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.

The potential of the gut microbiome for identifying Alzheimer’s disease diagnostic biomarkers and future therapies

“…In addition to the intestinal bacteria noted by most researchers, some studies have also found specific alterations in MCI patients in the genus Fungi and a clear correlation with AD biomarkers ( Nagpal et al, 2019 ). More importantly, the different microbiome and fungal biota composition in 3xTg-AD mice is similar to the microbial variation found in humans, and significantly different taxa may contribute to the pathogenic cues of AD being identified ( D’Argenio et al, 2022 ). However, there are some differences in studies regarding oral microbiology.…”

Role of Microbiota-Modified Bile Acids in the Regulation of Intracellular Organelles and Neurodegenerative Diseases

“…Therefore, increased secondary BAs may be associated with Alzheimer’s disease, and the status of the gut microbiome may affect the progression and suppression of Alzheimer’s disease. In addition, the increase in Lactobacillus , which has BSH that deconjugates conjugated-BAs, in feces is related to Alzheimer’s disease [ 120 , 121 ].…”

Biomarkers associated with the pathogenesis of Alzheimer’s disease

“… D’Argenio et al (2022) investigated the changes in bacterial and fungal composition in the intestines of wild-type (WT) mice and AD (3xTg-AD mice, one of the most widely used AD models). Compared to WT mice, AD mice showed reduced relative abundance of the phyla Firmicutes, Lachnospiraceae-unclassified, Ruminococcaceae-unclassified, and Turicibacter.…”

“…Bacteroidetes is a gram-negative bacteria and the lipopolysaccharide in its outer membrane has pro-inflammatory effects and promotes amyloid protein deposition and tau protein-related pathology. In addition, the authors found a decrease in fungal richness in the feces of AD mice, which may be related to metabolic changes in AD ( D’Argenio et al, 2022 ). Liang et al (2023) transplanted Paenalcaligenes hominis isolated from the feces of elderly humans and mice into young mice and found a decline in cognitive function in the mice.…”