Penney Nicholas C, Yeung Derek K T, Garcia-Perez Isabel, Posma Joram M, Kopytek Aleksandra, Garratt Bethany, Ashrafian Hutan, Frost Gary, Marchesi Julian R, Purkayastha Sanjay, Hoyles Lesley, Darzi Ara, Holmes Elaine
Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, SW7 2AZ UK.
Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, W2 1NY UK.
Commun Med (Lond). 2022 Oct 7;2:127. doi: 10.1038/s43856-022-00185-6. eCollection 2022.
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.
To address this we compare the integrated serum, urine and faecal metabolic profiles of participants with obesity ± T2D ( = 80, T2D = 42) with participants who underwent Roux-en-Y gastric bypass or sleeve gastrectomy (pre and 3-months post-surgery; = 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.
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.
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.
2型糖尿病（T2D）在减肥手术后很常见，尤其是Roux-en-Y胃旁路手术。然而，其潜在机制尚未完全阐明。
为了解决这个问题，我们比较了肥胖±T2D参与者（n = 80，T2D = 42）与接受Roux-en-Y胃旁路手术或袖状胃切除术的参与者（术前和术后3个月；n = 27）的血清、尿液和粪便综合代谢谱，并考虑了饮食因素。我们将这些数据与肠道微生物群的鸟枪法宏基因组谱共同建模，以在系统水平上提供宿主-肠道微生物对减肥手术、体重减轻和血糖控制反应的综合图谱。
我们发现减肥手术逆转了T2D的几个特征性紊乱途径。代表减肥手术的差异代谢物集与糖尿病（19.3%的共性）和体重指数（18.6%的共性）都有重叠。然而，糖尿病和体重指数之间的重叠百分比最小（4.0%的共性），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与T2D的相关性更强，尽管我们确定了一些与肠道微生物群变化相关且影响血糖控制的途径，如氨基酸代谢。
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-宿主共代谢的更好理解可能会带来减肥或糖尿病的新疗法。然而，需要进一步的实验来深入了解肠道微生物群在宿主代谢中的作用并建立因果关系的证据。
