Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity

Background: Resolution of type-2 diabetes (T2D) is common following bariatric surgery, particularly Roux-en-Y gastric bypass. However, the underlying mechanisms have not been fully elucidated.

Methods: To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity +/- T2D (n=80, T2D=42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; n=27), taking diet into account. We co-model these data with shotgun metagenomic profiles of the gut microbiota to provide a comprehensive atlas of host-gut microbe responses to bariatric surgery, weight-loss and glycaemic control at the systems level.

Results: Here we show that bariatric surgery reverses several disrupted pathways characteristic of T2D. The differential metabolite set representative of bariatric surgery overlaps with both diabetes (19.3% commonality) and body mass index (18.6% commonality). However, the percentage overlap between diabetes and body mass index is minimal (4.0% commonality), consistent with weight-independent mechanisms of T2D resolution. The gut microbiota is more strongly correlated to body mass index than T2D, although we identify some pathways such as amino acid metabolism that correlate with changes to the gut microbiota and which influence glycaemic control.

Conclusion: We identify multi-omic signatures associated with responses to surgery, body mass index, and glycaemic control. Improved understanding of gut microbiota - host co-metabolism may lead to novel therapies for weight-loss or diabetes. However, further experiments are required to provide mechanistic insight into the role of the gut microbiota in host metabolism and establish proof of causality.

背景：在肥胖相关手术，尤其是Roux-en-Y胃旁路手术后，2型糖尿病（T2D）的缓解是常见的。然而，其潜在机制尚未得到充分阐明。

方法：为了解决这个问题，我们比较了肥胖患者（+/- T2D，n=80，T2D=42）与接受Roux-en-Y胃旁路术或袖状胃切除术的患者（手术前和术后3个月；n=27）的综合血清、尿液和粪便代谢谱，同时考虑了饮食因素。我们将这些数据与肠道微生物组的shotgun宏基因组学分析相结合，以提供关于宿主-肠道微生物对肥胖手术、体重减轻和血糖控制系统级反应的全面图谱。

结果：在此，我们展示了肥胖手术可以逆转T2D的特征性中断途径。代表肥胖手术的差异代谢物集合与糖尿病（19.3%的相似性）和体重指数（18.6%的相似性）均存在重叠。然而，糖尿病与体重指数之间的重叠百分比极小（4.0%的相似性），这与T2D缓解的体重独立机制一致。肠道微生物群与体重指数的相关性比T2D更强，尽管我们识别出一些途径，如氨基酸代谢，这些途径与肠道微生物群的变化相关，并影响血糖控制。

结论：我们确定了与手术反应、体重指数和血糖控制相关的多组学特征。对肠道微生物群-宿主共代谢的深入了解可能导致减肥或糖尿病的新疗法。然而，需要进一步的实验来揭示肠道微生物群在宿主代谢中的作用并提供因果关系的证据。