Login Register Cart 0
Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Connectivity between Gut Microbiota and Terminal Awakenings in Alzheimer’s Disease

Author(s): Mehmet Bostancıklıoğlu*

Volume 20, Issue 1, 2023

Published on: 24 May, 2023

Page: [3 - 10] Pages: 8

DOI: 10.2174/1567205020666230504153407

Price: $65

Abstract

Memory is empirically described as a brain function that connects the past to the present. This reductionist approach has focused on memory function within neurons and synapses, leading to an understanding that memory loss in dementia is caused by irreversible neuronal damage. However, recent palliative case reports and the Human Connectome Project have challenged the "irreversible" paradigm by indicating that some demented patients are able to retrieve supposed ‘lost’ memories and cognitive functions near death. The serotonin-centric hypothesis and the lifelong oligodendrocyte differentiation capacity may explain terminal awakening symptoms in these patients. Furthermore, an increased rate of serotonin-secreting and oligodendrocyte precursor cell-triggering gut bacteria near death temporally correlates with lucid improvements in demented patients. These findings may shift the context of terminal memory retrieval from a purely neuronal to a systemic idea that bridges terminal lucidity and gut microbiota. In this review, we take the systemic approach further and point out a temporal correlation between the gut microbiome and terminal lucid episodes in Alzheimer’s patients.

