increased levels of Aβ triggered by SCFA in vivo are not mediated by major quantitative or qualitative changes in Aβ production

(Fig. 1D).

conversion of microglia from proinflammatory profile to anti-inflammatory profile was associated with the inhibition of NF-κB signaling

mouse primary microglia cells

butyrate treatment suppressed the phosphorylation of NF-κB p65.

Figure 4

Images are representative of FJC staining,

Aβ-induced BV2 microglia are pretreated with butyrate

Discussion

SCFAs significantly improve cognition in AD, the pathologies of Aβ and tau, and neuroinflammation, suggesting that they have potential value in the treatment of AD. At present, the regulation of SCFA concentrations in the body is divided mainly into three types. First, the in vivo concentration of SCFAs can be regulated by oral or intravenous supplementation of SCFAs, as summarized above. The second approach is to rebuild a healthy homeostatic system of gut microbes through fecal transplants or probiotics [161]. For example, oral administration of Bifidobacterium breve strain A1, which can produce acetate, significantly ameliorated Aβ-induced cognitive impairment [162]. Clostridium butyricum, which produces butyrate, can ameliorate cognitive impairment, reduce Aβ deposition, and inhibit neuroinflammation by reducing both microglial activation and secretion of proinflammatory cytokines [148]. In addition, transplantation of wild-type mouse feces into APP/PS1 mice can improve pathological indicators by increasing the production of SCFAs [163]. The proportions of metabolic substrates that are converted into the corresponding SCFAs can be increased by adjusting the diet, including consuming prebiotics or a healthy diet [164]. It was recently reported in patients with mild cognitive impairment that a modified Mediterranean-ketogenic diet increases fecal propionate and butyrate levels, which are negatively correlated with Aβ-42 [165].