A small intestinal bile acid modulates the gut microbiome to improve host metabolic phenotypes following bariatric surgery,Cell Host & Microbe

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A small intestinal bile acid modulates the gut microbiome to improve host metabolic phenotypes following bariatric surgery
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2024-07-22 , DOI: 10.1016/j.chom.2024.06.014
Yingjia Chen ₁ , Snehal N Chaudhari ₂ , David A Harris ₃ , Cullen F Roberts ₁ , Andrei Moscalu ₁ , Vasundhara Mathur ₁ , Lei Zhao ₄ , Ali Tavakkoli ₁ , A Sloan Devlin ₅ , Eric G Sheu ₁

Affiliation

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 () operon and production of LCA both and . 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.

中文翻译：

小肠胆汁酸调节肠道微生物组，以改善减肥手术后的宿主代谢表型

袖状胃切除术 (SG) 等减肥手术可有效缓解人类患者的 2 型糖尿病 (T2D) 症状。先前的研究表明，在小鼠和人类中，SG 后细菌代谢物石胆酸 (LCA) 的胃肠道水平降低。在这里，我们发现 LCA 会恶化葡萄糖耐量并损害全身代谢。我们还表明，牛磺脱氧胆酸 (TDCA) 是唯一一种在 SG 后在小鼠小肠中浓度增加的胆汁酸，可抑制细菌胆汁酸诱导 () 操纵子和 LCA 的产生。用 TDCA 治疗饮食诱导的肥胖小鼠可降低 LCA 水平，并导致微生物组依赖性的葡萄糖处理改善。此外，2型糖尿病患者小肠组织中的 TDCA 丰度降低。这项工作揭示了 TDCA 是 LCA 产生的内源性抑制剂，并表明 TDCA 可能有助于减肥手术的血糖调节作用。

更新日期：2024-07-22

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