Chenodiol

点击蓝字 关注我们 2026年8月28日，北京大学肿瘤医院消化肿瘤内科沈琳/彭智教授团队、清华大学免疫学研究所郭晓欢教授团队合作的研究成果“Lactobacillus salivarius potentiates gastrointestinal cancer immunotherapy through its metabolite chenodeoxycholic acid”，正式发表于Cell出版社旗下权威学术期刊Cell Reports Medicine。研究基于278例接受免疫治疗的胃肠道癌患者粪便宏基因组测序结果，首次系统阐明了唾液乳杆菌及其代谢产物CDCA（鹅去氧胆酸）增效消化道肿瘤免疫治疗的完整分子机制，为微生态联合免疫治疗的临床应用提供了核心靶点与科学依据，是国内肠道菌群与肿瘤免疫领域的重要原创突破。 免疫检查点抑制剂（ICI）的出现为胃肠道癌症治疗带来了突破，但并非所有患者都能获益，客观缓解率长期徘徊在10%–20%。如何克服耐药、让更多人从免疫治疗中受益，是当前肿瘤免疫领域的核心难题。本研究锁定了一种能够增强抗PD-1疗效的肠道共生菌——唾液乳杆菌（Lactobacillus salivarius），并首次系统阐明其通过代谢物"一箭双雕"重塑肿瘤微环境、激活抗肿瘤免疫的完整通路。 从患者队列到动物模型：锁定一株"有益菌" 研究团队首先对278例接受免疫治疗的胃肠道癌患者进行粪便宏基因组测序，发现唾液乳杆菌在治疗响应者体内显著富集，且其丰度越高，患者的无进展生存期越长。在小鼠结肠癌（MC38）与胃癌（YTN16）模型中，单独补充唾液乳杆菌即可抑制肿瘤生长；与抗PD-1抗体联用时，抑瘤效果进一步增强，肿瘤内杀伤性CD8⁺ T细胞的浸润与效应功能（分泌IFN-γ、颗粒酶B）同步提升。抗体清除实验证实，这一抗肿瘤效应依赖CD8⁺ T细胞的存在。 揭开"代谢物信使"：鹅去氧胆酸（CDCA） 细菌如何"隔空"调控免疫？团队通过跨越小鼠血浆、细菌培养上清与临床患者血浆三组数据的代谢组学比对，锁定了关键"信使"——初级胆汁酸“鹅去氧胆酸（CDCA）”。补充唾液乳杆菌的小鼠血浆CDCA水平显著升高；在临床队列中，血浆CDCA较高的患者无进展生存期更长；菌群丰度与CDCA浓度呈正相关。研究推测，该菌借助自身的胆汁盐水解酶活性，将结合型胆汁酸去结合，从而释放出有活性的CDCA。 "一箭双雕"：既攻击肿瘤，又武装免疫细胞 CDCA的独特之处在于它的"双靶点"作用。 一方面，它在多种胃肠道癌细胞中引发活性氧（ROS）爆发，触发GRP78–PERK–eIF2α内质网应激，促使肿瘤细胞暴露钙网蛋白、释放ATP，发生免疫原性细胞死亡（ICD），相当于为免疫系统点亮"攻击靶标"。 另一方面，CDCA通过ROS–NF-κB信号轴，将免疫抑制性的M2型肿瘤相关巨噬细胞"重编程"为促炎抗癌的M1型，并上调趋化因子CXCL9，进一步放大CD8⁺ T细胞的杀伤能力。 单细胞测序进一步显示，CDCA联合抗PD-1治疗不仅能增加肿瘤内活化的CD8⁺ T细胞、减少其耗竭表型，还能增强T细胞与巨噬细胞之间的免疫激活对话。功能实验表明，特异性清除CD8⁺ T细胞或巨噬细胞，均会完全消除CDCA增强抗PD-1的疗效。 临床转化前景：无创标志物与辅助策略 该研究将"肠道菌群—胆汁酸代谢—肿瘤免疫"精妙串联，提示粪便中的唾液乳杆菌或血浆中的CDCA，有望成为预测胃肠道癌免疫治疗疗效的无创生物标志物；而口服补充相应益生菌或代谢物，则可能成为提升免疫治疗获益的辅助策略。 研究团队也指出，CDCA诱导ROS的精确分子靶点、相关结论在更大规模临床队列中的验证等问题，仍有待进一步探索。但无论如何，这项研究为"微生态—代谢—免疫"的精准调控开辟了新视野，也让"从肠道中挖掘抗癌武器"更具现实可能。 推荐阅读 彭智教授：胃癌围手术期的关键问题与未来方向 北京癌症防治学会胃癌防治专委会换届 彭智教授任主委 声明：本文由“肿瘤界”整理与汇编，欢迎分享转载，如需使用本文内容，请务必注明出处。 编辑：Lagertha 审核：阿希雅

FOSTER CITY, Calif.--(BUSINESS WIRE)--Mirum Pharmaceuticals, Inc. (Nasdaq: MIRM), a leading rare disease company, today announced the appointment of Rob Myers, M.D., as Chief Medical Officer, effective September 21, 2026. Dr. Myers will join the company’s leadership team and lead Mirum's global medical and clinical development functions. Dr. Myers is an accomplished physician-scientist and drug development leader with more than two decades of experience developing novel medicines. A widely recognized hepatologist, he has held senior development leadership roles in industry and academia, contributed to the advancement of numerous clinical programs, and built a distinguished scientific record that includes more than 200 peer-reviewed publications. His development experience spans primary sclerosing cholangitis (PSC) and broader hepatology, including contributions to the understanding of PSC natural history, diagnosis, and management, and extends beyond liver disease through recent work in metabolism and endocrine-related disorders. Dr. Myers joins Mirum from OrsoBio, where he served as Chief Medical Officer and Head of Development. Prior to OrsoBio, he held senior leadership positions at Gilead Sciences, overseeing clinical development programs across liver fibrosis, cholestatic liver diseases and gastrointestinal inflammation. Dr. Myers earned his M.D. and completed his Internal Medicine training at Western University, followed by a Gastroenterology fellowship at the University of Calgary and a Hepatology fellowship at Université de Paris VI. He additionally earned a master's degree in Epidemiology from the University of Calgary. “Rob is a proven development leader whose experience is exceptionally well aligned with both Mirum’s portfolio today and where we are headed,” said Chris Peetz, Chief Executive Officer of Mirum. “His deep expertise in liver disease, combined with broad clinical development leadership, comes at an important moment in Mirum’s evolution with expected growth in our commercial portfolio and an increasingly diverse late-stage pipeline. Rob will play a critical role in helping us bring breakthrough medicines forward for people living with rare diseases.” ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); "Mirum has built a distinctive rare disease company by combining deep drug development and delivery expertise with a clear focus on conditions where patients have historically had too few options," said Dr. Myers. "I am excited to join at such an important stage of the company’s growth and to work with the team to advance a pipeline of medicines with the potential to make a meaningful difference for patients and families." The company also announced that Joanne Quan, M.D. will be departing Mirum. Mirum thanks Dr. Quan for her leadership and many contributions to advance Mirum’s medicines for rare disease patients. About Mirum Pharmaceuticals Mirum Pharmaceuticals (NASDAQ: MIRM) is a leading rare disease company with a global footprint of approved products and a broad pipeline of investigational medicines. Purpose-built to bring forward breakthrough medicines for people with overlooked conditions, Mirum focuses on rare liver and rare genetic diseases, where it has built deep expertise and strong connections to patient communities. The company’s commercial portfolio includes LIVMARLI® (maralixibat) for Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC), CHOLBAM® (cholic acid) for bile-acid synthesis disorders, and CTEXLI® (chenodiol) for cerebrotendinous xanthomatosis (CTX). ezstandalone.cmd.push(function () { ezstandalone.showAds(132); }); Mirum’s clinical-stage pipeline includes volixibat, an IBAT inhibitor in late-stage development for primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), brelovitug, a fully human monoclonal antibody in late-stage development for chronic hepatitis delta virus (HDV), zilurgisertib, an ALK2 inhibitor under regulatory review with the FDA for fibrodysplasia ossificans progressiva (FOP), and MRM-3379, a PDE4D inhibitor being evaluated for Fragile X syndrome (FXS). Mirum’s success is driven by a team dedicated to advancing high impact medicines through strategic development, disciplined execution and purposeful collaboration across the rare disease ecosystem. Learn more at and follow Mirum on Facebook , LinkedIn , Instagram and X . Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, expected growth in our commercial portfolio, the anticipated benefits of our pipeline of medicines for patients and families, the anticipated hiring of our incoming Chief Medical Officer and the impact that Dr. Myers is expected to have on our medicines and our business. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “anticipate,” “expected,” “will,” “could,” “would,” “guidance,” “target,” “intend,” “plan,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Mirum’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Mirum’s business in general, risks and uncertainties associated with pharmaceutical development and commercialization in general, the impact of geopolitical and macroeconomic events, and the other risks described in Mirum’s Annual Report on Form 10-K for the year ended December 31, 2025 and subsequent filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Mirum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. ezstandalone.cmd.push(function () { ezstandalone.showAds(133); }); Mirum and the Mirum logo are trademarks of Mirum Pharmaceuticals, Inc. Contacts Investor Contact: Andrew McKibben ir@mirumpharma.com Media Contact: Meredith Kiernan media@mirumpharma.com