Diet management has been linked to a reduced risk of several chronic diseases, which mediates gut microbiota structure and functions. Modified Mediterranean-ketogenic diet modulates gut microbiome and metabolites in association with cerebrospinal fluid (CSF) AD biomarkers [10]. Fermentation of dietary fiber is one of the dominant functions of the caecal and colonic microbiota and a major source for SCFAs, which have an important role in maintaining intestinal immune homeostasis and protecting against inflammation [11]. Capsaicin is a natural product isolated from chili pepper, and it is consumed as a vegetable and spice. There is much epidemiological and research evidence linking capsaicin-rich diets with AD incidence. A higher consumption of chili pepper causes mild differences in incidence rates for AD between eastern and western regions [12]. Liu et al. observed that spicy diets improved the cognitive deficits of people that were over 40 years old [13]. Wang et al. found that capsaicin reduced Aβ depositions by boosting the maturation of ADAM10 and shifting the APP processing pathway [14]. Capsaicin alleviates cognitive impairments of the APP23/PS45 mouse model of AD [15]. Dietary capsaicin beneficially alters the composition of the gut microbiota and short-chain fatty acid metabolism against obesity [16]. Capsaicin inhibits the increase in abundance of the genus Lactobacillus and its bile acid metabolism Type 2 diabetic db/db mice [17]. However, few researchers have evaluated the changes in the gut microbiome and serum metabolism by capsaicin administration and their correlation in APP/PS1 mice. Here, we studied the effects of capsaicin on cognition, Aβ plaques, gut microbiota, and serum profile in APP/PS1 mice.
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