The balance of microbial species making up the gut microbiome changes with age. More inflammatory microbes win out over microbes that generate beneficial metabolites, and this contributes to degenerative aging. Restoring a more youthful composition of the gut microbiome has been demonstrated to improve health and extend life in aged animals. Human data for gut microbiome rejuvenation remains very sparse, however. That said, a growing body of observational data from human patients demonstrates that various age-related conditions correlate with an altered, pro-inflammatory gut microbiome. In particular, evidence suggests that Alzheimer's disease - and the mild cognitive impairment that marks its earliest stages - correlate well with specific harmful alterations in the gut microbiome.
The gut microbiome serves a central role in maintaining homeostatic balance or disease pathogenesis, including neurological disorders such as Alzheimer's disease (AD). The mechanisms by which the microbiota and associated metabolites influence the development and/or exacerbation of disease states are multifaceted and multidirectional, involving the central and autonomic nervous systems and neuroimmune, neuroendocrine, and enteroendocrine pathways. This complex interplay involves a bidirectional communication system, often referred to as the microbiota-gut-brain-immune relationship, which connects the brain and gastrointestinal tract through various pathways.
Communication from the brain to the gut occurs via sympathetic and parasympathetic nervous systems and hormones. Conversely, the gut communicates with the brain through pathways such as the vagus nerve, the hypothalamic-pituitary-adrenal (HPA) axis, and a range of microbial products including bacterially synthesized neurotransmitters (e.g., GABA, dopamine, serotonin, noradrenaline), branched-chain amino acids, short-chain fatty acids (SCFAs), aryl hydrocarbon receptor agonists, and bile acids.
This scoping review of gut microbiomes in mild cognitive impairment (MCI) and AD included dietary and probiotic interventions. Our results demonstrated that gut dysbiosis was frequently reported in MCI and AD, including increased Pseudomonadota and Actinomycetota in AD and reduced diversity in some cases. Probiotic and dietary interventions showed promise in modulating cognition and microbiota, but inconsistently. Emerging evidence links dysbiosis to cognitive decline; however, methodological heterogeneity and limited follow-up impede causal inference. Research should prioritize standardized protocols, functional microbiome analysis, and longitudinal human studies to clarify therapeutic potential.
Link: https://doi.org/10.1002/alz.71023
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