Obesity, Metabolism & Nutrition Institute and Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Sci Transl Med. 2013 Mar 27;5(178):178ra41. doi: 10.1126/scitranslmed.3005687.
Roux-en-Y gastric bypass (RYGB) results in rapid weight loss, reduced adiposity, and improved glucose metabolism. These effects are not simply attributable to decreased caloric intake or absorption, but the mechanisms linking rearrangement of the gastrointestinal tract to these metabolic outcomes are largely unknown. Studies in humans and rats have shown that RYGB restructures the gut microbiota, prompting the hypothesis that some of the effects of RYGB are caused by altered host-microbial interactions. To test this hypothesis, we used a mouse model of RYGB that recapitulates many of the metabolic outcomes in humans. 16S ribosomal RNA gene sequencing of murine fecal samples collected after RYGB surgery, sham surgery, or sham surgery coupled to caloric restriction revealed that alterations to the gut microbiota after RYGB are conserved among humans, rats, and mice, resulting in a rapid and sustained increase in the relative abundance of Gammaproteobacteria (Escherichia) and Verrucomicrobia (Akkermansia). These changes were independent of weight change and caloric restriction, were detectable throughout the length of the gastrointestinal tract, and were most evident in the distal gut, downstream of the surgical manipulation site. Transfer of the gut microbiota from RYGB-treated mice to nonoperated, germ-free mice resulted in weight loss and decreased fat mass in the recipient animals relative to recipients of microbiota induced by sham surgery, potentially due to altered microbial production of short-chain fatty acids. These findings provide the first empirical support for the claim that changes in the gut microbiota contribute to reduced host weight and adiposity after RYGB surgery.
胃旁路术（RYGB）导致体重迅速减轻、体脂减少和葡萄糖代谢改善。这些效果不仅仅归因于热量摄入或吸收的减少，而是将胃肠道重新排列与这些代谢结果联系起来的机制在很大程度上是未知的。人类和大鼠的研究表明，RYGB 重塑了肠道微生物群，这促使人们假设 RYGB 的一些效果是由宿主-微生物相互作用的改变引起的。为了验证这一假设，我们使用了一种 RYGB 小鼠模型，该模型重现了人类的许多代谢结果。对 RYGB 手术后、假手术或假手术后与热量限制相结合的小鼠粪便样本中的 16S 核糖体 RNA 基因进行测序，结果表明，RYGB 后肠道微生物群的改变在人类、大鼠和小鼠中是保守的，导致 Gammaproteobacteria（大肠杆菌）和 Verrucomicrobia（阿克曼氏菌）的相对丰度迅速而持续增加。这些变化与体重变化和热量限制无关，在整个胃肠道长度上均可检测到，在手术操作部位下游的远端肠道最为明显。将 RYGB 治疗小鼠的肠道微生物群转移到未手术的无菌小鼠中，导致受体动物的体重减轻和脂肪量减少，相对于假手术诱导的受体动物，这可能是由于微生物产生的短链脂肪酸发生了改变。这些发现为改变肠道微生物群有助于 RYGB 手术后宿主体重和体脂减少的说法提供了第一个经验支持。
