Gut dysbiosis in oncology: a risk factor for immunoresistance

Gut dysbiosis in oncology: a risk factor for immunoresistance

  • Bender, M. J. et al. Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment. Cell 186, 1846–1862.e26 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Derosa, L., Routy, B., Kroemer, G. & Zitvogel, L. The intestinal microbiota determines the clinical efficacy of immune checkpoint blockers targeting PD-1/PD-L1. Oncoimmunology 7, e1434468 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Derosa, L. et al. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer. Nat. Med. 28, 315–324 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fidelle, M. et al. A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers. Science 380, eabo2296 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hakozaki, T. et al. The gut microbiome associates with immune checkpoint inhibition outcomes in patients with advanced non-small cell lung cancer. Cancer Immunol. Res. 8, 1243–1250 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Matson, V. et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359, 104–108 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Messaoudene, M. et al. The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteers. Nat. Commun. 15, 8083 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Park, J. S. et al. Targeting PD-L2–RGMb overcomes microbiome-related immunotherapy resistance. Nature 617, 377–385 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Phelps, C. M. et al. Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy. Cell 188, 5680–5700.e28 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pinato, D. J. et al. Antibiotic therapy and outcome from immune-checkpoint inhibitors. J. Immunother. Cancer 7, 287 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Routy, B. et al. The gut microbiota influences anticancer immunosurveillance and general health. Nat. Rev. Clin. Oncol. 15, 382–396 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shatila, M. et al. Gastrointestinal infection before immune checkpoint inhibition hinders treatment efficacy and increases the risk of colitis. Cancer Med. 14, e71123 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Spencer, C. N. et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science 374, 1632–1640 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Derosa, L. et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann. Oncol. 29, 1437–1444 (2018).

  • Winter, S. E. & Bäumler, A. J. Gut dysbiosis: Ecological causes and causative effects on human disease. Proc. Natl. Acad. Sci. USA 120, e2316579120 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • The Human Microbiome Project Consortium Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).

    Article 
    PubMed Central 

    Google Scholar
     

  • The Integrative HMP (iHMP) Research Network Consortium The integrative human microbiome project. Nature 569, 641–648 (2019).

    Article 

    Google Scholar
     

  • Hooks, K. B. & O’Malley, M. A. Dysbiosis and its discontents. mBio 8, e01492–17 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Olesen, S. W. & Alm, E. J. Dysbiosis is not an answer. Nat. Microbiol1, 16228 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yong, E. There is no ‘healthy’ microbiome. The New York Times (2 November 2014).

  • Ponziani, F. R. et al. Gut dysbiosis and fecal calprotectin predict response to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Hepatol. Commun. 6, 1492–1501 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Birebent, R. et al. Surrogate markers of intestinal dysfunction associated with survival in advanced cancers. Oncoimmunology 14, 2484880 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • World Health Organization. Constitution of the World Health Organization 1–18 (World Health Organization, 1946).

