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Solveiga Samulenaite, Aurelijus Burokas, José Manuel Fernández Real Lemos, Jordi Mayneris Perxachs, Elena Martín García, Rafael Maldonado López
La pérdida del control de la ingesta alimentaria es un factor crucial en el desarrollo de la obesidad. Una alteración cognitiva importante asociada con la pérdida del control de la ingesta alimentaria y la obesidad es el deterioro de la flexibilidad cognitiva y el control inhibitorio. Un número cada vez mayor de estudios confirman que la microbiota intestinal contribuye significativamente a la pérdida del control de la ingesta alimentaria, la obesidad y la función cognitiva. En base a estos datos, hemos investigado si la transferencia de microbiota intestinal de humanos con obesidad/normopeso y flexibilidad cognitiva deteriorada/no deteriorada podría afectar sustancialmente esta respuesta conductual en ratones expuestos a una dieta obesogénica frente a una dieta estándar. Los ratones fueron tratados previamente con un cóctel de antibióticos y luego recibieron un trasplante de microbiota intestinal de humanos. Posteriormente, se realizaron diferentes test de comportamiento para evaluar la flexibilidad cognitiva como una medida del control inhibitorio. El tratamiento con antibióticos deterioró significativamente la memoria a corto plazo en ratones, como se ha informado previamente. Es importante destacar que los ratones que recibieron microbiota de sujetos con alta y baja flexibilidad cognitiva modificaron su rendimiento de memoria a corto y largo plazo en función de la exposición a la dieta. En resumen, este estudio muestra que la microbiota intestinal es un factor que contribuye de manera importante a la flexibilidad cognitiva, lo que puede abrir nuevas estrategias terapéuticas para combatir la pérdida de control de la ingesta alimentaria y las comorbilidades metabólicas asociadas.
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.
