Background Both genetic factors and environmental hazards, including environmental noise stress, have been 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 The molecular pathways underlying EOAD pathophysiology following environmental noise exposure were evaluated using C57BL/6 wild-type (WT) and APP/PS1 Tg mouse models. The composition differences in intestinal microbiota were analyzed by 16S rRNA sequencing and Tax4Fun to predict the metagenome content from sequencing results. An assessment of the flora dysbiosis-triggered dyshomeostasis of oxi-inflamm-barrier and the effects of the CNS end of the gut–brain axis was conducted to explore the underlying pathological mechanisms. Results Both WT and APP/PS1 mice showed a 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 following noise exposure. Mechanistically, axis-series experiments demonstrated that following noise exposure, intestinal and hippocampal tight junction protein levels reduced, whereas serum levels of inflammatory mediator were elevated. Regarding 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. Conclusion 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.

BackgroundEnvironmental noise exposure is linked to neuroinflammation and imbalance of the gut microbiota. Promoting gut microbiota homeostasis may be a key factor in relieving the deleterious non-auditory effects of noise. This study aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) intervention on noise-induced cognitive deficits and systemic inflammation in rats.MethodsLearning and memory were assessed using the Morris water maze, while 16S rRNA sequencing and gas chromatography-mass spectrometry were used to analyze the gut microbiota and short-chain fatty acid (SCFA) content. Endothelial tight junction proteins and serum inflammatory mediators were assessed to explore the underlying pathological mechanisms.ResultsThe results indicated that Lactobacillus rhamnosus GG intervention ameliorated noise-induced memory deterioration, promoted the proliferation of beneficial bacteria, inhibited the growth of harmful bacteria, improved dysregulation of SCFA-producing bacteria, and regulated SCFA levels. Mechanistically, noise exposure led to a decrease in tight junction proteins in the gut and hippocampus and an increase in serum inflammatory mediators, which were significantly alleviated by Lactobacillus rhamnosus GG intervention.ConclusionTaken together, Lactobacillus rhamnosus GG intervention reduced gut bacterial translocation, restored gut and blood-brain barrier functions, and improved gut bacterial balance in rats exposed to chronic noise, thereby protecting against cognitive deficits and systemic inflammation by modulating the gut-brain axis.

Environmental noise is a common hazard in military operations. Military service members during long operations are often exposed to around-the-clock noise and suffer massive emotional and cognitive dysfunction related to an Alzheimer’s disease (AD)-like neuropathology. It is essential to clarify the mechanisms underlying the effects of around-the-clock noise exposure on the central nervous system. Here, Wistar rats were continuously exposed to white noise (95 dB during the on-duty phase [8:00–16:00] and 75 dB during the off-duty phase (16:00–8:00 the next day)) for 40 days. The levels of phosphorylated tau, amyloid-β (Aβ), and neuroinflammation in the cortex and hippocampus were assessed and autophagosome (AP) aggregation was observed by transmission electron microscopy. Dyshomeostasis of autophagic flux resulting from around-the-clock noise exposure was assessed at different stages to investigate the potential pathological mechanisms. Around-the-clock noise significantly increased Aβ peptide, tau phosphorylation at Ser396 and Ser404, and neuroinflammation. Moreover, the AMPK-mTOR signaling pathway was depressed in the cortex and the hippocampus of rats exposed to around-the-clock noise. Consequently, autophagosome–lysosome fusion was deterred and resulted in AP accumulation. Our results indicate that around-the-clock noise exposure has detrimental influences on autophagic flux homeostasis and may be associated with AD-like neuropathology in the cortex and the hippocampus.