They differ from the non-intestinal lineages in genome size, GC content, coding density, an increased number of pseudogenes and adhesin-like proteins, and show numerous adaptations to the copiotrophic gut environment. A decreased biosynthetic potential led to a dependence on other community members and limits the dispersal of intestinal species into other habitats, which is reflected in coevolutionary patterns with their major host groups among arthropods, ungulates, and primates. Certain lineages even engaged in symbiotic associations with intestinal protists, presumably benefiting from the H₂ produced by the hydrogenosomes of their anaerobic hosts.</p><p><strong>Conclusions: </strong>Our results reveal that the transition of free-living Methanobacteriota to a host-associated lifestyle involves the same genomic changes that were previously recognized in gut bacteria and bacterial endosymbionts of protists, reflecting resemblances between the two prokaryotic domains that are caused by evolutionary convergence in similar environments.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":"14 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capsaicin ameliorates glycemic levels via gut microbiota-derived 5-aminolevulinic acid in mice.","authors":"Qingying Fang, Shi Huang, Chengcheng Zhang, Mingyang Li, Zi Ye, Hang Guo, Meifang Xiao, Shunhe Wang, Leilei Yu, Hao Zhang, Jianxin Zhao, Fengwei Tian, Wei Chen, Qixiao Zhai","doi":"10.1186/s40168-026-02415-8","DOIUrl":"10.1186/s40168-026-02415-8","url":null,"abstract":"<p><strong>Background: </strong>Capsaicin, a natural alkaloid in chili peppers, regulates glycemic levels; however, its mechanisms and therapeutic potential remain unclear. This study aimed to elucidate the role of gut microbiota and their metabolites in mediating capsaicin's glycemic regulatory effects. We conducted experiments in specific pathogen-free (SPF) and germ-free (GF) mice, transient receptor potential vanilloid 1 (TRPV1) receptor ablation studies, and fecal microbiota transplantation (FMT) to demonstrate the involvement of gut microbiota in capsaicin-mediated glycemic control. Metagenomics and metabolomics analyses were employed to identify key microbial strains and metabolic pathways. Keystone strains and metabolites were supplemented in GF mice without capsaicin intervention to validate their effects on glycemic regulation. In vitro co-culture experiments were performed to investigate the mutualistic relationships among keystone strains under capsaicin treatment.</p><p><strong>Results: </strong>Gut microbiota constitute an important component of capsaicin-mediated glycemic regulation, acting in concert with but not solely dependent on TRPV1 signaling. Gut microbiota altered by capsaicin promote the production of 5-aminolevulinic acid (5-ALA), which contributes to heme synthesis and enhances glycemic control. Supplementation with Akkermansia muciniphila, Ligilactobacillus murinus, or 5-ALA in GF mice recapitulates the glycemic benefits of capsaicin. Furthermore, capsaicin enriches Akkermansia muciniphila, which in turn supports the growth of Ligilactobacillus murinus.</p><p><strong>Conclusion: </strong>Capsaicin-induced changes in the gut microbiota promote 5-ALA synthesis, leading to improved glycemic control. These findings suggest that dietary or probiotic interventions targeting gut microbiota, particularly Akkermansia muciniphila and 5-ALA, may offer promising strategies for managing glycemic disorders, including type 2 diabetes (T2D). Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":12.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Puerarin modulates the gut-liver-ovarian axis to ameliorate reproductive aging in breeder hens.","authors":"Zhenwu Huang, Dandan Ma, Guangju Wang, Yanru Shi, Jinghai Feng, Chunmei Li, Minhong Zhang","doi":"10.1186/s40168-026-02404-x","DOIUrl":"https://doi.org/10.1186/s40168-026-02404-x","url":null,"abstract":"<p><strong>Background: </strong>Puerarin (PU), a natural bioactive isoflavone derived from the edible root of Pueraria lobata, exhibits multi-pharmacological activities, including antioxidant, lipid metabolism-regulating, and immunomodulatory properties. The decline in the reproductive performance of hens is primarily attributed to age-related dysbiosis of gut function and reduced function of the liver-ovary axis. However, the systemic mechanisms linking puerarin-induced microbiota changes to improvements in hepatic and ovarian function in aged hens remain poorly defined. In this study, we performed a multi-omics investigation to explore the effects on gut microbiota, liver metabolism, ovarian function, and the associations among them induced by dietary puerarin in aged hens.