Dr. Mauro Costa-Mattioli, Cullen Foundation professor and Chair of Endowment in Neuro-science and director of the Center for Memory and Brain Research at Baylor College of Medicine, Texas, discovered with his team that various abusive behaviors interdependently regulated by the host’s genes and microbiome.
The findings, published in the journal Cell, Concludes that, in mouse models with neurodevelopmental disorders, depression is controlled by the host genetics, whereas social behavioral deficits are mediated by the gut microbiome.
In addition, they found that treatment with a specific microbe that stimulates production in the biopterin family in the gut or treatment with a metabolically active biopterin molecule improved social behavior, but not motor activity.
Costa-Mattioli says: “In my wildest dreams, I could never have imagined that microbes in the gut could alter behavior and brain function. Thinking now is that established strategies could microbial has been a working method for the treatment of neurological dysfunction, still wild, but very interesting. “
The work with the Costa-Mattioli group offers a different way of thinking about brain disorders in which both human and microbial genes interact with each other and contribute to the condition.
The co-author, Dr. Shelly Buffington, a former postdoctoral fellow in the Costa-Mattioli laboratory and now an assistant professor at the University of Texas Medical Branch, says: “Our work reinforces the emerging concept of a new frontier for the development of a safe and effective therapeutic drug targeting of the gut mosquito repellent with selective sequences of bacteria or medications that are prescribed. stimulated by bacteria. “
Their findings also suggest that effective treatments would likely require both brain and sciatic nerve management to fully address the symptoms. In addition, they open up the possibility that other complex conditions, such as cancer, diabetes, viral disease or other brain disorders, may have a microbiome component.
Gut-Brain
“It is very difficult to study these complex interactions in humans, so in this study, we worked with a mouse model for neurodevelopmental disorders in which both halves were not. of the Cntnap2 (Cntnap2 – / – mice) gene of the animals, “Co-author Sean Dooling, Ph.D. candidate in molecular and human genetics in the Costa-Mattioli laboratory. “These mice were presented with social deficits and depression, similar to those seen in autism spectrum disorders (ASD). In addition, these mice, like many people with ASD, also on changes in the bacteria that make up the midge compared to the mice without the genetic modification. “
Further experiments showed that modeling the gut microbome altered the social behavior in the mutant mice, but did not alter the depression, indicating that the changes in the microbome contribute to selective to the social behavior of the animals.
“We were able to differentiate between the midge mutation and the animal’s genetic contribution to the behavioral changes,” Dooling said. “This shows that gut midges should not be neglected as an important variable in the study of health and disease.”
The researchers dug deeper into the machinery that underlies the influence of the microbiome on the social deficiencies of the animal. Based on their previous work, the researchers treated the mice with the probiotic microbe, L. reuteri.
“We found that L. reuteri can also restore normal social behavior but cannot correct the depression in Cntnap2 – / – mice,”Buffington said
In addition, the researchers found that when administering an increased metabolite or compound in the guest’s gut with L. reuteri,That the social deficiencies of the animals have improved.
“This gives us at least two ways that can alter the brain from the brain, with the bacteria or the bacteria-induced metabolite,”Buffington said.
Source: Cell
Buffington. SA, et al
“Eliminates the contribution of host genetics and the midge in complex behaviors”
DOI: https: //doi.org/10.1016/j.cell.2021.02.009