UCLA Researchers in the Department of Integrative Biology and Physiology have determined the necessary role for maternal gut microbes in neurodevelopment and that select microbes may prevent abnormal neurodevelopmental phenotypes.
BACKGROUND:
The gastrointestinal tract and brain are intimately linked, and in the past decade there have been increasing evidence for the role of the microbiome in neurological diseases. In particular, the gut microbiota plays an important function in modulating brain function and behavior. However, it is not clearly understood if there exist early periods in maturation, where the microbiota impacts the development of the nervous system. Previous studies in various model organisms have shown that the absence of microbiota leads to altered neurophysiology and behavior compared to animals with a healthy microbiota. The restoration of microbiota during postnatal development, led to the restoration of some brain and behavioral phenotypes suggesting that the presence of microbiota early in life impact brain function and behavior. However, it is unclear whether the influence of the microbiota on neurodevelopment originate pre- or postnatally. Additionally, it is unclear if the indigenous maternal microbiota impacts normal neurodevelopment in the absence of environmental challenge. The findings to both questions could shed light on the origin of some neurological diseases, and potentially serve as a treatment focus.
INNOVATION:
UCLA Researchers in the Department of Integrative Biology and Physiology have determined the necessary role for maternal gut microbes in neurodevelopment and that select microbes may prevent abnormal neurodevelopment. The researchers investigated whether embryonic axon development required the presence of maternal gut microbes. Transcriptomic analysis of embryonic brains from germ-free and antibiotic depleted compared to specific pathogen free dams showed differences in key axonogenesis genes. This decrease in key axonogenesis genes led to reduced thalamocortical axons (TCAs), that resulted in tactile hypersensitivity in offspring. The researchers then showed that the introduction of select microbes could restore the loss of axonogenesis gene expression and mitigate the development of tactile hypersensitivity. The researchers also found select metabolites in maternal serum and fetal brains that were abundant in animals from dams with an intact microbiota compared to germ-free and antibiotic depleted. When these metabolites were supplemented, they restored TCA growth properties that were initially stunted in depleted microbiota populations. These findings therefore support the need for maternal microbiota in supporting normal neurodevelopment characteristics, and key metabolites that may mitigate abnormal neurodevelopment.
POTENTIAL APPLICATIONS:
• The discovery that maternal gut microbiota is necessary for neurodevelopment and select microbes could prevent neurodevelopmental disorders led to the finding of specific metabolites that are reduced in maternal microbiota depleted animals. These metabolites may be an interesting point of treatment for neurodevelopmental diseases.
ADVANTAGES:
• There is no current elucidation as to the need for the indigenous maternal microbiota for neurodevelopmental characteristics: the research presented is therefore the only mechanism supported by preliminary research
DEVELOPMENT-TO-DATE:
The transcriptomic analysis between microbiota depleted and intact populations showed abnormal gene differences that led to decreased TCA growth dynamics. Key metabolites were identified in intact maternal gut microbiota animals that when supplemented to maternal gut microbiota depleted animals, restored TCA growth.
RELATED PAPERS:
Annu Rev Neurosci. 2017 Jul 25;40:21-49. doi: 10.1146/annurev-neuro-072116-031347. Epub 2017 Mar 8.