Metabolic surgery profoundly influences gut microbial-host metabolic cross-talk - PubMed (original) (raw)

. 2011 Sep;60(9):1214-23.

doi: 10.1136/gut.2010.234708. Epub 2011 May 14.

Hutan Ashrafian, Marco Bueter, James Kinross, Caroline Sands, Carel W le Roux, Stephen R Bloom, Ara Darzi, Thanos Athanasiou, Julian R Marchesi, Jeremy K Nicholson, Elaine Holmes

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

Jia V Li et al. Gut. 2011 Sep.

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 gut-brain-liver metabolic axis is inferred from modulated faecal γ-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 metabolic-microbial cross-talk augments our understanding of the metabolic phenotype of bariatric procedures and can facilitate enhanced treatments for obesity-related diseases.

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Figures

Figure 1

Figure 1

Metabolic modulation following Metabolic Roux-en-Y Gastric Bypass Surgery (RYGB). The surgical diagram of our animal model of RYGB is categorized according to the B.R.A.V.E. effects (coloured box outlines) at relevant anatomical sites. Within each box we describe the physiological, biochemical and microbiological effects of surgery at each site (coloured text), and further describe whether these effects were noted in this study, derived from the literature or our hypothesis (numbered label key).

Figure 2

Figure 2

A heatmap (A) shows pairwise similarities between gut communities generated using MOTHUR and a cutoff of 0.10**.** Microbial composition of individual rat from sham control and RYGB-operated groups at week 2 and 8 (B). The pie chart (C) shows the mean of each bacterial class level within the control (N=6) and RYGB (N=6) groups at week 2 and 8. * The Student’s t test was used to calculate the difference of each bacterial class between 2 groups for each time point. Of note was the anomalous behaviour of one of the sham rats (S06) which exhibited a high level of Proteobacteria at week 2, more consistent with the response of the RYGB-operated animals. This animal was reported to be unwell immediately following the sham surgical intervention, but subsequently recovered by week 8 post surgery, at which stage the microbial profile of this animal was similar to that of the other sham operated animals.

Figure 3

Figure 3

Cross validation plots and O-PLS-DA coefficient plots of urinary (A, B (R2_X_ =32%; Q2_Y_ =0.86)) and faecal (C, D, (R2_X_ =33.5%; Q2_Y_ =0.84)) NMR spectral data obtained from sham control (blue) and Roux-en-Y Gastric Bypass-operated rats (red) at week 8, reflecting the discrimination between these two groups. Keys: AP: 2-oxoadipate; Asp: aspartate; AV: 5-aminovalerate; Cre: creatine; Crn: creatinine; DE: diaminoethane; ET: ethanol; FA: formate; FM: fumarate; GABA: γ-animo _N_-butyrate; Gly: glycine; GT: 2-oxoglutarate; HA: _p_-hydroxyphenylacetate; HP: hippurate; IS: indoxyl sulfate; Lac: lactate; MA: methylamine; OS: oligosaccharides; PAG: phenylacetylglycine; PG: _p_-cresyl glucuronide; PS: _p_-cresyl sulfate; PT: putrescine; Suc: succinate; TMA: trimethylamine; TMAO: trimethylamine _N_-oxide; Ura: uracil.

Figure 4

Figure 4

O-PLS regression loadings plot shows the correlation between the combination of urinary and faecal NMR spectral data and γ-proteobacteria (Q2_Y_=0.58; R2_X_=18.0%) and Clostridia Q2_Y_=0.45; R2_X_=18.7%) levels.

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References

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