Acta Scientific Nutritional Health (ASNH)(ISSN: 2582-1423)

Mini Review Volume 7 Issue 7

The role of Microbiota in the Pathogenesis of Alzheimer’s Disease

Aastha Sharma and Ian James Martins*

Edith Cowan University, Sarich Neuroscience Research Institute, Nedlands, Australia

*Corresponding Author: Ian James Martins, Edith Cowan University, Sarich Neuroscience Research Institute, Nedlands, Australia

Received: May 23, 2023; Published: June 29, 2023


The World Health Organization has reported that in 2020 approximately 55 million people live with dementia worldwide with 10 million new cases every year. Alzheimer’s disease (AD) is the most common form of dementia and contributes to 60-70% of dementia cases. The role of gut microbiota with host metabolic regulation that acts as a bridge between the food lipids and the health of AD individuals has become of major concern. Microbiome composition has been linked to neurodegenerative disease and plays a critical role in the gut and brain axis. Microbial fermentation may release short-chain fatty acids such as butyric acid that have a major influence on the gut-brain axis with effects on brain amyloid beta levels and plaque deposition. Butyric acid is involved in brain histone acetylation and deacetylation plays an important role in metabolic regulation, brain amyloidosis and the pathogenesis of AD. Several mechanistic studies are required to determine the underlying mechanisms for effective and safe probiotic treatment for AD and the relevance of gut dysbiosis may be the cause of the induction of the pathogenesis of AD. The safety of probiotic therapy for AD patients requires investigation with relevance to the induction of dyslipidemia and the release of bacterial lipopolysaccharides and amyloid beta from gram-negative bacteria needs to be controlled in these probiotic formulations. In this review, we will summarize the knowledge of the characteristics of the gut microbiota and the communication pathways of the microbiota-gut-brain axis, analyse the role of dysbiosis of the gut microbiota in the pathogenesis of AD, and highlight the modification of gut microbiota composition as a preventive or therapeutic approach for AD) and the benefits, limitations and safety of gut microbiota and probiotics on the metabolic regulation by LPS and lipids are required to delay or reverse the pathogenesis of Alzheimer’s disease.

Keywords: Alzheimer’s Disease; Probiotic; Short Chain Fatty Acid (SCFA); Lipopolysaccharide (LPS)


