The Gut Brain Axis and Cognitive Decline: A Narrative Review of Microbiota Dynamics in MCI and Alzheimer’s Disease
Keywords:
Gut Brain Axis, Microbiota, Cognitive Impairment, Alzheimer’s Disease, Dysbiosis, Neuroinflammation, Short Chain Fatty AcidsAbstract
The gut brain axis has emerged as a pivotal framework for understanding the relationship between gut microbiota and cognitive function. This narrative review aimed to explore the influence of gut microbial composition and metabolites on the progression of cognitive decline, particularly from Mild Cognitive Impairment (MCI) to Alzheimer’s Disease (AD). A systematic search of academic databases including Scopus, PubMed, and Google Scholar was conducted using predetermined keywords and Boolean operators. Eligible studies included peer reviewed research articles, systematic reviews, and meta analyses published between 2015 and 2025. The review found consistent evidence linking gut dysbiosis notably decreased microbial diversity and elevated pro inflammatory taxa to neurodegenerative processes. Specific mechanisms such as reduced short chain fatty acid production, microbial induced inflammation, and vagus nerve signaling disruptions were implicated in cognitive impairment. Furthermore, socio economic factors such as dietary quality and healthcare access significantly influenced microbiota composition and, by extension, cognitive health. Interventions including dietary modulation, probiotic and prebiotic supplementation, and fecal microbiota transplantation demonstrated potential in mitigating cognitive decline. However, the review also identified limitations in current literature, including a lack of longitudinal and population diverse studies. Future research should address these gaps to enable personalized and equitable microbiota targeted therapies. Overall, this review affirms gut microbiota as a modifiable factor with significant implications for cognitive aging and public health.
References
Viana TRX. Relationship of Gut Microbiota and Mental Health: The Influence of the Gut Brain Axis. Int J Health Sci. 2024;4(25):2–6.
Alzubide S, Alhalafi M. The Gut Brain Connection. J Behav Brain Sci. 2024;14(03):103–17.
Curti C, Bossolani JA, Camargo RA d., Caramelo AAF, Maria Gabriela Lisboa da Silva, Favaro MEF, et al. The Gut Brain Axis: Exploring the Role of Microbiota in Depression and Anxiety Disorder. Int J Health Sci. 2024;4(26):2–13.
Mittal R, Debs LH, Patel A, Nguyen D, Patel K, O’Connor G, et al. Neurotransmitters: The Critical Modulators Regulating Gut–Brain Axis. J Cell Physiol. 2017;232(9):2359–72.
Chen M, Patel T, Chang F. The Impact of a Primary Care, Pharmacist Driven Intervention in Patients With Chronic Non Cancer Pain A Pilot Study. Pharmacy. 2020;8(3):113.
Cordero EMG, Cuevas‐Budhart MÁ, Morán DP, Villeda MÁT, Mercedes Gómez del Pulgar García Madrid. Relationship Between the Gut Microbiota and Alzheimer’s Disease: A Systematic Review. J Alzheimer Dis. 2022;87(2):519–28.
Sittipo P, Choi JY, Lee S, Lee YK. The Function of Gut Microbiota in Immune Related Neurological Disorders: A Review. J Neuroinflammation. 2022;19(1).
Post Z, Manfready RA, Keshavarzian A. Overview of the Gut–Brain Axis: From Gut to Brain and Back Again. Semin Neurol. 2023;43(04):506–17.
Pang S, Wen Yi J, Zi W. The Interplay Between the Gut Microbiome and Neurological Disorders: Exploring the Gut Brain Axis. Neurol Lett. 2023;2(1):25–9.
Jones LD, Kumar J, Mistry A, Mana TS, Perry G, Reddy VP, et al. The Transformative Possibilities of the Microbiota and Mycobiota for Health, Disease, Aging, and Technological Innovation. Biomedicines. 2019;7(2):24.
Park SH, Lee JH, Shin J, Kim J, Cha B, Lee S, et al. Cognitive Function Improvement After Fecal Microbiota Transplantation in Alzheimer’s Dementia Patient: A Case Report. Curr Med Res Opin. 2021;37(10):1739–44.
Vandemoortele B, Vermeirssen V. Molecular Systems Biology Approaches to Investigate Mechanisms of Gut−brain Communication in Neurological Diseases. Eur J Neurol. 2023;30(11):3622–32.
Hulme H, Meikle LM, Strittmatter N, Justin J. J. van der Hooft, Swales JG, Bragg RA, et al. Microbiome Derived Carnitine Mimics as Previously Unknown Mediators of Gut Brain Axis Communication. Sci Adv. 2020;6(11).
