Characterization of Two Parabacteroides distasonis Candidate Strains as New Live Biotherapeutics against Obesity.

The gut microbiota is now considered as a key player in the development of metabolic dysfunction. Therefore, targeting gut microbiota dysbiosis has emerged as a new therapeutic strategy, notably through the use of live gut microbiota-derived biotherapeutics. We previously highlighted the anti-inflammatory abilities of two Parabacteroides distasonis strains. We herein evaluate their potential anti-obesity abilities and show that the two strains induced the secretion of the incretin glucagon-like peptide 1 in vitro and limited weight gain and adiposity in obese mice. These beneficial effects are associated with reduced inflammation in adipose tissue and the improvement of lipid and bile acid metabolism markers. P. distasonis supplementation also modified the Actinomycetota, Bacillota and Bacteroidota taxa of the mice gut microbiota. These results provide better insight into the capacity of P. distasonis to positively influence host metabolism and to be used as novel source of live biotherapeutics in the treatment and prevention of metabolic-related diseases.

Identification of New Potential Biotherapeutics from Human Gut Microbiota-Derived Bacteria.

The role of the gut microbiota in health and disease is well recognized and the microbiota dysbiosis observed in many chronic diseases became a new therapeutic target. The challenge is to get a better insight into the functionality of commensal bacteria and to use this knowledge to select live biotherapeutics as new preventive or therapeutic products. In this study, we set up a screening approach to evaluate the functional capacities of a set of 21 strains isolated from the gut microbiota of neonates and adults. For this purpose, we selected key biological processes involved in the microbiome-host symbiosis and known to impact the host physiology i.e., the production of short-chain fatty acids and the ability to strengthen an epithelial barrier (Caco-2), to induce the release of the anti-inflammatory IL-10 cytokine after co-culture with human immune cells (PBMC) or to increase GLP-1 production from STC-1 endocrine cell line. This strategy highlighted fifteen strains exhibiting beneficial activities among which seven strains combined several of them. Interestingly, this work revealed for the first time a high prevalence of potential health-promoting functions among intestinal commensal strains and identified several appealing novel candidates for the management of chronic diseases, notably obesity and inflammatory bowel diseases.

In Vitro Characterization of Gut Microbiota-Derived Commensal Strains: Selection of Parabacteroides distasonis Strains Alleviating TNBS-Induced Colitis in Mice.

Alterations in the gut microbiota composition and diversity seem to play a role in the development of chronic diseases, including inflammatory bowel disease (IBD), leading to gut barrier disruption and induction of proinflammatory immune responses. This opens the door for the use of novel health-promoting bacteria. We selected five Parabacteroides distasonis strains isolated from human adult and neonates gut microbiota. We evaluated in vitro their immunomodulation capacities and their ability to reinforce the gut barrier and characterized in vivo their protective effects in an acute murine model of colitis. The in vitro beneficial activities were highly strain dependent: two strains exhibited a potent anti-inflammatory potential and restored the gut barrier while a third strain reinstated the epithelial barrier. While their survival to in vitro gastric conditions was variable, the levels of P. distasonis DNA were higher in the stools of bacteria-treated animals. The strains that were positively scored in vitro displayed a strong ability to rescue mice from colitis. We further showed that two strains primed dendritic cells to induce regulatory T lymphocytes from naïve CD4+ T cells. This study provides better insights on the functionality of commensal bacteria and crucial clues to design live biotherapeutics able to target inflammatory chronic diseases such as IBD.