Skip to main content
SpringerLink
Log in

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

  • Article
  • Published:
International Journal of Obesity Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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.

Similar content being viewed by others

References

  1. Pareek M, Schauer PR, Kaplan LM, Leiter LA, Rubino F, Bhatt DL. Metabolic surgery: weight loss, diabetes, and beyond. J Am Coll Cardiol. 2018;71:670–87.

    Article  Google Scholar 

  2. Schauer PR, Nor Hanipah Z, Rubino F. Metabolic surgery for treating type 2 diabetes mellitus: Now supported by the world’s leading diabetes organizations. Cleve Clin J Med. 2017;84:S47–56.

    Article  PubMed  Google Scholar 

  3. Dixon JB, le Roux CW, Rubino F, Zimmet P. Bariatric surgery for type 2 diabetes. The Lancet. 2012;379:2300–11.

    Article  Google Scholar 

  4. Baraboi ED, Li W, Labbe SM, Roy MC, Samson P, Hould FS, et al. Metabolic changes induced by the biliopancreatic diversion in diet-induced obesity in male rats: the contributions of sleeve gastrectomy and duodenal switch. Endocrinology. 2015;156:1316–29.

    Article  CAS  PubMed  Google Scholar 

  5. Marceau P, Biron S, Marceau S, Hould FS, Lebel S, Lescelleur O, et al. Biliopancreatic diversion-duodenal switch: independent contributions of sleeve resection and duodenal exclusion. Obes Surg. 2014;24:1843–9.

    Article  PubMed  Google Scholar 

  6. Li W, Baraboi ED, Cluny NL, Roy MC, Samson P, Biertho L, et al. Malabsorption plays a major role in the effects of the biliopancreatic diversion with duodenal switch on energy metabolism in rats. Surg Obes Relat Dis. 2015;11:356–66.

    Article  PubMed  Google Scholar 

  7. Pereira SS, Guimaraes M, Almeida R, Pereira AM, Lobato CB, Hartmann B, et al. Biliopancreatic diversion with duodenal switch (BPD-DS) and single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) result in distinct post-prandial hormone profiles. Int J Obes (Lond). 2019;43:2518–27.

    Article  CAS  Google Scholar 

  8. le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V, et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006;243:108–14.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Anhe FF, Varin TV, Schertzer JD, Marette A. The gut microbiota as a mediator of metabolic benefits after bariatric surgery. Can J Diabetes. 2017;41:439–47.

    Article  PubMed  Google Scholar 

  10. Debedat J, Clement K, Aron-Wisnewsky J. Gut microbiota dysbiosis in human obesity: impact of bariatric surgery. Curr Obes Rep. 2019;8:229–42.

    Article  PubMed  Google Scholar 

  11. Hagen ME, Jung MK, Fakhro J, Buchs NC, Buehler L, Mendoza JM, et al. Robotic versus laparoscopic stapling during robotic Roux-en-Y gastric bypass surgery: a case-matched analysis of costs and clinical outcomes. Surg Endosc. 2018;32:472–7.

    Article  PubMed  Google Scholar 

  12. Sanchez-Pernaute A, Rubio Herrera MA, Perez-Aguirre E, Garcia Perez JC, Cabrerizo L, Diez Valladares L, et al. Proximal duodenal-ileal end-to-side bypass with sleeve gastrectomy: proposed technique. Obes Surg. 2007;17:1614–8.

    Article  PubMed  Google Scholar 

  13. Nestoridi E, Kvas S, Kucharczyk J, Stylopoulos N. Resting energy expenditure and energetic cost of feeding are augmented after Roux-en-Y gastric bypass in obese mice. Endocrinology. 2012;153:2234–44.

    Article  CAS  PubMed  Google Scholar 

  14. Mukorako P, Lopez C, Baraboi ED, Roy MC, Plamondon J, Lemoine N, et al. Alterations of gut microbiota after biliopancreatic diversion with duodenal switch in wistar rats. Obes Surg. 2019;29:2831–42.

