Figure 3.

Overview of the interplay between microbiota and stroke or vascular cognitive impairment. Beside the traditional risk factors, including HT, DM, DL, physical activity, and aging, mounting evidence has shown the role of gut microbiota in the development of stroke. Delivery, breastfeeding, aging, diet, and physical activity are bidirectionally related to dysbiosis. There are several possible mechanisms between oral and gut microbiota and the development of stroke and VCI. Microbes in the oral cavity can act directly on the cerebrovascular system via bacteremia. PRRs recognize MAMPs, for example TLRs and LPS, lipoteichoic acid, or peptidoglycan, which subsequently stimulate immune cells and induce the production of inflammatory cytokines. Among bacterial metabolites, TMA and TMAO interact with coagulation and inflammatory cascades in atherosclerotic plaque. SCFAs and indoles affect the absorption rate of nutrients and have hormonal activity in metabolic homeostasis via various types of GPRs. Bacteria-derived functional amyloid induces Aβ aggregation in CAA through inflammasome secretion or the ASC-SPECK system. Aβ: Amyloid β; ASC-SPECK: adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain; CAA: cerebral amyloid angiopathy; GPRs: G-protein-coupled receptors; DL dyslipidemia; DM: diabetes mellitus; HT: hypertension; LPS: lipopolysaccharide; MAMPs: microorganism-associated molecular patterns; SCFAs: short-chain fatty acids; SVD: small vessel disease; TLRs: toll-like receptors; TMA: trimethylamine; TMAO: Trimethylamine N-oxide; VCI: vascular cognitive impairment; PRRs: pattern recognition receptors