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

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Title: Multi-omic phenotyping reveals host-microbe responses to bariatric surgery, glycaemic control and obesity
Authors: Penney, N
Yeung, K
Garcia Perez, I
Posma, J
Kopytek, A
Garratt, B
Ashrafian, H
Frost, G
Marchesi, J
Purkayastha, S
Hoyles, L
Darzi, A
Holmes, E
Item Type: Journal Article
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.
Issue Date: 7-Oct-2022
Date of Acceptance: 12-Sep-2022
URI: http://hdl.handle.net/10044/1/99645
DOI: 10.1038/s43856-022-00185-6
ISSN: 2730-664X
Publisher: Nature Research
Start Page: 1
End Page: 18
Journal / Book Title: communications medicine
Volume: 2
Issue: 127
Copyright Statement: © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council
Diabetes Research and Wellness Foundation
Funder's Grant Number: MR/S004033/1
MR/S004033/1
Sutherland-Earl CRF 2015
Keywords: Dynamical systems
Microbiome
Obesity
Type 2 diabetes
Publication Status: Published
Article Number: 127
Online Publication Date: 2022-10-07
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Faculty of Medicine
Institute of Global Health Innovation



This item is licensed under a Creative Commons License Creative Commons