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Roux-en-Y gastric bypass-induced bacterial perturbation contributes to altered host-bacterial co-metabolic phenotype

Li, Jia V., Ashrafian, Hutan, Sarafian, Magali, Homola, Daniel, Rushton, Laura, Barker, Grace, Cabrera, Paula Momo, Lewis, Matthew R., Darzi, Ara, Lin, Edward, Gletsu-Miller, Nana Adwoa, Atkin, Stephen L., Sathyapalan, Thozhukat, Gooderham, Nigel J., Nicholson, Jeremy K., Marchesi, Julian R. ORCID:, Athanasiou, Thanos and Holmes, Elaine 2021. Roux-en-Y gastric bypass-induced bacterial perturbation contributes to altered host-bacterial co-metabolic phenotype. Microbiome 9 (1) , 139. 10.1186/s40168-021-01086-x

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Background Bariatric surgery, used to achieve effective weight loss in individuals with severe obesity, modifies the gut microbiota and systemic metabolism in both humans and animal models. The aim of the current study was to understand better the metabolic functions of the altered gut microbiome by conducting deep phenotyping of bariatric surgery patients and bacterial culturing to investigate causality of the metabolic observations. Methods Three bariatric cohorts (n = 84, n = 14 and n = 9) with patients who had undergone Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) or laparoscopic gastric banding (LGB), respectively, were enrolled. Metabolic and 16S rRNA bacterial profiles were compared between pre- and post-surgery. Faeces from RYGB patients and bacterial isolates were cultured to experimentally associate the observed metabolic changes in biofluids with the altered gut microbiome. Results Compared to SG and LGB, RYGB induced the greatest weight loss and most profound metabolic and bacterial changes. RYGB patients showed increased aromatic amino acids-based host-bacterial co-metabolism, resulting in increased urinary excretion of 4-hydroxyphenylacetate, phenylacetylglutamine, 4-cresyl sulphate and indoxyl sulphate, and increased faecal excretion of tyramine and phenylacetate. Bacterial degradation of choline was increased as evidenced by altered urinary trimethylamine-N-oxide and dimethylamine excretion and faecal concentrations of dimethylamine. RYGB patients’ bacteria had a greater capacity to produce tyramine from tyrosine, phenylalanine to phenylacetate and tryptophan to indole and tryptamine, compared to the microbiota from non-surgery, normal weight individuals. 3-Hydroxydicarboxylic acid metabolism and urinary excretion of primary bile acids, serum BCAAs and dimethyl sulfone were also perturbed following bariatric surgery. Conclusion Altered bacterial composition and metabolism contribute to metabolic observations in biofluids of patients following RYGB surgery. The impact of these changes on the functional clinical outcomes requires further investigation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: This article is licensed under a Creative Commons Attribution 4.0 International License
Publisher: BioMed Central
ISSN: 2049-2618
Date of First Compliant Deposit: 10 January 2022
Date of Acceptance: 27 April 2021
Last Modified: 15 May 2023 00:10

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