Gut–Brain Axis: Role of Gut Microbiota in Neurodegenerative Disease

Abstract

The role of gut bacteria in neurodegenerative disease has long been speculated; however, the extent of influence and the exact composition of microflora that mechanistically alter outcomes are less understood.

While aging was thought to be a major contributor to neurodegenerative disease, the role of the immune system started to become more appreciated bringing the hypothesis of “inflammaging” to the forefront. Gut bacteria serve to prime our immune system and therefore play a role in shaping our immune response to infection and disease. The differences in gut flora between healthy individuals and ones suffering from Alzheimer’s or Parkinson’s disease have been widely documented; however, it is not understood if they are the cause or the effect of the disease. The second hypothesis in the field is the antimicrobial response hypothesis or infection hypothesis, which proposes that the neurodegenerative disease is an undesired outcome of the brain’s immune response against pathogens. In this context, it is important to understand whether it is the presence of microbes themselves in the brain or just the microbes in the gut that prime the immune system and cause an amplified immune response in the brain cumulatively leading to neurodegenerative disease. It is also important to understand the concept of pathogen-associated molecular patterns (PAMPs) that serve to trigger innate immunity by engaging toll-like receptors (TLRs) and that these PAMPs or molecular patterns may be present and trigger inflammation without the presence of actual pathogen.

The ultimate goal of delineating these mechanisms is to then use this knowledge to develop treatments. Some approaches that have been tested in preclinical and clinical studies including fecal transplants have been summarized here as well.