ISSN: 2161-0460

Journal of Alzheimers Disease & Parkinsonism
Open Access

Our Group organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations
700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)
  • Review Article   
  • J Alzheimers Dis Parkinsonism,
  • DOI: 10.4172/2161-0460.1000525

Gastrointestinal (GI)-Tract Microbiome Derived Neurotoxins and their Potential Contribution to Inflammatory Neurodegeneration in Alzheimer’s Disease (AD)

Walter J. Lukiw1,2,3*, Lisa Arceneaux1, Wenhong Li1,4, Taylor Bond1 and Yuhai Zhao1,5
1LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA, United States
2Department of Ophthalmology, LSU Health Sciences Center, New Orleans, LA, United States
3Department of Neurology, Louisiana State University Health Sciences Center, New Orleans, LA, United States
4Department of Pharmacology, School of Pharmacy, Jiangxi University of Traditional Chinese Medicine (TCM), Nanchang, China
5Department of Anatomy and Cell Biology, Louisiana State University, New Orleans, LA, United States
*Corresponding Author : Dr. Walter J. Lukiw, LSU Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, LA, United States, Email: wlukiw@lsuhsc.edu

Received Date: May 04, 2021 / Accepted Date: May 18, 2021 / Published Date: May 25, 2021

Abstract

The human gastrointestinal (GI)-tract microbiome is a rich, complex and dynamic source of microorganisms that possess a staggering diversity and complexity. Importantly there is a significant variability in microbial complexity even amongst healthy individuals-this has made it difficult to link specific microbial abundance patterns with age-related neurological disease. GI-tract commensal microorganisms are generally beneficial to human metabolism and immunity, however enterotoxigenic forms of microbes possess significant potential to secrete what are amongst the most neurotoxic and pro-inflammatory biopolymers known. These include toxic glycolipids such as lipopolysaccharide (LPS), enterotoxins, microbial-derived amyloids and small non-coding RNA. One major microbial species of the GI-tract microbiome, about ~100-fold more abundant than Escherichia coli in deep GI-tract regions is Bacteroides fragilis, an anaerobic, rod-shaped Gram-negative bacterium. B. fragilis can secrete: (i) a particularly potent, pro-inflammatory and unique LPS subtype (BF-LPS); and (ii) a zinc-metalloproteinase known as B. fragilis-toxin (BFT) or fragilysin. Ongoing studies indicate that BF-LPS and/or BFT disrupt paracellular-and transcellular-barriers by cleavage of intercellular-proteins resulting in 'leaky' barriers. These barriers: (i) become defective and more penetrable with aging and disease; and (ii) permit entry of microbiome-derived neurotoxins into the systemic-circulation from which they next transit the blood-brain barrier and gain access to the CNS. Here LPS accumulates and significantly alter homeostatic patterns of gene expression. The affinity of LPS for neuronal nuclei is significantly enhanced in the presence of amyloid beta 42 (Aβ42) peptides. Recent research on the appearance of the brain thanatomicrobiome at the time of death and the increasing likelihood of a complex brain microbiome are reviewed and discussed. This paper will also highlight some recent advances in this extraordinary research area that links the pro-inflammatory exudates of the GI-tract microbiome with innate-immune disturbances and inflammatory-signaling within the CNS with reference to Alzheimer's disease (AD) wherever possible.

Keywords: Aging; Alzheimer’s disease; Bacteroides fragilis; Brain microbiome; Dysbiosis; Lipopolysaccharide; microRNA-146a; miRNA-155; Necrobiome; NF-kB; Reactive oxygen species; Thanatomicrobiome

Citation: Lukiw WJ, Arceneaux LS, Li W, Bond T, Zhao Y (2021) Gastrointestinal (GI): Tract Microbiome-Derived Neurotoxins and their Potential Contribution to Inflammatory Neurodegeneration in Alzheimer’s Disease (AD). J Alzheimers Dis Parkinsonism 11: 525. Doi: 10.4172/2161-0460.1000525

Copyright: © 2021 Lukiw WJ, et al. 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.

Top