« Previous Next »
[1]
Rovelli C. Memory and entropy. ArXiv 2020. arXiv:2003.06687
[2]
Schrodinger E. What is life?: With mind and matter and autobiographical sketches. Cambridge, UK: Cambridge University Press 2012.
[http://dx.doi.org/10.1017/CBO9781107295629]
[3]
Khachaturian ZS, Khachaturian AS. The paradox of research on Dementia-Alzheimer’s Disease. J Prev Alzheimers Dis 2016; 3(4): 189-91.
[PMID: 29199320]
[4]
Tolar M, Abushakra S, Sabbagh M. The path forward in Alzheimer’s disease therapeutics: Reevaluating the amyloid cascade hypothesis. Alzheimers Dement 2020; 16(11): 1553-60.
[PMID: 31706733]
[5]
Bostancıklıoğlu M. An update on memory formation and retrieval: An engram‐centric approach. Alzheimers Dement 2020; 16(6): 926-37.
[http://dx.doi.org/10.1002/alz.12071] [PMID: 32333509]
[6]
Nahm M, Greyson B, Kelly EW, Haraldsson E. Terminal lucidity: A review and a case collection. Arch Gerontol Geriatr 2012; 55(1): 138-42.
[http://dx.doi.org/10.1016/j.archger.2011.06.031] [PMID: 21764150]
[7]
Mashour GA, Frank L, Batthyany A, et al. Paradoxical lucidity: A potential paradigm shift for the neurobiology and treatment of severe dementias. Alzheimers Dement 2019; 15(8): 1107-14.
[http://dx.doi.org/10.1016/j.jalz.2019.04.002] [PMID: 31229433]
[8]
Bostanciklioğlu M. Unexpected awakenings in severe dementia from case reports to laboratory. Alzheimers Dement 2021; 17(1): 125-36.
[http://dx.doi.org/10.1002/alz.12162] [PMID: 33064369]
[9]
Daumer G. The death of the body - no death of the soul. Dresden: Woldemar Türk 1865.
[10]
Hainmueller T, Bartos M. Dentate gyrus circuits for encoding, retrieval and discrimination of episodic memories. Nat Rev Neurosci 2020; 21(3): 153-68.
[http://dx.doi.org/10.1038/s41583-019-0260-z] [PMID: 32042144]
[11]
Kawaguchi Y, Shindou T. Noradrenergic excitation and inhibition of GABAergic cell types in rat frontal cortex. J Neurosci 1998; 18(17): 6963-76.
[http://dx.doi.org/10.1523/JNEUROSCI.18-17-06963.1998] [PMID: 9712665]
[12]
Wutzler A, Mavrogiorgou P, Winter C, Juckel G. Elevation of brain serotonin during dying. Neurosci Lett 2011; 498(1): 20-1.
[http://dx.doi.org/10.1016/j.neulet.2011.04.051] [PMID: 21545826]
[13]
Sengupta A, Holmes A. A discrete dorsal raphe to basal Amygdala 5-HT circuit calibrates aversive memory. Neuron 2019; 103(3): 489-505.e7.
[http://dx.doi.org/10.1016/j.neuron.2019.05.029] [PMID: 31204082]
[14]
Bostancıklıoğlu M. Optogenetic stimulation of serotonin nuclei retrieve the lost memory in Alzheimer’s disease. J Cell Physiol 2020; 235(2): 836-47.
[http://dx.doi.org/10.1002/jcp.29077] [PMID: 31332785]
[15]
Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, et al. A core gut microbiome in obese and lean twins. nature 2009; 457(7228): 480.
[16]
Song SJ, Lauber C, Costello EK, Lozupone CA, Humphrey G, Berg-Lyons D, et al. Cohabiting family members share microbiota with one another and with their dogs. elife 2013; 2: e00458.
[17]
De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA 2010; 107(33): 14691-6.
[http://dx.doi.org/10.1073/pnas.1005963107] [PMID: 20679230]
[18]
Jangi S, Gandhi R, Cox LM, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun 2016; 7(1): 12015.
[http://dx.doi.org/10.1038/ncomms12015] [PMID: 27352007]
[19]
Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011; 334(6052): 105-8.
[http://dx.doi.org/10.1126/science.1208344] [PMID: 21885731]
[20]
David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature 2014; 505(7484): 559-63.
[http://dx.doi.org/10.1038/nature12820] [PMID: 24336217]
[21]
O’Keefe SJD, Li JV, Lahti L, et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun 2015; 6(1): 6342.
[http://dx.doi.org/10.1038/ncomms7342] [PMID: 25919227]
[22]
Hibberd MC, Wu M, Rodionov DA, et al. The effects of micronutrient deficiencies on bacterial species from the human gut microbiota. Sci Transl Med 2017; 9(390): eaal4069.
[http://dx.doi.org/10.1126/scitranslmed.aal4069] [PMID: 28515336]
[23]
Namasivayam S, Maiga M, Yuan W, et al. Longitudinal profiling reveals a persistent intestinal dysbiosis triggered by conventional anti-tuberculosis therapy. Microbiome 2017; 5(1): 71.
[http://dx.doi.org/10.1186/s40168-017-0286-2] [PMID: 28683818]
[24]
Berer K, Gerdes LA, Cekanaviciute E, et al. Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice. Proc Natl Acad Sci USA 2017; 114(40): 10719-24.
[http://dx.doi.org/10.1073/pnas.1711233114] [PMID: 28893994]
[25]
