What does your gut have to do with your brain?

A relatively new field of investigation in science studying the neurological effects of microbiota on neurodegenerative disease and mental health is showing promising results and implications for our future. Trillions of microorganisms live in the body and outnumber human cells 10:1. It seems almost crazy to think a population of bacteria in your gut could have an influence on processes in the brain, however, research is pointing in that direction. 

One study identifies a relationship between gut microbiome and Alzheimer’s Disease (AD) neurological phenotypes. Dodiya and colleagues investigate the microbiome perturbations onto Aβ amyloidosis and microglia phenotypes (2019). In this study, researchers used male and female APP_SWE/PS1∆_E9 transgenic mouse model for Aβ amyloidosis to mimic the AD phenotype and an ABX antibiotic cocktail treatment for their experiments. After administering a long-term ABX treatment to the APPPS1-21 mice, significantly reduced Aβ plaques were discovered in male mice. This indicates a relationship of some kind between microorganisms and AD. To further explore this, researchers performed a fecal transplant from AD phenotype APPPS1-21 male mice to germ free male mice (ABX treated APPPS1-21) with reduced plaques. Increases of Aβ amyloidosis and microglial inflammation after the transplant indicate a causal relationship between microbiota and AD phenotypes.

Scientists have also demonstrated significant changes in depression-like behavior and neurological inflammation upon fecal transplant in a group of rats. In a recent study, rats were categorized as being vulnerable or resilient based on how they coped with stressors. Vulnerable rats responded passively to social stress and were characterized as having depressive-like behaviors and anxiety-like behaviors. Vulnerable rats also exhibited unique patterns of brain inflammation. Resilient rats were able to cope more actively with social stress. Control rats who did not experience social stressors were also included in this study. The depressed model rats showed higher proportions of Clostridia bacteria than resilient rats or controls. Three fecal transplants were performed from each of the three groups into naïve rats who had not been stressed. Transplants from the vulnerable rats increased depressive-like behavior and promoted inflammation. No transplants influenced anxiety-like behavior in the naïve rats. Researchers concluded the Clostridia bacteria may have an immune modulating effect promoting neuroinflammation. They also suspected microbiota are likely modulating the effects of depressive behaviors but not anxiety behaviors because those behaviors are likely modulated by neurocircuitry alone. 

Together, these recent studies shed a new light on neurodegenerative disorders and mental health suggesting the problem may be in our stomach! As strange as it may seem, these studies highlight the powerful relationships between the brain and gut established via microbiota transplants. This is particularly interesting given our country’s problem of over prescribing antibiotics. It is clear that the fragile ecosystem of microorganisms in our body can influence AD and depression, so we should be looking forward to researching the harm or benefits of over prescribed antibiotic treatments. The future of this field is very promising in discovering better treatments for AD and depression. It is also likely to see in the coming years new discoveries of gut bacteria influences on other neurological processes. 

Sources: 

Children's Hospital of Philadelphia. (2019, May 6). Transplanting gut bacteria alters depression-related behavior, brain inflammation in animals: Knowledge of stress biology may eventually yield bacterial treatments for psychiatric disorders. ScienceDaily. www.sciencedaily.com/releases/2019/05/190506163642.htm

Hemraj B. Dodiya, Thomas Kuntz, Shabana M. Shaik, Caroline Baufeld, Jeffrey Leibowitz, Xulun Zhang, Neil Gottel, Xiaoqiong Zhang, Oleg Butovsky, Jack A. Gilbert, Sangram S. Sisodia; Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes. J Exp Med 1 July 2019; 216 (7): 1542–1560. doi: https://doi.org/10.1084/jem.20182386