Safety Evaluation of Christensenella Minuta as a Novel Microbiome-Based Biotherapy to Treat Obesity

• Published in: Obesity (Silver Spring, Md.) Vol. 29; p. 158
• Main Authors: Claus, Sandrine, Mazier, Wilfrid, Frederic, Elustondo, Paquet, Jeanne-Celeste, Rinaldi, Laure, Dejean, Guillaume, Rasmussen, Scott, Rawadi, Georges
• Format: Journal Article
• Language: English
• Published: Silver Spring Blackwell Publishing Ltd 01-12-2021
• Subjects: Obesity
• ISSN: 1930-7381; 1930-739X

Background: Obesity is associated with a dysbiotic gut microbiome characterized by low microbial diversity and a loss of Christensenella minuta, which are low abundance human gut dwelling anaerobic bacteria. A newly isolated strain of C. minuta DSM 33407 was recently demonstrated to carry a strong anti-obesity potential in diet-induced obesity mouse models. In a human ex vivo model of obese gastrointestinal tract, the same strain demonstrated a keystone effect as it increased the diversity of the gut microbiota and stimulated the production of short chain fatty acids, indicating that this specific strain was able to repair some functions of the obese dysbiotic microbiome. To develop the strain for clinical applications, a gastroresistant capsule containing 109 CFU of C. minuta DSM 33407 was prepared for daily oral use. Here are presented the results of the first clinical trial ever evaluating safety and tolerability of a christensenellabased biotherapy to treat obesity Methods: The trial included two study arms: one open label arm included 8 healthy volunteers (HV) with BMI withing the normal range (18-24.9); one randomized double-blind placebo-controlled arm included 30 metabolically unhealthy overweight volunteers (OV) with elevated BMI (27-34.9). All HV received the investigational product (IP) while twenty OV received the IP and 10 received the placebo. Treatment period was 12 weeks followed by a 4-week wash-out period. Adverse events were monitored during the entire study period. Fecal samples were collected at baseline, week 2, 8, 12 and 16 to monitor persistence of C. minuta DSM 33407 in stools using targeted qPCR. Results: Twenty-eight patients were enrolled in the study and only one withdrew for personal reasons. No Serious Adverse Events (SAEs) were reported in both study groups. A single HV reported an adverse event (active stomach), while four adverse events were recorded for the OV group. C. minuta DSM 33407 were not detected in stools at baseline but were detected in all samples during the treatment period. Only 3 HV still displayed a low level signal after 4 weeks of wash-out. Conclusions: C. minuta DSM 33407 demonstrated good safety and tolerability in both HV and OV, opening a new path towards development of microbiome-based biotherapies to treat obesity and associated metabolic disorders.