The Gut Microbiota, Neuroinflammation, and Cognitive Decline: Connecting Dysbiosis to Alzheimer’s Disease and Aging Brain Health

Alzheimer's disease (AD) and cognitive decline in aging are increasingly linked with chronic neuroinflammation and gut microbiome alterations. Gut microbiome dysbiosis exacerbates the neuroinflammatory effects of aging and, by extension, cognitive deficits (Harach et al., 2017; Hung et al., 2022). This systematic review investigates how gut microbiota dysbiosis affects neuroinflammation and cognition in AD and aging-related cognitive decline. To this end, the prevalence of AD and cognitive decline in the aging population is assessed, and the microbiotagut-brain axis is identified as an underlying regulatory pathway of concern. Next, the means by which dysbiosis leads to CNS inflammatory response are detailed, including leaky gut, systemic inflammatory mediators, and microbiome metabolites such as lipopolysaccharides, SCFAs, amyloids, and bile acids. In humans, microbiota diversity is lower in AD patients, and microbiota generating SCFA are decreased, as are increased SCFA in AD patients, and younger patients with mild cognitive impairment (occurring sooner than normal) have dementia earlier in life than age-matched controls (Hung et al., 2022; Jemimah et al., 2023). This is observed in inflammatory markers in blood and cognitive assessments via standardized assessment tools. In animal models, gut microbiome modulation occurs via germ-free models, fecal transplant, and antibiotics or probiotics to see effects on amyloid burden and cognition (Harach et al., 2017; Zhang et al., 2023). Potential therapeutic interventions include dietary fiber, prebiotics, probiotics, synbiotics, and fecal microbiota transplantations with promising clinical outcomes (Akbari et al., 2016; Hung et al., 2022). The gut-brain axis is a potentially modifiable target to alleviate age-related cognitive decline or prevent its onset.