The Relationship Between Microbiota and Alzheimer’s Disease

Abstract

The term microbiota refers to the micro-organisms that interact with the host from birth to death. These interactions can reach the brain via the bloodstream or the gut-brain nervous system. The microbiota performs important beneficial functions, such as contributing to digestive processes, breaking down toxins and creating defense mechanisms against pathogenic bacteria. However, this positive situation only takes place when the microbiota is also positive, i.e. when the probiotics, known as eubiosis, are dominant. Factors such as nutritional habits, age and the use of antibiotics can impair the balance of the microbiota and lead to a situation where harmful microorganisms, known as dysbiosis, are dominant in the gut. In this case, the production of many microbial products that are normally beneficial to the body, such as neurotransmitters and some short-chain fatty acids, reduces and pathogenic metabolites are produced. In the case of dysbiosis, intestinal permeability increases, allowing harmful pathogenic metabolites to enter the bloodstream and even reach the brain via the bloodstream. For these reasons, prolonged dysbiosis is known to pave the way for many diseases such as depression, anxiety, schizophrenia, autism, diabetes, and Alzheimer’s disease. Alzheimer’s disease is characterized by the death of nerve cells in the brain and loss of cognitive abilities. The disease is associated with amyloid plaques and tau protein. It has been argued that disruption of the intestinal microbiota may contribute to the pathology of Alzheimer’s disease and may also have therapeutic potential. Amyloid production may be triggered by the intestinal microbiome, causing a way for the studies on Alzheimer’s disease. This review examines the relationship between the intestinal microbiota and Alzheimer’s disease.

Keywords

• Microbiota
• Alzheimer’s
• Probiotics

References

1. Akbari, E., Asemi, Z., Daneshvar Kakhaki, R., Bahmani, F., Kouchaki, E., Tamtaji, O.R., Hamidi, G.A., & Salami, M. (2016). Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer’s disease: a randomized, double-blind and controlled trial. Frontiers in Aging Neuroscience, 8, 256. https://doi.org/10.3389/fnagi.2016.00256.
2. Angelucci, F., Cechova, K., Amlerova, J., & Hort, J. (2019). Antibiotics, gut microbiota, and Alzheimer’s disease. Journal of Neuroinflammation, 16(1), 108. https://doi.org/10.1186/s12974-019-1494-4.
3. Barnard, N.D., Bunner, A.E., & Agarwal, U. (2014). Saturated and trans fats and dementia: a systematic revew. Neurobiology of Aging, 35(2), 65-73. https://doi.org/10.1016/j.neurobiolaging.2014.02.030.
4. Bezirtzoglou, E., Tsiotsias, A., & Welling, G.W. (2011). Microbiota profile in feces of breast- and formula-fed newborns by using fluorescence in situ hybridization (FISH). Anaerobe, 17(6), 478–482. https://doi.org/10.1016/j.anaerobe.2011.03.009.
5. Bremner, J.D., Moazzami, K., Wittbrodt, M.T., Nye, J.A., Lima, B.B., Gillespie, C.F., Rapaport, M.H., Pearce, B., Shah, A.J., & Vaccarino, V. (2020). Diet, stress and mental health. Nutrients, 12(8), 2428. https://doi.org/10.3390/nu12082428.
6. Carabotti, M., Scirocco, A., Maselli, M.A., & Severi, C. (2015). The gutbrain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of Gastroenterology, 28(2), 203-209.
7. Chen, S.G., Stribinskis, V., Rane, M.J., Demuth, D.R., Gozal, E., Roberts., A.M., Jagadapillai, R., Liu, R., Choe, K., Shivakumar, B., Son, F., Jin, S., Kerber, R., Adame, A., Masliah, E., & Friedland R.P. (2016). Exposure to the functional bacterial amyloid protein curli enhances alphasynuclein aggregation in aged fischer 344 rats and caenorhabditis elegans. Scientific Reports, 6, 34477. https://doi.org/10.1038/srep34477.
8. Coelho, G.D.P., Ayres, L.F.A., Barreto, D.S., Henriques, B.D., Prado, M.R.M.C., & Passos, C.M.D. (2021). Acquisition of microbiota according to the type of birth: An integrative review. Revista Latinoamericana de Enfermagem, 29, e3446. https://doi.org/10.1590/1518.8345.4466.3446.