  1. Hooper LV., et al. “Interactions between the microbiota and the immune system”. Science 336 (2012): 1268-1273.
  2. Lynch SV and Pedersen O. “The human intestinal microbiome in health and disease”. The New England Journal of Medicine 375 (2016): 2369-2379. 
  3. Cryan JF and Dinan TG. “Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour”. Nature Reviews Neuroscience 13 (2012): 701-712. 
  4. Hillman ET., et al. “Microbial ecology along the gastrointestinal tract”. Microbes and Environments 32 (2017): 300-313. 
  5. Silva YP., et al. “The role of short-chain fatty acids from gut microbiota in gut-brain communication”. Frontiers in Endocrinology. 11 (2020): 25.
  6. Yan R., et al. “Interaction between tea polyphenols and intestinal microbiota in host metabolic diseases from the perspective of the gut-brain axis”. Molecular Nutrition and Food Research 64 (2020): 2000187.
  7. Wang HX and Wang YP. “Gut microbiota-brain axis”. Chinese Medical Journal 129 (2016): 2373-2380.
  8. Martins IJ. “Overnutrition Determines LPS Regulation of Mycotoxin Induced Neurotoxicity in Neurodegenerative Diseases”. International Journal of Molecular Sciences 16 (2015): 29554-29573.
  9. Martins IJ. “Bacterial Lipopolysaccharides and Neuron Toxicity in Neurodegenerative Diseases”. Neurology Research and Surgery 1 (2018): 1-3.
  10. Naomi R., et al. “Probiotics for Alzheimer's Disease: A Systematic Review”. Nutrients 14 (2021): 20.
  11. Marzban A., et al. “The Role of Probiotics in Improving Alzheimer's Disease”. Journal of Nutrition and Food Security 7 (2022): 136-138.
  12. Xiang S., et al. “Efficacy and Safety of Probiotics for the Treatment of Alzheimer's Disease, Mild Cognitive Impairment, and Parkinson's Disease: A Systematic Review and Meta-Analysis”. Frontiers in Aging Neuroscience 14 (2022): 730036.
  13. Kandasamy S., et al. “Unraveling the Differences between Gram-Positive and Gram-Negative Probiotics in Modulating Protective Immunity to Enteric Infections”. Frontiers in Immunology 8 (2017): 334.
  14. Behnsen J., et al. “Probiotics: properties, examples, and specific applications”. Cold Spring Harbor Perspectives in Medicine 3 (2013): a010074.
  15. Cross ML., et al. “Patterns of cytokine induction by gram-positive and gram-negative probiotic bacteria”. FEMS Immunology and Medical Microbiology 42 (2004) 173-180.
  16. Mazzoli R and Pessione E. “The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling”. Frontiers in Microbiology 7 (2016): 1934.
  17. Clarke G., et al. “Minireview: Gut microbiota: the neglected endocrine organ”. Molecular Endocrinology 28 (2014)1221-1238.
  18. Rios-Covian D., et al. “An Overview on Fecal Branched Short-Chain Fatty Acids Along Human Life and as Related with Body Mass Index: Associated Dietary and Anthropometric Factors”. Frontiers in Microbiology 11 (2020): 973.
  19. Kelly JR., et al. “Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders”. Frontiers in Cellular Neuroscience 9 (2015): 392.
  20. Samuel B.S. et al. “Effects of the gut microbiota on host adiposity are modulated by the Short-chain fatty-acid binding G protein-coupled receptor, Gpr41”. Proceedings of the National Academy of Sciences of the United States of America A 105 (2008)16767-16772.
  21. Bairamian D., et al. “Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease”. Molecular Neurodegeneration 17 (2022): 1-23.
  22. Sun Y., et al. “Neuroprotection of Food Bioactives in Neurodegenerative Diseases: Role of the Gut Microbiota and Innate Immune Receptors”. Journal of Agricultural and Food Chemistry (2023).
  23. Asadi A., et al. “Obesity and gut-microbiota-brain axis: A narrative review”. Journal of Clinical Laboratory Analysis 36 (2022): e24420.
  24. Dowling LR., et al. “Enteric nervous system and intestinal epithelial regulation of the gut-brain axis”. Journal of Allergy and Clinical Immunology 150 (2022): 513-522.
  25. Dicks LM. “Gut Bacteria and Neurotransmitters”. Microorganisms 10 (2022): 1838.
  26. Ojeda J., et al. “Gut Microbiota Interaction with the Central Nervous System throughout Life”. Journal of Clinical Medicine 10 (2021): 1299.
  27. Ma Q., et al. “Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis”. Journal of Neuroinflammation 16 (2019): 53.
  28. Carabotti M., et al. “The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems”. Annals of Gastroenterology 28 (2015): 203-209.
