Comparative Metagenomics and Metabolomes Reveals Abnormal Metabolism Activity Is Associated with Gut Microbiota in Alzheimer’s Disease Mice

Abstract

A common symptom in Alzheimer’s disease (AD) is cognitive decline, of which the potential pathogenesis remains unclear. In order to understand the mechanism of gut microbiota in AD, it is necessary to clarify the relationship between gut microbiota and metabolites. Behavioral tests, pathological examination, metagenomics, and metabolomics were applied to analyze the difference of gut microbiota and metabolome between APPswe/PS1ΔE9 (PAP) mice with cognitive decline and age-matched controls, and their possible correlations. Our results showed that PAP mice and health mice had different structures of the bacterial communities in the gut. The abundances and diversities of the bacterial communities in health mice were higher than in PAP mice by metagenomics analysis. The abundances of Libanicoccus massiliensis, Paraprevotella clara, and Lactobacillus amylovorus were significantly increased in PAP mice, while the abundances of Turicibacter sanguinis, Dubosiella newyorkensis, and Prevotella oris were greatly reduced. Furthermore, PAP mice possessed peculiar metabolic phenotypes in stool, serum, and hippocampus relative to WT mice, as is demonstrated by alterations in neurotransmitters metabolism, lipid metabolism, aromatic amino acids metabolism, energy metabolism, vitamin digestion and absorption, and bile metabolism. Microbiota–host metabolic correlation analysis suggests that abnormal metabolism in stool, serum, and hippocampus of PAP mice may be modulated by the gut microbiota, especially T. sanguinis, D. newyorkensis, and P. oris. Therefore, abnormal metabolism activity is associated with gut microbiota in Alzheimer’s disease mice. Our results imply that modifying host metabolism through targeting gut microbiota may be a novel and viable strategy for the prevention and treatment of AD in the future.

Dubosiella newyorkensis modulates immune tolerance in colitis via the L-lysine-activated AhR-IDO1-Kyn pathway

“…The intestinal abundance of Dub has been reported to be associated with obesity 42 and Alzheimer’s disease 43 in mouse models, however no functional studies have been performed to confirm its biological relevance in vivo. For the very first time, we comprehensively analyzed its potential role as a probiotic in both conventional and microbiota-depleted mouse models.…”

Lactobacillus plantarum LLY-606 Supplementation Ameliorates the Cognitive Impairment of Natural Aging in Mice: The Potential Role of Gut Microbiota Homeostasis

“…Both in Alzheimer's disease and mice with SOD1 knockout as a model of aging, we observed a significant increase in the abundance of P. clara. 60,61 Jongoh Shin and colleagues demonstrated that Paraprevotella, a bacterial species positively associated with age-related changes, exhibits a significantly increased abundance in aging mice. However, when A. muciniphila was reintroduced to the aging mice, phenotypic improvements were observed, and the abundance of Paraprevotella decreased.…”

Experimental colitis in young Tg2576 mice accelerates the onset of an Alzheimer’s-like clinical phenotype

“…In line with our results, a significantly decreased abundance of bacteria belonging to the Clostridia_UCG-014 family has been documented in relation to increased cognitive frailty index scores [ 53 ]. Notably, the abundance of both Turicibacter and Dubosiella genera was also decreased in APP swe /PS1 ΔE9 mice [ 54 ].…”