Intestinal microbiota after RYGB

Objective: Roux-Y gastric bypass (RYGB) surgery is a last treatment resort to induce substantial and sustained weight loss in severe obesity. The anatomical rearrangement affects the intestinal microbiota but so far, little information is available how it interferes with microbial functionality and microbial-host interaction independent from weight loss. Design: A RYGB rat model was utilized and compared to sham-operated controls which were kept at matched body weight as RYGB animals by food restriction. We assessed microbial taxonomy by 16S rRNA gene sequencing and functional activity by metaproteomics and metabolomics on microbiota samples collected separately from the ileum, the cecum as well as the colon and separately analysed the lumen and mucus associated microbiota. Results: Altered gut architecture in RYGB strongly affected the occurrence of Actinobacteria, especially Bifidobacteriaceae and Proteobacteria which were increased, whereas Firmicutes were decreased, although Streptococcaceae and Clostridium perfringens were observed at higher abundances. A decrease of conjugated as well as secondary bile acids was observed in the RYGB-gut lumen. In addition the arginine biosynthesis pathway in the microbiota was altered, indicated by the changes in abundance of upstream metabolites and enzymes, resulting in lower levels of arginine and higher levels of aspartate in the colon after RYGB. Conclusion: The anatomical rearrangement in RYGB affects microbiota composition and functionality by changes in amino acid and bile acid metabolism, independent of weight loss. The shift in microbiota taxonomic structure after RYGB may be mediated by the resulting change in composition of the bile acid pool in the gut lumen.

研究目的：Roux-Y胃转流术（Roux-Y gastric bypass, RYGB）是重度肥胖患者实现显著且持久体重减轻的最后一线治疗手段。该手术引发的肠道解剖结构重排会影响肠道菌群，但目前关于其在不依赖体重减轻的前提下，如何干预微生物功能与微生物-宿主互作的相关研究仍较为匮乏。

研究设计：本研究采用RYGB大鼠模型，并设置假手术对照组，通过食物限制使对照组大鼠的体重与RYGB组保持一致。研究分别从回肠、盲肠及结肠采集菌群样本，采用16S rRNA基因测序（16S rRNA gene sequencing）技术评估微生物分类学特征，同时利用宏蛋白质组学（metaproteomics）和代谢组学（metabolomics）分析菌群的功能活性；此外还分别对肠腔与黏液相关菌群进行了独立分析。

研究结果：RYGB术后肠道结构的改变显著影响了菌群的组成：放线菌门（Actinobacteria）尤其是双歧杆菌科（Bifidobacteriaceae）和变形菌门（Proteobacteria）的丰度显著升高，而厚壁菌门（Firmicutes）丰度整体降低，但链球菌科（Streptococcaceae）与产气荚膜梭菌（Clostridium perfringens）的丰度却有所上升。RYGB组肠腔中的结合胆汁酸（conjugated bile acids）与次级胆汁酸（secondary bile acids）水平均出现下降。此外，菌群的精氨酸生物合成通路（arginine biosynthesis pathway）发生改变，表现为上游代谢物与酶的丰度变化，最终导致RYGB术后结肠内精氨酸水平降低，天冬氨酸水平升高。

研究结论：RYGB手术引发的解剖结构重排，可通过改变氨基酸与胆汁酸代谢，在不依赖体重减轻的情况下影响菌群的组成与功能；RYGB术后菌群分类学结构的改变，可能由肠腔胆汁酸池（bile acid pool）组成的变化所介导。