Caputi V, Giron MC. Microbiome Gut Brain Axis and Toll Like Receptors in Parkinson’s Disease. Int J Mol Sci. 2018;19(6):1689.
Jiang C, Li G, Huang P, Liu Z, Zhao B. The Gut Microbiota and Alzheimer’s Disease. J Alzheimer Dis. 2017;58(1):1–15.
Kim CS, Cha L, Sim M, Jung S, Chun WY, Baik HW, et al. Probiotic Supplementation Improves Cognitive Function and Mood With Changes in Gut Microbiota in Community Dwelling Older Adults: A Randomized, Double Blind, Placebo Controlled, Multicenter Trial. J Gerontol Ser A. 2020;76(1):32–40.
Chen A, Wang Y, Hu Y. Exploring Causal Relationships Between Gut Microbiota and Alzheimer’s Disease: A Bidirectional Mendelian Randomization Study. J Alzheimer Dis Rep. 2024;8(1):1031–40.
Seo D oh, O’Donnell D, Jain N, Ulrich JD, Herz J, Li Y, et al. ApoE Isoform– And Microbiota Dependent Progression of Neurodegeneration in a Mouse Model of Tauopathy. Science. 2023;379(6628).
Jakubiec J, Gmitrzuk J, Malinka Z, Wiśniewska K, Jachymek A, Opatowska M, et al. The Impact of Gut Microbiota on Parkinson’s and Alzheimer’s Diseases: A Review of Medical Literature. Qual Sport. 2024;15:52004.
Schächtle M, Rosshart SP. The Microbiota Gut Brain Axis in Health and Disease and Its Implications for Translational Research. Front Cell Neurosci. 2021;15.
Varesi A, Pierella E, Romeo M, Piccini GB, Alfano C, Bjørklund G, et al. The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment. Nutrients. 2022;14(3):668.
Ayten Ş, Bilici S. Modulation of Gut Microbiota Through Dietary Intervention in Neuroinflammation and Alzheimer’s and Parkinson’s Diseases. Curr Nutr Rep. 2024;13(2):82–96.
Kowalski K, Mulak A. Brain Gut Microbiota Axis in Alzheimer’s Disease. J Neurogastroenterol Motil. 2019;25(1):48–60.
Giovanni SD, Serger E, Chadwick J, Luengo L, Kong G, Zhou L, et al. The Intermittent Fasting Dependent Gut Microbial Metabolite Indole 3 Propionate Promotes Nerve Regeneration and Recovery After Injury. 2020;
Chu X, Hou Y, Meng Q, Croteau DL, Wei Y, De S, et al. Nicotinamide Adenine Dinucleotide Supplementation Drives Gut Microbiota Variation in Alzheimer’s Mouse Model. Front Aging Neurosci. 2022;14.
Zhang C, Liang D, Li X, Liu J, Fan M, Mei J, et al. Characteristics of Gut Microbial Profiles of Offshore Workers and Its Associations With Diet. Front Nutr. 2022;9.
Matz M, Shah NS, Porterfield L, Stuyck OM, Jochum MD, Kayed R, et al. Microbial Determinants of Dementia Risk in Subjects of Mexican Descent With Type 2 Diabetes Living in South Texas. 2024;
Mitra S, Munni YA, Dash R, Sadhu T, Barua L, Islam MA, et al. Gut Microbiota in Autophagy Regulation: New Therapeutic Perspective in Neurodegeneration. Life. 2023;13(4):957.
Pan Q, Li Y, Guo K, Xue M, Gan Y, Wang K, et al. Elderly Patients of Mild Cognitive Impairment Exhibit Altered Profiles of the Gut Microbiota. 2020;
Rouskas K, Mamalaki E, Ntanasi E, Pantoura M, Anezaki M, Emmanouil C, et al. Distinct Gut Microbiota Profiles May Characterize Amyloid Beta Pathology and Mild Cognitive Impairment. 2024;
Bao QN, Liu Y, Zhang X, Li Y, Wang Z, Ye F, et al. Clinical Observation and Mechanism of Acupuncture on Amnestic Mild Cognitive Impairment Based on the Gut Brain Axis: Study Protocol for a Randomized Controlled Trial. Front Med. 2023;10.
Kim E, Kim JJ, Park SE, Seo SH, Cho K, Kwon SJ, et al. Association Between Mild Cognitive Impairment and Gut Microbiota in Elderly Korean Patients. J Microbiol Biotechnol. 2023;33(10):1376–83.
Chen G, Zhou X, Zhu Y, Shi W, Kong L. Gut Microbiome Characteristics in Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer’s Disease: A Systematic Review and Meta‐analysis. Eur J Neurol. 2023;30(11):3568–80.
