Objective: We examined the association between environmental phthalates (PAEs) exposure and gut microbiota and metabolome in dementia with Lewy bodies (DLB).

Background: Alongside genetic factors, the potential involvement of environmental factors in the development of DLB is gaining recognition, with a particular focus on the emerging role of PAEs. Moreover, gut microbiota and metabolites are also important factors affecting neurodegenerative diseases.

Method: A total of 43 DLB patients and 45 normal subjects were included in this study. Liquid chromatography was used to analyze the levels of PAEs metabolites in the urine of the two populations. High-throughput sequencing and liquid chromatography-mass spectrometry were used to analyze gut microbiota and the profile of gut metabolome, respectively.

Results: Compared with the control group, we found that 3 DEHP metabolites (MEOHP, MEHHP and MEHP), MMP and MnBP increased, while MBP and MBzP decreased in the DLB group. A significantly higher abundance of Ruminococcus gnavus and lower Prevotella copri, Prevotella stercorea and Bifidobacterium were observed in DLB. Higher 3 DEHP metabolites, MMP and MnBP and lower MBP and MBzP were significantly negatively associated with P. copri, P. stercorea and Bifidobacterium. Additionally, metabolomics data revealed that PAEs exposure was associated with gut metabolic homeostasis of bile acids, short-chain fatty acids and amino acids.

Conclusion: This is the first study to show the association between the metabolites of PAEs, gut bacterial dysbiosis and metabolite profiles in DLB, which suggested that PAEs exposure may alter the microbiota-gut-brain axis and highlighted the value of multi-omics approaches to detect the interactions among environmental perturbations and microbiome-host.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/association-between-environmental-phthalates-exposure-and-gut-microbiota-and-metabolome-in-dementia-with-lewy-bodies/