Mental Health Disorders Due to Gut Microbiome Alteration and NLRP3 Inflammasome Activation After Spinal Cord Injury: Molecular Mechanisms, Promising Treatments, and Aids from Artificial Intelligence.

Abstract

Aside from its immediate traumatic effects, spinal cord injury (SCI) presents multiple secondary complications that can be harmful to those who have been affected by SCI. Among these secondary effects, gut dysbiosis (GD) and the activation of the NOD (nucleotide-binding oligomerization domain) like receptor-family pyrin-domain-containing three (NLRP3) inflammasome are of special interest for their roles in impacting mental health. Studies have found that the state of the gut microbiome is thrown into disarray after SCI, providing a chance for GD to occur. Metabolites such as short-chain fatty acids (SCFAs) and a variety of neurotransmitters produced by the gut microbiome are hampered by GD. This disrupts healthy cognitive processes and opens the door for SCI patients to be impacted by mental health disorders. Additionally, some studies have found an increased presence and activation of the NLRP3 inflammasome and its respective parts in SCI patients. Preclinical and clinical studies have shown that NLRP3 inflammasome plays a key role in the maturation of pro-inflammatory cytokines that can initiate and eventually aggravate mental health disorders after SCI. In addition to the mechanisms of GD and the NLRP3 inflammasome in intensifying mental health disorders after SCI, this review article further focuses on three promising treatments: fecal microbiome transplants, phytochemicals, and melatonin. Studies have found these treatments to be effective in combating the pathogenic mechanisms of GD and NLRP3 inflammasome, as well as alleviating the symptoms these complications may have on mental health. Another area of focus of this review article is exploring how artificial intelligence (AI) can be used to support treatments. AI models have already been developed to track changes in the gut microbiome, simulate drug-gut interactions, and design novel anti-NLRP3 inflammasome peptides. While these are promising, further research into the applications of AI for the treatment of mental health disorders in SCI is needed.