nutrients Review Probiotics for Alzheimer’s Disease: A Systematic Review Ruth Naomi 1 , Hashim Embong 2 , Fezah Othman 3 , Hasanain Faisal Ghazi 4 , Nithiyah Maruthey 5 and Hasnah Bahari 1, *   Citation: Naomi, R.; Embong, H.; Othman, F.; Ghazi, H.F.; Maruthey, N.; Bahari, H. Probiotics for Alzheimer’s Disease: A Systematic Review. Nutrients 2022, 14, 20. https:// doi.org/10.3390/nu14010020 Academic Editor: Ben Witteman Received: 24 October 2021 Accepted: 15 November 2021 Published: 22 December 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Human Anatomy, Universiti Putra Malaysia, Serdang 43400, Malaysia; ruthmanuel2104@gmail.com 2 Department of Emergency Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; hashimembong77@ukm.edu.my 3 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia; fezah@upm.edu.my 4 College of Nursing, Al-Bayan University, Baghdad 10071, Iraq; dr.hasanainhabasha@gmail.com 5 Department of Physiotherapy, Faculty of Health and Life Sciences, Inti International University, Persiaran Perdana BBN Putra Nilai, Nilai 71800, Malaysia; nithiyah.maruthey@newinti.edu.my * Correspondence: haba@upm.edu.my; Tel.: +60-19-388-9528 Abstract: Alzheimer’s disease (AD) is the most common form of neurodegenerative disorders affecting mostly the elderly. It is characterized by the presence of Aβ and neurofibrillary tangles (NFT), resulting in cognitive and memory impairment. Research shows that alteration in gut microbial diversity and defects in gut brain axis are linked to AD. Probiotics are known to be one of the best preventative measures against cognitive decline in AD. Numerous in vivo trials and recent clinical trials have proven the effectiveness of selected bacterial strains in slowing down the progression of AD. It is proven that probiotics modulate the inflammatory process, counteract with oxidative stress, and modify gut microbiota. Thus, this review summarizes the current evidence, diversity of bacterial strains, defects of gut brain axis in AD, harmful bacterial for AD, and the mechanism of action of probiotics in preventing AD. A literature search on selected databases such as PubMed, Semantic Scholar, Nature, and Springer link have identified potentially relevant articles to this topic. However, upon consideration of inclusion criteria and the limitation of publication year, only 22 articles have been selected to be further reviewed. The search query includes few sets of keywords as follows. (1) Probiotics OR gut microbiome OR microbes AND (2) Alzheimer OR cognitive OR aging OR dementia AND (3) clinical trial OR in vivo OR animal study. The results evidenced in this study help to clearly illustrate the relationship between probiotic supplementation and AD. Thus, this systematic review will help identify novel therapeutic strategies in the future as probiotics are free from triggering any adverse effects in human body. Keywords: probiotics; Alzheimer; mechanism; clinical trials; beneficial; brain-gut axis 1. Introduction Probiotics are living microorganisms that promote health benefits when consumed in adequate quantity. They regulate the level of pH in the body, help preserve the integrity of the intestinal lining, act as antibiotics, and enhance the brain-derived neurotrophic factor [1]. These neurotrophic factors are made up of a type of protein in the brain that facilitates the survival and differentiation of neurons. Hence, it plays a crucial role in neurological development. Learning disabilities and memory impairments are some of the common issues that tend to arise if these factors are missing from the brain [2]. The effects of probiotics on the central nervous system (CNS) are achieved by alteration of gut microbiota, by increasing the diversity of the good bacterial composition, thereby boosting CNS functions. Apart from brain neurotrophic factor, probiotics tend to provide good prognosis in curing memory deficits and psychiatric disorders by directly modifying brain biochemical components such as serotonin, γ-aminobutyric acid (GABA) and dopamine [3]. Nutrients 2022, 14, 20. https://doi.org/10.3390/nu14010020 https://www.mdpi.com/journal/nutrients