  29. Salami M and Soheili M. “The microbiota-gut- hippocampus axis”. Frontiers in Neuroscience 16 (2022): 1065995.
  30. Amato A., et al. “Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity and neurotransmission-related proteins in young recipients”. Microbiome 8 (2020): 140.
  31. Kumar M., et al. “Human gut microbiota and healthy aging: Recent developments and future prospective”. Nutrition Healthy Aging 4 (2016): 3-16.
  32. Principi N and Esposito S. “Gut microbiota and central nervous system development”. Journal of Infection 73 (2016): 536-546.
  33. Hirschberg S., et al. “Implications of diet and the gut microbiome in neuroinflammatory and neurodegenerative diseases”. International Journal of Molecular Sciences 20 (2019): 3109.
  34. Maiuolo J., et al. “The contribution of gut microbiota-brain axis in the development of brain disorders”. Frontiers in Neuroscience 15 (2021): 616883.
  35. D’Amato A., et al. “Faecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity-and neurotransmission-related proteins in young recipients”. Microbiome. 8 (2020): 1-9.
  36. Boehme M., et al. “Microbiota from young mice counteracts selective age-associated behavioral deficits”. Nature Aging 1 (2021): 666-676.
  37. Serra N., et al. “Human bile microbiota: a retrospective study focusing on age and gender”. Journal of Infection and Public Health 14 (2021): 206-213.
  38. Roy J., et al. “Regulation of melatonin and neurotransmission in Alzheimer’s disease”. International Journal of Molecular Sciences 22 (2021): 6841.
  39. Liu Y., et al. “Fiber derived microbial metabolites prevent acute kidney injury through G-protein coupled receptors and HDAC inhibition”. Frontiers in Cell and Developmental Biology 9 (2021): 648639.
  40. Dalile B., et al. “The role of short-chain fatty acids in microbiota-gut-brain communication”. Nature Reviews Gastroenterology and Hepatology 16 (2019): 461-478.
  41. Portincasa P., et al. “Gut microbiota and short chain fatty acids: implications in glucose homeostasis”. International Journal of Molecular Sciences 23 (2022): 1105.
  42. Kim CH. “Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids”. Cellular and Molecular Immunology 18 (2021): 1161-1171.
  43. Ohkubo M., et al. “Nicotinate uptake by two kinetically distinct Na+-dependent carrier-mediated transport systems in the rat small intestine”. Drug Metabolism and Pharmacokinetics 27 (2012): 255-262.
  44. Yang Q., et al. “Short-chain fatty acids: a soldier fighting against inflammation and protecting from tumorigenesis in people with diabetes”. Frontiers in Immunology. 11 (2020): 590685.
  45. Dalile B., et al. “The role of short-chain fatty acids in microbiota-gut-brain communication”. Nature Reviews Gastroenterology and Hepatology 16 (2019): 461-478.
  46. Amagase Y., et al. “Peripheral Regulation of Central Brain-Derived Neurotrophic Factor Expression through the Vagus Nerve”. International Journal of Molecular Sciences. 24 (2023): 3543.
  47. Grover M and Kashyap PC. “Germ‐free mice as a model to study effect of gut microbiota on host physiology”. Neurogastroenterology and Motility 26 (2014): 745-748.
  48. Segarra M., et al. “Blood-brain barrier dynamics to maintain brain homeostasis”. Trends in Neurosciences 44 (2021): 393-405.
  49. Knox EG., et al. “The blood-brain barrier in aging and neurodegeneration”. Molecular Psychiatry 27 (2022): 2659-2673.
  50. Qian XH., et al. “Mechanisms of short-chain fatty acids derived from gut microbiota in Alzheimer's disease”. Aging and Disease 13 (2022): 1252.
  51. Derome N and Filteau M. “A continuously changing selective context on microbial communities associated with fish, from egg to fork”. Evolutionary Applications 13 (2020): 1298-319.
  52. Yukgehnaish K., et al. “Gut microbiota metagenomics in aquaculture: Factors influencing gut microbiome and its physiological role in fish”. Reviews in Aquaculture 12 (2020): 1903-1927.
  53. Overby HB and Ferguson JF. “Gut microbiota-derived short-chain fatty acids facilitate microbiota: host cross talk and modulate obesity and hypertension”. Current Hypertension Reports 23 (2021): 1-10.
  54. Gu C., et al. “Isoleucine plays an important role for maintaining immune function”. Current Protein and Peptide Science 20 (2019): 644-651.
