The Role of Gut Flora in the Pathogenesis of Alzheimer’s Disease

doi:10.3969/j.issn.2095-1396.2017.05.005

Abstract

Abstract:

Along with aggravation of aging of population，the incidence of Alzheimer’s disease is getting higher and higher. However，etiological treatment of this disease is still unsatisfying. In recent years，the role of gut flora in the pathogenesis of AD has received more and more attention. Types and ratios of gut flora change along with the growth of the age，and the variety of quantities of metabolites makes a difference in the cognitive behavior. Besides，gut flora interacts with gut-brain axis. Nowadays，we have confirmed the role of gut flora in mechanisms of the pathogenesis of AD，including amyloidosis，hyperphosphorylation of tau protein，neuro-inflammation，oxidative stress damage，increase of the permeability of the bloodbrain barrier neurotransmitter imbalance and insulin resistance. In the future，specific regulation of pathogenesis-related gut bacteria will be an important research area.

Key words: gut flora, Alzheimer’s disease, mechanisms of pathogenesis

CLC Number:

R964

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LIU Nuo，WANG Zhen-zhen，CHEN Nai-hong. The Role of Gut Flora in the Pathogenesis of Alzheimer’s Disease[J]. Acta Neuropharmacologica, DOI: 10.3969/j.issn.2095-1396.2017.05.005.

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References

1 William E Reichman, Nathan S Rose. History and experience: the direction of Alzheimer's disease[J]. Menopause, 2012, 19(7): 724-734.

2 Adele Costabile, Eddie R Deaville, Agustin Martin Morales, et al. Prebiotic potential of a maize-based soluble fibre and impact of dose on the human gut microbiota[J]. PloS one, 2016, 11(1): e0144457.

3 James M Hill, Walter J Lukiw. Microbial-generated amyloids and Alzheimer's disease (AD)[J]. Frontiers in Aging Neuroscience, 2015, 7: 9.

4 Surjyadipta Bhattacharjee, Walter J Lukiw. Alzheimer's disease and the microbiome[J]. Frontiers in Cellular Neuroscience, 2013, 7: 153.

5 Masami Minemura, Yukihiro Shimizu. Gut microbiota and liver diseases[J]. J World Gastroenterology, 2015, 21(6): 1691-1702.

6 Kiyofumi Yamada, Toshitaka Nabeshima. Interaction of BDNF/TrkB signaling with NMDA receptor in learning and memory[J]. Drug News Perspect, 2004, 17(7): 435-438.

7 Premysl Bercik, Emmanuel Denou, Josh Collins, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice[J]. Gastroenterology, 2011, 141(2): 599-609. e3.

8 Liang S, Wang T, Hu X, et al. Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress[J]. Neuroscience, 2015, 310: 561-577.

9 Bhattacharjee S, Lukiw WJ. Alzheimer's disease and the microbiome. Frontiers in cellular neuroscience 7: 153 ; Matsumoto M, Benno Y (2004) Consumption of Bifidobacterium lactis LKM512 yogurt reduces gut mutagenicity by increasing gut polyamine contents in healthy adult subjects[J]. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 568: 147-153,

10 Salazar N, López P, Valdés Let al. Microbial targets for the development of functional foods accordingly with nutritional and immune parameters altered in the elderly[J]. J American College of Nutrition, 2013, 32(6): 399-406.

11 Marcus J Claesson, Siobhan Cusack, Orla O'Sullivan, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly[J]. Proceedings of the National Academy of Sciences, 2011, 108(suppl1): 4586-4591.

12 Claesson M J, Jeffery I B, Conde S, et al. Gut microbiota composition correlates with diet and health in the elderly[J]. Nature, 2012, 488(7410): 178.

13 Odamaki T, Kato K, Sugahara H, et al. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study[J]. BMC Microbiology, 2016, 16: 90.

14 Augusto J Montiel-Castro, Rina M González-Cervantes, Gabriela Bravo-Ruiseco, et al. The microbiota-gut-brain axis: neurobehavioral correlates, health and sociality[J]. Frontiers in Integrative Neuroscience, 2013, 7: 70.

15 Yunes R A, Poluektova E U, Dyachkova M S, et al. GABA production and structure of gadB/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota[J]. Anaerobe, 2016, 42: 197-204.

16 Sun Yun-dong, Zhang Min, Chen Chun-chia, et al. Stress-induced corticotropin-releasing hormone-mediated NLRP6 inflammasome inhibition and transmissible enteritis in mice[J]. Gastroenterology, 2013, 144(7): 1478-1487. e8.

17 O'Mahony S M, Marchesi J R, Scully P, et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses[J]. Biological Psychiatry, 2009, 65: 263-267.

18 Zhao Yu-hai, Walter Lukiw. Microbiome-generated amyloid and potential impact on amyloidogenesis in Alzheimer’s disease (AD)[J]. J Nature and Science, 2015, 1(7), pii: e138:

19 Rashid Deane, Shi Du Yan, Ram Kumar Submamaryan, et al. RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain[J]. Nature Medicine, 2003, 9: 907-913.