  • López-Otín, C. & Kroemer, G. Hallmarks of health. Cell 184, 33–63 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Martino, C. et al. Microbiota succession throughout life from the cradle to the grave. Nat. Rev. Microbiol. 20, 707–720 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gomez de Agüero, M. et al. The maternal microbiota drives early postnatal innate immune development. Science 351, 1296–1302 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Thorburn, A. N. et al. Evidence that asthma is a developmental origin disease influenced by maternal diet and bacterial metabolites. Nat. Commun. 6, 7320 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rasmussen, M. A. et al. Ecological succession in the vaginal microbiota during pregnancy and birth. ISME J. 14, 2325–2335 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ardic, C., Usta, O., Omar, E., Yıldız, C. & Memis, E. Caesarean delivery increases the risk of overweight or obesity in 2-year-old children. J. Obstet. Gynaecol. 41, 374–379 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Shao, Y. et al. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature 574, 117–121 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stokholm, J. et al. Maturation of the gut microbiome and risk of asthma in childhood. Nat. Commun. 9, 141 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Munblit, D., Verhasselt, V. & Warner, J. O. Editorial: human milk composition and health outcomes in children. Front. Pediatr. 7, 319 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Thaiss, C. A. et al. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell 159, 514–529 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Thaiss, C. A. et al. Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell 167, 1495–1510.e12 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bailey, M. T. et al. Exposure to a social stressor alters the structure of the intestinal microbiota: implications for stressor-induced immunomodulation. Brain Behav. Immun. 25, 397–407 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhao, S. et al. Adaptive evolution within gut microbiomes of healthy people. Cell Host Microbe 25, 656–667.e8 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Biagi, E. et al. Gut microbiota and extreme longevity. Curr. Biol. 26, 1480–1485 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ghosh, T. S., Shanahan, F. & O’Toole, P. W. The gut microbiome as a modulator of healthy ageing. Nat. Rev. Gastroenterol. Hepatol. 19, 565–584 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grajeda-Iglesias, C. et al. Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites. Aging 13, 6375–6405 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pang, S. et al. Longevity of centenarians is reflected by the gut microbiome with youth-associated signatures. Nat. Aging 3, 436–449 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Thomas, A. M. et al. Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy. Nat. Rev. Clin. Oncol. 20, 583–603 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sinha, T. et al. Analysis of 1135 gut metagenomes identifies sex-specific resistome profiles. Gut Microbes 10, 358–366 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, X. et al. Sex- and age-related trajectories of the adult human gut microbiota shared across populations of different ethnicities. Nat. Aging 1, 87–100 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Zhernakova, A. et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science 352, 565–569 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • d’Afflitto, M., Upadhyaya, A., Green, A. & Peiris, M. Association between sex hormone levels and gut microbiota composition and diversity—a systematic review. J. Clin. Gastroenterol. 56, 384–392 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Peters, B. A. et al. Menopause is associated with an altered gut microbiome and estrobolome, with implications for adverse cardiometabolic risk in the hispanic community health study/study of Latinos. mSystems 7, e0027322 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Santos-Marcos, J. A. et al. Influence of gender and menopausal status on gut microbiota. Maturitas 116, 43–53 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Zhao, H. et al. Compositional and functional features of the female premenopausal and postmenopausal gut microbiota. FEBS Lett. 593, 2655–2664 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Conforti, F. et al. Sex-based heterogeneity in response to lung cancer immunotherapy: a systematic review and meta-analysis. J. Natl. Cancer Inst. 111, 772–781 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Conforti, F. et al. Cancer immunotherapy efficacy and patients’ sex: a systematic review and meta-analysis. Lancet Oncol. 19, 737–746 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Graham, J., Abdel-Rahman, O., Choueiri, T. K. & Heng, D. Y. C. Re: Fabio Conforti, Laura Pala, Vincenzo Bagnardi, et al. Cancer immunotherapy efficacy and patients’ sex: A systematic review and meta-analysis. Lancet Oncol 2018; 19:737–46: Outcomes of metastatic renal cell carcinoma by gender: Contrasting results from the International mRCC Database Consortium. Eur. Urol. 74, e139–e140 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Conforti, F. et al. Reply to Jeffrey Graham, Omar Abdel-Rahman, Toni K. Choueiri, and Daniel Y. C. Heng’s Letter to the Editor re: Fabio Conforti, Laura Pala, Vincenzo Bagnardi, et al. Cancer immunotherapy efficacy and patients’ sex: a systematic review and meta-analysis. Lancet Oncol 2018;19:737–746: Outcomes of Metastatic Renal Cell Carcinoma by Gender: Contrasting Results from the International mRCC Database Consortium. Eur. Urol. 75, e34–e35 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Haupt, S., Caramia, F., Klein, S. L., Rubin, J. B. & Haupt, Y. Sex disparities matter in cancer development and therapy. Nat. Rev. Cancer 21, 393–407 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ye, Y. et al. Sex-associated molecular differences for cancer immunotherapy. Nat. Commun. 11, 1779 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wallis, C. J. D. et al. Association of patient sex with efficacy of immune checkpoint inhibitors and overall survival in advanced cancers. JAMA Oncol. 5, 529–536 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gacesa, R. et al. Environmental factors shaping the gut microbiome in a Dutch population. Nature 604, 732–739 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rothschild, D. et al. Environment dominates over host genetics in shaping human gut microbiota. Nature 555, 210–215 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Turpin, W. et al. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat. Genet. 48, 1413–1417 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lopera-Maya, E. A. et al. Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project. Nat. Genet. 54, 143–151 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Qin, Y. et al. Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort. Nat. Genet. 54, 134–142 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kurilshikov, A. et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat. Genet. 53, 156–165 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhernakova, D. V. et al. Host genetic regulation of human gut microbial structural variation. Nature 625, 813–821 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Goodrich, J. K. et al. Human genetics shape the gut microbiome. Cell 159, 789–799 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Goodrich, J. K. et al. Genetic determinants of the gut microbiome in UK twins. Cell Host Microbe 19, 731–743 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl. Acad. Sci. USA 107, 14691–14696 (2010).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Deschasaux, M. et al. Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography. Nat. Med. 24, 1526–1531 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Falony, G. et al. Population-level analysis of gut microbiome variation. Science 352, 560–564 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • He, Y. et al. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat. Med. 24, 1532–1535 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mueller, S. et al. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl. Environ. Microbiol72, 1027–1033 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Monda, V. et al. Exercise modifies the gut microbiota with positive health effects. Oxid. Med. Cell. Longev. 2017, 3831972 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sohail, M. U., Yassine, H. M., Sohail, A. & Thani, A. A. A. Impact of physical exercise on gut microbiome, inflammation, and the pathobiology of metabolic disorders. Rev. Diabet. Stud. 15, 35–48 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Varghese, S., Rao, S., Khattak, A., Zamir, F. & Chaari, A. Physical exercise and the gut microbiome: A bidirectional relationship influencing health and performance. Nutrients 16, 3663 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • GBD 2017 Diet Collaborators Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 393, 1958–1972 (2019).

