The role of Lactobacillus in dibutyl phthalate-induced gut and liver injury: Probiotic intervention and multi-omics evidence.

2026-04
Ecotoxicology and environmental safety 314

PubMed: 41895142
DOI: 10.1016/j.ecoenv.2026.120051

Study Design

Population: Mice
Methods: Mice were exposed to DBP (0, 50, 100, 200 mg/kg/day) for 28 days. An intervention group received DBP (100 mg/kg/day) co-administered with Lactobacillus rhamnosus GG (LGG, 1 × 10^9 CFU/day). Systemic toxicity was assessed via serum biochemistry and histopathology, and multi-omics analyses including 16S rDNA sequencing, liver transcriptomics, and serum metabolomics were integrated.

Animal Study

Background

Dibutyl phthalate (DBP), a widespread environmental contaminant, induces hepatotoxicity. While the gut-liver axis is implicated, the specific role of gut microbiota, particularly key beneficial genera, remains obscure.

Objective

This study aimed to elucidate whether Lactobacillus depletion is a central event in DBP-induced gut-liver axis disruption and to evaluate the therapeutic potential of probiotic intervention.

Methods

Mice were exposed to DBP (0, 50, 100, 200 mg/kg/day) for 28 days. An intervention group received DBP (100 mg/kg/day) co-administered with Lactobacillus rhamnosus GG (LGG, 1 ×10⁹ CFU/day). Systemic toxicity was assessed via serum biochemistry and histopathology. Gut barrier integrity, oxidative stress, and inflammation were evaluated in the ileum and liver. Multi-omics analyses, including 16S rDNA sequencing of ileal microbiota, liver transcriptomics, and serum metabolomics, were integrated to uncover mechanistic links.

Results

DBP exposure induced dose-dependent hepatotoxicity (steatosis, elevated ALT/AST, oxidative stress, inflammation) and ileal injury (barrier disruption, dysbiosis). Crucially, DBP specifically and significantly depleted ileal Lactobacillus. Multi-omics integration revealed that Lactobacillus depletion was strongly correlated with disrupted sphingolipid metabolism, a pathway concurrently altered in the serum metabolome and liver transcriptome. Intervention with LGG significantly ameliorated both intestinal barrier dysfunction (restored tight junctions, reduced permeability) and hepatic injury (attenuated steatosis, oxidative stress, and inflammation).

Conclusion

Our findings demonstrate that DBP-induced hepatotoxicity is mediated, in part, through the specific depletion of intestinal Lactobacillus, leading to gut barrier failure and systemic metabolic disturbances, notably in sphingolipid signaling. Probiotic supplementation with LGG effectively counteracts these defects. This study identifies Lactobacillus as a critical target of DBP and highlights microbiota-directed strategies as a promising avenue for mitigating phthalate toxicity.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus	—	Improved Intestinal Barrier Function	Beneficial	Moderate	View source Intervention with LGG significantly ameliorated both intestinal barrier dysfunction (restored tight junctions, reduced permeability) and hepatic injury (attenuated steatosis, oxidative stress, and inflammation).
Lactobacillus	—	Reduced Liver Injury	Beneficial	Moderate	View source Intervention with LGG significantly ameliorated both intestinal barrier dysfunction (restored tight junctions, reduced permeability) and hepatic injury (attenuated steatosis, oxidative stress, and inflammation).