Zhuang Z, Shen L, Li W, Fu X, Zeng F, Gui L, et al. Gut Microbiota Is Altered in Patients With Alzheimer’s Disease. J Alzheimer Dis. 2018;63(4):1337–46.
Jemimah S, Chabib C, Hadjileontiadis LJ, AlShehhi A. Gut Microbiome Dysbiosis in Alzheimer’s Disease and Mild Cognitive Impairment: A Systematic Review and Meta Analysis. Plos One. 2023;18(5):e0285346.
Pan Q, Li Y, Guo K, Xue M, Gan Y, Wang K, et al. Elderly Patients With Mild Cognitive Impairment Exhibit Altered Gut Microbiota Profiles. J Immunol Res. 2021;2021:1–7.
Li L, Wang L, Ding W, Wu J, Liu F, Liu J, et al. The Improvement Effects of Sika Deer Antler Protein in an Alzheimer’s Disease Mouse Model via the Microbe–Gut–Brain Axis. Food Sci Nutr. 2024;13(1).
Jin Y, Chen J, Chai Q, Zhu J, Jin X. Exploration of Acupuncture Therapy in the Treatment of MCI Patients With the ApoE Ε4 Gene Based on the Brain Gut Axis Theory. BMC Complement Med Ther. 2023;23(1).
He Z, Liu Y, Li Z, Sun T, Li Z, Manyande A, et al. Gut Microbiota Regulates Circadian Oscillation in Hepatic Ischemia–reperfusion Injury Induced Cognitive Impairment by Interfering With Hippocampal Lipid Metabolism in Mice. Hepatol Int. 2023;17(6):1645–58.
Colombo A, Sadler R, Llovera G, Singh V, Roth S, Heindl S, et al. Microbiota Derived Short Chain Fatty Acids Modulate Microglia and Promote Aβ Plaque Deposition. Elife. 2021;10.
Husso A, Pessa‐Morikawa T, Koistinen V, Kärkkäinen O, Kwon HN, Lahti L, et al. Impacts of Maternal Microbiota and Microbial Metabolites on Fetal Intestine, Brain, and Placenta. BMC Biol. 2023;21(1).
Saji N, Murotani K, Hisada T, Kunihiro T, Tsuduki T, Sugimoto T, et al. Relationship Between Dementia and Gut Microbiome Associated Metabolites: A Cross Sectional Study in Japan. Sci Rep. 2020;10(1).
Donaldson A, Fyfe C, Martin JC, SMITH E, Horgan G, Myint PK, et al. Aging Gut Brain Interactions: Pro Inflammatory Gut Bacteria Are Elevated in Fecal Samples From Individuals Living With Alzheimer’s Dementia. Geriatrics. 2025;10(2):37.
Nota MHC, Dohm Hansen S, Nicolas S, Harris EP, Foley T, Nolan YM, et al. A Cafeteria Diet Blunts Effects of Exercise on Adult Hippocampal Neurogenesis but Not Neurogenesis Dependent Behaviours in Adult Male Rats. 2024;
Park JC, Im S. The Gut Immune Brain Axis in Neurodevelopment and Neurological Disorders. Microbiome Res Rep. 2022;1(4):23.
Vogt N, Kerby RL, Dill‐McFarland KA, Harding S, Merluzzi AP, Johnson SC, et al. Gut Microbiome Alterations in Alzheimer’s Disease. Sci Rep. 2017;7(1).
Kamer AR, Pushalkar S, B. Pourmolaee M. Haghighi H. Eshraghi M. Hamidi, Janal MN, Tang VA, Annam KRC, et al. Periodontal Inflammation and Dysbiosis Relate to Microbial Changes in the Gut. Microorganisms. 2024;12(6):1225.
Favero F, Barberis E, Gagliardi M, Espinoza S, Contu L, Gustincich S, et al. A Metabologenomic Approach Reveals Alterations in the Gut Microbiota of a Mouse Model of Alzheimer’s Disease. Plos One. 2022;17(8):e0273036.
Shabbir U, Tyagi A, Elahi F, Aloo SO, Oh D. The Potential Role of Polyphenols in Oxidative Stress and Inflammation Induced by Gut Microbiota in Alzheimer’s Disease. Antioxidants. 2021;10(9):1370.
Sha H, He X, Yan K, Li J, Xu L, Xie Y, et al. Blocking Coprophagy Increases the Levels of Inflammation and Depression in Healthy Mice as Well as Mice Receiving Fecal Microbiota Transplantation From Disease Model Mice Donors. Apmis. 2023;131(7):351–68.
