Microbial Immuno-Communication in Neurodegenerative Diseases

Abstract

Neuro-inflammation is a critical process by which the brain coordinates chemokine-regulated cellular recruitment, cytokine release, and cell-mediated removal of pathogenic material to protect against infection or brain injury. Dysregulation of this immune response is involved in multiple neurodegenerative disorders, however the precise contribution of neuro-inflammation to the exacerbation and progression of these diseases remains unclear. Evidence now suggests that commensal micro-organisms populating the host and their metabolites, collectively termed the microbiome, regulate innate immunity by influencing peripheral immune cell populations, and modulating microglial phenotype. Recent preclinical studies now demonstrate that perturbations in the host microbiome can induce alterations in pathological phenotypes associated with numerous neurodegenerative diseases. How perturbations in the host microbiome and subsequently altered peripheral immune status are communicated to the brain to influence neuro-inflammatory processes in these neurodegenerative disease settings is far from understood. This review provides insight into the regulation of neuro-inflammatory processes by the host microbiome in the context of neurodegenerative disease and highlights the potential importance of the blood-brain barrier and blood-cerebrospinal fluid-brain barrier, functioning as “immune barriers,” to communicate host immune status to the brain. Understanding the mechanisms by which the commensal microbiome communicates with the brain to influence neuro-inflammatory processes will be critical in the development of microbially-targeted therapeutics in the potential treatment of neurodegenerative disorders.

The hypothesis that Helicobacter pylori predisposes to Alzheimer’s disease is biologically plausible

“…Also, it has been proposed that the immune response to H. pylori causes apoptosis and neural cell destruction by releasing pro-inflammatory molecules and inducing reactive oxygen metabolites 51 , 62 . There is evidence that H. pylori damages the brain-blood barrier 63 , 64 and the gut metabolites reaches the brain through direct interaction with enteric neurons 42 . Microbial metabolites can also influence the peripheral immune response, which in sequence affects the blood- brain barrier 64 .…”

“…There is evidence that H. pylori damages the brain-blood barrier 63 , 64 and the gut metabolites reaches the brain through direct interaction with enteric neurons 42 . Microbial metabolites can also influence the peripheral immune response, which in sequence affects the blood- brain barrier 64 .…”

Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression

“…20,[29][30][31] Previous studies have suggested that gut microbiota is involved in triggering neuroinflammation in the brain. 18,32 We hypothesized that the observed gut microbiota alteration during AD progression might be associated with neuroinflammation. To test this hypothesis, we evaluated the inflammatory status of Tg mice.…”

“…16,17 It remains unknown which types of infiltrated immune cells are functionally involved in AD development. 18,19 The underlying driving force that promotes peripheral immune cells to infiltrate the brain, leading to the enhancement of the residential neuroinflammation, remains obscure. Moreover, as the importance of microbiota metabolites is starting to unveil, it will be imperative to comprehend the specific metabolites that are involved in linking gut microbiota and brain neuroinflammation in AD progression.…”

Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspired Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents

“…A thought-provoking hypothesis is that curli-producing bacteria influence human neurodegenerative and aggregation diseases by nucleating, accelerating or deterring fibrillation of human amyloids. Another mechanism could be affecting the immune system, leading to inflammation and stress that are correlated with neurodegenerative diseases (122,123). Future work is needed to characterize more microbial amyloids at the molecular and atomic level, study their inter-species interactions, and modulate their activities (38).…”