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.
Highlights
Obesity is worldwide epidemic with 1.5 billion adults and 43 million children under the age of 5 overweight, of which approximately 500 million are clinically obese (BMI > 30; WHO, 2006)
Contrary to our initial expectations, based on recent epidemiological findings that bariatric surgery is associated with lower cancer risk, this exploratory study has clearly shown that Roux-en-Y gastric bypass (RYGB) surgery in a Wistar rat model increases the cytotoxicity of fecal matter as indicated by marked reduction in (RSG) as a measure of cell death in a well-established rodent reporter cell line
This cytotoxicity profile of fecal water post-RYGB operation was strongly correlated with the fecal and urinary metabolic phenotypes with fecal concentrations of putrescine, uracil, tyramine, gamma-aminobutyric acid (GABA), and methylamine being inversely correlated with cell survival, whereas butyrate was positively associated with cell survival
Summary
Obesity is worldwide epidemic with 1.5 billion adults (age > 20 years) and 43 million children under the age of 5 overweight, of which approximately 500 million are clinically obese (BMI > 30; WHO, 2006). The small bowel (jejunum) is bypassed approximately 50 cm below the stomach outlet (“biliopancreatic limb”) in a Y-structured configuration This anatomical rearrangement allows food from the outlet of the small stomach pouch to enter directly into the small intestine (“alimentary limb”). Both biliopancreatic and alimentary limbs are attached to a “common channel” to complete the Y-configuration (Ashrafian et al, 2010). This surgical procedure induces a series of physical and metabolic sequelae characterized as the BRAVE effects: Bile flow alteration; Reduction of gastric size; Anatomical gut rearrangement and altered flow of nutrients; Vagal manipulation; and Enteric gut hormone modulation (Ashrafian et al, 2010) leading to effective weight loss and resolution of type 2 diabetes
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