Pasteurized Akkermansia muciniphila improves glucose metabolism is linked with increased hypothalamic nitric oxide release

Anne Abot; Amandine Brochot; Nicolas Pomié; Gwendoline Astre; Céline Druart; Willem M de Vos; Claude Knauf; Patrice D Cani

doi:10.1016/j.heliyon.2023.e18196

Pasteurized Akkermansia muciniphila improves glucose metabolism is linked with increased hypothalamic nitric oxide release

Heliyon. 2023 Jul 13;9(7):e18196. doi: 10.1016/j.heliyon.2023.e18196. eCollection 2023 Jul.

Authors

Anne Abot¹, Amandine Brochot², Nicolas Pomié¹, Gwendoline Astre¹, Céline Druart², Willem M de Vos^{3

4}, Claude Knauf^{5

6}, Patrice D Cani^{6

7

8}

Affiliations

¹ Enterosys SAS, 31670, Labège, France.
² The Akkermansia Company, 1435, Mont-Saint-Guibert, Belgium.
³ Laboratory of Microbiology, Wageningen University, 6700, EH Wageningen, the Netherlands.
⁴ Human Microbiome Research Program, University of Helsinki, 00014 Helsinki, Finland.
⁵ INSERM U1220, Institut de Recherche en Santé Digestive (IRSD), Université Paul Sabatier, Toulouse III, CHU Purpan, Place du Docteur Baylac, CS, 60039, CEDEX 3, 31024, Toulouse, France.
⁶ NeuroMicrobiota, International Research Program (IRP) INSERM/UCLouvain, France.
⁷ Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain, Université Catholique de Louvain, Brussels, Belgium.
⁸ WELBIO-Walloon Excellence in Life Sciences and Biotechnology, WELBIO department, WEL Research Institute, Avenue Pasteur, 6, 1300, Wavre, Belgium.

Abstract

Background and objective: Pasteurized Akkermansia muciniphila cells have shown anti-diabetic effects in rodents and human. Although, its primary site of action consists in maintaining the gut barrier function, there are no study exploring if A. muciniphila controls glycemia via a gut to brain axis. Targeting the gut motility represents an alternative pathway to treat hyperglycemia. Here, we tested the impact of pasteurized A. muciniphila on gut motility, gut-brain axis and glucose metabolism.

Methods: We used mice fed a 45% high-fat (HFD) treated or not with pasteurized A. muciniphila Muc^T during 12 weeks. We measured the effects of the treatment on body weight gain, glucose metabolism (insulin, glycemia, glucose tolerance), gut contraction and enteric neurotransmitter release, and hypothalamic nitric oxide (NO) release.

Results: We show that pasteurized A. muciniphila exerts positive effects on different metabolic parameters such as body weight, fat mass, insulin, glycemia and glucose tolerance. This could be explained by the ability of pasteurized A. muciniphila supplementation to decrease duodenal contraction and to increase hypothalamic NO release in HFD mice.

Conclusion: We demonstrate a novel mode of action of pasteurized A. muciniphila explaining its beneficial impact on the control of glycemia in a preclinical model of type 2 diabetes via gut-brain axis signaling.

Keywords: Diabetes; Enteric nervous system; Gut-brain axis; Paraprobiotics.