Gut dysbiosis in stroke and its implications on Alzheimer’s disease‐like cognitive dysfunction

Abstract

Various neurological disorders, such as stroke and Alzheimer's disease (AD), involve neuroinflammatory responses. The advent of the gut‐brain axis enhances our understanding of neurological disease progression and secondary cell death. Gut microbiomes, especially those associated with inflammation, may reflect the dysbiosis of both the brain and the gut, opening the possibility to utilize inflammatory microbiomes as biomarkers and therapeutic targets. The gut‐brain axis may serve as a contributing factor to disease pathology and offer innovative approaches in cell‐based regenerative medicine for the treatment of neurological diseases. In reviewing the pathogenesis of stroke and AD, we also discuss the effects of gut microbiota on cognitive decline and brain pathology. Although the underlying mechanism of primary cell death from either disease is clearly distinct, both may be linked to gut‐microbial dysfunction as a consequential aberration that is unique to each disease. Targeting peripheral cell death pathways that exacerbate disease symptoms, such as those arising from the gut, coupled with conventional central therapeutic approach, may improve stroke and AD outcomes.

Alterations in the gut microbiome with hemorrhagic transformation in experimental stroke

“…It often coexists in stroke patients with adverse effects on patient outcome (53). Various neurological disorders including stroke and Alzheimer's disease involve the changed gut‐brain axis and similar cognitive decline (54). Compared to the group with greater Bacteroides abundance, the Prevotella group showed more negative emotional responses and reduced functional activation of the hippocampus (55).…”

Ketogenic diet ameliorates cognitive impairment and neuroinflammation in a mouse model of Alzheimer’s disease

“…to play an important role in AD pathogenesis. [53][54][55][56] Thus, KD might ameliorate AD pathology by regulating gut microbiota and reducing neuroinflammation. 44,57 In the future, it would be very interesting to examine the precise underlying mechanism of KD on the cognitive functions.…”

APOE genotype moderates the relationship between LRP1 polymorphism and cognition across the Alzheimer's disease spectrum via disturbing default mode network

“… 53 Therefore, future work will focus on cerebral vascular issues and design effective intervention strategies to delay the disease progression in preclinical stage of AD. Fourthly, hypotheses such as autophagy 54 and gut dysbiosis 55 represented distinct signaling pathways in AD, and more genes were implicated in Aβ clearance, including APOE , 56 clusterin, 57 α2‐Macroglobulin, 58 and triggering receptor expressed on myeloid cells 2. 59 Thus, future research will focus on pathway‐based polygenic effects on brain networks that can better translate the underlying mechanism of AD.…”