Cekanaviciute E, Yoo BB, Runia TF, et al. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models. Proc Natl Acad Sci USA 2017; 114(40): 10713-8.
[http://dx.doi.org/10.1073/pnas.1711235114] [PMID: 28893978]
[26]
Katz Sand I, Zhu Y, Ntranos A, et al. Disease-modifying therapies alter gut microbial composition in MS. Neurol Neuroimmunol Neuroinflamm 2019; 6(1): e517.
[http://dx.doi.org/10.1212/NXI.0000000000000517] [PMID: 30568995]
[27]
Tremlett H, Fadrosh DW, Faruqi AA, et al. Gut microbiota in early pediatric multiple sclerosis: A case−control study. Eur J Neurol 2016; 23(8): 1308-21.
[http://dx.doi.org/10.1111/ene.13026] [PMID: 27176462]
[28]
Rumah KR, Linden J, Fischetti VA, Vartanian T. Isolation of Clostridium perfringens type B in an individual at first clinical presentation of multiple sclerosis provides clues for environmental triggers of the disease. PLoS One 2013; 8(10): e76359.
[http://dx.doi.org/10.1371/journal.pone.0076359] [PMID: 24146858]
[29]
Gacias M, Gaspari S, Santos P-MG, Tamburini S, Andrade M, Zhang F, et al. Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior. elife 2016; 5: e13442.
[30]
Hoban AE, Stilling RM, Ryan FJ, Shanahan F, Dinan TG, Claesson MJ, et al. Regulation of prefrontal cortex myelination by the microbiota. Translat psychiat 2016; 6(4): e774.
[http://dx.doi.org/10.1038/tp.2016.42]
[31]
Lu J, Synowiec S, Lu L, et al. Microbiota influence the development of the brain and behaviors in C57BL/6J mice. PLoS One 2018; 13(8): e0201829.
[http://dx.doi.org/10.1371/journal.pone.0201829] [PMID: 30075011]
[32]
Neufeld KM, Kang N, Bienenstock J, Foster JA. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 2011; 23(3): 255-e119. e119
[http://dx.doi.org/10.1111/j.1365-2982.2010.01620.x] [PMID: 21054680]
[33]
Friedland RP. Mechanisms of molecular mimicry involving the microbiota in neurodegeneration. J Alzheimers Dis 2015; 45(2): 349-62.
[http://dx.doi.org/10.3233/JAD-142841] [PMID: 25589730]
[34]
Chen SG, Stribinskis V, Rane MJ, et al. Exposure to the functional bacterial amyloid protein curli enhances alpha-synuclein aggregation in aged Fischer 344 rats and Caenorhabditis elegans. Sci Rep 2016; 6(1): 34477.
[http://dx.doi.org/10.1038/srep34477] [PMID: 27708338]
[35]
Sampson TR, Challis C, Jain N, et al. A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice. eLife 2020; 9: e53111.
[http://dx.doi.org/10.7554/eLife.53111] [PMID: 32043464]
[36]
Bostancıklıoğlu M. SARS-CoV2 entry and spread in the lymphatic drainage system of the brain. Brain Behav Immun 2020; 87: 122-3.
[http://dx.doi.org/10.1016/j.bbi.2020.04.080] [PMID: 32360606]
[37]
Svensson E, Horváth-Puhó E, Thomsen RW, et al. Vagotomy and subsequent risk of Parkinson’s disease. Ann Neurol 2015; 78(4): 522-9.
[http://dx.doi.org/10.1002/ana.24448] [PMID: 26031848]
[38]
Blacher E, Bashiardes S, Shapiro H, et al. Potential roles of gut microbiome and metabolites in modulating ALS in mice. Nature 2019; 572(7770): 474-80.
[http://dx.doi.org/10.1038/s41586-019-1443-5] [PMID: 31330533]
[39]
Bostanciklioğlu M. The role of gut microbiota in pathogenesis of Alzheimer’s disease. J Appl Microbiol 2019; 127(4): 954-67.
[http://dx.doi.org/10.1111/jam.14264] [PMID: 30920075]
[40]
Bostanciklioğlu M. Intestinal bacterial flora and Alzheimer’s disease. Neurophysiology 2018; 50(2): 140-8.
[http://dx.doi.org/10.1007/s11062-018-9728-0]
[41]
Xu R, Tan C, Zhu J, et al. Dysbiosis of the intestinal microbiota in neurocritically ill patients and the risk for death. Crit Care 2019; 23(1): 195.
[http://dx.doi.org/10.1186/s13054-019-2488-4] [PMID: 31151471]
[42]
Kvasnovsky CL, Leong LEX, Choo JM, et al. Clinical and symptom scores are significantly correlated with fecal microbiota features in patients with symptomatic uncomplicated diverticular disease. Eur J Gastroenterol Hepatol 2018; 30(1): 107-12.
[http://dx.doi.org/10.1097/MEG.0000000000000995] [PMID: 29084074]
[43]
Kaakoush NO. Insights into the role of Erysipelotrichaceae in the human host. Front Cell Infect Microbiol 2015; 5: 84.
[http://dx.doi.org/10.3389/fcimb.2015.00084] [PMID: 26636046]
[44]
Stenman LK, Burcelin R, Lahtinen S. Establishing a causal link between gut microbes, body weight gain and glucose metabolism in humans – towards treatment with probiotics. Benef Microbes 2016; 7(1): 11-22.
[http://dx.doi.org/10.3920/BM2015.0069] [PMID: 26565087]
[45]
Luan Z, Sun G, Huang Y, et al. Metagenomics study reveals changes in gut microbiota in centenarians: A cohort study of hainan centenarians. Front Microbiol 2020; 11: 1474.
