Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk

Abstract

Background and aims Bariatric surgery is increasingly performed worldwide to treat morbid obesity and is also known as metabolic surgery to reflect its beneficial metabolic effects especially with respect to improvement in type 2 diabetes. Understanding surgical weight loss mechanisms and metabolic modulation is required to enhance patient benefits and operative outcomes.Methods The authors applied a parallel and statistically integrated bacterial profiling and metabonomic approach to characterise Roux-en-Y gastric bypass (RYGB) effects in a non-obese rat model. Results Substantial shifts of the main gut phyla towards higher concentrations of Proteobacteria (52-fold), specifically Enterobacter hormaechei, are shown. Low concentrations of Firmicutes (4.5-fold) and Bacteroidetes (twofold) in comparison with sham-operated rats were also found. Faecal extraction studies revealed a decrease in faecal bile acids and a shift from protein degradation to putrefaction through decreased faecal tyrosine with concomitant increases in faecal putrescine and diaminoethane. Decreased urinary amines and cresols were found and indices of modulated energy metabolism were demonstrated after RYGB, including decreased urinary succinate, 2-oxoglutarate, citrate and fumarate. These changes could also indicate renal tubular acidosis, which is associated with increased flux of mitochondrial tricarboxylic acid cycle intermediates. A surgically induced effect on the gutebraineliver metabolic axis is inferred from modulated faecal g-aminobutyric acid and glutamate. Conclusion This profound co-dependence of mammalian and microbial metabolism, which is systematically altered after RYGB surgery, suggests that RYGB exerts local and global metabolic effects. The effect of RYGB surgery on the host metabolicemicrobial cross-talk augments our understanding of the metabolic phenotype of bariatric procedures and can facilitate enhanced treatments for obesity-related diseases.

Roux-en-Y gastric bypass surgery in rats alters gut microbiota profile along the intestine

“…Gut microbiota analysis of fecal samples from humans and rats after RYGB suggested that the reduction of Firmicutes and Bacteroidetes may partly explain the weight loss and beneficial effects on metabolism and inflammation associated with the RYGB surgery [7][8][9]. Liou [10] et al confirmed these findings and also showed that cecal transplants from mice after RYGB to unoperated germ free mice decreased body weight and adiposity compared to recipients of microbiota from sham-operated mice.…”

Increased Risk of Colorectal Cancer After Obesity Surgery

“…This could be due to increased mucosal bile salt exposure or changes in intestinal microbiota, which are both recognized after gastric bypass. 28,29 Because there is no overall increased risk of obesity-related cancer after obesity surgery, [8][9][10][11] the rectal mucosal changes are compatible with the concept that increased cancer risk after obesity surgery may be restricted to the colorectum. Importantly, we found that the increased risk of colorectal cancer was similar for all 3 obesity surgery procedures, including vertical banded gastroplasty and adjustable gastric banding, which are both restrictive, rather than malabsorptive, surgical strategies.…”

“…There are currently no studies that address changes in colorectal mucosal proliferation state or inflammation after gastroplasty or gastric banding, but a unifying hypothesis is that each of the obesity surgery procedures could lead to the promotion of colorectal carcinogenesis via altered colorectal metabolite profiles, secondary to changes to the gut microbiota, combined with modified dietary intake postoperatively. [28][29][30] For example, a diet high in protein is one of the cornerstones of postoperative nutritional care, 31,32 but it has recently been shown that a high-protein, low-carbohydrate diet can promote detrimental metabolite profiles in the colorectum, including a decrease in short-chain fatty acid concentrations and increased exposure to N-nitroso compounds, both of which have been implicated in driving colorectal carcinogenesis. 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.…”

Gut Microbiome-Brain Communications Regulate Host Physiology and Behavior

“…Reduced food reservoir and malabsorption have been suggested as possible mechanisms underlying the health-promoting influences of bariatric surgery, but a growing body of evidence suggests a beneficial role of altered gut microbiota profile following the surgery [179]. Indeed, certain procedures such as the Roux-en-Y Gastric Bypass [RYGB] have been reported in humans and animals to cause a marked increase in Gammaproteobacteria, decrease in Firmicutes, and loss of methanogen bacteria [179], which are associated with metabolic improvements after treatment [180,181]. The RYGB surgery in rats with normal weight caused a decrease in Firmicutes with significantly higher proportion of Proteobacteria compared to the control rats treated with sham operation [182].…”