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La dieta puede cambiar el microbioma intestinal y los microbios intestinales pueden influir en el cerebro emergente
La ausencia de una especie específica de las bacterias del intestino provoca déficits sociales en modelos experimentales, según revelan investigadores de la Escuela de Medicina de Baylor del Centro Médico de Texas, en Estados Unidos, en la edición de Cell.
Mediante la adición de esta especie bacteriana de nuevo al intestino del individuo afectado, los investigadores fueron capaces de revertir algunos de los déficits de comportamiento de los modelos, que son una reminiscencia de los síntomas de los trastornos del espectro autista (TEA) en los seres humanos. Los investigadores están buscando ahora cómo explorar los efectos de los probióticos en los trastornos del neurodesarrollo en el futuro.
“Otros grupos de investigación están tratando de utilizar fármacos o la estimulación eléctrica del cerebro como una forma de revertir algunos de los síntomas de comportamiento asociados con trastornos del desarrollo neurológico, pero aquí tienen, tal vez, un nuevo enfoque”, señala el autor principal, el doctor Mauro Costa-Mattioli, profesor asociado de Neurociencia en Baylor. “No sabemos todavía si resultará eficaz en seres humanos, pero es una forma muy interesante de afectación al cerebro desde el intestino”, añade.
La inspiración para el papel llegó a partir de estudios epidemiológicos en humanos que han encontrado que la obesidad materna durante el embarazo podría elevar el riesgo de desarrollar trastornos del desarrollo neurológico, como trastornos del espectro autista infantil. Además, algunas personas con TEA también informan de trastornos gastrointestinales recurrentes.
Con la investigación que muestra cómo la dieta puede cambiar el microbioma intestinal y cómo los microbios intestinales pueden influir en el cerebro emergente, Costa-Mattioli y sus co-autores sospechaban que podría haber una conexión.
Para empezar, los investigadores alimentaron a aproximadamente 60 ratones hembra con una dieta alta en grasa que era el equivalente aproximado de comer consistentemente comida rápida varias veces al día. Alimentaron los ratones y esperaron a que fueran jóvenes.
La descendencia se quedó con su madre durante tres semanas y luego fue destetada a una dieta normal. Después de un mes, estas crías mostraron anomalías de comportamiento, como pasar menos tiempo en contacto con sus compañeros y no iniciar interacciones.
“En primer lugar queríamos ver si había una diferencia en el microbioma entre los hijos de madres de ratones alimentados con una dieta normal frente a los de las madres alimentadas con una dieta alta en grasas. Por lo tanto, se utilizó la secuenciación del gen que codifica el ARN ribosomal 16S para determinar la composición bacteriana de su intestino.
Encontramos una clara diferencia en la microbiota de los dos grupos de la dieta matern –dice la primera autora Shelly Buffington, estudiante postdoctoral en el laboratorio de Costa-Mattioli–.
Los datos de secuenciación eran tan consistentes que mirando el microbioma de un ratón individual podríamos predecir si su comportamiento se deterioraba”.
Entonces, Buffington probó si las diferencias específicas en el microbioma fueron factores causales subyacentes a las deficiencias sociales en los hijos de madres alimentadas con una dieta alta en grasas. Como los ratones comen caca de los demás, los científicos mantuvieron a los animales juntos para que adquirieran la microbiota de sus compañeros de jaula.
Cuando los ratones de tres semanas de edad con problemas sociales nacidos de madres con una dieta alta en grasas se emparejaron con ratones normales, se observó una restauración completa del microbioma intestinal y una mejora del comportamiento concurrente en un plazo de cuatro semanas.
Los investigadores concluyen que una o más especies de bacterias beneficiosas pueden ser importantes para el comportamiento social normal.
Experimentos de transplante fecal en ratones sin microbiota (ratones libres de gérmenes) proporcionan evidencia causal de que una ecología microbiana desequilibrada en los roedores nacidos de madres con una dieta alta en grasas es responsable de sus déficits sociales.
Los investigadores entones querían saber las especies de bacterias específicas que podrían estar afectando al comportamiento social de los animales. La secuenciación de todo el genoma reveló un tipo de bacterias, ‘Lactobacillus reuteri’, que se redujo más nueve veces en el microbioma de los animales nacidos de madres con la dieta alta en grasas.
“Hemos cultivado una cepa de ‘L. Reuteri’ aislada originalmente de la leche materna humana y la introdujimos en el agua de la descendencia de madres con muchas grasas en la dieta. Encontramos que el tratamiento con esta cepa bacteriana fue capaz de restaurar su comportamiento social”, destaca Buffington.
Otras conductas relacionadas con los TEA, como la ansiedad, no se han restaurado mediante la reconstitución de las bacterias. Curiosamente, los autores encontraron que ‘L. Reuteri’ también promovió la producción de la hormona oxitocina, que se sabe que juega un papel crucial en el comportamiento social y se ha vinculado con el autismo en los seres humanos.
Los autores se preguntaron si el circuito de recompensa en los ratones socialmente deteriorado era disfuncional. “Hemos detectado que en respuesta a la interacción social había una falta de potenciación sináptica en un área de recompensa clave del cerebro que se podía ver en los ratones normales de control”, dice Costa-Mattioli.
“Cuando ponemos las bacterias de nuevo en la descendencia con una dieta materna con alto contenido de grasa, también podríamos restaurar los cambios en la función sináptica en el circuito de recompensa”, dice.
Los investigadores creen que su trabajo, que empleó una especie bacteriana humana para promover los niveles de oxitocina y mejorar los déficits de comportamiento social en ratones deficientes, podría explorarse como una intervención de probióticos para el tratamiento de trastornos del neurodesarrollo en los seres hmanos.
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