The Prospects for Treating Neurodegenerative Conditions by Modifying the Gut Microbiome
The gut microbiome interacts with the body via a wide range of mechanisms, including induction of chronic inflammatory responses and delivery of both harmful and beneficial metabolites. With advancing age, the balance of populations making up the gut microbiome changes in ways that increase the harms while reducing the benefits. This may happen because the aged immune system becomes less able to clear problem microbes, but other mechanisms such as lifestyle changes and intestinal tissue aging may also contribute meaningfully. Fortunately, studies have demonstrated that making sizable, lasting changes to the gut microbiome is possible, such as via fecal microbiota transplant using a young donor. In animal studies, this can restore a more youthful balance of populations and thereby improve health and extend life.
Trillions of microbes live symbiotically in the host, specifically in mucosal tissues such as the gut. Recent advances in metagenomics and metabolomics have revealed that the gut microbiota plays a critical role in the regulation of host immunity and metabolism, communicating through bidirectional interactions in the microbiota-gut-brain axis (MGBA). The gut microbiota regulates both gut and systemic immunity and contributes to the neurodevelopment and behaviors of the host. With aging, the composition of the microbiota changes, and emerging studies have linked these shifts in microbial populations to age-related neurological diseases (NDs).
Preclinical studies have demonstrated that gut microbiota-targeted therapies can improve behavioral outcomes in the host by modulating microbial, metabolomic, and immunological profiles. In this review, we discuss the pathways of brain-to-gut or gut-to-brain signaling and summarize the role of gut microbiota and microbial metabolites across the lifespan and in disease. We highlight recent studies investigating 1) microbial changes with aging; 2) how aging of the maternal microbiome can affect offspring health; and 3) the contribution of the microbiome to both chronic age-related diseases (e.g., Parkinson's disease, Alzheimer's disease and cerebral amyloidosis), and acute brain injury, including ischemic stroke and traumatic brain injury.