Opening avenues for treatment of neurodegenerative disease using post-biotics: Breakthroughs and bottlenecks in clinical translation

Recent studies have indicated the significant involvement of the gut microbiome in both human physiology and pathology. Additionally, therapeutic interventions based on microbiome approaches have been employed to enhance overall health and address various diseases including aging and neurodegenerative disease (ND). Researchers have explored potential links between these areas, investigating the potential pathogenic or therapeutic effects of intestinal microbiota in diseases. This article provides a summary of established interactions between the gut microbiome and ND. Post-biotic is believed to mediate its neuroprotection by elevating the level of dopamine and reducing the level of α-synuclein in substantia nigra, protecting the loss of dopaminergic neurons, reducing the aggregation of NFT, reducing the deposition of amyloid β peptide plagues and ameliorating motor deficits. Moreover, mediates its neuroprotective activity by inhibiting the inflammatory response (decreasing the expression of TNFα, iNOS expression, free radical formation, overexpression of HIF-1α), apoptosis (i.e. active caspase-3, TNF-α, maintains the level of Bax/Bcl-2 ratio) and promoting BDNF secretion. It is also reported to have good antioxidant activity. This review offers an overview of the latest findings from both preclinical and clinical trials concerning the use of post-biotics in ND. [Display omitted] •Intestinal dysbiosis causes neuroinflammatory cascade worsening the homeostasis of brain.•The brain-gut-microbiome axis enables exchange of information between gut microbes and brain.•Microbiome based treatments can be employed for the management of NDs.•Post-biotics (PBs) positively influence the gut-brain axis and potentially exert neuroprotection.•PBs influence gene expression in the nucleus accumbens of the brain associated with NDs.