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

Jia V Li,Nana Adwoa Gletsu-Miller,Daniel Homola,Magali Sarafian,Stephen L Atkin,Grace Barker,Julian R Marchesi,Nigel J Gooderham,Ara Darzi,Matthew R Lewis,Edward Lin,Elaine Holmes,Paula Momo Cabrera,Jeremy K Nicholson,Thozhukat Sathyapalan,Hutan Ashrafian,Laura Rushton,Thanos Athanasiou

doi:10.1186/s40168-021-01086-x

Abstract

BackgroundBariatric 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.MethodsThree 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.ResultsCompared 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.ConclusionAltered 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.1v6mePHgvKoyyAii3YMczBVideo abstract

Highlights

Obesity affects almost half a billion adults worldwide and almost one-third of children under 11 years old in Europe, and is a risk factor for cardiovascular events, type 2 diabetes, non-alcoholic fatty liver disease and some cancers [1]
Altered bacterial composition and metabolism contribute to metabolic observations in biofluids of patients following Roux-en-Y gastric bypass (RYGB) surgery
A trend in weight loss induced by laparoscopic gastric banding (LGB) was observed for cohort 1 but was not statistically significant and the reduction of BMI in cohort 3 was significant at 6-month post-op compared to pre-op (p = 0.005) (Fig. 1C)

Summary

Introduction

Obesity affects almost half a billion adults worldwide and almost one-third of children under 11 years old in Europe, and is a risk factor for cardiovascular events, type 2 diabetes, non-alcoholic fatty liver disease and some cancers [1]. Bariatric surgery is currently the most effective strategy for achieving sustained weight loss in patients who have severe obesity and refers to a suite of surgical procedures that are carried out to achieve sustained weight loss where diet and exercise programs have failed. Weight loss is the primary aim, bariatric surgery has additional beneficial effects including the resolution of type 2 diabetes, hypertension and obstructive sleep apnoea [2]. 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

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