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4-Hydroxyphenanthrene exacerbates obesity by altering gut microbiota and bile acid metabolism

ABSTRACT:

Elevated exposure to 4-hydroxyphenanthrenes (4-OHPhe) is positively associated with obesity risk. However, the specific pathogenic mechanism remains unclear. Here, we used SHapley Additive exPlanations (SHAP) and logistic regression analysis to identify a strong association between 4-OHPhe and obesity. Mechanistically, exposure to 4-OHPhe significantly downregulates the expression of hydroxylamine reductase (hcp) genes in Bacteroides uniformis (B. uniformis), thereby inhibiting the removal of reactive oxygen species (ROS) and reducing the abundance of B. uniformis. The decline in B. uniformis abundance reduces hyodeoxycholic acid (HDCA) production and consequent activation of the intestinal farnesoid X receptor (FXR)-ceramide pathway, which ultimately results in the downregulation of white adipose tissue (WAT) thermogenic genes and obesity. Both B. uniformis colonization and HDCA treatment were found to promote this thermogenic effect. These findings demonstrate that 4-OHPhe exacerbates obesity via impairment of gut microbiota composition, thereby establishing a mechanistic link between environmental toxins and host metabolism.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase

PROVIDER: MTBLS13496 | MetaboLights | 2025-12-21

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13496_LC-MS_negative_reverse-phase_metabolite_profiling-1.txt	Txt
	a_MTBLS13496_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13496_LC-MS_positive_hilic_metabolite_profiling_v2_maf_1.tsv	Tabular
	m_MTBLS13496_LC-MS_positive_hilic_metabolite_profiling_v2_maf_2.tsv	Tabular

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