    Article 

    Google Scholar
     

  • David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Do, M. H., Lee, E., Oh, M. J., Kim, Y. & Park, H. Y. High-glucose or -fructose diet cause changes of the gut microbiota and metabolic disorders in mice without body weight change. Nutrients 10, 761 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fackelmann, G. et al. Gut microbiome signatures of vegan, vegetarian and omnivore diets and associated health outcomes across 21,561 individuals. Nat. Microbiol. 10, 41–52 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fajstova, A. et al. Diet rich in simple sugars promotes pro-inflammatory response via gut microbiota alteration and TLR4 signaling. Cells 9, 2701 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • de Vos, W. M., Tilg, H., Van Hul, M. & Cani, P. D. Gut microbiome and health: mechanistic insights. Gut 71, 1020–1032 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Oliver, A. et al. High-fiber, whole-food dietary intervention alters the human gut microbiome but not fecal short-chain fatty acids. mSystems 6, e00115–e00121 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Siddiqui, M. T. & Cresci, G. A. M. The immunomodulatory functions of butyrate. J. Inflamm. Res. 14, 6025–6041 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ferrere, G. et al. Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade. JCI Insight 6, e145207 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sofi, F., Cesari, F., Abbate, R., Gensini, G. F. & Casini, A. Adherence to Mediterranean diet and health status: meta-analysis. BMJ 337, a1344 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, D. D. et al. The gut microbiome modulates the protective association between a Mediterranean diet and cardiometabolic disease risk. Nat. Med. 27, 333–343 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Alves Costa Silva, C., Fidelle, M., Almonte, A. A., Derosa, L. & Zitvogel, L. Gut microbiota-related biomarkers in immuno-oncology. Annu. Rev. Pharm. Toxicol. 65, 333–354 (2025).

    Article 

    Google Scholar
     

  • Almonte, A. A., Thomas, S. & Zitvogel, L. Microbiota-centered interventions to boost immune checkpoint blockade therapies. J. Exp. Med. 222, e20250378 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rousseau, A. et al. Concomitant comedications and survival with first-line pembrolizumab in advanced non-small-cell lung cancer. JAMA Netw. Open 8, e2529225 (2025).

  • Montégut, L. et al. Benzodiazepines interfere with the efficacy of pembrolizumab-based cancer immunotherapy. Results of a nationwide cohort study including over 50,000 participants with advanced lung cancer. Oncoimmunology 14, 2528955 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vich Vila, A. et al. Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. Nat. Commun. 11, 362 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bavishi, C. & Dupont, H. L. Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection. Aliment. Pharm. Ther. 34, 1269–1281 (2011).

    Article 
    CAS 

    Google Scholar
     

  • Clooney, A. G. et al. A comparison of the gut microbiome between long-term users and non-users of proton pump inhibitors. Aliment. Pharm. Ther. 43, 974–984 (2016).

    Article 
    CAS 

    Google Scholar
     

  • Jackson, M. A. et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut 65, 749–756 (2016).

