Ribas, A. & Wolchok, J. D. Cancer immunotherapy using checkpoint blockade. Science 359, 1350–1355 (2018).
Google Scholar
Robert, C. et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 384, 1109–1117 (2014).
Google Scholar
Motzer, R. J. et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 20, 1370–1385 (2019).
Google Scholar
Reck, M. et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N. Engl. J. Med. 375, 1823–1833 (2016).
Google Scholar
Bagchi, S., Yuan, R. & Engleman, E. G. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu. Rev. Pathol. 16, 223–249 (2021).
Google Scholar
Topalian, S. L. et al. Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with nivolumab. JAMA Oncol. 5, 1411–1420 (2019).
Google Scholar
Postow, M. A., Sidlow, R. & Hellmann, M. D. Immune-related adverse events associated with immune checkpoint blockade. N. Engl. J. Med. 378, 158–168 (2018).
Google Scholar
Vetizou, M. et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350, 1079–1084 (2015).
Google Scholar
Sivan, A. et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350, 1084–1089 (2015).
Google Scholar
Jin, Y. et al. The diversity of gut microbiome is associated with favorable responses to anti-programmed death 1 immunotherapy in Chinese patients with NSCLC. J. Thorac. Oncol. 14, 1378–1389 (2019).
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).
Google Scholar
Pinato, D. J. et al. Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer. JAMA Oncol. 5, 1774–1778 (2019).
Google Scholar
Routy, B. et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 359, 91–97 (2018).
Google Scholar
Gopalakrishnan, V. et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359, 97–103 (2018).
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).
Google Scholar
Baruch, E. N. et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 371, 602–609 (2020).
Google Scholar
Davar, D. et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 371, 595–602 (2021).
Google Scholar
Fernandes, M. R., Aggarwal, P., Costa, R. G. F., Cole, A. M. & Trinchieri, G. Targeting the gut microbiota for cancer therapy. Nat. Rev. Cancer 22, 703–722 (2022).
Google Scholar
Simpson, R. C., Shanahan, E. R., Scolyer, R. A. & Long, G. V. Towards modulating the gut microbiota to enhance the efficacy of immune-checkpoint inhibitors. Nat. Rev. Clin. Oncol. 20, 697–715 (2023).
Google Scholar
Lee, K. A., Shaw, H. M., Bataille, V., Nathan, P. & Spector, T. D. Role of the gut microbiome for cancer patients receiving immunotherapy: dietary and treatment implications. Eur. J. Cancer 138, 149–155 (2020).
Google Scholar
Vazquez-Castellanos, J. F., Biclot, A., Vrancken, G., Huys, G. R. & Raes, J. Design of synthetic microbial consortia for gut microbiota modulation. Curr. Opin. Pharmacol. 49, 52–59 (2019).
Google Scholar
Cheng, A. G. et al. Design, construction, and in vivo augmentation of a complex gut microbiome. Cell 185, 3617–3636.e19 (2022).
Google Scholar
Kelly, B. J., Kwon, J. H. & Woodworth, M. H. Escape velocity—the launch of microbiome therapies. J. Infect. Dis. 230, 2–4 (2024).
Google Scholar
Terveer, E. M. et al. Human transmission of blastocystis by fecal microbiota transplantation without development of gastrointestinal symptoms in recipients. Clin. Infect. Dis. 71, 2630–2636 (2020).
Google Scholar
Skelly, A. N., Sato, Y., Kearney, S. & Honda, K. Mining the microbiota for microbial and metabolite-based immunotherapies. Nat. Rev. Immunol. 19, 305–323 (2019).
Google Scholar
Tanoue, T. et al. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. Nature 565, 600–605 (2019).
Google Scholar
Spreafico, A. et al. First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO Trial). Ann. Oncol. 34, 520–530 (2023).
Google Scholar
Oliva, I. G. et al. 607 MCGRAW trial: evaluation of the safety and efficacy of an oral microbiome intervention (SER-401) in combination with nivolumab in first line metastatic melanoma patients. J. Immunother. Cancer https://doi.org/10.1136/jitc-2022-SITC2022.0607 (2022).
Kang, X., Lau, H. C.-H. & Yu, J. Modulating gut microbiome in cancer immunotherapy: harnessing microbes to enhance treatment efficacy. Cell Rep. Med. 5, 101478 (2024).
Google Scholar
Glitza, I. C. et al. Randomized placebo-controlled, biomarker-stratified phase Ib microbiome modulation in melanoma: impact of antibiotic preconditioning on microbiome and immunity. Cancer Discov. 14, 1161–1175 (2024).
Google Scholar
Derosa, L. et al. Gut bacteria composition drives primary resistance to cancer immunotherapy in renal cell carcinoma patients. Eur. Urol. 78, 195–206 (2020).
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).
Google Scholar
Andrews, M. C. et al. Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade. Nat. Med. 27, 1432–1441 (2021).
Google Scholar
Ramoneda, J., Jensen, T. B. N., Price, M. N., Casamayor, E. O. & Fierer, N. Taxonomic and environmental distribution of bacterial amino acid auxotrophies. Nat. Commun. 14, 7608 (2023).
Google Scholar
Gould, A. L. et al. Microbiome interactions shape host fitness. Proc. Natl Acad. Sci. USA 115, E11951–E11960 (2018).
Google Scholar
Van Der Lelie, D. et al. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nat. Commun. 12, 3015 (2021).
