Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease

Abstract

Gut microbiota represents a diverse and dynamic population of microorganisms harboring the gastrointestinal tract, which influences the host health and disease. Gut microbiota communicates with the brain and vice versa through complex bidirectional communication systems - the gut-brain axis, which integrates the peripheral intestinal function with emotional and cognitive brain centers via neuro-immuno-endocrine mediators. Aging alters the gut microbial population, which not only leads to gastrointestinal disturbances but also causes central nervous system (CNS) disorders such as dementia. Alzheimer's disease (AD) is the most common form of dementia affecting the older person, characterized by beta-amyloid (Aβ) plaques and neurofibrillary tangles leading to the cognitive deficit and memory impairment. Multiple experimental and clinical studies revealed the role of gut microbiota in host cognition, and its dysbiosis associated with aging leads to neurodegeneration. Gut microbial dysbiosis leads to the secretion of amyloid and lipopolysaccharides (LPS), which disturbs the gastrointestinal permeability and blood-brain barrier. Thereby modulates the inflammatory signaling pathway promoting neuroinflammation, neuronal injury, and ultimately leading to neuronal death in AD. A recent study revealed the antimicrobial property of Aβ peptide as an innate immune response against pathogenic microbes. Another study showed that bacterial amyloid shares molecular mimicry with Aβ peptide, which elicits misfolding and aggregation of Aβ peptide, it's seeding, and propagation through the gut-brain axis followed by microglial cell activation. As aging together with poor diet and gut-derived inflammatory response due to dysbiosis contributes to the pathogenesis of AD, modification of gut microbial composition by uptake of probiotic-rich food can act as a preventive/therapeutic option for AD. The objective of the present review is to summarize the recent findings on the role of gut microbiota in the development of AD. Understanding the relationship between gut microbiota and CNS will help identify novel therapeutic strategies, especially probiotic-based supplementation, for the treatment of AD.

Keywords: Alzheimer's disease; Amyloid protein; Gut microbiome; Inflammation; Lipopolysaccharides.