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Gastrointestinal (GI) Tract Microbiome-Derived Neurotoxins-Potent Neuro-Inflammatory Signals From the GI Tract via the Systemic Circulation Into the Brain
Ist Teil von
Frontiers in cellular and infection microbiology, 2020-02, Vol.10, p.22
Ort / Verlag
Switzerland: Frontiers Research Foundation
Erscheinungsjahr
2020
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
The microbiome of the human gastrointestinal (GI)-tract is a rich and dynamic source of microorganisms that together possess a staggering complexity and diversity. Collectively these microbes are capable of secreting what are amongst the most neurotoxic and pro-inflammatory biopolymers known. These include lipopolysaccharide (LPS), enterotoxins, microbial-derived amyloids and small non-coding RNA (sncRNA). One of the major microbial species in the human GI-tract microbiome, about ~100-fold more abundant than
, is
, an anaerobic, rod-shaped Gram-negative bacterium that secretes: (i) a particularly potent, pro-inflammatory LPS glycolipid subtype (BF-LPS); and (ii) a hydrolytic, extracellular zinc metalloproteinase known as
toxin (BFT) or
. Ongoing studies support multiple observations that BF-LPS and BFT (
disrupt paracellular barriers by cleavage of intercellular proteins, such as E-cadherin, between epithelial cells, resulting in '
' barriers. These defective barriers, which also become more penetrable with age, in turn permit entry of microbiome-derived neurotoxic biopolymers into the systemic circulation from which they can next transit the blood-brain barrier (BBB) and gain access into the brain. This short communication will 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 human central nervous system (CNS) with reference to Alzheimer's disease (AD) wherever possible.