Commensal Hafnia alveistrain reduces food intake and fat mass in obese mice—a new potential probiotic for appetite and body weight management

Autor: Legrand, Romain, Lucas, Nicolas, Dominique, Manon, Azhar, Saida, Deroissart, Camille, Le Solliec, Marie-Anne, Rondeaux, Julie, Nobis, Séverine, Guérin, Charlène, Léon, Fatima, do Rego, Jean-Claude, Pons, Nicolas, Le Chatelier, Emmanuelle, Ehrlich, S. Dusko, Lambert, Gregory, Déchelotte, Pierre, Fetissov, Sergueï O.
Zdroj: International Journal of Obesity (formerly International Journal of Obesity and Related Metabolic Disorders); May 2020, Vol. 44 Issue: 5 p1041-1051, 11p
Abstrakt: Background/objectives: Based on the recent identification of E.coliheat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity. Methods: The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.coli. A food-grade H. alveiHA4597 strain synthetizing the ClpB protein with an α-MSH-like motif was selected as a candidate probiotic to be tested in ob/oband high-fat diet (HFD)-fed obese and overweight mice. The relevance of the enterobacterial ClpB gene to human obesity was studied by in silico analysis of fecal metagenomes of 569 healthy individuals from the “MetaHIT” database. Results: Chronic per os administration of native but not ClpB-deficient E.colistrain reduced body weight gain (p< 0.05) and daily meal frequency (p< 0.001) in ob/obmice. Oral gavage of H.alveifor 18 and 46 days in ob/oband HFD-fed obese mice, respectively, was well tolerated, reduced body weight gain and fat mass in both obesity models (p< 0.05) and decreased food intake in hyperphagic ob/obmice (p< 0.001). Elevated fat tissue levels of phosphorylated hormone-sensitive lipase were detected in H.alvei-treated ob/obmice (p< 0.01). Enterobacterial ClpB gene richness was lower in obese vs. non-obese humans (p < 0.0001) and correlated negatively with BMI in genera of Enterobacter, Klebsiellaand Hafnia. Conclusions: H.alveiHA4597 strain reduces food intake, body weight and fat mass gain in hyperphagic and obese mice. These data combined with low enterobacterial ClpB gene abundance in the microbiota of obese humans provide the rationale for using H.alveias a probiotic for appetite and body weight management in overweight and obesity.
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