A small intestinal bile acid modulates the gut microbiome to improve host metabolic phenotypes following bariatric surgery

IF 20.6 1区 医学 Q1 MICROBIOLOGY Cell host & microbe Pub Date : 2024-07-22 DOI:10.1016/j.chom.2024.06.014
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Abstract

Bariatric surgical procedures such as sleeve gastrectomy (SG) provide effective type 2 diabetes (T2D) remission in human patients. Previous work demonstrated that gastrointestinal levels of the bacterial metabolite lithocholic acid (LCA) are decreased after SG in mice and humans. Here, we show that LCA worsens glucose tolerance and impairs whole-body metabolism. We also show that taurodeoxycholic acid (TDCA), which is the only bile acid whose concentration increases in the murine small intestine post-SG, suppresses the bacterial bile acid-inducible (bai) operon and production of LCA both in vitro and in vivo. Treatment of diet-induced obese mice with TDCA reduces LCA levels and leads to microbiome-dependent improvements in glucose handling. Moreover, TDCA abundance is decreased in small intestinal tissue from T2D patients. This work reveals that TDCA is an endogenous inhibitor of LCA production and suggests that TDCA may contribute to the glucoregulatory effects of bariatric surgery.

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一种小肠胆汁酸能调节肠道微生物组,改善减肥手术后宿主的代谢表型
袖带胃切除术(SG)等减肥手术能有效缓解人类患者的 2 型糖尿病(T2D)病情。以前的研究表明,小鼠和人类接受袖带胃切除术后,胃肠道中细菌代谢产物石胆酸(LCA)的水平会下降。在这里,我们发现 LCA 会恶化葡萄糖耐量并损害全身代谢。我们还发现,牛磺脱氧胆酸(TDCA)是小鼠小肠中唯一一种在 SG 后浓度增加的胆汁酸,它在体外和体内都能抑制细菌胆汁酸诱导(bai)操作子和 LCA 的产生。用 TDCA 治疗饮食诱导的肥胖小鼠可降低 LCA 水平,并导致葡萄糖处理的微生物依赖性改善。此外,在 T2D 患者的小肠组织中,TDCA 的丰度也有所下降。这项研究揭示了 TDCA 是 LCA 生成的内源性抑制剂,并表明 TDCA 可能有助于减肥手术的血糖调节效果。
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来源期刊
Cell host & microbe
Cell host & microbe 生物-微生物学
CiteScore
45.10
自引率
1.70%
发文量
201
审稿时长
4-8 weeks
期刊介绍: Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.
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