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Hypoabsorptive surgeries cause limb-dependent changes in the gut endocannabinoidome and microbiome in association with beneficial metabolic effects

International Journal of Obesity volume 47, pages 630–641 (2023)Cite this article

Subjects

Abstract

Objective

To determine whether the metabolic benefits of hypoabsorptive surgeries are associated with changes in the gut endocannabinoidome (eCBome) and microbiome.

Methods

Biliopancreatic diversion with duodenal switch (BPD-DS) and single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) were performed in diet-induced obese (DIO) male Wistar rats. Control groups fed a high-fat diet (HF) included sham-operated (SHAM HF) and SHAM HF-pair-weighed to BPD-DS (SHAM HF-PW). Body weight, fat mass gain, fecal energy loss, HOMA-IR, and gut-secreted hormone levels were measured. The levels of eCBome lipid mediators and prostaglandins were quantified in different intestinal segments by LC-MS/MS, while expression levels of genes encoding eCBome metabolic enzymes and receptors were determined by RT-qPCR. Metataxonomic (16S rRNA) analysis was performed on residual distal jejunum, proximal jejunum, and ileum contents.

Results

BPD-DS and SADI-S reduced fat gain and HOMA-IR, while increasing glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) levels in HF-fed rats. Both surgeries induced potent limb-dependent alterations in eCBome mediators and in gut microbial ecology. In response to BPD-DS and SADI-S, changes in gut microbiota were significantly correlated with those of eCBome mediators. Principal component analyses revealed connections between PYY, N-oleoylethanolamine (OEA), N-linoleoylethanolamine (LEA), Clostridium, and Enterobacteriaceae_g_2 in the proximal and distal jejunum and in the ileum.

Conclusions

BPD-DS and SADI-S caused limb-dependent changes in the gut eCBome and microbiome. The present results indicate that these variables could significantly influence the beneficial metabolic outcome of hypoabsorptive bariatric surgeries.

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Fig. 1: Representation of the collection sites in different bariatric surgeries.
Fig. 2: Impact of the treatments on eCBome lipid levels.
Fig. 3: Heatmap representations of log10-transformed abundance of microbial genera in distal jejunum, proximal jejunum and ileum of SHAM HF, SHAM HF-PW, BPD-DS HF and SADI-S HF rats.
Fig. 4: The gut eCBome mediator levels are associated with microbial absolute abundances.
Fig. 5: The gut endocannabinoidome and microbiota are associated with positive effects of the hypoabsorptive bariatric surgeries.

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Data availability

The data highlighted in this article will be available upon reasonable request to the corresponding authors.

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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). VD is the holder of the Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND), which is supported by the Canadian Federal Tri-Agency.

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Authors and Affiliations

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

    Paulette Mukorako, Nicolas Flamand, Laurent Biertho, Stéfane Lebel, André Marette, Cristoforo Silvestri, Vincenzo Di Marzo & Denis Richard

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

    Paulette Mukorako, Nicolas Flamand, Laurent Biertho, Stéfane Lebel, Natacha Lemoine, Julie Plamondon, Marie-Claude Roy, André Tchernof, André Marette, Cristoforo Silvestri, Vincenzo Di Marzo & Denis Richard

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

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

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

    David H. St-Pierre

  5. School of Nutrition, Faculty of Agriculture and Food Sciences, Québec, QC, Canada

    David H. St-Pierre, André Tchernof & Vincenzo Di Marzo

  6. Canada Excellence Research Chair on the Microbiome-Endocannabinoidome Axis in Metabolic Health (CERC-MEND), Québec, QC, Canada

    Nicolas Flamand, Cristoforo Silvestri & Vincenzo Di Marzo

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  1. Paulette Mukorako
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Contributions

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

Corresponding authors

Correspondence to Cristoforo Silvestri, Vincenzo Di Marzo or Denis Richard.

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Competing interests

AT and LB receive research funding from Johnson & Johnson, Medtronic and GI Windows for studies on bariatric surgery. AT acted as a consultant for Bausch Health, Novo Nordisk, and Biotwin. AT and LB are codirectors of the Research Chair in Bariatric and Metabolic Surgery at Université Laval.

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Mukorako, P., St-Pierre, D.H., Flamand, N. et al. Hypoabsorptive surgeries cause limb-dependent changes in the gut endocannabinoidome and microbiome in association with beneficial metabolic effects. Int J Obes 47, 630–641 (2023). https://doi.org/10.1038/s41366-023-01307-3

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