Does gut brain axis has an impact on Parkinson's disease (PD)?

Parkinson's Disease (PD) is becoming a growing global concern by being the second most prevalent disease next to Alzheimer's Disease (AD). Henceforth new exploration is needed in search of new aspects towards the disease mechanism and origin. Evidence from recent studies has clearly stated the role of Gut Microbiota (GM) in the maintenance of the brain and as a root cause of various diseases and disorders including other neurological conditions. In the case of PD, with an unknown etiology, the GM is said to have a larger impact on the disease pathophysiology. Although GM and its metabolites are crucial for maintaining the normal physiology of the host, it is an undeniable fact that there is an influence of GM in the pathophysiology of PD. As such the Enteroendocrine Cells (EECs) in the epithelium of the intestine are one of the significant regulators of the gut-brain axis and act as a communication mediator between the gut and the brain. The communication is established via the molecules of neuroendocrine which are said to have a crucial part in neurological diseases such as AD, PD, and other psychiatry-related disorders. This review is focused on understanding the proper role of GM and EECs in PD. Here, we also focus on some of the metabolites and compounds that can interact with the PD genes causing various dysfunctions in the cell and facilitating the disease conditions using bioinformatical tools. Various mechanisms concerning EECs and PD, their identification, the latest studies, and available current therapies have also been discussed.

Association Study Between Kynurenine 3-Monooxygenase (KMO) Gene and Parkinson's Disease Patients.

The influence of various risk factors such as aging, intricate cellular molecular processes, and lifestyle factors like smoking, alcohol consumption, caffeine intake, and occupational factors has received increased focus in relation to the risk and development of Parkinson's disease (PD). Limited research has been conducted on the assessment of lifestyle impact on kynurenine 3-monooxygenase (KMO) gene in PD. A total of 164 subjects, including 82 PD cases and 82 healthy individuals, were recruited based on specific inclusion and exclusion criteria. The severity of PD and clinical assessment were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (HY) scaling. Sanger sequencing was performed to analyse the KMO gene in the recruited subjects, and case-control studies were conducted. The UPDRS assessment revealed significant impairments in smell, tremors, walking, and posture instability in the late-onset PD cohorts. The HY scaling indicated a higher proportion of late-onset cohorts in stage 2. Moreover, both alcoholic and non-alcoholic groups showed significantly increased levels of 3-HK in late-onset PD. Gene analysis identified missense variants at position g.241593373 T > A (rs752312199) and intronic variants at positions g.241592623A > G (rs640718), g.241592800C > A (rs990388262), g.241592802A > C (rs1350160268), g.241592808 T > C (rs1478255936), and g.241592812G > T (rs948928931). The alterations in the KMO gene were found to influence the levels of kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK). Genomic analysis revealed a high prevalence of missense mutations in the late-onset PD groups, leading to a decline in 3-HK levels in patients. This leads to the reduction of the progression of disease in late-onset groups which shows that this mutation may lead to the protective effect on the PD subjects. This study suggests the use of KYNA and 3-HK as potential biomarkers in analysing the progression of disease. This study is limited by its small sample size. To overcome this limitation, a larger study involving in greater number of participants is needed to thoroughly investigate the KMO gene and KP metabolites, to enhance our understanding of Parkinson's disease progression, and to enhance diagnostic capabilities.