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Pathological manifestations of AD include the loss of synaptic plasticity, reduction in synaptic strength by amyloid-beta, aggregation, and neurotoxicity from tau protein post-translational modifications, all contributing to the disruption of neural networks. Despite its current pharmacological treatment for AD, different approaches to treat such disease are being developed, from a microbiome perspective. The microbiome encompasses a diverse microorganism, including beneficial bacteria that create a positive impact to diminish AD pathogenesis. Growing evidence suggests that probiotic, prebiotic, synbiotic, and postbiotics can positively modulate the gut\u2013brain axis, reducing systemic inflammation, restoring neurotransmitter balance, and improving gut health, thereby possibly mitigating AD pathogenesis. Moreover, there is paraprobiotics as the most recently developed biotherapeutic with beneficial effects. This review explores the correlation between AD and gut\u2013brain axis as a novel biotherapeutic target. The underlying mechanism of the microbiota\u2013gut\u2013brain axis in AD is examined. Novel insights into the current applications as potential treatment and its limitations are highlighted.<\/jats:p>","DOI":"10.3390\/ijms26115351","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:40:32Z","timestamp":1748864432000},"page":"5351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Microbiome Engineering for Biotherapeutic in Alzheimer\u2019s Disease Through the Gut\u2013Brain Axis: Potentials and Limitations"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1635-528X","authenticated-orcid":false,"given":"Editha","family":"Renesteen","sequence":"first","affiliation":[{"name":"Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline L.","family":"Boyajian","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-2611","authenticated-orcid":false,"given":"Paromita","family":"Islam","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Kassab","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-9465","authenticated-orcid":false,"given":"Ahmed","family":"Abosalha","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"},{"name":"Pharmaceutical Technology Department, Faculty of Pharmacy, Tanta University, Tanta Al-Geish St., The Medical Campus, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Makhlouf","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0169-0917","authenticated-orcid":false,"given":"Madison","family":"Santos","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Chen","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedrique","family":"Shum-Tim","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satya","family":"Prakash","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine and Health Sciences, McGill University, Montr\u00e9al, QC H3A 2B4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","article-title":"Alzheimer disease","volume":"7","author":"Knopman","year":"2021","journal-title":"Nat. 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