Gut dysbiosis: the effects of a high-fat diet on brain-derived neurotrophic factor (BDNF) and pro-BDNF expression in the brain-gut axis
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Abstract
The human microbiome and its role in the ‘brain-gut’ bi-directional axis are becoming increasingly relevant to our understanding of the effects of gastro-intestinal microbiota on brain development and on various neurological diseases. One protein that may mediate the effects of this brain-gut axis is brain-derived neurotrophic factor (BDNF). BDNF is found not only in the brain but also in peripheral tissues. BDNF is essential in learning and memory through stabilization of long-term potentiation (LTP). Research has shown that its expression levels have been found to be greatly affected by diet and exercise. In events such as aging, decreased levels of BDNF has been associated with cognitive decline and increased susceptibility to neurodegenerative diseases such as Alzheimer’s disease (AD). This study aims to explore how the human microbiome maintained in a Western diet (high protein, high fat, high carbohydrate), affects BDNF expression and its levels in the ‘brain-gut’ bi-directional axis. Understanding BDNF and its relation to the brain-gut axis may prove invaluable towards further research to prevent the cognitive decline that comes with decreased BDNF expression.
In this project, we compared BDNF and its precursor, proBDNF, levels in the brain, jejunum, and distal colon of mice. The mice used were necropsied at either three or six months and were either on a normal or high fat diet. Protein levels were stained and analyzed using MANOVAs, correlations, and regressions to observe any statistically significant relationship between the two proteins in their tissue location of origin. The results confirmed the hypothesized: proBDNF increased with age and was higher in a high fat diet versus a normal diet, while BDNF decreased with age. There was also a strong, positive correlation found between brain proBDNF and brain BDNF.
These results suggest an intricate, yet complex relationship between proBDNF and BDNF and that proBDNF may play a significant role in gut dysbiosis. On this basis, future studies need to be done to further understand this relationship in the brain-gut axis. An important focus looking at the vagus nerve and these proteins and their high-affinity receptors, TrkB and p75, will uncover key information that will aid in preventative medicine for cognitive decline and neurodegenerative diseases.