Experimental bariatric surgery in rats generates a cytotoxic chemical environment in the gut contents

Abstract

Bariatric surgery, also known as metabolic surgery, is an effective treatment for morbid obesity, which also offers pronounced metabolic effects including the resolution of type 2 diabetes and a decrease in cardiovascular disease and long-term cancer risk. However, the mechanisms of surgical weight loss and the long-term consequences of bariatric surgery remain unclear. Bariatric surgery has been demonstrated to alter the composition of both the microbiome and the metabolic phenotype. We observed a marked shift toward Gammaproteobacteria, particularly Enterobacter hormaechei, following Roux-en-Y gastric bypass (RYGB) surgery in a rat model compared with sham-operated controls. Fecal water from RYGB surgery rats was highly cytotoxic to rodent cells (mouse lymphoma cell line). In contrast, fecal water from sham-operated animals showed no/very low cytotoxicity. This shift in the gross structure of the microbiome correlated with greatly increased cytotoxicity. Urinary phenylacetylglycine and indoxyl sulfate and fecal gamma-aminobutyric acid, putrescine, tyramine, and uracil were found to be inversely correlated with cell survival rate. This profound co-dependent response of mammalian and microbial metabolism to RYGB surgery and the impact on the cytotoxicity of the gut luminal environment suggests that RYGB exerts local and global metabolic effects which may have an influence on long-term cancer risk and cytotoxic load.

Increased Risk of Colorectal Cancer After Obesity Surgery

“…33 Recently, it has been reported that alterations in the intestinal microbiota and fecal metabolite profile after Roux-en-Y gastric bypass in a rat model are associated with increased fecal cytotoxicity compatible with increased carcinogenicity. 34 This emphasizes that a complex interaction between the gut microflora and diet exists that could explain increased carcinogenic risk after obesity surgery. The effect of the different restrictive and malabsorptive obesity surgery procedures on the gut microbiota and colonic metabolite profiles deserves further investigation, particularly in view of recent observations that Bacterioides/Prevotella species are increased after gastric bypass 35 and Bacterioides/Prevotella species are higher in patients with colorectal cancer compared with body weight-matched controls.…”

Influence of Intestinal Microbiota on Body Weight Gain: a Narrative Review of the Literature

“…RYGB results in significant changes in gut anatomy and physiology, so potential changes in gut microbiota composition may also be likely [72][73][74][75].…”

Right Colon Carcinoma Infiltrating the Alimentary Limb in a Patient With Biliopancreatic Diversion

“…[14][15][16] Effect of postsurgical neurohormonal modulation on longterm cancer risk also requires further investigation. 17 However the results obtained in Scopinaro's cohort [18][19][20] provide support for the hypothesis that the incidence rate of colorectal cancer among subjects at long term following BPD is not substantially different from that observed in the general population.…”