Corroborating evidence supports that intestinal dysbiosis is key to the development of a variety of metabolic, inflammatory, and autoimmune disorders, such as obesity, type 1 and type 2 diabetes, rheumatoid arthritis, inflammatory bowel disease and cancer. Dysbiosis is characterized by an imbalance in bacterial composition, changes in bacterial metabolic activities and/or changes in bacterial distribution within the gut. Our technology consists of using a therapeutically active compound (CO-RM) that interacts with the gut microbiota by delivering controlled amount of carbon monoxide (CO) in vivo, as this endogenous gas is known to exert anti-inflammatory actions and modulate energetic metabolism. We report that gut dysbiosis induced by obesity in mice fed a high fat diet is prevented by oral administration of CO-RM leading to a reduced body weight gain, improved glucose metabolism and increased insulin resistance. The impaired gut dysbiosis in obese mice is exemplified by a marked decrease in the abundance of beneficial bacteria, such as Akkermansia muciniphila, and the ability of CO-RM to restore the impaired microbiota composition (see Figure). Our data provide strong evidence on the efficacy of CO-RM in the treatment of obesity by reprogramming the gut microbiota to a healthy phenotype, indicating that CO might be equally effective against other dysbiosis-associated diseases.
Patent Application 05/2022 (priority)
EP22305704.3, international filing
(05.2023) PCT/EP2023/062644
Carbon monoxide - CO-releasing molecule (CO-RM) - Gut microbiota - Dysbiosis - Obesity - Metabolism
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