</p><p><strong>Results: </strong>The results demonstrated that dietary supplementation with 200 mg/kg puerarin significantly improved egg quality, laying rate, and feed conversion efficiency, restored endocrine hormone homeostasis, and reduced ovarian oxidative stress and apoptosis. Puerarin stimulated carbon flux partitioning through the hepatic citrate cycle (TCA) and pentose phosphate pathway, thereby enhancing vitellogenin (VTG) synthesis and its transport to the ovary. Furthermore, puerarin activated the cytokine-cytokine receptor interaction pathway and reversed microbial dysbiosis (e.g., Lactobacillus and Bacteroides), thereby ameliorating intestinal functional decline. Significant correlations were also observed among hepatic tauroursodeoxycholic acid levels, intestinal expression of the lipid metabolism genes CD36 and GPAT3, and the relative abundance of Lactobacillus. Multi-omics analyses revealed that puerarin ameliorated age-related hepatic lipid metabolism disorders by targeted regulation of the peroxisome proliferator-activated receptor (PPAR) signaling pathway in the gut and liver. We elucidated the direct effects of puerarin-induced alterations in gut microbial abundance and reproductive performance in aging hens, highlighting the mediating role of liver function.</p><p><strong>Conclusions: </strong>These findings collectively indicate that puerarin positively redirected the gut-liver-ovary axis function to mitigate reproductive aging, suggesting potential to improve metabolic health in aging hens.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":12.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147775644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota induces dysspermatogenesis via microbial-derived phenylacetylglycine in Ggt1-deficient mice.","authors":"Jinhua Tang, Ling Wang, Zhaolin Yang, Yuyang Song, Shang Wu, Qiqi Liang, Zesheng Li, Shiqin Zhou, Hao Xiong, Dake Chen, Jialian Li, Fenge Li","doi":"10.1186/s40168-026-02401-0","DOIUrl":"https://doi.org/10.1186/s40168-026-02401-0","url":null,"abstract":"<p><strong>Background: </strong>Male infertility represents a global health concern, with emerging evidence linking gut microbiota dysbiosis to dysspermatogenesis and subfertility. However, the molecular mediators and regulatory mechanisms by which gut microbiota influences testicular functions remain poorly defined.</p><p><strong>Results: </strong>This study demonstrates that male gamma-glutamyl transferase 1-deletion (Ggt1^-/-) mice exhibits infertility phenotypes, including reduced germ and testicular Leydig cell numbers, increased rates of abnormal sperm, and altered reproductive hormone levels. Metabolomic analysis reveals elevated levels of the gut microbial-derived metabolite phenylacetylglycine (PAGly) in serum and testes of Ggt1^-/- mice, with in vivo injection experiments indicating its role in impairing spermatogenesis. Moreover, blocking PAGly effectively restores the impaired spermatogenesis in Ggt1^-/- mice. Fecal metagenomic and metabolomic analyses show that gut microbiota in Ggt1^-/- mice induces elevation of phenylacetic acid, a precursor metabolite of PAGly. Strikingly, fecal microbiota transplantation from Ggt1^-/- mice (Ggt1^-/--FMT) recapitulates the infertility phenotypes including reduced germ cells and increased rates of abnormal sperm. Mechanistically, integrated CUT&Tag and ATAC-Seq analyses reveal that transcription factor STAT5B occupies regulatory elements near Klk1b transcription start sites (TSS), confirming that transcription factor STAT5B directly regulates Klk1b gene transcription. Concretely, PAGly activates β2-adrenergic receptor (β2AR) on Leydig cells, triggering STAT3 phosphorylation, subsequent SOCS3 upregulation, and STAT5B phosphorylation suppression; p-STAT5B with transcriptional activation function is reduced, then Klk1b gene transcription is compromised, and therefore spermatogenesis is disrupted.</p><p><strong>Conclusion: </strong>Ggt1 deletion-induced gut microbiota dysbiosis disrupts spermatogenesis via β2AR-STAT3-SOCS3-STAT5B-Klk1bs signaling pathway. Specifically, PAGly-induced β2AR activation promotes STAT3 phosphorylation, which induces SOCS3 to suppress p-STAT5B dependent Klk1bs transcription. This mechanism underscores the critical role of gut-derived metabolites in regulating testicular function and identifies potential targets for microbiota-modulated male infertility. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":12.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal microbial nitrogen metabolic landscape underlies nitrogen utilization efficiency of goats fed distinct dietary protein sources.","authors":"Yechan Zhao, Zhiliang Tan, Zhixiong He, Jian Wu, Jinzhen Jiao","doi":"10.1186/s40168-026-02398-6","DOIUrl":"https://doi.org/10.1186/s40168-026-02398-6","url":null,"abstract":"<p><strong>Background: </strong>Improving nitrogen (N) utilization efficiency in ruminant livestock is vital for coping with global protein scarcity and lowering environmental pollution. The biogeographically stratified microorganisms in the gastrointestinal tract (GIT) fulfill the pivotal role of metabolizing dietary N into bioavailable nutrients. In this study, we deciphered the microbial N utilization dynamics in the rumen and colon under different protein source interventions, soybean meal (SBM) and corn gluten meal (CGM) which differed in rumen degradation rate and amino acid (AA) profile, using goats as a model.