Microbiome or Infections: Amyloid-Containing Biofilms as a Trigger for Complex Human Diseases

Abstract

The human microbiota is the community of microorganisms that live upon or within their human host. The microbiota consists of various microorganisms including bacteria, fungi, viruses, and archaea; the gut microbiota is comprised mostly of bacteria. Many bacterial species within the gut microbiome grow as biofilms, which are multicellular communities embedded in an extracellular matrix. Studies have shown that the relative abundances of bacterial species, and therefore biofilms and bacterial byproducts, change during progression of a variety of human diseases including gastrointestinal, autoimmune, neurodegenerative, and cancer. Studies have shown the location and proximity of the biofilms within the gastrointestinal tract might impact disease outcome. Gram-negative enteric bacteria secrete the amyloid curli, which makes up as much as 85% of the extracellular matrix of enteric biofilms. Curli mediates cell-cell attachment and attachment to various surfaces including extracellular matrix components such as fibronectin and laminin. Structurally, curli is strikingly similar to pathological and immunomodulatory human amyloids such as amyloid-β, which has been implicated in Alzheimer's disease, α-synuclein, which is involved in Parkinson's disease, and serum amyloid A, which is secreted during the acute phase of inflammation. The immune system recognizes both bacterial amyloid curli and human amyloids utilizing the same receptors, so curli also induces inflammation. Moreover, recent work indicates that curli can participate in the self-assembly process of pathological human amyloids. Curli is found within biofilms of commensal enteric bacteria as well as invasive pathogens; therefore, evidence suggests that curli contributes to complex human diseases. In this review, we summarize the recent findings on how bacterial biofilms containing curli participate in the pathological and immunological processes in gastrointestinal diseases, systemic autoimmune diseases, and neurodegenerative diseases.

Beneficial reconstitution of gut microbiota and control of alpha-synuclein and curli-amyloids-producing enterobacteria, by beta 1,3-1,6 glucans in a clinical pilot study of autism and potentials in neurodegenerative diseases

“…Gram-negative enteric bacteria such as the Enterobacter and E coli secrete the amyloid curli that constitutes 85% of the extracellular matrix of enteric biofilms. The curli has similarities and associations with pathological and immunomodulatory human amyloids such as amyloid-β implicated in AD, αSyn involved in ASD and PD, and serum amyloid A associated with neuroinflammation [21]. Curli causes misfolding [22] and accumulation of the neuronal protein αSyn in the form of insoluble amyloid aggregations, leading to inflammation and neuronal dysfunction that is central to pathogenesis of Lewy-body-associated synucleinopathies, including PD and AD.…”

The Gut-Brain Axis in Multiple Sclerosis. Is Its Dysfunction a Pathological Trigger or a Consequence of the Disease?

“…The influence of the microbiota in AD appears related not only to dysbiosis, but also to the ability of amyloids to traverse the gut wall. Gut microbiota produces a high quantity of amyloids in the biofilm that covers the gastrointestinal tract, among which curli is the most studied; it is produced by Escherichia coli in stressful conditions (55,56) and promotes intestinal inflammation (56)(57)(58). Interestingly, bacterial amyloids may act as prion proteins, eliciting cross-seeding, through molecular mimicry with amyloid-b (Ab), in vitro and in vivo, suggesting that they could induce the formation of Ab aggregates in the CNS (59,60).…”

Drosophila as a Model for Microbiota Studies of Neurodegeneration

“…There are two keywords for the relationship between gut microbiota and neurodegenerative diseases: inflammation and cross-seeding (Fig. 2) [56][57][58]. A dysbiotic gut microbiome and damaged enteric epithelia can provoke systemic inflammation via activation of immune cells and release of cytokines [59,60].…”