The microbiome is the population of microorganisms, some helpful and some pathological, that exists inside each of us. Our bodies contain more than 10 times the number of microbial cells than they do human cells. The largest population of microbes exists in the intestinal tract, thought of by some as the largest immune organ in the body. Intriguing research from across neurological diseases has raised the possibility that some microbes in the gut can modify the production of chemicals occurring in the brain. Cure Alzheimer’s Fund researchers are investigating whether the microbiome may modulate the progression of early Alzheimer’s disease (AD) pathology.
More than a century a go, the Nobel laureate Elie Metchnikoff postulated that ‘good gut bacteria’ may delay senility and have beneficial effects for the symptoms of anxiety and depression associated with deteriorating cognition. Manipulation of the gut microbiome since has become common practice with widespread consumption of probiotics, a concentrated bacterial cocktail. While the broad array of health benefits claimed for probiotics has failed to be substantiated in controlled clinical studies, findings have shown that the gut microbiome is essential for normal brain function.
Signal molecules from the microbiome can enter the central nervous system (CNS) and modulate brain activities, sometimes producing profound effects in animal models. The complex interaction between the microbiome and brain has come to be called the microbiota-gut-brain axis. An abnormal microbiota-gut-brain axis can potentiate existing pathologies or even cause new disease.
Particularly germane to AD has been recent revelations that the pathways of the microbiota-gut-brain axis include a comprehensive two-way communication system between the microbiome and brain. Findings suggest that under disease conditions, the “back-and-forth” between the brain and microbiome may become disrupted and reinforce harmful pathways that promote pathology. Abnormal brain activity can shift conditions in the gut and lead to a rise in gut bacteria linked to neuroinflammation and poor health outcomes. Change in the gut microbiome lead, in turn, to increases in metabolites that exacerbate neuroinflammation, anxiety and depression in the brain.
Mechanisms By Which the Gut Microbiome Influences Amyloid Deposition and Neuroinflammation in Mouse Models of Alzheimer’s Disease
In our earlier proposal, we tested the hypothesis that the composition of the intestinal microbiome might play a key role in modulating neuroinflammation that, in turn, influences Abeta deposition. We have demonstrated that long-term treatment with an antibiotic (ABX) cocktail does not alter total bacterial abundance in either the cecum or feces, but rather, induces a distinct perturbation in gut microbial diversity. The alterations in bacterial diversity are paralleled by selective changes in the levels of several circulating cytokines/chemokines in the blood sera.
The Role of Microbial Immune Responses in Alzheimer’s Disease
Animal models of Alzheimer’s disease (AD) recapitulate the severe amyloidosis and neuroinflammation that is evident in the human disease. While it long has been assumed that inflammation associated with amyloid deposition reflects the activation of astrocytes and microglia into proinflammatory M1 states in response to injury, there is a paucity of information regarding the potential role of peripheral tissues and, more importantly, the microbiota in regulating innate immunity that in turn leads to CNS dysfunction.
Role of the Gut Microbiome in AD Pathology and the Potential of Probiotic Therapeutic Strategies
The human gut contains a myriad of microorganisms collectively referred to as the microbiome. We propose to investigate if the microbiome may modulate the progression of early Alzheimer’s disease (AD) pathology.