Experimental bariatric surgery in rats generates a cytotoxic chemical environment in the gut contents - PubMed (original) (raw)

doi: 10.3389/fmicb.2011.00183. eCollection 2011.

Reshat Reshat, Qianxin Wu, Hutan Ashrafian, Marco Bueter, Carel W le Roux, Ara Darzi, Thanos Athanasiou, Julian R Marchesi, Jeremy K Nicholson, Elaine Holmes, Nigel J Gooderham

Affiliations

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

Jia V Li et al. Front Microbiol. 2011.

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.

Keywords: 16S rRNA; Roux-en-Y gastric bypass; bariatric surgery; cytotoxicity; gammaproteobacteria; metabolic profile; microbial profile; obesity.

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Figures

Figure 1

Figure 1

Determination of the relative suspension growth as a measure of cytotoxicity (A) and genotoxicity (B) of fecal water extracts following treatment of L5178Y mouse lymphoblastoid cells for 24 h. Data represent mean ± SEM of six independent samples. The negative control (NC) replaced fecal material with water and EMS (20 μg/ml) was used as a positive genotoxin. ***p < 0.001 vs. negative control by one way ANOVA test.

Figure 2

Figure 2

Determination of the relative suspension growth (RSG) of L5178Y mouse lymphoblastoid cells after 24 h exposure to individual fecal water extracts from four sham and four RYGB-operated rats at pre-surgery, 2, 4, 6, and 8 weeks post surgery. The negative control (NC) replaced fecal material with water and EMS (20 μg/ml) was used as a positive genotoxin whilst etoposide (73.5 ng/ml) was used as a positive cytotoxin. **p < 0.01, ***p < 0.001 vs. negative control by one way ANOVA test.

Figure 3

Figure 3

O-PLS regression analyses of fecal water (A) and urine extracts (B) against relative suspension growth values obtained from a 24-h treatment of L5178Y cells with sham or RYGB-operated rat fecal extracts (week 2 and week 8) or O-PLS regression analyses of fecal water extracts against relative suspension growth obtained from 24 h treatment of L5178Y cells with two sham or two RYGB fecal water extracts [pre-surgery and 2, 4, 6, and 8 weeks post surgery (C)]. Peaks pointing upward in the loadings plots represent the metabolites are positively correlated to the cell growth and visa versa. Red peaks reach a significance level of p < 0.005. Keys: GABA, gamma-aminobutyric acid; IS, indoxyl sulfate; PAG, phenylacetylglycine; _p_-cresyl sulf, _p_-cresyl sulfate; _p_-cresyl glu, _p_-cresyl glucuronide.

Figure 4

Figure 4

Scatter plots of normalized bacterial levels (Enterobacteriaceae, Pasteurellaceae, Lachnospiraceae, and Ruminococcaceae) and relative suspension growth of L5178Y mouse lymphoblastoid cells exposed to fecal water extracts of six sham and six RYGB rats at weeks 2 and 8 post intervention. Orange: RYGB-2 weeks post op; Red: RYGB-8 weeks post op; Green: Sham-2 weeks post op; Blue: Sham-8 weeks post op.

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