Welsch Elizabeth C, Barron Matthew R, Storage Katelyn M, Kazen Alexis B, Aboulalazm Fatima A, Kirby John R, Kindel Tammy L
Medical College of Wisconsin College of Medicine, Milwaukee, Wisconsin, United States.
Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Am J Physiol Regul Integr Comp Physiol. 2025 Sep 1;329(3):R410-R421. doi: 10.1152/ajpregu.00297.2024. Epub 2025 Jul 22.
Understanding how a sleeve gastrectomy (SG) achieves metabolic improvement is challenging due to the complex relationship between the liver, bile acid (BA) pool, and gut microbiome. We hypothesized that SG alters the gut microbiome, which then increases the BA pool, leading to metabolic efficacy. We performed fecal material transfer (FMT) from SG or sham mice to surgically naïve mice with an intact microbiome. We evaluated the effect of surgery and FMT on BA-related liver enzymes, BA concentrations, and gut microbiome composition via 16S and metagenomic analysis. SG significantly deflected weight gain compared with sham surgery, 5 ± 2 g versus 10 ± 3 g, respectively ( = 0.004). SG significantly increased the BA pool and decreased liver transcription of slc10a1 ( = 0.04) and cyp8b1 ( = 0.03). Random forest analysis identified several features with significantly increased relative abundance in SG compared with sham mice, including . Examination of metabolic profiles with metagenomic analysis revealed a BA salt hydrolase produced by the species. FMT of SG stool to surgically naïve mice significantly decreased the BA pool compared with sham FMT ( = 0.034). Unlike SG surgery, we found no effect of SG or sham FMT on bile acid-related enzymes in the liver after 14 wk of treatment. Overall, we propose that the metabolic benefits of SG surgery are related to decreased liver transcription of cyp8b1 and slc10a1 with subsequent increases in the systemic and enterohepatic BA pool, including lithocholic acid. The gut microbiome adapts to the altered BA pool with associated increases in and bile salt hydrolase production. We propose that the metabolic benefits of sleeve gastrectomy are initiated by decreased liver transcription of cyp8b1 and slc10a1. A notable downstream effect includes changes in systemic bile acid composition and circulation, including increased LCA. An altered gut microbiome after surgery includes increases in that was shown to express a bile salt hydrolase, which could be a contributor to the post-sleeve gastrectomy gut microbiome changes.
由于肝脏、胆汁酸（BA）池和肠道微生物群之间的复杂关系，了解袖状胃切除术（SG）如何实现代谢改善具有挑战性。我们假设SG会改变肠道微生物群，进而增加BA池，从而产生代谢功效。我们将SG或假手术小鼠的粪便物质转移（FMT）到微生物群完整的未接受过手术的小鼠体内。我们通过16S和宏基因组分析评估了手术和FMT对BA相关肝酶、BA浓度和肠道微生物群组成的影响。与假手术相比，SG显著减少了体重增加，分别为5±2克和10±3克（P = 0.004）。SG显著增加了BA池，并降低了slc10a1（P = 0.04）和cyp8b1（P = 0.03）的肝脏转录水平。随机森林分析确定了与假手术小鼠相比，SG中相对丰度显著增加的几个特征，包括……。通过宏基因组分析对代谢谱的检查发现了由……物种产生的一种BA盐水解酶。与假手术FMT相比，将SG粪便进行FMT到未接受过手术的小鼠体内显著降低了BA池（P = 0.034）。与SG手术不同，我们发现在治疗14周后，SG或假手术FMT对肝脏中与胆汁酸相关的酶没有影响。总体而言，我们认为SG手术的代谢益处与cyp8b1和slc10a1的肝脏转录水平降低有关，随后全身和肠肝循环中的BA池增加，包括石胆酸。肠道微生物群适应改变后的BA池，同时……和胆汁盐水解酶的产生相关增加。我们认为袖状胃切除术的代谢益处是由cyp8b1和slc10a1的肝脏转录水平降低引发的。一个显著的下游效应包括全身胆汁酸组成和循环的变化，包括LCA增加。手术后肠道微生物群的改变包括……增加，其被证明表达一种胆汁盐水解酶，这可能是袖状胃切除术后肠道微生物群变化的一个促成因素。