  55. Alagawany M., et al. “Nutritional significance of amino acids, vitamins and minerals as nutraceuticals in poultry production and health-a comprehensive review”. Veterinary Quarterly 41 (2021): 1-29.
  56. Thriene K and Michels KB. “Human Gut Microbiota Plasticity throughout the Life Course”. International Journal of Environmental Research and Public Health 20 (2023): 1463.
  57. Ramires LC., et al. “The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut?” International Journal of Molecular Sciences 23 (2022): 1494.
  58. Zhao J. “Th17 cells in inflammatory bowel disease: cytokines, plasticity, and therapies”. Journal of Immunology Research 22 (2021): 2021.
  59. Radu AF and Bungau SG. “Management of rheumatoid arthritis: an overview”. Cells. 10 (2021): 2857.
  60. Norris JM., et al. “Type 1 diabetes-early life origins and changing epidemiology”. The lancet Diabetes and Endocrinology 8 (2020): 226-238.
  61. Hauser SL and Cree BA. “Treatment of multiple sclerosis: a review”. The American Journal of Medicine 133 (2020): 1380-1390.
  62. Paolini Paoletti F., et al. “The contribution of small vessel disease to neurodegeneration: focus on Alzheimer’s disease, Parkinson’s disease and multiple sclerosis”. International Journal of Molecular Sciences 22 (2021): 4958.
  63. Di Lorenzo F., et al. “A journey from structure to function of bacterial lipopolysaccharides”. Chemical Reviews 122 (2021): 15767-15821.
  64. Chen J., et al. “New insights into the mechanisms of high‐fat diet mediated gut microbiota in chronic diseases”. iMeta (2023): e69.
  65. Xiao X., et al. “Gut immunity and microbiota dysbiosis are associated with altered bile acid metabolism in LPS-challenged piglets”. Oxidative Medicine and Cellular Longevity 2021 (2021): 1-5.
  66. Kim MS., et al. “Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model”. Gut 69 (2020): 283-294.
  67. Kowalski K and Mulak A. “Brain-gut-microbiota axis in Alzheimer’s disease”. Journal of Neurogastroenterology and Motility 25 (2019): 48.
  68. Goel A and Singh S. “Emerging approaches for the treatment of Alzheimer disease: Targeting NF-κB pathway”. Authorea (2020).
  69. Van Gerven N., et al. “Bacterial amyloid formation: structural insights into curli biogenesis”. Trends in Microbiology 23 (2015): 693-706.
  70. Benomar S., et al. “Plasmid-encoded H-NS controls extracellular matrix composition in a modern Acinetobacter baumannii urinary isolate”. Journal of Bacteriology 203 (2021): e00277-321.
  71. Ariza ME., et al. “The EBV-encoded dUTPase activates NF-κB through the TLR2 and MyD88-dependent signaling pathway”. The Journal of Immunology 182 (2009): 851-859.
  72. Zhan X., et al. “Lipopolysaccharide associates with amyloid plaques, neurons and oligodendrocytes in Alzheimer’s disease brain: a review”. Frontiers in aging neuroscience. 10 (2018): 42.
  73. García-Fernández P., et al. “From the low-density lipoprotein receptor-related protein 1 to neuropathic pain: a potentially novel target”. Pain Reports 6 (2021).
  74. Gabarin RS., et al. “Intracellular and extracellular lipopolysaccharide signaling in sepsis: avenues for novel therapeutic strategies”. Journal of Innate Immunity 13 (2021): 323-332.
  75. Cai SY., et al. “C-reactive protein/serum amyloid P promotes pro-inflammatory function and induces M1-type polarization of monocytes/macrophages in mudskipper, Boleophthalmus pectinirostris”. Fish and Shellfish Immunology 94 (2019): 318-326.
  76. Chan EW., et al. “The NLRP3 inflammasome is involved in the neuroprotective mechanism of neural stem cells against microglia-mediated toxicity in SH-SY5Y cells via the attenuation of tau hyperphosphorylation and amyloidogenesis”. Neurotoxicology 70 (2019): 91-98.
  77. Heidari A., et al. “The role of Toll-like receptors and neuroinflammation in Parkinson’s disease”. Journal of Neuroinflammation 19 (2022): 1-21.
  78. Khodabakhsh P., et al. “Does Alzheimer's disease stem in the gastrointestinal system?” Life Sciences 287 (2021): 120088.
  79. Blagov AV., et al. “Role of impaired mitochondrial dynamics processes in the pathogenesis of Alzheimer’s disease”. International Journal of Molecular Sciences 23 (2022): 6954.
  80. Memon RA., et al. “Endotoxin and cytokines increase hepatic sphingolipid biosynthesis and produce lipoproteins enriched in ceramides and sphingomyelin”. Arteriosclerosis, Thrombosis, and Vascular Biology 18 (1998): 1257-1265.
