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

Dutta, Moumita; Weigel, Kris M.; Patten, Kelley T; Valenzuela, Anthony; Wallis, Christopher; Bein, Keith J.; Wexler, Anthony S.; Lein, Pamela J.; Cui, Julia Yue

doi:10.1016/j.toxrep.2022.03.003

Cited by 9 publications

(4 citation statements)

References 129 publications

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“…A number of factors may contribute to inconsistent associations between TCA and GDM. First, circulating metabolites are influenced by many factors, including diet, 40 heterogeneity of populations, 41 physical behaviours, 42 assay methodology and types of biological sample, 43 environmental factors, 44 and subject nutritional status 45 . For example, fasting total taurine‐conjugated bile acid levels are not associated with insulin resistance, but the change from basal to maximal postprandial levels is significantly different between women with and without insulin resistance 38 .…”

Section: Discussionmentioning

confidence: 99%

Bile acid metabolites in early pregnancy and risk of gestational diabetes mellitus: Results from a prospective cohort study

Wang

Zhao

et al. 2023

Diabetes Obesity Metabolism

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Aims To evaluate the associations of plasma bile acid metabolites, especially in early pregnancy, with gestational diabetes mellitus (GDM) risk among pregnant women. Materials and Methods Plasma concentrations of 15 bile acid metabolites were measured in 645 women at early pregnancy from the Jiashan Birth Cohort using a liquid chromatography‐tandem mass spectrometry metabolomics platform. Using logistic and cubic spline models, we examined associations between baseline plasma bile acid metabolites and GDM risk during mid‐late pregnancy. A meta‐analysis of prospective studies of bile acid and GDM risk was performed. Results The linear and nonlinear univariate models identified eight metabolites associated with GDM, including cholic acid, taurocholic acid (TCA), glycocholic acid, glycochenodeoxycholic acid, deoxycholic acid, lithocholic acid (LCA), ursodeoxycholic acid and taurolithocholic acid (all P <0.05). Multivariable analysis indicated that TCA and LCA levels were positively (odds ratio [OR] 2.07, 95% confidential interval [CI] 1.05, 3.96; P = 0.030) and negatively (OR 0.83, 95% CI 0.68, 1.01; P = 0.065) associated with GDM, respectively, after adjusting for confounders. The TCA‐GDM association showed a positive linear shaped relationship (OR 2.07, 95% CI 1.05, 3.96; P = 0.030); while LCA was negatively related with GDM risk in linearity (OR 0.83, 95% CI 0.68, 1.01; P = 0.065). The meta‐analysis of five studies showed a consistent bile acid and GDM association, with a risk ratio (RR) of 2.43 (1.95, 3.03). Conclusions This study indicated that, the levels of circulating bile acids in early pregnancy were associated with risk of GDM, independent of GDM risk factors. Most GDM‐associated bile acids were primary conjugated and secondary unconjugated bile acids.

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Section: Discussionmentioning

confidence: 99%

Bile acid metabolites in early pregnancy and risk of gestational diabetes mellitus: Results from a prospective cohort study

Wang

Zhao

et al. 2023

Diabetes Obesity Metabolism

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“…( Bernard et al, 1998 ) It is also interesting that bile acid biosynthesis was implicated as the absorption of lipid-soluble vitamins (such as vitamins D and A) from the diet requires bile acids and high levels of these vitamins may also repress bile acid synthesis to protect against potentially toxic levels of lipid-soluble vitamins in the diet. ( Schmidt et al, 2010 ) Traffic-related air pollution has been known to alter bile acid homeostasis ( Dutta et al, 2022 ) and previous studies on air pollution and the blood metabolome ( Gaskins et al, 2021 ; Liang et al, 2018 ; Liang et al, 2019 ) have also found bile acid biosynthesis to be commonly dysregulated pathway with higher exposure to air pollution.…”

Section: Discussionmentioning

confidence: 99%

Using follicular fluid metabolomics to investigate the association between air pollution and oocyte quality

Hwang

Hood

Hauser

et al. 2022

Environment International

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“…The neurological functions of bile acids have been reviewed recently [30][31][32], and neurological impairment has been reported with increased blood bile acid levels [33]. Air pollution [34] and genetic variations [35] may alter bile acid metabolism in the body and promote developing AD. In addition, elevated serum/plasma levels of toxic bile acids such as lithocholic acid (LCA) may originate from defective D-BP in the liver of patients with AD, which could play major roles in developing AD.…”

Section: Liver Disfunction Contributing To Admentioning

confidence: 99%

The Pathological Effects of Circulating Hydrophobic Bile Acids in Alzheimer’s Disease

Ehtezazi

Rahman

Davies

et al. 2023

ADR

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Recent clinical studies have revealed that the serum levels of toxic hydrophobic bile acids (deoxy cholic acid, lithocholic acid [LCA], and glycoursodeoxycholic acid) are significantly higher in patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) when compared to control subjects. The elevated serum bile acids may be the result of hepatic peroxisomal dysfunction. Circulating hydrophobic bile acids are able to disrupt the blood-brain barrier and promote the formation of amyloid-β plaques through enhancing the oxidation of docosahexaenoic acid. Hydrophobic bile acid may find their ways into the neurons via the apical sodium-dependent bile acid transporter. It has been shown that hydrophobic bile acids impose their pathological effects by activating farnesoid X receptor and suppressing bile acid synthesis in the brain, blocking NMDA receptors, lowering brain oxysterol levels, and interfering with 17β-estradiol actions such as LCA by binding to E2 receptors (molecular modelling data exclusive to this paper). Hydrophobic bile acids may interfere with the sonic hedgehog signaling through alteration of cell membrane rafts and reducing brain 24(S)-hydroxycholesterol. This article will 1) analyze the pathological roles of circulating hydrophobic bile acids in the brain, 2) propose therapeutic approaches, and 3) conclude that consideration be given to reducing/monitoring toxic bile acid levels in patients with AD or aMCI, prior/in combination with other treatments.

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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

Cited by 9 publications

References 129 publications

Bile acid metabolites in early pregnancy and risk of gestational diabetes mellitus: Results from a prospective cohort study

Bile acid metabolites in early pregnancy and risk of gestational diabetes mellitus: Results from a prospective cohort study

Using follicular fluid metabolomics to investigate the association between air pollution and oocyte quality

The Pathological Effects of Circulating Hydrophobic Bile Acids in Alzheimer’s Disease

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