Loss of eating control and cognitive flexibility: Involvement of gut microbiota

Loss of eating control is a crucial factor in developing obesity, which has become a global health concern, causing important cardiovascular, metabolic, emotional, and cognitive co-morbidities. A major cognitive alteration associated with loss of eating control and obesity is the impairment of cognitive flexibility and inhibitory control. An increasing number of studies confirm that gut microbiota is a significant contributor to loss of eating control, obesity, and cognitive function. Therefore, we have investigated whether gut microbiota transfer from humans with impaired/not impaired cognitive flexibility could substantially affect this behavioral response in mice in the context of obesogenic versus standard diet. Mice were pretreated with an antibiotic cocktail and later received a gut microbiota transplant from human subjects. The transferred microbiota was maintained in mice for seven weeks. Afterward, behavioral tests were performed to evaluate different cognitive responses, locomotor activity, anxiety-like, and depression-like behaviors. Antibiotic treatment significantly impaired short-term memory in mice, as previously reported. Furthermore, mice that received microbiota from high and low cognitive flexibility subjects modified their short-term and long-term memory performance depending on the diet exposure. Slight changes were observed in the locomotor activity, primarily in the high-fat diet-fed antibiotic-treated mice, and no significant alterations were observed in anxiety-like or depressive-like behaviors. In summary, this study shows that gut microbiota is a major contributor to cognitive flexibility, which may open novel therapeutic strategies for combating loss of eating control and related metabolic co-morbidities.