Microbiota gut-brain axis dysfunction in Alzheimer’s Disease: From pathogenesis to potential treatments – A review

• GM dysbiosis is increasingly recognized as a key contributor to AD pathogenesis. • This review explores recent advances in understanding the MGBA and its role in AD. • GM targeting offers AD therapy using GLP-1RA (Semaglutide), FMT, and phage therapy. • Semaglutide may reverse GM dysbiosis, reducing Aβ, NFTs, and neuroinflammation. • FMT and phage therapy may restore GM balance, MGBA signaling, and cognition. Alzheimer’s Disease (AD) is a neurodegenerative disease whose incidence continues to steadily escalate and recently, Gut Microbiome (GM) dysbiosis has been identified as a prominent player in AD pathophysiology. The following review delves deeper into the recent developments over the last decade in the Microbiota Gut-Brain Axis (MGBA), its association with AD, and its modulation as a mean of treating AD patients. This review explores the possibility of treating AD by attempting to reverse GM dysbiosis using Glucagon-Like Peptide Receptor Agonists (GLP1RA) such as Semaglutide, Fecal Microbiota Transplantation (FMT), and Phage therapy. The compiled evidence shows that Semaglutide’s neuroprotective effect lies in its ability to reduce the burden of Amyloid-β (Aβ), Neurofibrillary Tangles (NFTs), and neuroinflammation in AD patients by reversing GM dysbiosis, glucose hypometabolism, and oxidative stress. Similarly, FMT reverses GM dysbiosis and changes the metabolic profile by modulating the release of Short Chain Fatty Acids (SCFAs), improving MGBA communication, delaying cognitive impairment, and ameliorating neurodegeneration. Phage therapy can be used to modulate the diversity and the genera that constitute GM by targeting and eliminating the pathogenic microbes, improving MGBA communication and enhancing cognition, memory, and executive function.