Modulation of Gut Microbiota through Mediterranean Diet as a New Insight for the Alzheimer's Disease Therapy

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Alessa Fahira
Hansel Tengara Widjaja
Nathaniel Aditya


Despite the fact that Alzheimer’s disease (AD) is one of the most common form of dementia, its underlying pathogenesis has not yet fully known. As it is an intricate and multifactorial disease, finding a potential therapy intercepting its pathological process is still out of reach. With an increase in evidence of the success of gut microbiota modulation as a therapy to other diseases, one should consider the same possibility in AD. Therefore, this literature review focuses on exploring the possibility of dietary intervention as an innovative therapy for AD by modulating the gut microbiota composition, based on recent researches. The method used to assemble this literature review is by performing a comprehensive literature search with corresponding keywords. The result is that Mediterranean dietary intervention, characterized by the high intake of omega-3 polyunsaturated fatty acids, antioxidant nutrients, and vitamins, has shown to be beneficial for brain functions development, targeting the gut-brain axis. However, a higher level of evidence-based research is still needed to more confirm the findings in hope for a future implementation of this new insight as a therapy for AD and to unfold the gut microbiota role in it.

Keywords: ‘Alzheimer Disease’, ‘Gut Microbiota’, ‘Gut-brain axis’ and ‘Mediterranean Diet’.

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How to Cite
Fahira, A., Widjaja, H. T. and Aditya, N. (2019) “Modulation of Gut Microbiota through Mediterranean Diet as a New Insight for the Alzheimer’s Disease Therapy”, Journal of Asian Medical Students’ Association. Kuala Lumpur, Malaysia, 7(1). Available at: (Accessed: 6July2022).
Review Article


Duthey B. Alzheimer disease and other dementias [Internet]. WHO; 2013 [cited 2017 Jan 28]. Available from:

WHO | Dementia [Internet]. WHO; 2016 [cited 2017 Jan 28]. Available from:

Kemenkes RI | Menkes: Lansia yang sehat, lansia yang jauh dari demensia [Internet]. Kemenkes RI; 2016 [cited 2017 Jan 28]. Available from:

Swerdlow RH. Pathogenesis of Alzheimer's disease. Clin Interv Aging. 2007 Sep;2(3):347.

Carmo Carreiras M, Mendes E, Jesus Perry M, Paula Francisco A, Marco-Contelles J. The multifactorial nature of Alzheimer’s disease for developing potential therapeutics. Curr Top Med Chem. 2013 Aug 1;13(15):1745-70.

DuPont HL. Review article: evidence for the role of gut microbiota in irritable bowel syndrome and its potential influence on therapeutic targets. Aliment Pharmacol Ther. 2014 May 1;39(10):1033–42.

Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkïla J, Monti D, Satokari R, Franceschi C, Brigidi P. Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PloS One. 2010 May 17;5(5):e10667.

Sampson TR, Mazmanian SK. Control of brain development, function, and behavior by the microbiome. Cell Host Microbe. 2015 May 13;17(5):565-76.

Minter MR, Zhang C, Leone V, Ringus DL, Zhang X, Oyler-Castrillo P, Musch MW, Liao F, Ward JF, Holtzman DM, Chang EB. Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease. Sci Rep. 2016;6.

Rodgers AB. Alzheimer's disease: unraveling the mystery. National Institutes of Health; 2008.

Puzzo D, Gulisano W, Arancio O, Palmeri A. The keystone of Alzheimer pathogenesis might be sought in Aβ physiology. Neuroscience. 2015 Oct 29;307:26-36.

Hooper LV, Gordon JI. Commensal host-bacterial relationships in the gut. Science. 2001 May;292(5519):1115-8.

Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende DR, et al. Enterotypes of the human gut microbiome. Nature. 2011 May;473(7346):174-80.

Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjorkholm B, Samuelsson A, et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A. 2011 Feb;108(7):3047-52.

Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol London. 2004 May;558(1):263–75.

Hu X, Wang T, Jin F. Alzheimer’s disease and gut microbiota. Sci China Life Sci. 2016 Oct;59(10):1006–23.

Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol. 2009 Nov;9(11):799-809.

Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland N. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015 Oct;9:392.

Kahn MS, Kranjac D, Alonzo CA, Haase JF, Cedillos RO, McLinden KA, et al. Prolonged elevation in hippocampal A beta and cognitive deficits following repeated endotoxin exposure in the mouse. Behav Brain Res. 2012 Apr;229(1):176-84.

Deane R, Wu ZH, Zlokovic BV. RAGE (Yin) versus LRP (Yang) balance regulates Alzheimer amyloid beta-peptide clearance through transport across the blood-brain barrier. Stroke. 2004 Nov;35(11 Suppl 1):2628-31.

