Examination of Shared Gut Microbiome Signatures in Ageing and Parkinson's Disease

Teddy Jia Wei Tng^1,2,3Sarivin Vanan^1,2,4Li Zeng^1,2,4,5Wilson Wen Bin Goh^1,2,6Sunny H Wong^1,2,7*Kah-Leong Lim^1,2,4*

• ¹Lee Kong Chian School of Medicine, Singapore, Singapore
• ²Nanyang Technological University, Singapore, Singapore
• ³Interdisciplinary Graduate Programme (IGP-Neuroscience), Singapore, Singapore
• ⁴National Neuroscience Institute, Singapore, Singapore
• ⁵Duke-NUS Medical School, Singapore, Singapore
• ⁶Centre for Biomedical Informatics, Singapore, Singapore
• ⁷Centre for Microbiome Medicine, Singapore, Singapore

Abstract Parkinson's disease (PD) is a prevalent neurodegenerative disorder that is characterized clinically by a constellation of motoric deficits including resting tremors, bradykinesia, and rigidity. In recent years, there has been increasing interest in the gut-brain axis with several studies examining the relationship between gut microbiome and PD. Although association studies have reported multidimensional microbiome changes in PD, these observed changes may be confounded by various factors, especially age. Notably, existing literature on gut microbiome tends to consider ageing and PD separately. This review thus examines the gut microbiome factors associated with both ageing and PD. Our comprehensive analysis of the available literature reveals significant overlaps in gut microbes that are associated with ageing and PD. For example, the bacterial genera Akkermansia, and Alistipes have shown increased abundance in both conditions, while Faecalibacterium and Blautia conversely show decreased abundance. Our findings were temporally consistent with more recent studies. These shared gut microbiome signatures were identified in patients across the clinical spectrum of PD symptom severity, and may influence ageing and disease pathogenesis via depletion of butyrate, a beneficial anti-inflammatory microbial metabolite, since major producers of butyrate (such as Faecalibacterium and Blautia) were constantly decreased with age (across both Asian and Western populations). Given these observations, we wish to highlight the need to consider age-related factors in understanding microbiome changes in PD; the intersection of which could reveal gut microbes and their corresponding microbial metabolites such as butyrate as potential therapeutic targets for PD.