Magnusdottir, S. et al. Generation of genome-scale metabolic reconstructions for 773 members of the human gut microbiota. Nat. Biotechnol. 35, 81–89 (2017).
Google Scholar
Zelezniak, A. et al. Metabolic dependencies drive species co-occurrence in diverse microbial communities. Proc. Natl Acad. Sci. USA 112, 6449–6454 (2015).
Google Scholar
Kost, C., Patil, K. R., Friedman, J., Garcia, S. L. & Ralser, M. Metabolic exchanges are ubiquitous in natural microbial communities. Nat. Microbiol. 8, 2244–2252 (2023).
Google Scholar
Derosa, L. et al. Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome. Cell 187, 3373–3389.e16 (2024).
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).
Google Scholar
Liu, R. et al. Gut microbial structural variation associates with immune checkpoint inhibitor response. Nat. Commun. 14, 7421 (2023).
Google Scholar
Zhang, H. et al. The cyanobacterial ornithine–ammonia cycle involves an arginine dihydrolase. Nat. Chem. Biol. 14, 575–581 (2018).
Google Scholar
Gabrielli, N. et al. Unravelling metabolic cross-feeding in a yeast–bacteria community using 13C-based proteomics. Mol. Syst. Biol. 19, e11501 (2023).
Google Scholar
Mager, L. F. et al. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science 369, 1481–1489 (2020).
Google Scholar
Zmora, N. et al. Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features. Cell 174, 1388–1405.e21 (2018).
Google Scholar
Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 1079–1094 (2015).
Google Scholar
Liu, H. et al. Ecological dynamics of the gut microbiome in response to dietary fiber. ISME J. 16, 2040–2055 (2022).
Google Scholar
Randall, D. W. et al. Batch effect exerts a bigger influence on the rat urinary metabolome and gut microbiota than uraemia: a cautionary tale. Microbiome 7, 127 (2019).
Google Scholar
Buckel, W. Energy conservation in fermentations of anaerobic bacteria. Front. Microbiol. 12, 703525 (2021).
Google Scholar
Pedley, A. M. & Benkovic, S. J. A new view into the regulation of purine metabolism: the purinosome. Trends Biochem. Sci. 42, 141–154 (2017).
Google Scholar
He, Y. et al. Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity. Cell Metab. 33, 988–1000.e7 (2021).
Google Scholar
Suez, J. et al. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell 185, 3307–3328.e19 (2022).
Google Scholar
Afrizal, A. et al. Enhanced cultured diversity of the mouse gut microbiota enables custom-made synthetic communities. Cell Host Microbe 30, 1630–1645.e25 (2022).
Google Scholar
Xin, W. et al. Root microbiota of tea plants regulate nitrogen homeostasis and theanine synthesis to influence tea quality. Curr. Biol. 34, 868–880.e6 (2024).
Google Scholar
Heras-Murillo, I., Adán-Barrientos, I., Galán, M., Wculek, S. K. & Sancho, D. Dendritic cells as orchestrators of anticancer immunity and immunotherapy. Nat. Rev. Clin. Oncol. 21, 257–277 (2024).
Google Scholar
Garris, C. S. et al. Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-gamma and IL-12. Immunity 49, 1148–1161.e7 (2018).
Google Scholar
Luu, M. et al. Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. Nat. Commun. 12, 4077 (2021).
Google Scholar
Wang, T. et al. Inosine is an alternative carbon source for CD8+ T cell function under glucose restriction. Nat. Metab. 2, 635–647 (2020).
Google Scholar
Poyet, M. et al. A library of human gut bacterial isolates paired with longitudinal multiomics data enables mechanistic microbiome research. Nat. Med. 25, 1442–1452 (2019).
Google Scholar
Soto-Martin, E. C. et al. Vitamin biosynthesis by human gut butyrate-producing bacteria and cross-feeding in synthetic microbial communities. mBio 11, e00886–00820 (2020).
Google Scholar
Desai, M. S. et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell 167, 1339–1353.e21 (2016).
Google Scholar
Watson, A. R. et al. Metabolic independence drives gut microbial colonization and resilience in health and disease. Genome Biol. 24, 78 (2023).
Google Scholar
Han, Y. et al. scRNA-seq profiling of neonatal and adult thymus-derived CD4+ T cells by a T cell origin-time tracing model. J. Mol. Cell. Biol. 14, mjac072 (2022).
Google Scholar
Zeng, X. et al. Gut bacterial nutrient preferences quantified in vivo. Cell 185, 3441–3456.e19 (2022).
Google Scholar
Han, S. et al. A metabolomics pipeline for the mechanistic interrogation of the gut microbiome. Nature 595, 415–420 (2021).
Google Scholar
Xi, H. et al. A bacterial spermidine biosynthetic pathway via carboxyaminopropylagmatine. Sci. Adv. 9, eadj9075 (2023).
Google Scholar
Han, J., Lin, K., Sequeira, C. & Borchers, C. H. An isotope-labeled chemical derivatization method for the quantitation of short-chain fatty acids in human feces by liquid chromatography-tandem mass spectrometry. Anal. Chim. Acta 854, 86–94 (2015).
Google Scholar
Zhou, H. et al. A clinic responder-derived defined microbial consortium enhances anti-PD-1 immunotherapy efficacy in mice. Zenodo https://doi.org/10.5281/zenodo.18265182 (2026).