  81. Régnier M., et al. “Sphingolipid metabolism in non-alcoholic fatty liver diseases”. Biochimie 159 (2019): 9-22.
  82. Simon J., et al. “Sphingolipids in Non-Alcoholic Fatty Liver Disease and Hepatocellular Carcinoma: Ceramide Turnover”. International Journal of Molecular Sciences 21 (2019): 40.
  83. Carpino G., et al. “Increased Liver Localization of Lipopolysaccharides in Human and Experimental NAFLD”. Hepatology 72 (2020): 470-485.
  84. Fukunishi S., et al. “Lipopolysaccharides accelerate hepatic steatosis in the development of nonalcoholic fatty liver disease in Zucker rats”. Journal of Clinical Biochemistry and Nutrition 54 (2014): 39-44.
  85. Mielke MM., et al. “Serum ceramides increase the risk of Alzheimer disease: the Women's Health and Aging Study II”. Neurology 79 (2012): 633-641.
  86. Chowdhury M.R et al. “Diverse Roles of Ceramide in the Progression and Pathogenesis of Alzheimer’s Disease”. Biomedicines 10 (2022): 1956.
  87. Feingold KR., et al. “Effect of endotoxin on cholesterol biosynthesis and distribution in serum lipoproteins in Syrian hamsters”. Journal of Lipid Research 34 (1993): 2147-2158.
  88. Tan LY., et al. “Association of gut microbiome dysbiosis with neurodegeneration: can gut microbe-modifying diet prevent or alleviate the symptoms of neurodegenerative diseases?” Life 11 (2021): 698.
  89. Kim M and Benayoun BA. “The microbiome: an emerging key player in aging and longevity”. Translational Medicine of Aging (2020): 103-116.
  90. Agatonovic-Kustrin S., et al. “A molecular approach in drug development for Alzheimer’s disease”. Biomedicine and Pharmacotherapy 106 (2018): 553-565.
  91. Portincasa P., et al. “Gut microbiota and short chain fatty acids: implications in glucose homeostasis”. International Journal of Molecular Sciences 23 (2022): 1105.
  92. Bianchi VE., et al. “Effect of nutrition on neurodegenerative diseases. A systematic review”. Nutritional Neuroscience 24 (2021): 810-834.
  93. Chen X., et al. “Dietary patterns and cognitive health in older adults: a systematic review”. Journal of Alzheimer's Disease2 (2019): 583-619.
  94. Mietelska-Porowska A., et al. “Induction of Brain Insulin Resistance and Alzheimer’s Molecular Changes by Western Diet”. International Journal of Molecular Sciences 23 (2022): 4744.
  95. Ruiz-Gonzalez C., et al. “Effects of probiotics supplementation on dementia and cognitive impairment: A systematic review and meta-analysis of preclinical and clinical studies”. Progress in Neuro-Psychopharmacology and Biological Psychiatry 108 (2021): 110189.
  96. Mitić M and Lazarević-Pašti T. “Does the application of acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease lead to depression?” Expert Opinion on Drug Metabolism and Toxicology. 17 (2021): 841-856.
  97. Tang W., et al. “Roles of gut microbiota in the regulation of hippocampal plasticity, inflammation, and hippocampus-dependent behaviors”. Frontiers in Cellular and Infection Microbiology 10 (2021): 611014.
  98. Bairamian D., et al. “Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease”. Molecular Neurodegeneration 17 (2022): 1-23.
  99. Bonfili L., et al. “Microbiota modulation as preventative and therapeutic approach in Alzheimer’s disease”. The FEBS Journal 288 (2021): 2836-2855.
  100. Jha R., et al. “Probiotics (direct-fed microbials) in poultry nutrition and their effects on nutrient utilization, growth and laying performance, and gut health: A systematic review”. Animals 10 (2020): 1863.
  101. Baillo A., et al. “Lactiplantibacillus plantarum Strains Modulate Intestinal Innate Immune Response and Increase Resistance to Enterotoxigenic Escherichia coli Infection”. Microorganisms 11 (2023): 63.
  102. Lin WY., et al. “Probiotics and their metabolites reduce oxidative stress in middle-aged mice”. Current Microbiology 79 (2022): 104.
  103. Averina OV., et al. “Biomarkers and utility of the antioxidant potential of probiotic Lactobacilli and Bifidobacteria as representatives of the human gut microbiota”. Biomedicines 9 (2021): 1340.


Citation: Aastha Sharma and Ian James Martins. “The role of Microbiota in the Pathogenesis of Alzheimer’s Disease".Acta Scientific Nutritional Health 7.7 (2023): 108-118.


Copyright: © 2023 Aastha Sharma and Ian James Martins. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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