Immunomodulatory effects of microbiota-derived metabolites at the crossroad of neurodegenerative diseases and viral infection: network-based bioinformatics insights

Bidirectional cross-talk between commensal microbiota and the immune system is essential for the regulation of immune responses and the formation of immunological memory. Perturbations of microbiome-immune system interactions can lead to dysregulated immune responses against invading pathogens and/or to the loss of self-tolerance, leading to systemic inflammation and genesis of several immune-mediated pathologies, including neurodegeneration. In this paper, we first investigated the contribution of the immunomodulatory effects of microbiota (bacteria and fungi) in shaping immune responses and influencing the formation of immunological memory cells using a network-based bioinformatics approach. In addition, we investigated the possible role of microbiota-host-immune system interactions and of microbiota-virus interactions in a group of neurodegenerative diseases (NDs): Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Parkinson's disease (PD) and Alzheimer's disease (AD). Our analysis highlighted various aspects of the innate and adaptive immune response systems that can be modulated by microbiota, including the activation and maturation of microglia which are implicated in the development of NDs. It also led to the identification of specific microbiota components which might be able to influence immune system processes (ISPs) involved in the pathogenesis of NDs. In addition, it indicated that the impact of microbiota-derived metabolites in influencing disease-associated ISPs, is higher in MS disease, than in AD, PD and ALS suggesting a more important role of microbiota mediated-immune effects in MS.