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

Abstract

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.

The Metabolomic Effects of Tripeptide Gut Hormone Infusion Compared to Roux-en-Y Gastric Bypass and Caloric Restriction

“…A reduction in paraxanthine after caffeine loading in post-RYGB patients was previously reported ( 56 ), which was attributed to the effects of the surgical procedure on hepatic cytochrome P450 enzyme induction ( 57 ). Of broader relevance, RYGB surgery profoundly alters the gut bacterial composition (eg, increased Gammaproteobacteria ) and metabolic functions (eg, increased protein putrefaction) ( 58 , 59 ), with the latter reflected by increased urinary host-bacterial metabolites following RYGB, such as 4-cresyl sulfate, 4-hydroxyphenylacetate phenylacetylglutamine, and indoxyl sulfate, the precursors of which are tyrosine, phenylalanine, and tryptophan ( 60 ). Thus, the significantly lower levels of plasma tyrosine, together with a trend toward lower phenylalanine, in the RYGB group compared to SAL or GOP could result from the incomplete digestion of protein and absorption of these amino acids in the foregut postsurgery.…”

The impact of bariatric surgery on serum tryptophan–kynurenine pathway metabolites

“…As a discovery study, the relatively small sample size limits the generalisability of the results and may decrease the power of the study. However, the widespread physiological and metabolic effects exerted by bariatric surgery means inter-individual variability is small compared to the overarching effects of the surgery 55 . The paired nature of this study also permitted us to measure and compare the differences in response between individuals as well as the surgical procedure.…”

Urinary Metabolomic Changes Accompanying Albuminuria Remission following Gastric Bypass Surgery for Type 2 Diabetic Kidney Disease

“…Compared with MTA, treatment with CSM resulted in a distinctive urinary metabolomic profile. The urinary metabolomic changes induced by CSM included increased excretion of the host-microbial co-metabolites N-phenylacetylglycine, trimethylamine N-oxide, and 4-aminobutyrate (GABA) [28][29][30][31][32][33], as well as increased excretion of the amino acids arginine and glutamine. CSM also reduced urinary concentrations of aromatic amino acids (phenylalanine and tyrosine) as well as BCAAs (valine and leucine) and related catabolic intermediates (3-hydroxyisobutyrate, 3-hydroxyisovalerate, and 3-methyl-2-oxovalerate).…”

“…BCAA catabolic intermediates were more weakly correlated with each other. Aromatic amino acids were more strongly correlated with BCAAs than they were with host-microbial co-metabolites, despite the fact that altered host-microbial aromatic amino acid metabolism resulting in the production of metabolites such as N-phenylacetylglycine and 4-hydroxyphenylacetate has been consistently reported following RYGB [28][29][30][31][32][33].…”