Executive Summary : | Gut dysbiosis is a condition where the gut microbiota, which includes bacteria, archaea, fungi, and viruses, is altered, leading to an inflammatory response in the intestine and distal organs. This can be influenced by gut infections, which can alter the permeability of the blood-brain barrier (BBB), exposing it to conditions that trigger inflammation. Gut dysbiosis and neuroinflammation may influence the genesis and progression of neurodegenerative diseases like Alzheimer's and Parkinson's disease. Neurogenesis is crucial for brain homeostasis and disease, and research shows that neural stem progenitor NSP cells of the subventricular zone and subgranular layer of the hippocampus retain the capacity of neurogenesis in the adult brain. Neurotrophic signaling through BDNF and CNTF under gut dysbiosis is a central focus of this project. Microglia, the brain's resident macrophages with immune and synaptic regulatory functions, are the first responders to nerve injury and inflammation. They have different activation states, including resting, activated, and alternatively-activated microglia. Probiotics can affect various central neuronal functions, including neurotransmission, neuropeptide expression, and behavior, and can amend neuroinflammation and promote neurogenesis.
The study investigates the effect of gut dysbiosis on the structure and function of the hippocampal network and the effect of microbial metabolites using an antibiotic-mediated gut dysbiosis model. The researchers found that CNTF-induced STAT3 signaling is essential for the formation and maintenance of the neurogenic subgranular zone in the adult dentate gyrus, suggesting that CNTF is required to maintain the balance between neural stem cell self-renewal and the generation of neuronal progenitors. The study also found that the pathogenesis of neurodegenerations may take a long time before symptoms arise, leading to changes at subcellular to synaptic levels, severely impairing cognitive functions. The neuroinflammatory pathways might influence cell types such as neuroblasts, neurons, glial cells, microglia, and astrocytes through impaired neurotrophic signaling. The findings could help develop therapeutic approaches for improving neurodegenerative conditions. |