González Dávila P, Schwalbe M, Danewalia A, Wardenaar R, Dalile B, Verbeke K, et al. Gut Microbiota Transplantation Drives the Adoptive Transfer of Colonic Genotype Phenotype Characteristics Between Mice Lacking Catestatin and Their Wild Type Counterparts. Gut Microbes. 2022;14(1).
He J, Wu J, Liu J, Wu H, Hua H. Cognitive Impairment and the Gut Brain Axis During 2014–2023: A Bibliometric Analysis. Front Neurol. 2024;15.
Kim J, Park H, Lee JH, Shin J, Cha B, Kwon KS, et al. Effect of Altered Gene Expression in Lipid Metabolism on Cognitive Improvement in Patients With Alzheimer’s Dementia Following Fecal Microbiota Transplantation: A Preliminary Study. Ther Adv Neurol Disord. 2024;17.
Wang Y, Zhang Z, Li B, He B, Li L, Nice EC, et al. New Insights Into the Gut Microbiota in Neurodegenerative Diseases From the Perspective of Redox Homeostasis. Antioxidants. 2022;11(11):2287.
Putri SSF, Irfannuddin I, Murti K, Kesuma Y, Darmawan H, Koibuchi N. The Role of Gut Microbiota on Cognitive Development in Rodents: A Meta Analysis. J Physiol Sci. 2023;73(1):10.
Singh R, Chandrashekharappa S, Bodduluri SR, Baby BV, Hegde B, Kotla NG, et al. Enhancement of the Gut Barrier Integrity by a Microbial Metabolite Through the Nrf2 Pathway. Nat Commun. 2019;10(1).
Lavelle A, Sokol H. Gut Microbiota Derived Metabolites as Key Actors in Inflammatory Bowel Disease. Nat Rev Gastroenterol Hepatol. 2020;17(4):223–37.
Wang X, Sun G, Feng T, Zhang J, Huang X, Wang T, et al. Sodium Oligomannate Therapeutically Remodels Gut Microbiota and Suppresses Gut Bacterial Amino Acids Shaped Neuroinflammation to Inhibit Alzheimer’s Disease Progression. Cell Res. 2019;29(10):787–803.
Zhao H, Wang D, Zhang Z, Xian J, Bai X. Effect of Gut Microbiota Derived Metabolites on Immune Checkpoint Inhibitor Therapy: Enemy or Friend? Molecules. 2022;27(15):4799.
Tian P, Hou Y, Wang Z, Jiang J, Qian X, Qu Z, et al. Probiotics Administration Alleviates Cognitive Impairment and Circadian Rhythm Disturbance Induced by Sleep Deprivation. Food Sci Hum Wellness. 2024;13(4):1951–61.
Jiang C, Wang H, Wang Q, Luo Y, Sidlow R, Han X. Prevalence of Chronic Pain and High Impact Chronic Pain in Cancer Survivors in the United States. Jama Oncol. 2019;5(8):1224.
Jia M, Shi L, Zhao Y, Hu X, Zhao J, Ding C, et al. Intermittent Fasting Mitigates Cognitive Deficits in Alzheimer’s Disease via the Gut Brain Axis. 2022;
Kossowska M, Olejniczak S, Karbowiak M, Mosiej W, Zielińska D, Brzezicka A. The Interplay Between Gut Microbiota and Cognitive Functioning in the Healthy Aging Population: A Systematic Review. Nutrients. 2024;16(6):852.
Stevens M, Matosevic T, Suárez‐Pinilla M, Pais S, Rossor MN, Knapp M. The Link Between Cognitive Health and Neighbourhood: Perceptions of the Public, and of Policy Makers, About Problems and Solutions. BMC Public Health. 2023;23(1).
Kartjito MS, Yosia M, Wasito E, Soloan G, Agussalim AF, Basrowi RW. Defining the Relationship of Gut Microbiota, Immunity, and Cognition in Early Life A Narrative Review. Nutrients. 2023;15(12):2642.
Strekalova YA, Modjarrad L, Midence S. Mechanisms of Young Professional Engagement in Health Policy Development: A Cultural Domain Approach. Front Public Health. 2024;12.
Cai W, Gao R, Qi J, Wang C, Hou N, Wei de L, et al. Doctor of Public Health Crisis Management and COVID 19 Prevention and Control: A Case Study in China. Front Public Health. 2022;10.
Hou K, Wu Z, Chen XY, Wang J, Zhang D, Xiao C, et al. Microbiota in Health and Diseases. Signal Transduct Target Ther. 2022;7(1).
Wilson L, Hamwi S, Zanni F, Lomazzi M. Global Public Health Policies: Gathering Public Health Associations’ Perspectives. Glob Health Action. 2023;16(1).