    Article 
    PubMed 

    Google Scholar
     

  • Lin, Y. T. et al. Anti-acid drug treatment induces changes in the gut microbiome composition of hemodialysis patients. Microorganisms 9, 286 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Seto, C. T., Jeraldo, P., Orenstein, R., Chia, N. & DiBaise, J. K. Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility. Microbiome 2, 42 (2014).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Singh, G. et al. The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial. Clin. Nutr. ESPEN 47, 70–77 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Palleja, A. et al. Recovery of gut microbiota of healthy adults following antibiotic exposure. Nat. Microbiol. 3, 1255–1265 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Aasmets, O. et al. A hidden confounder for microbiome studies: medications used years before sample collection. mSystems 10, e00541–25 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ricaurte, D. et al. High-throughput transcriptomics of 409 bacteria-drug pairs reveals drivers of gut microbiota perturbation. Nat. Microbiol. 9, 561–575 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Algavi, Y. M. & Borenstein, E. A data-driven approach for predicting the impact of drugs on the human microbiome. Nat. Commun. 14, 3614 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nagata, N. et al. Population-level metagenomics uncovers distinct effects of multiple medications on the human gut microbiome. Gastroenterology 163, 1038–1052 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ticinesi, A. et al. Gut microbiota composition is associated with polypharmacy in elderly hospitalized patients. Sci. Rep. 7, 11102 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Elkrief, A. et al. Antibiotics are associated with worse outcomes in lung cancer patients treated with chemotherapy and immunotherapy. NPJ Precis. Oncol. 8, 143 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lopes, S. et al. Do proton pump inhibitors alter the response to immune checkpoint inhibitors in cancer patients? A meta-analysis. Front. Immunol. 14, 1070076 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Montégut, L. et al. Benzodiazepines compromise the outcome of cancer immunotherapy. Oncoimmunology 13, 2413719 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hsu, C. L. & Schnabl, B. The gut-liver axis and gut microbiota in health and liver disease. Nat. Rev. Microbiol. 21, 719–733 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Crudele, L., Gadaleta, R. M., Cariello, M. & Moschetta, A. Gut microbiota in the pathogenesis and therapeutic approaches of diabetes. EBioMedicine 97, 104821 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Iliev, I. D., Ananthakrishnan, A. N. & Guo, C. J. Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities. Nat. Rev. Microbiol. 23, 509–524 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Masenga, S. K. et al. Recent advances in modulation of cardiovascular diseases by the gut microbiota. J. Hum. Hypertens. 36, 952–959 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bindels, L. B. et al. Increased gut permeability in cancer cachexia: mechanisms and clinical relevance. Oncotarget 9, 18224–18238 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pötgens, S. A. et al. Klebsiella oxytoca expands in cancer cachexia and acts as a gut pathobiont contributing to intestinal dysfunction. Sci. Rep. 8, 12321 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yonekura, S. et al. Cancer induces a stress ileopathy depending on β-adrenergic receptors and promoting dysbiosis that contributes to carcinogenesis. Cancer Discov. 12, 1128–1151 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kim, H. C. et al. Gut microbiota dysbiosis induced by brain tumors modulates the efficacy of immunotherapy. Cell Rep. 44, 115825 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Valles-Colomer, M. et al. Neuroblastoma is associated with alterations in gut microbiome composition subsequent to maternal microbial seeding. EBioMedicine 99, 104917 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kokolus, K. M. et al. Beta blocker use correlates with better overall survival in metastatic melanoma patients and improves the efficacy of immunotherapies in mice. Oncoimmunology 7, e1405205 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Wangel, A. G. & Deller, D. J. Malabsorption syndrome associated with carcinoma of the bronchus. Gut 6, 73–76 (1965).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Jukic, A., Bakiri, L., Wagner, E. F., Tilg, H. & Adolph, T. E. Calprotectin: from biomarker to biological function. Gut 70, 1978–1988 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lanas, Á et al. Fecal occult blood and calprotectin testing to prioritize primary care patients for colonoscopy referral: the advantage study. United Eur. Gastroenterol. J. 11, 692–699 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Bromke, M. A., Neubauer, K., Kempiński, R. & Krzystek-Korpacka, M. Faecal calprotectin in assessment of mucosal healing in adults with inflammatory bowel disease: a meta-analysis. J. Clin. Med. 10, 2203 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heinzel, S. et al. Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals. Sci. Rep. 14, 13513 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rocha, I. M. G. D. et al. Pro-inflammatory diet is correlated with high Veillonella rogosae, gut inflammation and clinical relapse of inflammatory bowel disease. Nutrients 15, 4148 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lu, F., Inoue, K., Kato, J., Minamishima, S. & Morisaki, H. Functions and regulation of lipocalin-2 in gut-origin sepsis: a narrative review. Crit. Care 23, 269 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sugi, K., Saitoh, O., Hirata, I. & Katsu, K. Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins. Am. J. Gastroenterol. 91, 927–934 (1996).

