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Dysbiosis, an imbalance in microbial composition, contributes to gastrointestinal cancers and extraintestinal malignancies. Mechanistic work highlights a gut–microbiota–cancer axis where metabolites such as bile acids, SCFAs, and tryptophan derivatives shape genetic, epigenetic, and immune pathways. Germ-free models show commensal signals are required for CD4+ and CD8+ T-cell differentiation, IgA production, and anti-tumor immunity. Dysbiosis can also impair immune checkpoint inhibitor efficacy, while taxa like Bifidobacterium and Akkermansia may enhance responses. The evidence links gut microbes to breast, lung, melanoma, and prostate cancer via pathways including estrogen metabolism, gut–lung signaling, systemic T-cell function, and androgen receptor signaling, supporting both oncogenic and protective roles. Microbiome-targeted interventions—including FMT, defined live biotherapeutics, probiotics, prebiotics, dietary modulation, and postbiotics—are under investigation despite feasibility and methodological variability challenges. 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N. U. Anirudh5   \n| Manjeet Kumar Goyal2  | Kirti Arora2  | Tanisha Sehgal3  | Prachi Dawer4  || Jeffrey Berinstein6  | Shrinivas Bishu6  | Laurie Matt-Amaral7   \n1Department of Medicine, MetroHealth Medical Center, Cleveland, Ohio, USA | 2Department of Internal Medicine, Cleveland Clinic Akron General, Akron, Ohio, USA | 3Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India | 4Department of Medicine, University College of Medical Sciences, New Delhi, India | 5Department of Internal Medicine, All India Institute of Medical Sciences, Bathinda, India | 6Division of Gastroenterology Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA | 7Department of Hematology-Oncology, Cleveland Clinic Akron General, Akron, Ohio, USA  \nCorrespondence: Manjeet Kumar Goyal ([goyalm3@ccf.org](goyalm3@ccf.org))  \nReceived: 23 October 2025 | Revised: 7 April 2026 | Accepted: 9 April 2026  \nABSTRACT  \nThe gut microbiota is a dynamic community of bacteria, viruses, fungi, and archaea that plays a pivotal role in regulating host immunity, metabolism, and systemic homeostasis. Dysbiosis, characterized by an imbalance in the microbial composition, is being increasingly recognized as a contributor not only to gastrointestinal cancers but also to extraintestinal malignancies. Mechanistic studies highlight the gut–microbiota–cancer axis, where microbial metabolites such as bile acids, short-chain fatty acids (SCFAs), and tryptophan derivatives influence genetic, epigenetic, and immune pathways, influencing carcinogenesis. Germ-free models demonstrate that commensal signals are essential for CD4+ and CD8+ T-cell differentiation, IgA production, and anti-tumor immunity. Dysbiosis-induced immune dysregulation is believed to impair immune checkpoint inhibitor (ICI) efficacy, while specific taxa such as Bifidobacterium and Akkermansia have been shown to enhance therapeutic responses. Emerging evidence links gut microbiota to breast cancer via estrogen metabolism “estrobolome” to lung cancer through the gut–lung axis and modulation of ICI responses, to melanoma by shaping systemic T-cell function and immunotherapy outcomes, and to prostate cancer through androgen receptor signaling and microbial metabolite interactions. These findings underscore the systemic oncogenic and tumor-suppressive potential of microbial communities. Microbiome-targeted interventions, including fecal microbiota transplantation (FMT), defined live biotherapeutics, probiotics, prebiotics, dietary modulation, and postbiotic delivery, are being actively investigated to optimize cancer treatment. While early trials have demonstrated feasibility, variability between individuals and methodological challenges remain significant hurdles. Hence, understanding how gut microbes influence extraintestinal cancers could revolutionize diagnostics, risk prediction, and treatment strategies.  \n1 | Introduction  \nThe gastrointestinal tract harbors a diverse community of microorganisms, collectively known as the gut microbiota, which includes bacteria, viruses, fungi, and archaea. These microbial inhabitants play a vital role in numerous physiological functions such as digestion and the production of vital metabolites  \nlike vitamins and short-chain fatty acids (SCFAs) . The gut microbiota is also instrumental in maintaining systemic homeostasis, regulating metabolic pathways, and protecting against pathogenic colonization. Gut dysbiosis has been implicated ina range of disorders, including metabolic diseases, autoimmune conditions such as inflammatory bowel disease, and various cancers [1] .  \n\n| Rishi Chowdhary and Manjeet Kumar Goyal are co-first authors. |\n| --- |\n| This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any ","cbCaiv2KnopRdhnL","https://ap.wps.com/l/cbCaiv2KnopRdhnL","pdf",1319706,18,"English","# Introduction\n## Gut microbiota functions and systemic homeostasis\n## Dysbiosis and links to cancers\n## Gut–microbiota–cancer axis\n## Microbial metabolites and immune modulation\n## Microbiota and specific cancer types\n## Microbiome-targeted interventions","[{\"question\":\"What role does gut microbiota play in the body beyond digestion?\",\"answer\":\"Gut microbiota maintains systemic homeostasis, regulates metabolic pathways, and protects against pathogenic colonization. It also contributes to production of vital metabolites such as vitamins and short-chain fatty acids (SCFAs).\"},{\"question\":\"How does dysbiosis relate to extraintestinal cancers?\",\"answer\":\"Dysbiosis is an imbalance in microbial composition and is recognized as a contributor not only to gastrointestinal cancers but also to extraintestinal malignancies. Mechanistic studies describe how altered microbial communities create immune and inflammatory changes that support cancer progression.\"},{\"question\":\"Which microbiome-targeted interventions are discussed for improving cancer treatment outcomes?\",\"answer\":\"The document highlights fecal microbiota transplantation (FMT), defined live biotherapeutics, probiotics, prebiotics, dietary modulation, and postbiotic delivery. It notes that early trials show feasibility, but variability between individuals and methodological challenges remain.\"}]","Gut Microbiota and Extraintestinal Cancers - Mechanistic Insights and Microbiome-Targeted Interventions | PDF",1790101846,45]