Abstract
Mounting evidence points to alterations in the gut microbiota-neuroendocrine immunomodulation (NIM) network that might drive Alzheimer’s Disease (AD) pathology. In previous studies, we found that Liuwei Dihuang decoction (LW) had beneficial effects on the cognitive impairments and gastrointestinal microbiota dysbiosis in an AD mouse model. In particular, CA-30 is an oligosaccharide fraction derived from LW. We sought to determine the effects of CA-30 on the composition and function of the intestinal microbiome in the senescence-accelerated mouse prone 8 (SAMP8) mouse strain, an AD mouse model. Treatment with CA-30 delayed aging processes, ameliorated cognition in SAMP8 mice. Moreover, CA-30 ameliorated abnormal NIM network in SAMP8 mice. In addition, we found that CA-30 mainly altered the abundance of four genera and 10 newborn genera. Advantageous changes in carbohydrate-active enzymes of SAMP8 mice following CA-30 treatment, especially GH85, were also noted. We further found that seven genera were significantly correlated with the NIM network and cognitive performance. CA-30 influenced the relative abundance of these intestinal microbiomes in SAMP8 mice and restored them to SAMR1 mouse levels. CA-30 ameliorated the intestinal microbiome, rebalanced the NIM network, improved the AD-like cognitive impairments in SAMP8 mice, and can thus be a potential therapeutic agent for AD.
Highlights
Alzheimer’s disease (AD) is a common, age-related neurodegenerative disorder with complex etiologies including genetics and other external environmental components [1]
Our results demonstrate that the body weight of senescence-accelerated mouse prone 8 (SAMP8) mice did not differ significantly from SAMR1 or CA-30 treated animals (Figure 1A)
We found that the concentration of corticotropin releasing hormone (CRH) was significantly increased in the SAMP8 group as compared to the SAMR1 group and significantly decreased with CA-30 administration (Figure 3A)
Summary
Alzheimer’s disease (AD) is a common, age-related neurodegenerative disorder with complex etiologies including genetics and other external environmental components [1]. Further supporting the role of gut microbes in AD, Aβ deposition in PrP-hAβPPswe/PS1ΔE9 transgenic mice was reduced by broad-spectrum antibiotic treatment [8] These results are consistent with reduced cerebral and serum Aβ levels in a mouse model of AD reared under germ-free conditions [9]. Manipulating the intestinal microbiota with antibiotics [10] or via probiotic therapy [11] alters cognition, such as novel object recognition, spatial learning and memory. Despite these results, the role of intestinal bacteriaimmune directed pathways in the pathogenesis of AD requires further interrogation with integrated and holistic approaches [12]
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