    CAS 
    PubMed 

    Google Scholar
     

  • Bachem, A. et al. Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8+ T cells. Immunity 51, 285–297.e5 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhu, X. et al. Microbial metabolite butyrate promotes anti-PD-1 antitumor efficacy by modulating T cell receptor signaling of cytotoxic CD8 T cell. Gut Microbes 15, 2249143 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Alvandi, E., Wong, W. K. M., Joglekar, M. V., Spring, K. J. & Hardikar, A. A. Short-chain fatty acid concentrations in the incidence and risk-stratification of colorectal cancer: a systematic review and meta-analysis. BMC Med. 20, 323 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Parada Venegas, D. et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front. Immunol. 10, 277 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, M. H. et al. How bile acids and the microbiota interact to shape host immunity. Nat. Rev. Immunol. 24, 798–809 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Casado-Bedmar, M. & Viennois, E. MicroRNA and gut microbiota: Tiny but mighty—novel insights into their cross-talk in inflammatory bowel disease pathogenesis and therapeutics. J. Crohns Colitis 16, 992–1005 (2021).

    Article 
    PubMed Central 

    Google Scholar
     

  • McCulloch, J. A. et al. Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1. Nat. Med. 28, 545–556 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Marino, M. et al. Serum zonulin and colorectal cancer risk. Sci. Rep. 14, 28171 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fux, A. C. et al. Heterogeneity of lipopolysaccharide as source of variability in bioassays and LPS-binding proteins as remedy. Int. J. Mol. Sci. 24, 8395 (2023).

  • Sardar, P. et al. Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses. Nat. Microbiol10, 795–807 (2025).

  • Sun, L. et al. Akkermansia muciniphila-derived hypoacylated rough-type lipopolysaccharides alleviate diet-induced obesity via activation of TLR4-IL-23-IL-22 immune axis. Imeta 4, e70066 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Garcia-Vello, P. et al. The lipooligosaccharide of the gut symbiont Akkermansia muciniphila exhibits a remarkable structure and TLR signaling capacity. Nat. Commun. 15, 8411 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Duerr, C. U. et al. O-antigen delays lipopolysaccharide recognition and impairs antibacterial host defense in murine intestinal epithelial cells. PLoS Pathog. 5, e1000567 (2009).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Koutsounas, I., Kaltsa, G., Siakavellas, S. I. & Bamias, G. Markers of bacterial translocation in end-stage liver disease. World J. Hepatol. 7, 2264–2273 (2015).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tabung, F. K. et al. Influence of dietary patterns on plasma soluble CD14, a surrogate marker of gut barrier dysfunction. Curr. Dev. Nutr. 1, e001396 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moreno-Navarrete, J. M. et al. Circulating lipopolysaccharide-binding protein (LBP) as a marker of obesity-related insulin resistance. Int. J. Obes. 36, 1442–1449 (2012).

    Article 
    CAS 

    Google Scholar
     

  • Liang, H., Hussey, S. E., Sanchez-Avila, A., Tantiwong, P. & Musi, N. Effect of lipopolysaccharide on inflammation and insulin action in human muscle. PLoS One 8, e63983 (2013).

  • Fedirko, V. et al. Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study. BMC Med. 15, 72 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhao, S. et al. Akkermansia muciniphila improves metabolic profiles by reducing inflammation in chow diet-fed mice. J. Mol. Endocrinol. 58, 1–14 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Marcos-Kovandzic, L. et al. Gut microbiota modulation through Akkermansia spp. supplementation increases CAR T-cell potency. Cancer Discov. 15, 1905–1926 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, G. et al. A core microbiome signature as an indicator of health. Cell 187, 6550–6565.e11 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gamrath, L. et al. Role of the microbiome and diet for response to cancer checkpoint immunotherapy: a narrative review of clinical trials. Curr. Oncol. Rep. 27, 45–58 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, Y. et al. Gut microbiota and SCFAs improve the treatment efficacy of chemotherapy and immunotherapy in NSCLC. NPJ Biofilms Microbiomes 11, 146 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Murayama, M. et al. Isobutyric acid enhances the anti-tumor effect of anti-PD-1 antibody. Sci. Rep. 14, 11325 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kang, X. et al. Roseburia intestinalis generated butyrate boosts anti-PD-1 efficacy in colorectal cancer by activating cytotoxic CD8+ T cells. Gut 72, 2112–2122 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Coutzac, C. et al. Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer. Nat. Commun. 11, 2168 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhu, R., Gu, S., Tao, Y. & Zhang, Y. Butyrate confers colorectal cancer cell resistance to anti-PD-1 therapy by promoting CPT1A-mediated fatty acid oxidation. Discov. Oncol. 16, 935 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chelvanambi, M. & Wargo, J. A. MAdCAM-1: a newly identified microbial “gut check” for T cells. Trends Immunol. 44, 568–570 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Saliby, R. M. et al. Gut-associated checkpoint as a prognostic biomarker in metastatic renal cell carcinoma (mRCC): results from a randomized first-line clinical trial. J. Clin. Oncol. 43, 4512 (2025).