[http://dx.doi.org/10.3389/fmicb.2020.01474] [PMID: 32714309]
[46]
Vaiserman AM, Koliada AK, Marotta F. Gut microbiota: A player in aging and a target for anti-aging intervention. Ageing Res Rev 2017; 35: 36-45.
[http://dx.doi.org/10.1016/j.arr.2017.01.001] [PMID: 28109835]
[47]
Salosensaari A, Laitinen V, Havulinna AS, et al. Taxonomic signatures of cause-specific mortality risk in human gut microbiome. Nat Commun 2021; 12(1): 2671.
[http://dx.doi.org/10.1038/s41467-021-22962-y] [PMID: 33976176]
[48]
Hsu SC, Johansson KR, Donahue MJ. The bacterial flora of the intestine of Ascaris suum and 5-hydroxytryptamine production. J Parasitol 1986; 72(4): 545-9.
[http://dx.doi.org/10.2307/3281505] [PMID: 3783348]
[49]
Özoğul F. Production of biogenic amines by Morganella morganii, Klebsiella pneumoniae and Hafnia alvei using a rapid HPLC method. Eur Food Res Technol 2004; 219(5): 465-9.
[http://dx.doi.org/10.1007/s00217-004-0988-0]
[50]
Tang WHW, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013; 368(17): 1575-84.
[http://dx.doi.org/10.1056/NEJMoa1109400] [PMID: 23614584]
[51]
Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011; 472(7341): 57-63.
[http://dx.doi.org/10.1038/nature09922] [PMID: 21475195]
[52]
Heianza Y, Ma W, Manson JE, Rexrode KM, Qi L. Gut microbiota metabolites and risk of major adverse cardiovascular disease events and death: A systematic review and meta‐analysis of prospective studies. J Am Heart Assoc 2017; 6(7): e004947.
[http://dx.doi.org/10.1161/JAHA.116.004947] [PMID: 28663251]
[53]
Lever M, George PM, Slow S, et al. Betaine and trimethylamine-N-oxide as predictors of cardiovascular outcomes show different patterns in diabetes mellitus: An observational study. PLoS One 2014; 9(12): e114969.
[http://dx.doi.org/10.1371/journal.pone.0114969] [PMID: 25493436]
[54]
Fields RD. A new mechanism of nervous system plasticity: Activity-dependent myelination. Nat Rev Neurosci 2015; 16(12): 756-67.
[http://dx.doi.org/10.1038/nrn4023] [PMID: 26585800]
[55]
Dutta DJ, Woo DH, Lee PR, et al. Regulation of myelin structure and conduction velocity by perinodal astrocytes. Proc Natl Acad Sci USA 2018; 115(46): 11832-7.
[http://dx.doi.org/10.1073/pnas.1811013115] [PMID: 30373833]
[56]
Zatorre RJ, Fields RD, Johansen-Berg H. Plasticity in gray and white: Neuroimaging changes in brain structure during learning. Nat Neurosci 2012; 15(4): 528-36.
[http://dx.doi.org/10.1038/nn.3045] [PMID: 22426254]
[57]
Pajevic S, Basser PJ, Fields RD. Role of myelin plasticity in oscillations and synchrony of neuronal activity. Neuroscience 2014; 276(2): 135-47.
[http://dx.doi.org/10.1016/j.neuroscience.2013.11.007] [PMID: 24291730]
[58]
Lu J, Lu L, Yu Y, Cluette-Brown J, Martin CR, Claud EC. Effects of intestinal microbiota on brain development in humanized gnotobiotic mice. Sci Rep 2018; 8(1): 5443.
[http://dx.doi.org/10.1038/s41598-018-23692-w] [PMID: 29615691]
[59]
Ye P, Li L, Richards RG, DiAugustine RP, D’Ercole AJ. Myelination is altered in insulin-like growth factor-I null mutant mice. J Neurosci 2002; 22(14): 6041-51.
[http://dx.doi.org/10.1523/JNEUROSCI.22-14-06041.2002] [PMID: 12122065]
[60]
Yan J, Herzog JW, Tsang K, et al. Gut microbiota induce IGF-1 and promote bone formation and growth. Proc Natl Acad Sci USA 2016; 113(47): E7554-63.
[http://dx.doi.org/10.1073/pnas.1607235113] [PMID: 27821775]
[61]
Sudo N, Chida Y, Aiba Y, et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol 2004; 558(1): 263-75.
[http://dx.doi.org/10.1113/jphysiol.2004.063388] [PMID: 15133062]
[62]
De Palma G, Blennerhassett P, Lu J, et al. Microbiota and host determinants of behavioural phenotype in maternally separated mice. Nat Commun 2015; 6(1): 7735.
[http://dx.doi.org/10.1038/ncomms8735] [PMID: 26218677]
[63]
Donia MS, Fischbach MA. Small molecules from the human microbiota. Science 2015; 349(6246): 1254766.
[http://dx.doi.org/10.1126/science.1254766] [PMID: 26206939]
[64]
Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes 2013; 20(1): 14-21.
[http://dx.doi.org/10.1097/MED.0b013e32835bc703] [PMID: 23222853]
[65]
Rothhammer V, Mascanfroni ID, Bunse L, et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med 2016; 22(6): 586-97.
[http://dx.doi.org/10.1038/nm.4106] [PMID: 27158906]
[66]
Bicknell BA, Häusser M. A synaptic learning rule for exploiting nonlinear dendritic computation. Neuron 2021; 109(24): 4001-17.
[http://dx.doi.org/10.1016/j.neuron.2021.09.044] [PMID: 34715026]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy