The Gut Microbiome and Alzheimer’s Disease: Can the Gut be Used to Prevent or Treat Dementia?


  • Samhitha Vundi Rising Tide Charter Public School
  • Zena Chatila



Alzheimer's Disease, Microbiome, Gut Microbiome, Gut-Brain Axis


Alzheimer’s disease (AD) is a neurodegenerative disease and the most common cause of dementia1. There are currently no effective therapies for AD and its etiology remains poorly understood. Recent research has suggested that the gut microbiome may modulate risk for AD, as well as the disease process itself. This paper reviews the current knowledge surrounding AD and the gut microbiome, and aims to explore how this relationship may be used to advance our clinical understanding of the disease; including whether the gut microbiome could be a novel drug target or even serve as a potential biomarker for AD. Although this relationship between AD and the microbiome has not yet been fully elucidated, the gut microbiome is known to dynamically respond to lifestyle factors including sleep, exercise, and nutrition, all of which impact AD-risk. This body of evidence suggests that there may be a relationship between microbiome health and AD. Early studies are investigating whether the microbiome is changed in individuals with AD, and whether any metabolites or bacterial signatures unique in AD populations could be used as a biomarker for early detection of the disease. This review will discuss these points and reflect on how the clinical landscape for AD may be improved by assaying the microbiome and implementing lifestyle factors that both improve microbiome health and reduce AD risk. 



Download data is not yet available.

References or Bibliography

Long, J. M. & Holtzman, D. M. Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. Cell vol. 179 312–339 (2019).

A Armstrong, R. Risk factors for Alzheimer’s disease. Folia Neuropathol. 57, 87–105 (2019).

Duyckaerts, C., Delatour, B. & Potier, M.-C. Classification and basic pathology of Alzheimer disease. Acta Neuropathol. 118, 5–36 (2009).

Selkoe, D. J. & Hardy, J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med. 8, 595–608 (2016).

Braak, H. & Braak, E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82, 239–259 (1991).

Giannakopoulos, P. et al. Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease. Neurology vol. 60 1495–1500 (2003).

Brookmeyer, R. et al. National estimates of the prevalence of Alzheimer’s disease in the United States. Alzheimer’s & Dementia vol. 7 61–73 (2011).

Wu, L. et al. Altered Gut Microbial Metabolites in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Signals in Host–Microbe Interplay. Nutrients vol. 13 228 (2021).

Sun, Y. et al. Intra-gastrointestinal amyloid-β1-42 oligomers perturb enteric function and induce Alzheimer’s disease pathology. J. Physiol. 598, 4209–4223 (2020).

Nagpal, R., Neth, B. J., Wang, S., Craft, S. & Yadav, H. Modified Mediterranean-Ketogenic Diet Modulates Gut Microbiome and Short-Chain Fatty Acids in Association with Alzheimer’s Disease Markers in Subjects with Mild Cognitive Impairment. SSRN Electronic Journal (2019).

Marizzoni, M. et al. Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer’s Disease. J. Alzheimers. Dis. 78, 683–697 (2020).

Kim, M.-S. et al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model. Gut vol. 69 283–294 (2020).

Davenport, E. R. et al. The human microbiome in evolution. BMC Biol. 15, 127 (2017).

Barko, P. C., McMichael, M. A., Swanson, K. S. & Williams, D. A. The Gastrointestinal Microbiome: A Review. J. Vet. Intern. Med. 32, 9–25 (2018).

Shanahan, F., Ghosh, T. S. & O’Toole, P. W. The Healthy Microbiome-What Is the Definition of a Healthy Gut Microbiome? Gastroenterology 160, 483–494 (2021).

Ursell, L. K., Metcalf, J. L., Parfrey, L. W. & Knight, R. Defining the human microbiome. Nutr. Rev. 70 Suppl 1, S38–44 (2012).

Turnbaugh, P. J. et al. The human microbiome project. Nature 449, 804–810 (2007).

Gilbert, J. A. et al. Current understanding of the human microbiome. Nat. Med. 24, 392–400 (2018).

Mohajeri, M. H. et al. The role of the microbiome for human health: from basic science to clinical applications. Eur. J. Nutr. 57, 1–14 (2018).

Arslanoglu, S. et al. Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. J. Nutr. 138, 1091–1095 (2008).

Flint, H. J., Scott, K. P., Louis, P. & Duncan, S. H. The role of the gut microbiota in nutrition and health. Nat. Rev. Gastroenterol. Hepatol. 9, 577–589 (2012).

Hamer, H. M. et al. Review article: the role of butyrate on colonic function. Aliment. Pharmacol. Ther. 27, 104–119 (2008).

Rakoff-Nahoum, S., Foster, K. R. & Comstock, L. E. The evolution of cooperation within the gut microbiota. Nature 533, 255–259 (2016).

Claesson, M. J. et al. Gut microbiota composition correlates with diet and health in the elderly. Nature 488, 178–184 (2012).

Feng, Y. et al. An examination of data from the American Gut Project reveals that the dominance of the genus Bifidobacterium is associated with the diversity and robustness of the gut microbiota. Microbiologyopen 8, e939 (2019).

Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006).

Ianiro, G., Tilg, H. & Gasbarrini, A. Antibiotics as deep modulators of gut microbiota: between good and evil. Gut 65, 1906–1915 (2016).

Ley, R. E. et al. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. U. S. A. 102, 11070–11075 (2005).

Frank, D. N. et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc. Natl. Acad. Sci. U. S. A. 104, 13780–13785 (2007).

Tong, M. et al. A modular organization of the human intestinal mucosal microbiota and its association with inflammatory bowel disease. PLoS One 8, e80702 (2013).

Gomaa, E. Z. Human gut microbiota/microbiome in health and diseases: a review. Antonie Van Leeuwenhoek 113, 2019–2040 (2020).

Thursby, E. & Juge, N. Introduction to the human gut microbiota. Biochem. J 474, 1823–1836 (2017).

David, L. A. et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 505, 559–563 (2014).

Belizário, J. E. & Faintuch, J. Microbiome and Gut Dysbiosis. Experientia Suppl. 109, 459–476 (2018).

Hufnagl, K., Pali-Schöll, I., Roth-Walter, F. & Jensen-Jarolim, E. Dysbiosis of the gut and lung microbiome has a role in asthma. Semin. Immunopathol. 42, 75–93 (2020).

Hughes, H. K., Rose, D. & Ashwood, P. The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders. Curr. Neurol. Neurosci. Rep. 18, 81 (2018).

Santacroce, L. et al. The Human Respiratory System and its Microbiome at a Glimpse. Biology 9, (2020).

Roda, G. et al. Crohn’s disease. Nat Rev Dis Primers 6, 22 (2020).

Fan, Y. & Pedersen, O. Gut microbiota in human metabolic health and disease. Nat. Rev. Microbiol. 19, 55–71 (2021).

Jia, W., Xie, G. & Jia, W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat. Rev. Gastroenterol. Hepatol. 15, 111–128 (2018).

Smith, R. P. et al. Gut microbiome diversity is associated with sleep physiology in humans. PLoS One 14, e0222394 (2019).

Liu, X. et al. Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) study: Rationale, design and baseline characteristics of a randomized control trial of the MIND diet on cognitive decline. Contemp. Clin. Trials 102, 106270 (2021).

Hamer, M. & Chida, Y. Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence. Psychol. Med. 39, 3–11 (2009).

Winer, J. R. et al. Association of Short and Long Sleep Duration With Amyloid-β Burden and Cognition in Aging. JAMA Neurol. 78, 1187–1196 (2021).

Marizzoni, M. et al. Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer’s Disease. Advances in Alzheimer’s Disease (2022).

Romijn, J. A., Corssmit, E. P., Havekes, L. M. & Pijl, H. Gut-brain axis. Curr. Opin. Clin. Nutr. Metab. Care 11, 518–521 (2008).

Kim, Y.-K. & Shin, C. The Microbiota-Gut-Brain Axis in Neuropsychiatric Disorders: Pathophysiological Mechanisms and Novel Treatments. Curr. Neuropharmacol. 16, 559–573 (2018).

Carabotti, M., Scirocco, A., Maselli, M. A. & Severi, C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann. Gastroenterol. Hepatol. 28, 203–209 (2015) .

Cryan, J. F. et al. The Microbiota-Gut-Brain Axis. Physiol. Rev. (2019).

Needham, B. D. et al. A gut-derived metabolite alters brain activity and anxiety behaviour in mice. Nature 602, 647–653 (2022).

Sudo, N. et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. 558, 263–275 (2004).

Sampson, T. R. & Mazmanian, S. K. Control of brain development, function, and behavior by the microbiome. Cell Host Microbe 17, 565–576 (2015).

Clarke, G. et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol. Psychiatry 18, 666–673 (2013).

Bercik, P. et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141, 599–609, 609.e1–3 (2011).

Bravo, J. A. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. U. S. A. 108, 16050–16055 (2011).

Wastyk, H. C. et al. Gut-microbiota-targeted diets modulate human immune status. Cell 184, 4137–4153.e14 (2021).

Cait, A. et al. Microbiome-driven allergic lung inflammation is ameliorated by short-chain fatty acids. Mucosal Immunol. 11, 785–795 (2018).

Smith, P. M. et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341, 569–573 (2013).

Yang, W. et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat. Commun. 11, 4457 (2020).

Lee, J. et al. Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice. Circ. Res. 127, 453–465 (2020).

Yang, I. et al. The Infant Microbiome: Implications for Infant Health and Neurocognitive Development. Nurs. Res. 65, 76–88 (2016).

