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Consistent gut bacterial and short-chain fatty acid signatures in hypoabsorptive bariatric surgeries correlate with metabolic benefits in rats

Subjects

Abstract

Objective

The study aimed at comparing how changes in the gut microbiota are associated to the beneficial effects of the most clinically efficient hypoabsorptive bariatric procedures, namely Roux-en-Y gastric bypass (RYGB), biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S).

Methods

Diet-induced obese (DIO) male Wistar rats were divided into seven groups. In addition to the groups subjected to RYGB, BPD-DS and SADI-S, the following four control groups were included: SHAM-operated rats fed a high-fat diet (SHAM HF), SHAM fed a low-fat diet (SHAM LF), SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW) and sleeve-gastrectomy (SG) rats. Body weight, food intake, glucose tolerance, insulin sensitivity/resistance, and L-cell secretion were assessed. The gut microbiota (16 S ribosomal RNA gene sequencing) as well as the fecal and cæcal contents of short-chain fatty acids (SCFAs) were also analyzed prior to, and after the surgeries.

Results

The present study demonstrates the beneficial effect of RYGB, BPD-DS and SADI-S on fat mass gain and glucose metabolism in DIO rats. These benefits were proportional to the effect of the surgeries on food digestibility (BPD-DS > SADI-S > RYGB). Notably, hypoabsorptive surgeries led to consonant microbial signatures characterized by decreased abundance of the Ruminococcaceae (Oscillospira and Ruminococcus), Oscillospiraceae (Oscillibacter) and Christensenellaceae, and increased abundance of the Clostridiaceae (Clostridium), Sutterellaceae (Sutterella) and Enterobacteriaceae. The gut bacteria following hypoabsorptive surgeries were associated with higher fecal levels of propionate, butyrate, isobutyrate and isovalerate. Increases in the fecal SCFAs were in turn positively and strongly correlated with the levels of peptide tyrosine-tyrosine (PYY) and with the beneficial effects of the surgery.

Conclusion

The present study emphasizes the consistency with which the three major hypoabsorptive bariatric procedures RYGB, BPD-DS and SADI-S create a gut microbial environment capable of producing a SCFA profile favorable to the secretion of PYY and to beneficial metabolic effects.

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Fig. 1: Bariatric surgeries effects on body composition and insulin sensitivity.
Fig. 2: Impact of the treatments on the gut microbiota.
Fig. 3: Fecal short-chain fatty acid (SCFA) production in response to the different treatments on weeks 0, 3 and 8.
Fig. 4: Heatmap representation of the associations between gut microbial absolute abundances of each taxa and SCFAs levels in feces.
Fig. 5: PYY correlations with microbial absolute abundances and S/BCFAs.
Fig. 6: Interrelationships between metabolic variables, SCFAs, BCFAs and absolute microbial abundances.

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Acknowledgements

This work was supported by grants from IRSC (TB2-138776), FRQS (32559) and the Sentinel North program 3.8 of Université Laval (Canada First Research Excellence Fund).

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PM, DR, AM: designed the study; PM, NL, LB, SL, MCR, JP: performed the experiments and collected the data; PM, TVV, DSP: analyzed the data and arranged the figures; PM: wrote the first draft of the paper. DR, DSP, AM, FFA, TVV, AT: reviewed the paper. All authors edited and approved the final draft of the paper.

Corresponding author

Correspondence to Denis Richard.

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Mukorako, P., Lemoine, N., Biertho, L. et al. Consistent gut bacterial and short-chain fatty acid signatures in hypoabsorptive bariatric surgeries correlate with metabolic benefits in rats. Int J Obes (2021). https://doi.org/10.1038/s41366-021-00973-5

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