Chronic exposure to ambient traffic-related air pollution (TRAP) alters gut microbial abundance and bile acid metabolism in a transgenic rat model of Alzheimer's disease. (2022)

• Record Type: Journal Article
• Authors: Dutta, Moumita; Weigel, Kris M.; Patten, Kelley T.; Valenzuela, Anthony E.; Wallis, Christopher; Bein, Keith J.; Wexler, Anthony S.; Lein, Pamela J.; Cui, Julia Yue
• Is Part Of: Toxicology reports. Volume 9(2022)
• Page Start: 432
• Page End: 444
• Publication Date: 2022
• Subjects: Traffic-related air pollution (TRAP) -- Gut microbiome -- Bile acid -- Rat -- Alzheimer's disease; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2022.03.003
• Languages: English
• ISSNs: 2214-7500

Abstract

Abstract: Background: Traffic-related air pollution (TRAP) is linked to increased risk for age-related dementia, including Alzheimer's disease (AD). The gut microbiome is posited to influence AD risk, and an increase in microbial-derived secondary bile acids (BAs) is observed in AD patients. We recently reported that chronic exposure to ambient TRAP modified AD risk in a sex-dependent manner in the TgF344 AD (TG) rat. Objectives: In this study, we used samples from the same cohort to test our hypothesis that TRAP sex-dependently produces gut dysbiosis and increases secondary BAs to a larger extent in the TG rat relative to wildtype (WT) controls. Methods: Male and female TG and age-matched WT rats were exposed to either filtered air (FA) or TRAP from 28 days up to 15 months of age (n = 5–6). Tissue samples were collected after 9 or 14months of exposure. Results: At 10 months of age, TRAP tended to decrease the alpha diversity as well as the beneficial taxa Lactobacillus and Ruminococcus flavefaciens uniquely in male TG rats as determined by 16 S rDNA sequencing. A basal decrease in Firmicutes/Bacteroidetes ( F/B) ratio was also noted in TG rats at 10 months. At 15 months of age, TRAP altered inflammation-related bacteria in the gut of female rats from both genotypes. BAs were more affected by chronic TRAP exposure in females, with a general trend of increase in host-produced unconjugated primary and microbiota-produced secondary BAs. Most of the mRNAs of the hepatic BA-processing genes were not altered by TRAP, except for a down-regulation of the BA-uptake transporter Ntcp in males. Conclusion: In conclusion, chronic TRAP exposure produced distinct gut dysbiosis and altered BA homeostasis in a sex and host genotype-specific manner. Graphical Abstract: ga1 Highlights: At 10 months, TRAP exposure tended to decrease beneficial taxa in male TG rats. A basal decrease in Firmicutes/Bacteriodetes ( F/B ) ratio was noted in TG rats. Bacteria-derived bile acid was increased uniquely in TG male rats at 10 months. TRAP altered gut homeostasis with increased inflammation-related taxa at 15 months. TRAP modified bile acid concentration in both sexes and genotypes.