Association between environmental phthalates exposure and gut microbiota and metabolome in dementia with Lewy bodies

Study information

Needs review

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

38908272

DOI Digital object identifier for electronic documents.

10.1016/j.envint.2024.108806

URI Uniform resource identifier for web resources.

Authors

Deng Z, Li L, Jing Z, Luo X, Yu F, Zeng W, Bi W, Zou J

Journal

Environment international

Year

2024

Keywords:

Dementia with Lewy bodies, Gut microbiota, Metabolites, Multi-omics, Phthalates

BACKGROUND: Emerging evidence has shown the potential involvement of phthalates (PAEs) exposure in the development of dementia with Lewy bodies (DLB). Metabolomics can reflect endogenous metabolites variation in the progress of disease after chemicals exposure. However, little is known about the association between PAEs, gut microbiota and metabolome in DLB. OBJECTIVE: We aim to explore the intricate relationship among urinary PAEs metabolites (mPAEs), dysbiosis of gut bacteria, and metabolite profiles in DLB. METHODS: A total of 43 DLB patients and 45 normal subjects were included in this study. Liquid chromatography was used to analyze the levels of mPAEs 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. The fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of mPAEs on gut dysbiosis contribute to aggravating cognitive dysfunction in α-synuclein tg DLB/PD mice. RESULTS: The DLB patients had higher DEHP metabolites (MEOHP, MEHHP and MEHP), MMP and MnBP, lower MBP and MBzP than the control group and different microbiota. A significantly higher abundance of Ruminococcus gnavus and lower Prevotella copri, Prevotella stercorea and Bifidobacterium were observed in DLB. Higher 3 DEHP metabolites, MMP, MnBP and lower MBP and MBzP were significantly negatively associated with Prevotella copri, Prevotella stercorea and Bifidobacterium. Additionally, using metabolomics, we found that altered bile acids, short-chain fatty acids and amino acids metabolism are linked to these mPAEs. We further found that FMT of fecal microbiota from highest DEHP metabolites donors significantly impaired cognitive function in the germ-free DLB/PD mice. CONCLUSION: Our study suggested that PAEs exposure may alter the microbiota-gut-brain axis and providing novel insights into the interactions among environmental perturbations and microbiome-host in pathogenesis of DLB.

Experiment 1

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Curated date: 2025/07/30

Curator: Kristin.abraham

Revision editor(s): Kristin.abraham

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Lewy body dementia dementia with Lewy bodies,dementia, Lewy body,diffuse Lewy body disease,diffuse Lewy body disease with gaze palsy,DLB,Lewy body dementia,Lewy body disease,Lewy body variant of Alzheimer disease,Senile dementia of the Lewy body type,lewy body dementia

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: DLB patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients diagnosed with Dementia with Lewy bodies

Group 0 sample size Number of subjects in the control (unexposed) group: 45

Group 1 sample size Number of subjects in the case (exposed) group: 43

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): excluded those with antibiotic use in the past 1 month

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: ANOVA; T-Test

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

Signature 1

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Mark reviewed

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Needs review

Curated date: 2025/07/30

Curator: Kristin.abraham

Revision editor(s): Kristin.abraham

Source: Figure 5

Description: Taxa enriched in DLB patients

Abundance in Group 1: increased abundance in DLB patients

NCBI	Quality Control	Links
Alistipes putredinis
Bacteroides intestinalis
Bacteroides stercoris
Faecalibacterium prausnitzii
Oscillibacter valericigenes
Phocaeicola vulgatus
Ruminococcus