ESPEN 2020 Abstract Submission

Topic: Obesity and the metabolic syndrome

Abstract Submission Identifier: ESPEN20-ABS-1461

GUT MICROBIOTA DEPLETION AFFECTS CAECAL SATIETY HORMONES EXPRESSION AND SATIATION IN RESPONSE TO WESTERN DIET.

M. Fouesnard^*, ¹, A. Benani ², F. Devime ³, S. Ben-Fradj ⁴, G. Boudry ¹, V. Douard ³

¹Institut NuMeCan, INRAE, INSERM, Univ Rennes, Rennes, ²Centre des Sciences du Goût et de l'Alimentation, UMR 6265, CNRS UMR 13241, INRAE, Univ Bourgogne, Dijon, ³Institut MICALIS, INRAE, AgroParisTech, Université Paris-Saclay, Jouy-en-Josas, ⁴Centres des Sciences du Goût et de l'Alimentation, UMR 6265, CNRS UMR 13241, INRAE, Univ Bourgogne, Dijon, France

Rationale: Intestinal epithelium function is essential to regulate host satiety response to diet whose dysregulation is linked to obesity development. Enteroendocrine cells (EEC) play a major role in feeding behavior regulation through a large panel of centrally active hormones secretion. Recent studies showed that EECs exhibit an unsuspected functional identity plasticity in response to nutrients or bacterial compounds. In order to clarify the link between microbiota and food intake, we explore EEC adaptation to gut microbiota depletion and its consequences on feeding behavior regulation in response to an obesogenic diet (Western Diet, WD).

Methods: Mice with or without antibiotics (ATB)-depleted gut microbiota and germfree (GF) mice were fed chow diet. Caecal satiety hormones mRNA levels and immune-staining were analyzed. Transcription factors involved in EEC differentiation mRNA and immuno-histochemistry of proliferation marker (Ki67) were performed in the caecum of ATB treated mice. To examine the functional consequences of changes in satiety hormones expression, food intake adaptation to WD was measured in mice with ATB.

Results: Under chow diet, gut microbiota depletion induced a dramatic caecal overexpression of glp-1 (x6.4), cck (x8.5) and neurotensin (x5.0), but not pyy, as observed in GF mice. Caecal EEC of the ATB treated mice displayed an unexpected co-expression of CCK and Glp-1. Microbiota depletion disrupted EEC differentiation by decreasing hes1 (x0.73) and math1 (x0.67) and increasing pax4 (x1.74) expression. Proliferation was also altered as shown by the fading of Ki67⁺ cells. Under WD, these EECs ATB adaptations were associated with an increased satiation.

Conclusion: Distal EEC satiety hormone expression is highly activated by gut microbiota depletion with an impact on their late differentiation. Under WD, this is associated with an increased satiation. Luminal factors involved in EEC adaptation to depleted microbiota are still to be discovered. 

Disclosure of Interest: None Declared

Keywords: eating behavior, enteroendocrine cells