Portrait of Hafnia alvei HA4597® – the first precision probiotic changing the game and paradigm in probiotic developments

Abstract

This article aims to summarize the development of Hafnia alvei HA4597® as the first precision probiotic – from its discovery and selection through preclinical and clinical evidence to commercialization. Hafnia is a leading probiotic strain in weight management backed by a precise mechanism of action – its effect is mediated through the production of the protein Caseinolytic peptidase B (ClpB), which is a molecular mimetic of the satiety hormone alpha-MSH. As ClpB activates the receptors of alpha-MSH in the gut, it stimulates the anorexigenic pathway, reducing the feeling of hunger and supporting weight loss. This result has been demonstrated in several mice models of obesity (Legrand et al., 2020 and Lucas et al., 2020) and in a double-blind, randomized, placebo-controlled study with overweight adults following a 20% caloric restriction diet for 12 weeks (Déchelotte et al., 2021). Tennoune et al. (2014) showed through sequence alignment the homology of sequence between alpha-MSH and ClpB, and by Western Blot the recognition of ClpB by anti-alpha-MSH immunoglobulins. Subsequently, Breton et al. (2015) showed by electrophysiology that ClpB activates the hypothalamic proopiomelanocortin neurons, and Dominique et al. (2019 also showed ClpB to stimulate PYY release. Legrand et al. (2020) Lucas et al. (2020) and Déchelotte et al. (2021) then confirmed the physiological effects of ClpB-delivering Hafnia alvei on food intake and weight loss in obese mice and overweight men and women. As such, Hafnia alvei HA4597® is referred to as a precision probiotic because of its targeted action and well-characterized mechanism of action at the molecular level.