{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:42:41Z","timestamp":1789166561032,"version":"build-2803163510"},"reference-count":123,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Small cell lung cancer (SCLC) with liver metastases (LM), represents a highly aggressive clinical challenge characterized by significant morbidity, poor durable responses to chemoimmunotherapy, and limited therapeutic options. While most research has focused on tumor-intrinsic driver mutations and the local liver microenvironment, the remote influence of the gut microbiota on LM-SCLC pathogenesis remains a largely unexplored area. Emerging evidence from other cancer types suggests that the gut microbiota composition and its derived metabolites can modulate systemic immune tolerance, influence hepatic immune surveillance, and affect the efficacy and toxicity of anticancer therapies. This review synthesizes current knowledge on the gut\u2013liver axis in cancer metastasis, with a specific focus on its pathogenesis. We discuss the molecular and immunological pathways through which gut microbial dysbiosis may promote an immunosuppressive liver microenvironment, facilitate the formation of a pro-metastatic niche, and impair anti-tumor responses. Specifically, we detail how translocated microbial products, such as lipopolysaccharide (LPS), and pro-tumorigenic secondary bile acids (SBAs) activate key hepatic immune cells (Kupffer cells, KCs) and stromal cells (hepatic stellate cells, HSCs). This activation modulates key signaling cascades and promotes the survival and outgrowth of circulating SCLC cells. Furthermore, we explore promising microbiota-based therapeutic strategies\u2014including probiotics, prebiotics, fecal microbiota transplantation (FMT), and next-generation microbial therapeutics (NGMTs)\u2014as novel approaches to augment standard-of-care treatments. A deeper understanding of the interplay between the gut microbiota and LM-SCLC is essential for opening new avenues for personalized combination therapies and improving outcomes for this high-risk patient population.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1767998","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:56:40Z","timestamp":1771397800000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The role of gut microbiota in liver metastasis of small cell lung cancer: mechanisms and therapeutic implications"],"prefix":"10.3389","volume":"16","author":[{"given":"Yaqiu","family":"Xiao","sequence":"first","affiliation":[{"name":"The Third Hospital of Mianyang","place":["Mianyang, Sichuan, China"]},{"name":"Sichuan Mental Health Center","place":["Mianyang, Sichuan, China"]},{"name":"The Affiliated Mianyang Hospital of Chongqing Medical University","place":["Mianyang, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weigang","family":"Xiu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3390\/cancers13010020","article-title":"The role of probiotics in cancer prevention","volume":"13","author":"\u015ali\u017cewska","year":"2020","journal-title":"Cancers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"430","DOI":"10.3390\/microorganisms12030430","article-title":"Next-generation probiotics as novel therapeutics for improving human health: current trends and future perspectives","volume":"12","author":"Abouelela","year":"2024","journal-title":"Microorganisms"},{"key":"B3","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/nrgastro.2017.20","article-title":"Gut microbiota modulation of chemotherapy efficacy and toxicity","volume":"14","author":"Alexander","year":"2017","journal-title":"Nat. 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