    Article 

    Google Scholar
     

  • Agus, A., Planchais, J. & Sokol, H. Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe 23, 716–724 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Janeiro, M. H., Ramírez, M. J., Milagro, F. I., Martínez, J. A. & Solas, M. Implication of trimethylamine N-oxide (TMAO) in disease: Potential biomarker or new therapeutic target. Nutrients 10, 1398 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tang, W. H. W. & Hazen, S. L. Microbiome, trimethylamine N-oxide, and cardiometabolic disease. Transl. Res. 179, 108–115 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lee, J. et al. Antibiotic-induced intestinal microbiota depletion can attenuate the acute kidney injury to chronic kidney disease transition via NADPH oxidase 2 and trimethylamine-N-oxide inhibition. Kidney Int. 105, 1239–1253 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wang, H. et al. The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer. Cell Metab. 34, 581–594.e8 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Mirji, G. et al. The microbiome-derived metabolite TMAO drives immune activation and boosts responses to immune checkpoint blockade in pancreatic cancer. Sci. Immunol. 7, eabn0704 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gupta, V. K. et al. A predictive index for health status using species-level gut microbiome profiling. Nat. Commun. 11, 4635 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zitvogel, L. & Kroemer, G. Cancer and the metaorganism. Cancer Discov. 14, 658–662 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Manor, O. et al. Health and disease markers correlate with gut microbiome composition across thousands of people. Nat. Commun. 11, 5206 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Duvallet, C., Gibbons, S. M., Gurry, T., Irizarry, R. A. & Alm, E. J. Meta-analysis of gut microbiome studies identifies disease-specific and shared responses. Nat. Commun. 8, 1784 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Matsuoka, K. & Kanai, T. The gut microbiota and inflammatory bowel disease. Semin Immunopathol. 37, 47–55 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Walters, W. A., Xu, Z. & Knight, R. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett. 588, 4223–4233 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arumugam, M. et al. Enterotypes of the human gut microbiome. Nature 473, 174–180 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cai, J. A. et al. Gut microbiota enterotypes mediate the effects of dietary patterns on colorectal neoplasm risk in a chinese population. Nutrients 15, 2940 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kovatcheva-Datchary, P. et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab. 22, 971–982 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Thomas, A. M. et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat. Med. 25, 667–678 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Park, S., Zhang, T. & Kang, S. Fecal microbiota composition, their interactions, and metagenome function in US adults with type 2 diabetes according to enterotypes. Int. J. Mol. Sci. 24, 9533 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, J. et al. Enterotype bacteroides is associated with a high risk in patients with diabetes: a pilot study. J. Diabetes Res. 2020, 6047145 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, S. et al. Different reactions in each enterotype depending on the intake of probiotic yogurt powder. Microorganisms 9, 1277 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heintz-Buschart, A. et al. Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes. Nat. Microbiol. 2, 16180 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xiao, L., Wang, J., Zheng, J., Li, X. & Zhao, F. Deterministic transition of enterotypes shapes the infant gut microbiome at an early age. Genome Biol. 22, 243 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Costea, P. I. et al. Enterotypes in the landscape of gut microbial community composition. Nat. Microbiol. 3, 8–16 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Koren, O. et al. A guide to enterotypes across the human body: meta-analysis of microbial community structures in human microbiome datasets. PLoS Comput. Biol. 9, e1002863 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rivas-Santisteban, J. et al. Quantifying microbial guilds. ISME Commun. 4, ycae042 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, G., Zhao, N., Zhang, C., Lam, Y. Y. & Zhao, L. Guild-based analysis for understanding gut microbiome in human health and diseases. Genome Med. 13, 22 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhao, L., Wu, G. & Zhao, N. Guild-based approach for mitigating information loss and distortion issues in microbiome analysis. J. Clin. Invest. 134, e185395 (2024).

  • Guo, M. et al. Guild-level microbiome signature associated with COVID-19 severity and prognosis. mBio 14, e0351922 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Zhao, L. et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science 359, 1151–1156 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Clavijo-Salomon, M. A. & Trinchieri, G. Unlocking the power of the microbiome for successful cancer immunotherapy. J. Immunother. Cancer 13, e011281 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tang, S. et al. Guild-level signature of gut microbiome for diabetic kidney disease. mBio 15, e0073524 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Jia, L. et al. A transmissible γδ intraepithelial lymphocyte hyperproliferative phenotype is associated with the intestinal microbiota and confers protection against acute infection. Muc. Immunol. 15, 772–782 (2022).