    Article  PubMed  Google Scholar 

  15. Garcia-Villalba R, Gimenez-Bastida JA, Garcia-Conesa MT, Tomas-Barberan FA, Carlos Espin J, Larrosa M. Alternative method for gas chromatography-mass spectrometry analysis of short-chain fatty acids in faecal samples. J Sep Sci. 2012;35:1906–13.

    Article  CAS  PubMed  Google Scholar 

  16. Wang T, Shen Y, Qiao Z, Wang Y, Zhang P, Yu B. Comparison of diabetes remission and micronutrient deficiency in a mildly obese diabetic rat model undergoing SADI-S versus RYGB. Obes Surg. 2019;29:1174–84.

    Article  PubMed  Google Scholar 

  17. Pata G, Crea N, Di Betta E, Bruni O, Vassallo C, Mittempergher F. Biliopancreatic diversion with transient gastroplasty and duodenal switch: long-term results of a multicentric study. Surgery. 2013;153:413–22.

    Article  PubMed  Google Scholar 

  18. Ding L, Fan Y, Li H, Zhang Y, Qi D, Tang S, et al. Comparative effectiveness of bariatric surgeries in patients with obesity and type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials. Obes Rev. 2020;21:e13030.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Pal A, Rhoads DB, Tavakkoli A. Customization of biliopancreatic limb length to modulate and sustain antidiabetic effect of gastric bypass surgery. Am J Physiol Gastrointest Liver Physiol. 2018;314:G287–G99.

    Article  CAS  PubMed  Google Scholar 

  20. Mahawar KK, Sharples AJ. Contribution of malabsorption to weight loss after Roux-en-Y Gastric Bypass: a systematic review. Obes Surg. 2017;27:2194–206.

    Article  PubMed  Google Scholar 

  21. Pucci A, Batterham RL. Mechanisms underlying the weight loss effects of RYGB and SG: similar, yet different. J Endocrinol Invest. 2019;42:117–28.

    Article  CAS  PubMed  Google Scholar 

  22. Lutz TA, Bueter M. The use of rat and mouse models in bariatric surgery experiments. Front Nutr. 2016;3:25.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sinclair P, Brennan DJ, le Roux CW. Gut adaptation after metabolic surgery and its influences on the brain, liver and cancer. Nat Rev Gastroenterol Hepatol. 2018;15:606–24.

    Article  CAS  PubMed  Google Scholar 

  24. Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol. 2014;20:16079–94.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Scopinaro N, Adami GF, Marinari GM, Gianetta E, Traverso E, Friedman D, et al. Biliopancreatic diversion. World J Surg. 1998;22:936–46.

    Article  CAS  PubMed  Google Scholar 

  26. Liou AP, Paziuk M, Luevano JM Jr., Machineni S, Turnbaugh PJ, Kaplan LM. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity. Sci Transl Med. 2013;5:178ra41.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ilhan ZE, DiBaise JK, Isern NG, Hoyt DW, Marcus AK, Kang DW, et al. Distinctive microbiomes and metabolites linked with weight loss after gastric bypass, but not gastric banding. ISME J. 2017;11:2047–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lin HV, Frassetto A, Kowalik EJ Jr., Nawrocki AR, Lu MM, Kosinski JR, et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS ONE. 2012;7:e35240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Psichas A, Sleeth ML, Murphy KG, Brooks L, Bewick GA, Hanyaloglu AC, et al. The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents. Int J Obes (Lond). 2015;39:424–9.

    Article  CAS  Google Scholar 

  30. Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG, Zac-Varghese SE, et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015;64:1744–54.

    Article  CAS  PubMed  Google Scholar 

  31. Perry RJ, Peng L, Barry NA, Cline GW, Zhang D, Cardone RL, et al. Acetate mediates a microbiome-brain-beta-cell axis to promote metabolic syndrome. Nature. 2016;534:213–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nadreau E, Baraboi ED, Samson P, Blouin A, Hould FS, Marceau P, et al. Effects of the biliopancreatic diversion on energy balance in the rat. Int J Obes (Lond). 2006;30:419–29.