</p><p><strong>Results: </strong>Goats fed with the SBM diet exhibited greater N utilization efficiency, as characterized by greater average daily gain (ADG), nutrient digestibility, and the concentration of free amino acids (AAs) in the GIT. The SBM diet, with its higher rumen-degradable protein (RDP) content, selectively enriched protein degraders Sodaliphilus, Limivicinus, and RUG472 spp., and upregulated genes encoding key peptidases (pepT, pepDA/B) in the rumen. Conversely, aligning with its higher rumen-undegradable protein (RUP) content, the CGM diet promoted the enrichment of proteolytic bacteria Alistipes spp. in the colon. Notably, in response to dietary AA deficiency, the CGM diet enriched AA producers-Ruminococcus, RUG563, UBA1179 spp. in the rumen, Treponema, UBA737, and Firm-07 spp. in the colon. This is accompanied by greater abundances of genes involved in de novo biosynthesis of aromatic AAs (trpA, trpB), lysine (dapA), and histidine (hisG), suggesting a microbial compensatory response for dietary deficiencies, though insufficient to fully offset the nutritional shortfall.</p><p><strong>Conclusions: </strong>This study depicts the microbial nitrogen metabolic landscapes integrating protein degradation, AA biosynthesis, and AA catabolism under distinct dietary protein sources, and provides potential microbial targets for optimizing N utilization efficiency in ruminants. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":12.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trimethylamine-producing microbe Bacillus megaterium KCTC 3007 promotes antitumor immunity in endometrial cancer via type I interferon response pathways.","authors":"Kyungchan Min, Se Ik Kim, Minji Lee, Yunjae Kim, Chanyeong Jeong, Sujeong Kim, Sang Jin Kim, Hyun Kim, Beomki Cho, Yanghyun Joo, Hansoo Park, Maria Lee","doi":"10.1186/s40168-026-02373-1","DOIUrl":"10.1186/s40168-026-02373-1","url":null,"abstract":"<p><strong>Background: </strong>Endometrial cancer (ECa) is one of the most common gynecologic malignancies, with limited therapeutic responses in metastatic or recurrent cases. The bacterial microbiota has emerged as a key modulator of carcinogenesis and antitumor immunity. However, the role of endometrial microbiota in ECa pathogenesis and prognosis remains poorly understood.</p><p><strong>Methods: </strong>We performed comprehensive multi-omics analysis integrating metatranscriptomics, transcriptomics, and targeted metabolomics from 60 ECa and 18 benign patients. RNA sequencing enabled simultaneous profiling of active tissue-resident microbiota and host gene expression. Serum metabolomics was conducted on all patients. Identified microbial-metabolite associations were validated through in vitro co-culture experiments using peripheral blood mononuclear cells (PBMCs), cancer cell lines, RNA sequencing, and live cell imaging.</p><p><strong>Results: </strong>ECa patients exhibited significantly altered microbial diversity and composition compared to benign controls. Through integrated multi-omics analysis, we identified Bacillus megaterium (BM) KCTC 3007 as a beneficial microbe associated with prolonged recurrence-free survival. In an exploratory analysis of ECa subtypes, Cupriavidus taiwanensis and Marinomonas primoryensis showed potential links to poor prognosis, although these observations warrant caution due to the limited size of certain subgroups. Tissue BM abundance positively correlated with serum trimethylamine N-oxide (TMAO) levels, particularly in postmenopausal women. In vitro experiments demonstrated that BM KCTC 3007 enhanced antitumor immunity by promoting interleukin and type I interferon expression, expanding CD8 + T cell populations, and increasing immune cell-tumor cell interactions. RNA sequencing revealed activation of interferon alpha response and immune cell proliferation pathways, with IFNAR1 identified as a key upstream regulator. TMAO treatment recapitulated these immune-activating effects, enhancing CD8 + T cell responses and preferentially inducing pyroptotic cancer cell death.</p><p><strong>Conclusions: </strong>We provide the first evidence that tissue-resident BM KCTC 3007 promotes antitumor immunity in ECa through TMAO production and subsequent type I interferon-mediated immune activation. This integrated multi-omics approach establishes a complete microbe-metabolite-host mechanistic pathway and highlights the therapeutic potential of TMAO-producing probiotic strains for ECa treatment. Video Abstract.</p>","PeriodicalId":18447,"journal":{"name":"Microbiome","volume":" ","pages":""},"PeriodicalIF":12.7,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13104324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}