    Article 
    CAS 

    Google Scholar
     

  • Derosa, L. et al. Microbiota-centered interventions: the next breakthrough in immuno-oncology? Cancer Discov. 11, 2396–2412 (2021).

  • Goel, A. et al. Toward a health-associated core keystone index for the human gut microbiome. Cell Rep. 44, 115378 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Macandog, A. D. G. et al. Longitudinal analysis of the gut microbiota during anti-PD-1 therapy reveals stable microbial features of response in melanoma patients. Cell Host Microbe 32, 2004–2018.e9 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Björk, J. R. et al. Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma. Nat. Med. 30, 785–796 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ferrari, V. et al. Sensitizing cancer cells to immune checkpoint inhibitors by microbiota-mediated upregulation of HLA class I. Cancer Cell 41, 1717–1730.e4 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rice, T. A. et al. Interspecies commensal interactions have nonlinear impacts on host immunity. Cell Host Microbe 30, 988–1002.e6 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bajaj, J. S. et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J. Hepatol. 60, 940–947 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Casén, C. et al. Deviations in human gut microbiota: a novel diagnostic test for determining dysbiosis in patients with IBS or IBD. Aliment Pharm. Ther. 42, 71–83 (2015).

    Article 

    Google Scholar
     

  • Lloyd-Price, J. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569, 655–662 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Saffouri, G. B. et al. Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders. Nat. Commun. 10, 2012 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Guo, Z. et al. Intestinal microbiota distinguish gout patients from healthy humans. Sci. Rep. 6, 20602 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mayerhofer, C. C. K. et al. Low fibre intake is associated with gut microbiota alterations in chronic heart failure. ESC Heart Fail. 7, 456–466 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xia, G. H. et al. Stroke Dysbiosis Index (SDI) in gut microbiome are associated with brain injury and prognosis of stroke. Front. Neurol. 10, 397 (2019).

