{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:05:36Z","timestamp":1788336336009,"version":"build-2803163510"},"reference-count":243,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T00:00:00Z","timestamp":1722643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The gastrointestinal (GI) tract, home to the largest microbial population in the human body, plays a crucial role in overall health through various mechanisms. Recent advancements in research have revealed the potential implications of gut-brain and vice-versa communication mediated by gut-microbiota and their microbial products in various diseases including type-2 diabetes and Alzheimer\u2019s disease (AD). AD is the most common type of dementia where most of cases are sporadic with no clearly identi\ufb01ed cause. However, multiple factors are implicated in the progression of sporadic AD which can be classi\ufb01ed as non-modi\ufb01able (e.g., genetic) and modi\ufb01able (e.g. Type-2 diabetes, diet etc.). Present review focusses on key players particularly the modi\ufb01able factors such as Type-2 diabetes (T2D) and diet and their implications in microbiota-gut-brain (MGB) and brain-gut (BG) communication and cognitive functions of healthy brain and their dysfunction in Alzheimer\u2019s Disease. Special emphasis has been given on elucidation of the mechanistic aspects of the impact of diet on gut-microbiota and the implications of some of the gut-microbial products in T2D and AD pathology. For example, mechanistically, HFD induces gut dysbiosis with driven metabolites that in turn cause loss of integrity of intestinal barrier with concomitant colonic and systemic chronic low-grade in\ufb02ammation, associated with obesity and T2D. HFD-induced obesity and T2D parallel neuroin\ufb02ammation, deposition of Amyloid \u03b2 (A\u03b2), and ultimately cognitive impairment. The review also provides a new perspective of the impact of diet on brain-gut and microbiota-gut-brain communication in terms of transcription factors as a commonly spoken language that may facilitates the interaction between gut and brain of obese diabetic patients who are at a higher risk of developing cognitive impairment and AD. Other commonality such as tyrosine kinase expression and functions maintaining intestinal integrity on one hand and the phagocytic clarence by migratory microglial functions in brain are also discussed. Lastly, the characterization of the key players future research that might shed lights on novel potential pharmacological target to impede AD progression are also discussed.<\/jats:p>","DOI":"10.3390\/nu16152558","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T11:28:54Z","timestamp":1722857334000},"page":"2558","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Brain-Gut and Microbiota-Gut-Brain Communication in Type-2 Diabetes Linked Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-8959","authenticated-orcid":false,"given":"Yomna S.","family":"Momen","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, ILR College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayshree","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, ILR College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1193-0954","authenticated-orcid":false,"given":"Narendra","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, ILR College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Juan, S.M.A., and Adlard, P.A. 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