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

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.

Facilitation of Gastrointestinal (GI) Tract Microbiome-Derived Lipopolysaccharide (LPS) Entry Into Human Neurons by Amyloid Beta-42 (Aβ42) Peptide.

Human gastrointestinal (GI)-tract microbiome-derived lipopolysaccharide (LPS): (i) has been recently shown to target, accumulate within, and eventually encapsulate neuronal nuclei of the human central nervous system (CNS) in Alzheimer's disease (AD) brain; and (ii) this action appears to impede and restrict the outward flow of genetic information from neuronal nuclei. It has previously been shown that in LPS-encased neuronal nuclei in AD brain there is a specific disruption in the output and expression of two AD-relevant, neuron-specific markers encoding the cytoskeletal neurofilament light (NF-L) chain protein and the synaptic phosphoprotein synapsin-1 (SYN1) involved in the regulation of neurotransmitter release. The biophysical mechanisms involved in the facilitation of the targeting of LPS to neuronal cells and nuclei and eventual nuclear envelopment and functional disruption are not entirely clear.