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

Abstract

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.

Gut microbiota profiles in feces and paired tumor and non-tumor tissues from Colorectal Cancer patients. Relationship to the Body Mass Index

“…In fact, we present comparisons between microbiota composition in tumor and non-tumor tissues, finding no significant differences in beta diversity between both groups of samples. Previously, slightly lower taxonomic diversity was observed in the tumor compared to the non-tumor tissues [ 19 ]. Our data (LEfSe analysis) revealed a significant preponderance of the Fusobacterium genus in tumor tissues.…”

Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy

“…Another study showed that Ruminococcaceae has been considered to be significantly increased in patients with insulin resistance, T2D and inflammatory disease [30][31] . Additionally, Ruminococcaceae_ UCG-002 was reported to be positively associated with verylow-density lipoprotein (VLDL) particles and triglycerides levels, which were clinical features in T2D [32] Studies had suggested that increased Parabacteroides were found in T1D and T2D patients, compared to HC [33][34][35][36] . The colonization of Parabacteroides in the gut microbiota would accelerate diabetes onset in mice [37] .…”