| First Author | Tettevi EJ | Year | 2025 |
| Journal | Brain Behav | Volume | 15 |
| Issue | 10 | Pages | e70946 |
| PubMed ID | 41069328 | Mgi Jnum | J:386662 |
| Mgi Id | MGI:8348548 | Doi | 10.1002/brb3.70946 |
| Citation | Tettevi EJ, et al. (2025) Antibiotic-Induced Gut Dysbiosis Modulates Alzheimer's Disease-Associated Gene Expression and Protein Aggregation in 3xTg-AD Mice via the Gut-Brain Axis. Brain Behav 15(10):e70946 |
| abstractText | INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that poses a major global health challenge due to its increasing prevalence and lack of effective treatments. Emerging evidence suggests the gut-brain axis may play a pivotal role in AD pathogenesis. However, causal links between dysbiosis and late-stage AD pathology remain unclear. METHODS: This study evaluated the effects of antibiotic-induced gut dysbiosis in aged 3xTg-AD mice (46-48 weeks). Female mice were randomly assigned to control or treatment groups and administered a broad-spectrum antibiotic cocktail (ampicillin, vancomycin, and neomycin) for 14 days. Behavioral tests (Y-maze, elevated plus maze) were performed to assess cognitive and anxiety-like behaviors. Gut microbiota composition was assessed via 16S rRNA qPCR. Gene expression of Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), and Tumor Necrosis Factor-Alpha (TNF-alpha) was analyzed via qRT-PCR, and cerebral amyloid-beta(1-42) and tau protein levels were quantified by ELISA. RESULTS: Antibiotic treatment induced significant dysbiosis, with > 90% reduction in Firmicutes and Bacteroidetes. Dysbiotic mice displayed impaired spatial working memory, heightened anxiety-like behavior, and reduced locomotor activity. Molecular analyses revealed region-specific dysregulation of cholinergic genes: AChE was upregulated in the hippocampus but downregulated in the cortex, while BChE showed the opposite trend. TNF-alpha was significantly elevated in both regions, indicating neuroinflammation. Dysbiosis also led to increased brain levels of amyloid-beta(1-42) and tau. CONCLUSION: Gut microbiome disruption exacerbates late-stage AD pathology, driving cognitive deficits, neuroinflammation, and hallmark protein aggregation. These findings support the gut-brain axis as a critical modulator of AD and highlight the microbiome as a potential therapeutic target. |
