Noise exposure-induced intestinal flora dysbiosis disrupts homeostasis of oxi-inflamm-barrier in the gut–brain axis of APP/PS1 mice: implications for early onset Alzheimer's disease

Abstract

Background: Environmental noise exposure and genetic risk factors are thought to be associated with gut microbiome that exacerbates Alzheimer’s disease (AD) pathology. However, the role and mechanism of environmental risk factors in early-onset AD (EOAD) pathogenesis remain unclear. Methods: We established APP/PS1 Tg and C57BL/6 (wild type [WT]) mouse models to evaluate the molecular pathways underlying EOAD pathophysiology following environmental noise exposure. 16S rRNA sequencing analyses were used for intestinal flora measurements and Tax4Fun were used to predict the metagenome content from 16S rRNA sequencing results; and assessment of the flora dysbiosis-triggered dyshomeostasis of oxi-inflamm-barrier and the effects of the CNS end of the gut–brain axis were conducted to explore the underlying pathological mechanisms. Results: Both WT and APP/PS1 mice showed statistically significant relationship between environmental noise and the taxonomic composition of the corresponding gut microbiome. Bacterial-encoded functional categories in noise-exposed WT and APP/PS1 mice included phospholipid and galactose metabolism, oxidative stress, and cell senescence. These alterations corresponded with imbalanced intestinal oxidation and anti-oxidation systems and low-grade systemic inflammation after noise exposure. Mechanistically, axis-series experiments demonstrated that after noise exposure, intestinal and hippocampal tight junction proteins levels reduced, whereas serum levels of inflammatory mediator were elevated. With regard to APP/PS1 overexpression, noise-induced abnormalities in the gut–brain axis may contribute to aggravation of neuropathology in the presymptomatic stage of EOAD mice model. Conclusions: Our results demonstrate that noise exposure has deleterious effects on the homeostasis of oxi-inflamm-barrier in the microbiome–gut–brain axis. Therefore, at least in a genetic context, chronic noise may aggravate the progression of EOAD.

The Effects of Anthropogenic Sound and Artificial Light Exposure on Microbiomes: Ecological and Public Health Implications

“…A recent mouse-model study demonstrated adverse effects of noise pollution on the gut microbiome (Cui et al, 2020). They used 16S rRNA sequencing to characterize the gut microbiome and the Tax4Fun package in R to predict metagenome content.…”

The Effects of Anthropogenic Sound and Artificial Light Exposure on Microbiomes: Ecological and Public Health Implications

“…recent mouse-model study demonstrated adverse effects of noise pollution on the gut microbiome(Cui et al 2020). They used 16S rRNA sequencing to characterise the gut microbiome and the Tax4Fun package in R to predict metagenome content.…”