20 Abdel-Latif M A, Ali H, Elbestawy A R, et al. Exogenous dietary lysozyme improves the growth performance and gut microbiota in broiler chickens targeting the antioxidant and non-specific immunity mRNA expression[J]. PloS One, 2017, 12(10): e0185153.

21 Rashid Deane, Wu Zhen-hua, Abhay Sagare, et al. LRP/amyloid β-peptide interaction mediates differential brain efflux of Aβ isoforms[J]. Neuron, 2004, 43(3): 333-344.

22 Nicolas Weiss, Florence Miller, Sylvie Cazaubon, et al. The blood-brain barrier in brain homeostasis and neurological diseases[J]. Biochimica et Biophysica Acta , 2009, 1788(4): 842-857.

23 James M Hill, Walter J Lukiw. Microbial-generated amyloids and Alzheimer's disease (AD)[J]. Frontiers in aging neuroscience , 2015, 7: 9.

24 Keshava Abbayya, Nagraj Y Puthanakar, Sanjay Naduwinmani, et al. Association between periodontitis and Alzheimer's disease[J]. North American J Medical Sciences, 2015, 7(6): 241.

25 Rebecca Wall, John F Cryan, R Paul Ross, et al. Bacterial neuroactive compounds produced by psychobiotics. Microbial endocrinology: The microbiota-gut-brain axis in health and disease[J]. Advances in Experimental Medicine & Biology, 2014, 817(817):221.

26 Yan Ming-hui, Han Jin, Xu Xiao-fen, et al. Gsy, a novel glucansucrase from Leuconostoc mesenteroides, mediates the formation of cell aggregates in response to oxidative stress[J]. Scientific Reports, 2016, 6: 38122.

27 Helene M Savignac, Yvonne Couch, Michael Stratford, et al. Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-β levels in male mice[J]. Brain, Behavior, and Immunity, 2016, 52: 120-131.

28 Lehnardt S .Innate immunity and neuroinflammation in the CNS: The role of microglia in Toll‐like receptor‐mediated neuronal injury[J]. Glia, 2010, 58(3): 253-263.

29 Patrice D Cani, Rodrigo Bibiloni, Claude Knauf, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet–induced obesity and diabetes in mice[J]. Diabetes, 2008, 57(6): 1470-1481.

30 Zhao Yu-hai, Vivian Jaber, Walter J Lukiw. Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer's Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus[J]. Frontiers in Cellular and Infection Microbiology, 2017, 7: 318.

31 Sandra Anne Banack, Tracie A Caller, Elijah W Stommel. The cyanobacteria derived toxin beta-N-methylamino-L-alanine and amyotrophic lateral sclerosis[J]. Toxins, 2010, 2: 2837-2850.

32 Brenner S R. Blue-green algae or cyanobacteria in the intestinal micro-flora may produce neurotoxins such as Beta-N-Methylamino-L-Alanine (BMAA) which may be related to development of amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson-Dementia-Complex in humans and Equine Motor Neuron Disease in horses[J]. Medical Hypotheses, 2013, 80: 103.

33 Marnie Potgieter, Janette Bester, Douglas B Kell, et al. The dormant blood microbiome in chronic, inflammatory diseases[J]. FEMS Microbiology Reviews, 2015, 39(4): 567-591.

34 雷曦, 王健辉, 程肖蕊等. 基于快速老化模型小鼠SAMP8的CA-30抗阿尔茨海默病的作用研究[J]. 神经药理学报, 2018, 8(02): 44-45.

35 Dalleau S, Baradat M, Gueraud F, et al . Cell death and diseases related to oxidative stress: 4-hydroxynonenal (HNE) in the balance[J]. Cell Death and Differentiation, 2013, 20: 1615.

36 Lap Ho, Qin Wei-ping, Patrick N Pompl, et al. Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer’s disease[J]. The FASEBJ, 2004, 18(7): 902-904.

37 Pjotr Bekkering, Ismael Jafri, Frans Van Overveld, et al. The intricate association between gut microbiota and development of type 1, type 2 and type 3 diabetes[J]. Expert Review of Clinical Immunology, 2013, 9(11): 1031-1041.

38 I Naseer M, Fehmida Bibi, Mohammed Al-Qahtani, et al. Role of gut microbiota in obesity, type 2 diabetes and Alzheimer’s disease[J]. CNS & Neurological Disorders-Drug Targets, 2014, 13(2): 305-311.

39 Masami Minemura, Yukihiro Shimizu. Gut microbiota and liver diseases[J]. World J Gastroenterology, 2015, 21(6): 1691-1702.

40 Leo Galland. The gut microbiome and the brain[J]. J Medicinal Food, 2014, 17(12): 1261-1272.

41 Anni Woting, Michael Blaut. The intestinal microbiota in metabolic disease[J]. Nutrients, 2016, 8(4): 202.

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