LaRue B, Hogg E, Sagare A, Jovanovic S, Maness L, Maurer C, et al. Method for measurement of the blood-brain barrier permeability in the perfused mouse brain: application to amyloid-beta peptide in wild type and Alzheimer’s Tg2576 mice. J Neurosci Methods. 2004 Sep;138(1-2):233-42.

Barrett E, Ross RP, O’Toole PW, Fitzgerald GF, Stanton C. gamma-Aminobutyric acid production by culturable bacteria from the human intestine. J Appl Microbiol. 2012 Aug;113(2):411-7.

Lanctot KL, Herrmann N, Mazzotta P, Khan LR, Ingber N. GABAergic function in Alzheimer’s disease: evidence for dysfunction and potential as a therapeutic target for the treatment of behavioural and psychological symptoms of dementia. Can J Psychiat. 2004 Jul;49(7):439-53.

Solas M, Puerta E, Ramirez MJ. Treatment options in Alzheimer’s disease: the GABA story. Curr Pharm Des. 2015;21(34):4960-71.

Cirrito JR, Disabato BM, Restivo JL, Verges DK, Goebel WD, Sathyan A, et al. Serotonin signaling is associated with lower amyloid-beta levels and plaques in transgenic mice and humans. Proc Natl Acad Sci U S A. 2011 Sep;108(36):14968-73.

Wang T, Hu X, Liang S, Li W, Wu X, Wang L, et al. Lactobacillus fermentum NS9 restores the antibiotic induced physiological and psychological abnormalities in rats. Benef Microbes. 2015;6(5):707-17.

Yiannopoulou KG, Papageorgiou SG. Current and future treatments for Alzheimer’s disease. Therapeutic advances in neurological disorders. 2013 Jan;6(1):19-33.

Lanctôt KL, Rajaram RD, Herrmann N. Review: Therapy for Alzheimer's disease: how effective are current treatments?. Therapeutic advances in neurological disorders. 2009 May 1;2(3):163-80.

Waite LM. Treatment for Alzheimer’s disease: has anything changed?. Australian prescriber. 2015 Apr;38(2):60.

Sofi F, Macchi C, Abbate R, Gensini GF, Casini A. Effectiveness of the Mediterranean diet: can it help delay or prevent Alzheimer's disease?. Journal of Alzheimer's Disease. 2010 Jan 1;20(3):795-801.

Graf D, Di Cagno R, Fåk F, Flint HJ, Nyman M, Saarela M, Watzl B. Contribution of diet to the composition of the human gut microbiota. Microbial ecology in health and disease. 2015 Feb 4;26.

Hu X, Wang T, Jin F. Alzheimer’s disease and gut microbiota. Science China Life Sciences. 2016;59(10):1006-1023.

Sandhu KV, Sherwin E, Schellekens H, Stanton C, Dinan TG, Cryan JF. Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry. Translational Research. 2017 Jan 31;179:223-44.

Safouris A, Tsivgoulis G, N Sergentanis T, Psaltopoulou T. Mediterranean diet and risk of dementia. Current Alzheimer Research. 2015 Oct 1;12(8):736-44.

Estruch RSalas-Salvadó J. “Towards an even healthier mediterranean diet”. Nutrition, Metabolism and Cardiovascular Diseases. 2013;23(12):1163-1166.

Marlow G, Ellett S, Ferguson I, Zhu S, Karunasinghe N, Jesuthasan A et al. Transcriptomics to study the effect of a Mediterranean-inspired diet on inflammation in Crohn's disease patients. Human Genomics. 2013;7(1):24.

Yehuda S, Rabinovitz S, Mostofsky D. Essential fatty acids and the brain: From infancy to aging. Neurobiology of Aging. 2005;26(1):98-102.

Liu T, Hougen H, Vollmer A, Hiebert S. Gut bacteria profiles of Mus musculus at the phylum and family levels are influenced by saturation of dietary fatty acids. Anaerobe. 2012;18(3):331-337.

Yu H, Zhu J, Pan W, Shen S, Shan W, Das U. Effects of Fish Oil with a High Content of n-3 Polyunsaturated Fatty Acids on Mouse Gut Microbiota. Archives of Medical Research. 2014;45(3):195-202.

Scarmeas N, Luchsinger JA, Schupf N, et al: Physical activity, diet, and risk of Alzheimer disease. JAMA 2009; 302:627-637

Tangney CC, Kwasny MJ, Li H, et al: Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population. Am J Clin Nutr 2011; 93:601-607

Mosconi L, Murray J, Tsui WH, Li Y, Davies M, Williams S, Pirraglia E, Spector N, Osorio RS, Glodzik L, McHugh P. Mediterranean diet and magnetic resonance imaging-assessed brain atrophy in cognitively normal individuals at risk for Alzheimer's disease. The journal of prevention of Alzheimer's disease. 2014 Jun;1(1):23.