  • Derosa, L. et al. Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome. Cell 187, 3373–3389.e16 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nakatsu, G. et al. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat. Commun. 6, 8727 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chang, D. et al. Gut Microbiome Wellness Index 2 enhances health status prediction from gut microbiome taxonomic profiles. Nat. Commun. 15, 7447 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Valdés-Mas, R. et al. Metagenome-informed metaproteomics of the human gut microbiome, host, and dietary exposome uncovers signatures of health and inflammatory bowel disease. Cell 188, 1062–1083.e36 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Wei, S., Bahl, M. I., Baunwall, S. M. D., Hvas, C. L. & Licht, T. R. Determining gut microbial dysbiosis: a review of applied indexes for assessment of intestinal microbiota imbalances. Appl. Environ. Microbiol. 87, e00395–21 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gevers, D. et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe 15, 382–392 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Duncan, S. H., Barcenilla, A., Stewart, C. S., Pryde, S. E. & Flint, H. J. Acetate utilization and butyryl coenzyme A (CoA):acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Appl. Environ. Microbiol. 68, 5186–5190 (2002).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zitvogel, L. et al. Impact of the ONCOBIOME network in cancer microbiome research. Nat. Med. 31, 1085–1098 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Elkrief, A. et al. The gut microbiome as a target in cancer immunotherapy: opportunities and challenges for drug development. Nat. Rev. Drug Discov. 24, 685–704 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vandeputte, D. et al. Quantitative microbiome profiling links gut community variation to microbial load. Nature 551, 507–511 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Tito, R. Y. et al. Microbiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development. Nat. Med. 30, 1339–1348 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vieira-Silva, S. et al. Quantitative microbiome profiling disentangles inflammation- and bile duct obstruction-associated microbiota alterations across PSC/IBD diagnoses. Nat. Microbiol. 4, 1826–1831 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wagner, S. et al. Absolute abundance calculation enhances the significance of microbiome data in antibiotic treatment studies. Front. Microbiol. 16, 1481197 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nishijima, S. et al. Fecal microbial load is a major determinant of gut microbiome variation and a confounder for disease associations. Cell 188, 222–236.e15 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Blanco-Míguez, A. et al. Extending and improving metagenomic taxonomic profiling with uncharacterized species using MetaPhlAn 4. Nat. Biotechnol. 41, 1633–1644 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Martín, R. et al. Faecalibacterium: a bacterial genus with promising human health applications. FEMS Microbiol. Rev. 47, fuad039 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lu, H. et al. Butyrate-producing Eubacterium rectale suppresses lymphomagenesis by alleviating the TNF-induced TLR4/MyD88/NF-κB axis. Cell Host Microbe 30, 1139–1150.e7 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Notting, F., Pirovano, W., Sybesma, W. & Kort, R. The butyrate-producing and spore-forming bacterial genus Coprococcus as a potential biomarker for neurological disorders. Gut Microbiome 4, e16 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Scott, K. P. et al. Substrate-driven gene expression in Roseburia inulinivorans: Importance of inducible enzymes in the utilization of inulin and starch. Proc. Natl. Acad. Sci. USA 108, 4672–4679 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vital, M., Karch, A. & Pieper, D. H. Colonic butyrate-producing communities in humans: an overview using omics data. mSystems 2, e00130–17 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, C. H. Complex regulatory effects of gut microbial short-chain fatty acids on immune tolerance and autoimmunity. Cell Mol. Immunol. 20, 341–350 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Litvak, Y., Byndloss, M. X. & Bäumler, A. J. Colonocyte metabolism shapes the gut microbiota. Science 362, eaat9076 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhu, Z. et al. Microbiome and spatially resolved metabolomics analysis reveal the anticancer role of gut Akkermansia muciniphila by crosstalk with intratumoral microbiota and reprogramming tumoral metabolism in mice. Gut Microbes 15, 2166700 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhu, Z. et al. Landscape of tumoral ecosystem for enhanced anti-PD-1 immunotherapy by gut Akkermansia muciniphila. Cell Rep. 43, 114306 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pasolli, E. et al. Accessible, curated metagenomic data through ExperimentHub. Nat. Methods 14, 1023–1024 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Antoniotti, C. et al. AtezoTRIBE: a randomised phase II study of FOLFOXIRI plus bevacizumab alone or in combination with atezolizumab as initial therapy for patients with unresectable metastatic colorectal cancer. BMC Cancer 20, 683 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Antoniotti, C. et al. Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 23, 876–887 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Antoniotti, C. et al. Upfront fluorouracil, leucovorin, oxaliplatin, and irinotecan plus bevacizumab with or without atezolizumab for patients with metastatic colorectal cancer: Updated and overall survival results of the ATEZOTRIBE study. J. Clin. Oncol. 42, 2637–2644 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Watson, A. R. et al. Metabolic independence drives gut microbial colonization and resilience in health and disease. Genome Biol. 24, 78 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Routy, B. et al. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial. Nat. Med. 29, 2121–2132 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schmidt, T. S. B. et al. Drivers and determinants of strain dynamics following fecal microbiota transplantation. Nat. Med. 28, 1902–1912 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Baruch, E. N. et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 371, 602–609 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Davar, D. et al. Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients. Science 371, 595–602 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Elkrief, A. et al. Immune-related colitis is associated with fecal microbial dysbiosis and can be mitigated by fecal microbiota transplantation. Cancer Immunol. Res. 12, 308–321 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ianiro, G. et al. Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases. Nat. Med. 28, 1913–1923 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Elkrief, A. & Routy, B. First clinical proof-of-concept that FMT can overcome resistance to ICIs. Nat. Rev. Clin. Oncol. 18, 325–326 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Elkrief, A. et al. Gut microbiota in immuno-oncology: a practical guide for medical oncologists with a focus on antibiotics stewardship. Am. Soc. Clin. Oncol. Educ. Book 45, e472902 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Stein-Thoeringer, C. K. et al. A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy. Nat. Med. 29, 906–916 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Smith, M. et al. Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy. Nat. Med. 28, 713–723 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chang, C.-C., Hayase, E. & Jenq, R. R. The role of microbiota in allogeneic hematopoietic stem cell transplantation. Expert Opin. Biol. Ther. 21, 1121–1131 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Varanasi, S. K. et al. Bile acid synthesis impedes tumor-specific T cell responses during liver cancer. Science 387, 192–201 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bertocchi, A. et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell 39, 708–724.e11 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Galván-Peña, S., Zhu, Y., Hanna, B. S., Mathis, D. & Benoist, C. A dynamic atlas of immunocyte migration from the gut. Sci. Immunol. 9, eadi0672 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Di Luccia, B. et al. TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy. Sci. Immunol. 9, eadi5374 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Carrier, A. et al. Gut microbiota: a new factor modulating the immunizing potential of viral and cancer vaccines. Res. Sq. https://doi.org/10.21203/rs.3.rs-4294379/v1 (2025).