9. Çetinbaş, S., Kemeriz, F., Göker, G., Biçer, İ., & Velioğlu, Y.S. (2017). İnsan mikrobiyomu: beslenme ve sağlık üzerindeki etkileri. Akademik Gıda, 15(4), 409-415.
10. Doenyas, C. (2018). Mikrobiyota ve otizm. Türkiye Sağlık Bilimleri ve Araştırmaları Dergisi, 1(2), 43-48.
11. Eskelinen, M.H., Ngandu, T., Tuomilehto, J., Soininen, H., & Kivipelto, M. (2009). Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study. Journal of Alzheimers Disease, 16(1), 85-91. https://doi.org/10.3233/JAD-2009-0920.
12. Flemer, B., Gaci, N., Borrel, G., Sanderson, I.R., Chaudhary, P.P., Tottey, W., O’Toole, P.W., & Brugère, J.F. (2017). Fecal microbiota variation across the lifespan of the healthy laboratory rat. Gut Microbes, 8(5), 428-439. https://doi.org/10.1080/19490976.2017.1334033.
13. Garcia-Mazcorro, J.F., Lanerie, D.J., Dowd, S.E., Paddock, C.G., Grützner, N., Steiner, J.M., Ivanek, R., & Suchodolski, J.S. (2011). Effect of a multi-species synbiotic formulation on fecal bacterial microbiota of healthy cats and dogs as evaluated by pyrosequencing. FEMS Microbiology Ecology, 78(3), 542-554. https://doi.org/10.1111/j.1574-6941.2011.01185.x.
14. Gerritsen, J., Smidt, H., Rijkers, G.T., & de Vos, W.M. (2011). Intestinal microbiota in human health and disease: the impact of probiotics. Genes & Nutrition, 6(3), 209-240. https://doi.org/10.1007/s12263-011-0229-7.
15. Green, M., Arora, K., & Prakash, S. (2020). Microbial medicine: prebiotic and probiotic functional foods to target obesity and metabolic syndrome. International Journal of Molecular Sciences, 21(8), 2890.
16. Guaraldi, F., & Salvatori, G. (2012). Effect of breast and formula feding on gut microbiota shaping in newborns. Frontiers in Cellular and Infection Microbiology, 2, 94. https://doi.org/10.3389/fcimb.2012.00094.
17. Hou, K., Wu. Z-X., Chen, X-Y., Wang, J-Q., Zhang, D., Xiao, C., Zhu, D., Koya, J.B., Wei, L., Li, J., & Chen, Z-S. (2022). Microbiota in health and diseases. Signal Transduction and Targeted Therapy, 7(1), 135. https://doi.org/10.1038/s41392-022-00974-4.
18. Kalip, K., & Nazlı, A. (2018). Bağırsak mikrobiyotası ve sağlık. Turkish Journal of Public Health, 16(1), 58-73.
19. Keleş, E., & Özalevli, S. (2018). Alzheimer hastalığı ve tedavi yaklaşımları. İzmir Kâtip Çelebi Üniversitesi Sağlık Bilimleri Fakültesi Dergisi, 3(2), 39-42.
20. Kelly, J.R., Clarke, G., Cryan, J.F., & Dinan, T.G. (2016). Brain-gutmicrobiota axis: challenges for translation in psychiatry. Annals of Epidemiology, 26(5), 366-372. https://doi.org/ 10.1016/j.annepidem.2016.02.008.
21. Koçak, T., & Şanlıer, N. (2017). Mikrobesin öğeleri ve mikrobiyota etkileşimi. Gümüşhane Üniversitesi Sağlık Bilimleri Dergisi, 6(4), 290-302.
22. Kowalski, K., & Mulak, A. (2019). Brain-gut-microbiota axis in Alzheimer’s disease. Journal of Neurogastroenterology and Motility, 25(1), 48-60. https://doi.org/10.5056/jnm18087.
23. Lamendella, R., Domingo, J.W., Ghosh, S., Martinson, J., & Oerther, D.B. (2011). Comparative fecal metagenomics unveils unique functional capacity of the swine gut. BMC Microbiology, 11, 103. https://doi.org/10.1186/1471-2180-11-103.
24. Li, Z., Zhu, H., Zhang, L., & Qin, C. (2018). The intestinal microbiome and Alzheimer’s disease: A review. Animal Models and Experimental Medicine, 1(3), 180-188. https://doi.org/10.1002/ame2.12033.
25. McKenna, P., Hoffmann, C., Minkah, N., Aye, P.P., Lackner, A., Liu, Z., Lozupone, C..A, Hamady, M., Knight, R., & Bushman, F.D. (2008). The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis. PLoS Pathogenes, 4(2), e20. https://doi.org/10.1371/journal.ppat.0040020.
