Pediatric multiple sclerosis: an integrated outlook at the interplay between genetics, environment and brain-gut dysbiosis

Abstract

Multiple sclerosis (MS) is a debilitating autoimmune condition caused by demyelination, neurodegeneration and persistent inflammation of the central nervous system. Pediatric multiple sclerosis (PMS) is a relatively rare form of the disease that affects a significant number of individuals with MS. Environmental exposures, such as viral infections and smoking, can interact with MS-associated human leukocyte antigens (HLA) risk alleles and influence the immune response. Upregulation of immune response results in the disruption of immune balance leading to cascade of inflammatory events. It has also been established that gut microbiome dysbiosis poses a higher risk for pro-inflammation, and it is essentially argued to be the greatest environmental risk factor for MS. Dysbiosis can cause an unusual response from the adaptive immune system and significantly contribute to the development of disease in the host by activating pro-inflammatory pathways that cause immune-mediated disorders such as PMS, rendering the body more vulnerable to foreign attacks due to a weakened immune response. All these dynamic interactions between biological, environmental and genetic factors based on epigenetic study has further revealed that upregulation or downregulation of some genes/enzyme in the central nervous system white matter of MS patients produces a less stable form of myelin basic protein and ultimately leads to the loss of immune tolerance. The diagnostic criteria and treatment options for PMS are constantly evolving, making it crucial to have a better understanding of the disease burden on a global and regional scale. The findings from this review will aid in deepening the understanding of the interplay between genetic and environmental risk factors, as well as the role of the gut microbiome in the development of pediatric multiple sclerosis. As a result, healthcare professionals will be kept abreast of the early diagnostic criteria, accurately delineating other conditions that can mimic pediatric MS and to provide comprehensive care to individuals with PMS based on the knowledge gained from this research.

Keywords

• pediatric neurodegeneration
• brain-gut axis
• epigenetics
• multiple sclerosis
• neuroimmunology