    Article  CAS  Google Scholar 

  33. Smith EA, Macfarlane GT. Dissimilatory amino Acid metabolism in human colonic bacteria. Anaerobe. 1997;3:327–37.

    Article  CAS  PubMed  Google Scholar 

  34. Aguirre M, Eck A, Koenen ME, Savelkoul PH, Budding AE, Venema K. Diet drives quick changes in the metabolic activity and composition of human gut microbiota in a validated in vitro gut model. Res Microbiol. 2016;167:114–25.

    Article  CAS  PubMed  Google Scholar 

  35. Schroeder BO, Backhed F. Signals from the gut microbiota to distant organs in physiology and disease. Nat Med. 2016;22:1079–89.

    Article  CAS  PubMed  Google Scholar 

  36. van der Beek CM, Canfora EE, Lenaerts K, Troost FJ, Damink S, Holst JJ, et al. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men. Clin Sci (Lond). 2016;130:2073–82.

    Article  Google Scholar 

  37. Larraufie P, Martin-Gallausiaux C, Lapaque N, Dore J, Gribble FM, Reimann F, et al. SCFAs strongly stimulate PYY production in human enteroendocrine cells. Sci Rep. 2018;8:74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Scheithauer TP, Dallinga-Thie GM, de Vos WM, Nieuwdorp M, van Raalte DH. Causality of small and large intestinal microbiota in weight regulation and insulin resistance. Mol Metab. 2016;5:759–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Manning S, Batterham RL. The role of gut hormone peptide YY in energy and glucose homeostasis: twelve years on. Annu Rev Physiol. 2014;76:585–608.

    Article  CAS  PubMed  Google Scholar 

  40. Guida C, Stephen SD, Watson M, Dempster N, Larraufie P, Marjot T, et al. PYY plays a key role in the resolution of diabetes following bariatric surgery in humans. EBioMedicine. 2019;40:67–76.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Chandarana K, Gelegen C, Karra E, Choudhury AI, Drew ME, Fauveau V, et al. Diet and gastrointestinal bypass-induced weight loss: the roles of ghrelin and peptide YY. Diabetes. 2011;60:810–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Boland B, Mumphrey MB, Hao Z, Gill B, Townsend RL, Yu S, et al. The PYY/Y2R-deficient mouse responds normally to high-fat diet and gastric bypass surgery. Nutrients. 2019;11:1–15.

    Article  Google Scholar 

  43. Ye J, Hao Z, Mumphrey MB, Townsend RL, Patterson LM, Stylopoulos N, et al. GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents. Am J Physiol Regul Integr Comp Physiol. 2014;306:R352–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

  1. Department of Medicine, Faculty of Medicine, Université Laval, Québec, QC, Canada

    Paulette Mukorako, Laurent Biertho, Stéfane Lebel, André Marette & Denis Richard

  2. Québec Heart and Lung Institute, Chemin Sainte-Foy, Québec, QC, Canada

    Paulette Mukorako, Natacha Lemoine, Laurent Biertho, Stéfane Lebel, Marie-Claude Roy, Julie Plamondon, André Tchernof, André Marette & Denis Richard

  3. Institute of Nutrition and Functional Foods, Québec, QC, Canada

    Thibault V. Varin, David H. St-Pierre & André Marette

  4. Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute and Center for Metabolism Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada

    Fernando F. Anhê

  5. Department of Exercise Sciences, Université du Québec à Montréal (UQAM), Montreal, QC, Canada

    David H. St-Pierre

Authors
  1. Paulette Mukorako
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Natacha Lemoine
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laurent Biertho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Stéfane Lebel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marie-Claude Roy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Julie Plamondon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. André Tchernof
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Thibault V. Varin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fernando F. Anhê
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. David H. St-Pierre
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. André Marette
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Denis Richard
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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 46, 297–306 (2022). https://doi.org/10.1038/s41366-021-00973-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41366-021-00973-5

  • Springer Nature Limited

This article is cited by

Search

Navigation