26. Morris, M.C., Evans, D.A., Bienias, J.L., Tangney, C.C., & Wilson, R.S. (2004). Dietary fat intake and 6-year cognitive change in an older biracial community population. Neurology, 62(9), 1573-1579. https://doi.org/10.1212/01.wnl.0000123250.82849.b6.
27. Nazlıkul, H.s., & Acarkan, T. (2014). Bağırsak ve enterik siṅ iṙ siṡ temiṅ iṅ regülasyondaki ̇ önemi.̇ Bilimsel Tamamlayıcı Tıp Regülasyon ve Nöral Terapi Dergisi, 8(1), 1-7.
28. Nguyen, T.L., Vieira-Silva, S., Liston, A., & Raes, J. (2015). How informative is the mouse for human gut microbiota research? Disease Models Mechanisms, 8(1), 1-16. https://doi.org/10.1242/dmm.017400.
29. Orel, R., & Trop, T.K. (2014). Intestinal microbiota, probiotics and prebiotics in inflammatory bowel disease. World Journal of Gastroenterology, 20(33), 11505-11524. https://doi.org/10.3748/wjg.v20.i33.11505.
30. Özer, M., Özyurt, G., & Harsa, Ş.T. (2019). Probiyotik ve prebiyotiklerin bağırsak-beyin aksına etkisi. Akademik Gıda, 17(2), 269-280.
31. Pedersen, R., Ingerslev, H.C., Sturek, M., Alloosh, M., Cirera, S., Christoffersen, B., Moesgaard, S.G., Larsen, N., & Boye, M. (2013). Characterisation of gut microbiota in ossabaw and göttingen minipigs as models of obesity and metabolic syndrome. PLoS One, 8(2), e56612. https://doi.org/ 10.1371/journal.pone.0056612.
32. Pistollato, F., Sumalla Cano, S., Elio, I., Masias Vergara, M., Giampieri, F., & Battino, M. (2016). Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease. Nutrition Reviews, 74(10), 624-634. https://doi.org/10.1093/nutrit/nuw023.
33. Porsteinsson, A.P., Isaacson, R.S., Knox, S., Sabbagh, M.N., & Rubino, I. (2021). Diagnosis of early Alzheimer’s disease: clinical practice in 2021. The Journal of Prevention of Alzheimer’s Disease, 8(3), 371-386. https://doi.org/10.14283/jpad.2021.23.
34. Rezaeiasl, Z., Salami, M., & Sepehri, G. (2019). The effects of probiotic Lactobacillus and Bifidobacterium strains on memory and learning behavior, long-term potentiation (LTP), and some biochemical parameters in β-amyloid-induced rat’s model of Alzheimer’s disease. Preventive Nutrition and Food Science, 24(3), 265-273. https://doi.org/10.3746/pnf.2019.24.3.265
35. Saka, E. (2010). Pathophysiology of Alzheimer’s diease: experimental and genetic findings. Turkish Journal of Geriatrics, 13(3), 21-26.
36. Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C.E., Cummings, J., & van der Flier, W.M. (2021). Alzheimer’s disease. Lancet, 397(10284), 1577 1590. https://doi.org/10.1016/S0140-6736(20)32205-4.
37. Taşdemir, A. (2017). Probiyotikler, prebiyotikler, sinbiyotikler. Sağlık Akademisi Kastamonu, 2(1), 71-88. https://doi.org/10.25279/sak.300045.
38. Thursby, E., & Juge, N. (2017). Introduction to the human gut microbiota. Biochemical Journal, 474(11), 1823-1836. https://doi.org/10.1042/BCJ20160510.
39. Ton, A., Arpini, C., & Campagnaro, B. (2018). Alzheimer’s disease: a brief update on the influence of gut microbiota and the impact of functional food. International Journal of Food Microbiology, 2(1), 11-15.
40. Tully, A.M., Roche, H.M., Doyle, R., Fallon, C., Bruce, I., Lawlor, B., Coakley, D., Gibney, M.J. (2003). Low serum cholesteryl esterdocosahexaenoic acid levels in Alzheimer’s disease: a case–control study. British Journal of Nutrition, 89(4), 483–489. https://doi.org/10.1079/bjn2002804
41. Turner, P.V. (2018). The role of the gut microbiota on animal model reproducibility. Animal Models and Experimental Medicine, 1(2), 109-115. https://doi.org/10.1002/ame2.12022.
42. Yılmaz, K., & Altındiş, M. (2017). Sindirim sistemi mikrobiyotasi ve fekal transplantasyon. Nobel Medicus, 13(1), 9-15.