Gut Dysbiosis: A Review of the Effects of a High‐Fat Diet on Iron Regulation and Brain‐Derived Neurotrophic Factor (BDNF) Expression in the Brain‐Gut Axis

The human microbiome in relation to the 'gut-brain' bi-directional axis is becoming increasingly relevant in our study to understand the effects of gastro-intestinal microbiota on brain development and neurological diseases such as Alzheimer's disease. One particular protein of interest is called brain-derived neurotrophic factor (BDNF), which is a protein found in the brain that is important for learning and memory through stabilization of long-term potentiation (LTP). Through past research, its expression levels have been found to be greatly affected by diet and exercise. Furthermore, in events such as aging, decreased levels of BDNF is associated with cognitive decline and increased susceptibility to neurodegenerative diseases such as Alzheimer's disease (AD). Our study aims to look at how the human microbiome, particularly that of a Western diet, affects BDNF expression levels and modulation in the 'gut-brain' bi-directional axis.In order to explore our research topic further, we conducted a literature review of about 80 papers using keywords: Small intestines, brain, liver, hepcidin, TMAO, BDNF, iron, astrocytes, Western Diet, microbiota, gut microbiome, gut dysbiosis, iron, inflammation, oxidative stress, IL-6, vagus nerve.After reviewing papers, it was concluded that a Western diet decreases brain BDNF expression. However, the exact mechanism of how gut microbiota modulates this expression and function in the brain is unclear. Some papers mentioned BDNF in the gut and the periphery, but not much else other than that they existed.This study sparked further questions: Does gut microbiota affect brain BDNF directly through the gut-brain axis? Or is it indirect through an intermediate such as gut BDNF? Is there a relationship between gut BDNF and brain BDNF? It is known that brain BDNF is associated with learning and memory and is important for preserving cognitive abilities, however little is known about how gut microbiota affects it through the gut-brain axis or even its relation to other peripheral BDNF. Looking forward, we plan on measuring different protein levels, including that of BDNF, in the brains and guts across different cohorts of mice. The cohorts will differ in diet, age, and having the APP gene. From this analysis we hope to find more insight on the unknown mechanism that bridges gut microbiota to BDNF in the brain, which may ultimately help in finding ways to prevent cognitive decline seen in many neurological diseases.