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Title Antibiotics-perturbed Microbiome and Its Effects in Alzheimer’s Disease Pathogenesis: A Potential Future for the Probiotic (Akkermansia Muciniphila) Pre-clinical Studies in This Model. |
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Type Poster Presentation |
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Theme Probiotics and Prebiotics: Excellence in Science and Clinical Translation |
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Topic Translational Microbiome Studies |
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Main Author Hemraj Dodiya1 |
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Presenting Author Hemraj Dodiya1 |
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Co-Author Thomas Kuntz1 Xiaoqiong Zhang1 Jack Gilbert1 Sangram Sisodia1 |
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Department / Institution / Country Neurobiology / The University of Chicago / United States1 |
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Background and Rationale Recent evidence suggests an involvement of the microbiota-gut-brain axis in Alzheimer’s disease (AD). Specific bacteria i.e. Akkermansia Muciniphila showed promising results in obesity and type 2 diabetes (T2DM) by reducing endotoxin and inflammation. Obesity is now considered a primary risk factor for the development of T2DM, and in turn, T2DM is a risk factor for the pathogenesis of AD. As these conditions share several anomalies such as impaired glucose metabolism and insulin signaling, low-grade chronic inflammation and oxidative stress, we hypothesize that A. Muciniphila could also impact AD pathogenesis. |
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Objectives: Indicates the purpose of the study To investigate the influence of microbiome in the AD, we used antibiotics in AD transgenic mice. We plan to investigate the role of A. Muciniphila in our proposed model. |
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Methodology: Describe pertinent experimental procedures Alzheimer's transgenic mice (APP/PS1) were gavaged with antibiotics during post-natal (p14-p22) and followed with 1:50 diluted antibiotics (drinking water) until the age of 7 weeks or 3 months. Gut, brain, feces and serum samples were collected. |
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Results: Summarize the results of the research Antibiotics (Abx) Tx resulted in significantly lower Abeta pathology in the cortex at 7 weeks (Abeta burden; control: 0.40±0.01, Abx: 0.06±0.001) and 3 months (control: 1.42±0.20, Abx: 0.61±0.07) as well as in the hippocampus at the 3 months (control: 0.50±0.07, Abx: 0.14±0.02). The Abx group also showed altered brain resident macrophages (microglia characteristics) and serum cytokine profile suggesting changes in inflammation. To correlate this data with the microbiome, we observed significant changes in the microbiome profile with Abx at the age of 3 months (p22 and 7 weeks of age: under evaluation). Among the significantly different taxa, Akkermansia Muciniphila showed higher abundance (also highest magnitude of changes among all other significant taxa) in Abx. |
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Conclusions: State the main conclusions Our data shows antibiotics-induced higher A. Muciniphila is associated with lower Alzheimer's pathology. Results from A. Muciniphila probiotics in this model will help us to understand its role in AD. |