The microbiota-gut-brain axis and circadian rhythms in Parkinson's disease – Correspondence

Dear Editor, Accumulating evidence from basic and clinical investigations indicates that disruption of circadian rhythms is closely related to neurodegenerative diseases like Parkinson's disease (PDs) [1–4]. In the context of modern lifestyle, disturbing factors of the circadian rhythm interrupt a dynamic interplay between the host circadian system and the microbiota. Since the function of the gastrointestinal tract is circadian rhythms and the balance of the microbiome is affected by diurnal variations, the production of Microbiota-Derived Metabolites and Short chain fatty acids (SCFAs) is also rhythmic [5,6]. In the light of this point of view, its important to involve the role of inextricably of the circadian rhythms as a critical component in the gut dysbiosis concept by considering circadian rhythms as an ‘extrinsic’ factor that influences the gut microbiome and subsequently the emergence of circadian-associated diseases like a PDs. Alterations of cardinal circadian parameters — period, phase, and amplitude — in addition to being the common risk factors for many neurodegenerative disorders, also exacerbate progression of the disease. Longitudinal studies showed that a reduction in the amplitude of the circadian rhythm (long daytime sleeping) precedes the risk of PDs [7]. More importantly, there is a bidirectional relationship between the gut microbiota and circadian rhythm to maintain the metabolic homeostasis of the host. Disruption of circadian rhythms can increase intestinal permeability, alter intestinal barrier function and gut microbiota composition. In this regard, SCFAs play a role of imperative in connecting the microbiota–gut–brain axis and circadian rhythms. Melatonin, a key hormone in sleep and circadian rhythmicity, can alter the composition of gut microbiota and improve the diurnal rhythmicity of gut microbiota. For example, Melatonin can entrain the circadian rhythms of some gut bacteria and cause negative chemotaxis of bacteria such as Escherichia coli. Seeing that Melatonin is one of the key components of the hypothalamic-pituitary-adrenal axis (HPA axis) which regulates the body's response to stress, changes in the gut microbiota can affect the circadian clock which controls the HPA axis [5,6]. Understanding alterations in single bacterial taxa (pathobionts) and/or complex microbial communities (dysbiosis), especially the role of functional and specificity is crucial to filling the gaps in the knowledge pertaining to sleep behavior disorder (SBD) and circadian dysfunction, and may offer novel insights into the pathophysiology of PDs. For example, the gut microbiota of patients with SBD or PDs are very similar and both are significantly different from the gut microbiota of healthy, control patients [8]. In conclusion, paying attention to the circadian rhythm as one of the ‘extrinsic’ factors contributing to PDs symptoms could help understand the degree of influence of circadian rhythm dysregulation on the disruption of sleep and activity rhythms in PDs, which may in turn unravel the evolving story of the causal relationships between PDs and the gut microbiota to offer novel insights into the pathophysiology, thus providing opportunities to lessen the prevalence and consequences of PDs. Provenance and peer review Not commissioned, internally peer-reviewed. Please state whether ethical approval was given, by whom and the relevant Judgement's reference number This article does not require any human/animal subjects to acquire such approval. Please state any sources of funding for your research This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author contribution M.Z, S.M.R.H., M.S wrote the manuscript. M.Z. designed, final edited and supervised the manuscript. Next, all authors critically reviewed the manuscript for relevant intellectual content. All authors critically reviewed and approved the final version of the manuscript. Please state any conflicts of interest All authors report no conflicts of interest relevant to this article. Research registration Unique Identifying number (UIN) 1. Name of the registry: Not applicable. 2. Unique Identifying number or registration ID: Not applicable. 3. Hyperlink to your specific registration (must be publicly accessible and will be checked): Not applicable. Guarantor Milad Zandi, PhD in medical virology, senior researcher in emerging and reemerging viruses, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Tel: +989372876578, Email. [email protected]. Data statement The data in this correspondence article is not sensitive in nature and is accessible in the public domain. The data is therefore available and not of a confidential nature. Milad Zandi Seyyed Mohammad Reza Hashemnia Maryam Shafaati 1Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 2Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 3Department of Microbiology, Faculty of Science, Jahrom Branch, Islamic Azad University, Jahrom, Iran 4Occupational Sleep Research, Baharloo Hospital, Tehran University of Medical Science, Tehran, Iran E-mail addresses:[email protected]