Gut Microbiome and Mycobiome Alterations in an In Vivo Model of Alzheimer's Disease.

ABSTRACT

Gut microbiota has emerged as an important key regulator of health and disease status. Indeed, gut microbial dysbiosis has been identified in an increasing number of diseases, including neurodegenerative disorders. Accordingly, microbial alterations have been reported also in Alzheimer's disease (AD), suggesting possible pathogenetic mechanisms contributing to the development of specific AD hallmarks and exacerbating metabolic alterations and neuroinflammation. The identification of these mechanisms is crucial to develop novel, targeted therapies and identify potential biomarkers for diagnostic purposes. Thus, the possibility to have AD in vivo models to study this microbial ecosystem represents a great opportunity for translational applications. Here, we characterized both gut microbiome and mycobiome of 3xTg-AD mice, one of the most widely used AD models, to identify specific microbial alterations with respect to the wild-type counterpart. Interestingly, we found a significant reduction of the Coprococcus and an increased abundance of Escherichia_Shigella and Barnesiella genera in the AD mice compatible with a pro-inflammatory status and the development of AD-related pathogenetic features. Moreover, the fungal Dipodascaceae family was significantly increased, thus suggesting a possible contribution to the metabolic alterations found in AD. Our data point out the strict connection between bacterial dysbiosis and AD and, even if further studies are required to clarify the underlining mechanisms, it clearly indicates the need for extensive metagenomic studies over the bacterial counterpart.