A New Strain of <i>Christensenella minuta</i> as a Potential Biotherapy for Obesity and Associated Metabolic Diseases

• Main Authors: Wilfrid Mazier, Katy Le Corf, Ccori Martinez, Héloïse Tudela, Déborah Kissi, Camille Kropp, Chrislain Coubard, Marion Soto, Frédéric Elustondo, Georges Rawadi, Sandrine P. Claus
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Cells
• Subjects: obesity; microbiome; metabolic disorders
• Online Access: https://www.mdpi.com/2073-4409/10/4/823

Obesity is associated with gut microbiota dysbiosis, characterized by a high Firmicutes/Bacteroidetes ratio. Gut-dwelling bacteria of the Christensenellaceae family have been proposed to act as keystones of the human gut ecosystem and to prevent adipogenesis. The objectives of the present study were to demonstrate the antiobesity potential of a new strain of <i>Christensenella minuta</i> in preclinical models and explore related mechanisms of action. The antiobesity potential of <i>C. minuta</i> DSM33407 was assessed in a diet-induced obesity mouse model. Changes in hepatic lipid metabolism were explored using targeted transcriptomics. Effects on gut microbiota were further assessed in a humanized Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®) model inoculated with obese fecal samples. Shotgun metagenomics was applied to study microbial community structures in both models. <i>C. minuta</i> DSM33407 protected from diet-induced obesity and regulated associated metabolic markers such as glycemia and leptin. It also regulated hepatic lipid metabolism through a strong inhibition of de novo lipogenesis and maintained gut epithelial integrity. In the humanized SHIME^® model, these effects were associated with modulations of the intestinal microbiota characterized by a decreased Firmicutes/Bacteroidetes ratio. These data indicate that <i>C. minuta</i> DSM33407 is a convincing therapeutic candidate for the management of obesity and associated metabolic disorders.