Hafnia alvei HA4597 Strain Reduces Food Intake and Body Weight Gain and Improves Body Composition, Glucose, and Lipid Metabolism in a Mouse Model of Hyperphagic Obesity

Abstract

Use of new generation probiotics may become an integral part of the prevention and treatment strategies of obesity. The aim of the present study was to test the efficacy of a potential probiotic strain of lactic bacteria Hafnia alvei (H. alvei) HA4597™, in a mouse model of obesity characterized by both hyperphagia and diet-induced adiposity. For this purpose, 10-week-old high-fat-diet (HFD)-fed hyperphagic ob/ob male mice received a daily treatment with 1.4 × 1010 CFU of H. alvei for 38 days. Effects of H. alvei were compared to those of a lipase inhibitor orlistat (80 mg/kg daily) and a vehicle (NaCl 0.9%) in HFD-fed ob/ob mice. A control untreated group of ob/ob mice received the standard diet throughout the experiment. The vehicle-treated HFD group displayed increased food intake, worsening of adiposity, and glycemia. Treatment with H. alvei was accompanied by decreased body weight and fat-mass gain along with reduced food intake to the level of the standard-diet-fed mice. At the end of the experiment, the group treated with H. alvei showed a decrease of glycemia, plasma total cholesterol, and alanine aminotransferase. The orlistat-treated mice showed a lower rate of body weight gain but were hyperphagic and hyperglycemic. These results demonstrate the beneficial anti-obesity and metabolic effects of H. alvei HA4597™ in mice with obesity resulting from hyperphagia and diet-induced adiposity.

Gut bacterial ClpB-like gene function is associated with decreased body weight and a characteristic microbiota profile

“…These results are in line with previous evidence in mouse models and in sillico findings. In a recent study, the administration of a probiotic, Hafnia alvei, a ClpBproducing bacterium reduced fat mass and food intake in ob/ob and after a high-fat diet in mice [12] and also improved their metabolic profile [14]. In this study, the enterobacterial ClpB gene was also tested in sillico analysis of fecal metagenomes from the MetaHIT database [12].…”

Host Starvation and Female Sex Influence Enterobacterial ClpB Production: A Possible Link to the Etiology of Eating Disorders

“…The reason for increased ClpB gene and protein expression during host starvation can be related to the need of an increased protein disaggregation function of this chaperon protein during various catabolic processes and enzymatic remodeling aimed at protecting the survival of the bacterial population [34]. Increased ClpB production itself is not pathogenic and can be, instead, health protective [35,36]. It will be of interest to test whether ClpB also may act as a caloric restriction mimetic, i.e., a substance igniting the protective effects of caloric restriction [37].…”

Circadian rhythms and the gut microbiome synchronize the host’s metabolic response to diet

“…Scientists have already identified potential therapies that include bacterial components and/or bacterial-derived small molecules to improve health outcomes in metabolic disease (Cani and Delzenne, 2011;Cavalcanti Neto et al, 2018;Gokhale and Bhaduri, 2020;Wallace and Redinbo, 2013). The use of Hafnia alvei HA4597 in the regulation of satiety through the activation of a-MSH and PYY pathways via the secretion of ClpB is one example of a successful probiotic therapy (Fetissov, 2017;Lucas et al, 2019). A placebocontrolled clinical trial demonstrated efficacy of HA4597 in addition to a hypocaloric diet (À20% kcal) in inducing up to 5% weight loss and a significant reduction in hip circumference in humans, as well as increasing feelings of fullness after 3 months of use.…”