Bron, P. A. et al. Can probiotics modulate human disease by impacting intestinal barrier function? Br. J. Nutr. 117, 93–107 (2017).

Wan, Y. et al. Underdevelopment of the gut microbiota and bacteria species as non-invasive markers of prediction in children with autism spectrum disorder. Gut 71, 910–918 (2022).

Li, S. et al. The gut microbiome is associated with brain structure and function in schizophrenia. Sci. Rep. 11, 9743 (2021).

Leong, K. S. W. et al. Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial. JAMA Netw Open 3, e2030415 (2020).

Gupta, A., Osadchiy, V. & Mayer, E. A. Brain-gut-microbiome interactions in obesity and food addiction. Nat. Rev. Gastroenterol. Hepatol. 17, 655–672 (2020).

Gareau, M. G. et al. Bacterial infection causes stress-induced memory dysfunction in mice. Gut 60, 307–317 (2011).

Hu, X., Wang, T. & Jin, F. Alzheimer’s disease and gut microbiota. Sci. China Life Sci. 59, 1006–1023 (2016).

Blennow, K. & Zetterberg, H. Biomarkers for Alzheimer’s disease: current status and prospects for the future. J. Intern. Med. 284, 643–663 (2018).

Tan, C.-C., Yu, J.-T. & Tan, L. Biomarkers for preclinical Alzheimer’s disease. J. Alzheimers. Dis. 42, 1051–1069 (2014).

Nho, K. et al. Altered bile acid profile in mild cognitive impairment and Alzheimer’s disease: Relationship to neuroimaging and CSF biomarkers. Alzheimers. Dement. 15, 232–244 (2019).

Irwin, M. R. & Vitiello, M. V. Implications of sleep disturbance and inflammation for Alzheimer’s disease dementia. Lancet Neurol. 18, 296–306 (2019).

Borges, C. R., Poyares, D., Piovezan, R., Nitrini, R. & Brucki, S. Alzheimer’s disease and sleep disturbances: a review. Arq. Neuropsiquiatr. 77, 815–824 (2019).

Wang, C. & Holtzman, D. M. Bidirectional relationship between sleep and Alzheimer’s disease: role of amyloid, tau, and other factors. Neuropsychopharmacology 45, 104–120 (2020).

Cass, S. P. Alzheimer’s Disease and Exercise: A Literature Review. Curr. Sports Med. Rep. 16, 19–22 (2017).

Valenzuela, P. L. et al. Exercise benefits on Alzheimer’s disease: State-of-the-science. Ageing Res. Rev. 62, 101108 (2020).

Cui, M. Y., Lin, Y., Sheng, J. Y., Zhang, X. & Cui, R. J. Exercise Intervention Associated with Cognitive Improvement in Alzheimer’s Disease. Neural Plast. 2018, 9234105 (2018).

Sohail, M. U., Yassine, H. M., Sohail, A. & Thani, A. A. A. Impact of Physical Exercise on Gut Microbiome, Inflammation, and the Pathobiology of Metabolic Disorders. Rev. Diabet. Stud. 15, 35–48 (2019).

Ticinesi, A. et al. Exercise and immune system as modulators of intestinal microbiome: implications for the gut-muscle axis hypothesis. Exerc. Immunol. Rev. 25, 84–95 (2019).

Clarke, S. F. et al. Exercise and associated dietary extremes impact on gut microbial diversity. Gut 63, 1913–1920 (2014).

Dhakal, S. et al. Amish (Rural) vs. non-Amish (Urban) Infant Fecal Microbiotas Are Highly Diverse and Their Transplantation Lead to Differences in Mucosal Immune Maturation in a Humanized Germfree Piglet Model. Front. Immunol. 10, 1509 (2019).

Das, B. et al. Analysis of the Gut Microbiome of Rural and Urban Healthy Indians Living in Sea Level and High Altitude Areas. Scientific Reports vol. 8 (2018).

Wang, W. et al. Exposure to concentrated ambient PM2.5 alters the composition of gut microbiota in a murine model. Particle and Fibre Toxicology vol. 15 (2018).

Attademo, L. & Bernardini, F. Air Pollution as Risk Factor for Mental Disorders: In Search for a Possible Link with Alzheimer’s Disease and Schizophrenia. J. Alzheimers. Dis. 76, 825–830 (2020).

Fu, P. & Yung, K. K. L. Air Pollution and Alzheimer’s Disease: A Systematic Review and Meta-Analysis. J. Alzheimers. Dis. 77, 701–714 (2020).



How to Cite

Vundi, S., & Chatila, Z. (2022). The Gut Microbiome and Alzheimer’s Disease: Can the Gut be Used to Prevent or Treat Dementia?. Journal of Student Research, 11(4).



HS Review Articles