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

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posted on 20.12.2021, 13:55 authored by Jian V. Li, Hutan Ashrafian, Magali Sarafian, Daniel Homola, Laura Rushton, Grace Barker, Paula Momo Cabrera, Matthew R Lewis, Ara Darzi, Edward Lin, Nana Adwoa Gletsu-Miller, Stephen L. Atkin, Thozhukat Sathyapalan, Nigel J Gooderham, Jeremy K. Nicholson, Julian Roberto Marchesi, Thanos Athanasiou, Elaine Holmes

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.

Funding

Imperial College Research Fellowship, Medical Research Council New Investigator Research Grant (MR/L009803/1)

Royal Society Research Grant (RG120583)

National Institute of Health Research (NIHR) Imperial Biomedical Research Centre (BRC) based at Imperial College Healthcare NHS Trust and Imperial College London

History

Comments

The original article is available at https://microbiomejournal.biomedcentral.com/

Published Citation

Li JV. et al. Roux-en-Y gastric bypass-induced bacterial perturbation contributes to altered host-bacterial co-metabolic phenotype. Microbiome. 2021;9(1):139.

Publication Date

14 June 2021

PubMed ID

34127058

Department/Unit

  • RCSI Bahrain

Publisher

BioMed Central

Version

  • Published Version (Version of Record)