Gastrointestinal (GI) Tract Microbes and Microbial Neurotoxins in the Human Central Nervous System (CNS) in Alzheimer’s Disease (AD)

Abstract

Our ongoing appreciation of the magnitude and complexity of the human microbiome has resulted in a reassessment of many fundamental concepts of the contribution of the microbial community to neurological health and disease. The assumption of the privileged immunological and compartmentalized status of the human central nervous system (CNS) has been recently challenged in multiple investigations - particularly because microbial-derived nucleic acid sequences and highly neurotoxic and pro-inflammatory exudates representative of gastrointestinal (GI) tract Gram-negative anaerobic bacteria are showing up within CNS compartments. Unanticipated microbial presence has also recently been discovered in the anatomical regions of the CNS implicated in pro-inflammatory pathological signaling and neuro-immune disruptions that characterize progressive and lethal neurodegenerative diseases of the CNS such as Alzheimer’s disease (AD). This communication (i) will briefly review some very recent research on the contribution of the GI tract microbiome and microbial neurotoxins to inflammatory neurodegeneration in the CNS with emphasis on AD wherever possible; (ii) will review the evidence that the GI tract microbiome may have an increasing inter-relationship with the CNS via leaky barriers as we age; and (iii) will review recent experimental findings that support the intriguing possibility that the CNS may possess its own microbiome whose basal complexity is in part derived from the GI tract microbiome of the host