title: Microbial Sources of Amyloid and Relevance to Amyloidogenesis and Alzheimer's Disease (AD).
abstract: Since the inception of the human microbiome project (HMP) by the US National Institutes of Health (NIH) in 2007 there has been a keen resurgence in our recognition of the human microbiome and its contribution to development, immunity, neurophysiology, metabolic and nutritive support to central nervous system (CNS) health and disease. What is not generally appreciated is that (i) the ~1014microbial cells that comprise the human microbiome outnumber human host cells by approximately one hundred-to-one; (ii) together the microbial genes of the microbiome outnumber human host genes by about one hundred-and-fifty to one; (iii) collectively these microbes constitute the largest 'diffuse organ system' in the human body, more metabolically active than the liver; strongly influencing host nutritive-, innate-immune, neuroinflammatory-, neuromodulatory- and neurotransmission-functions; and (iv) that these microbes actively secrete highly complex, immunogenic mixtures of lipopolysaccharide (LPS) and amyloid from their outer membranes into their immediate environment. While secreted LPS and amyloids are generally quite soluble as monomers over time they form into highly insoluble fibrous protein aggregates that are implicated in the progressive degenerative neuropathology of several common, age-related disorders of the human CNS including Alzheimer's disease (AD). This general commentary-perspective paper will highlight some recent findings on microbial-derived secreted LPS and amyloids and the potential contribution of these neurotoxic and proinflammatory microbial exudates to age-related inflammatory amyloidogenesis and neurodegeneration, with specific reference to AD wherever possible.
authors.affiliation: LSU Neuroscience Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans LA 70112 USA ; Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans LA 70112 USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Health Information Management, Louisiana State University Ruston LA 71270 USA.
authors.forename: P
authors.initials: P
authors.lastname: Dua
authors.affiliation: LSU Neuroscience Center, Louisiana State University Health Sciences Center, 2020 Gravier Street, New Orleans LA 70112 USA ; Department of Ophthalmology, Louisiana State University Health Sciences Center, 533 Bolivar Street, New Orleans LA 70112 USA ; Department of Neurology, Louisiana State University Health Sciences Center, 1542 Tulane Avenue, New Orleans LA 70112 USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Lukiw
keywords: Alzheimer’s disease (AD); Beta amyloid precursor protein (βAPP); Congo Red (CR); Curli fibers; Hologenome; Inflammation; Innate-immunity; Senile (amyloid) plaques (SP); Toll receptor type 2 (TLR2)