Arsenic Exposure Perturbs the Gut Microbiome and Its Metabolic Profile in Mice: An Integrated Metagenomics and Metabolomics Analysis Original paper

What was studied?

This original study asked whether arsenic exposure perturbs the gut microbiome and its metabolic outputs in vivo. Investigators exposed specific-pathogen-free mice to sodium arsenite in drinking water (10 ppm) for four weeks, then combined 16S rRNA sequencing with liquid chromatography mass spectrometry metabolomics of feces, urine, and plasma. The work quantified exposure-driven shifts in community structure and linked them to altered small-molecule profiles. It further tested whether microbe–metabolite correlations reveal functional pathways affected by arsenic, focusing on bacterial families, indole derivatives from tryptophan metabolism, bile acid intermediates, and other diet- and host-derived compounds relevant to barrier function, energy harvest, and immune tone.

Who was studied?

The experiment used female C57BL/6 mice (about six to eight weeks old), housed under controlled temperature, humidity, and light cycles, with identical diets and filtered water. Ten animals received arsenic and ten served as controls. Researchers collected fecal pellets at necropsy and obtained urine and plasma close to the endpoint to capture steady-state microbial and metabolic signals. Body weight, intake, and standard histology did not differ between groups, isolating gut microbial and metabolic changes to arsenic exposure rather than systemic illness. Sample processing followed validated pipelines for QIIME-based taxonomic assignment and untargeted LC-MS feature discovery with subsequent metabolite identification by MS/MS.

Most important findings

Arsenic exposure produced a clear separation of microbial communities from controls by principal coordinates analysis and hierarchical clustering. Several Firmicutes families fell significantly, whereas one Firmicutes group within Clostridiales (Family XIII Incertae Sedis) rose about two-fold, indicating a compositional tilt away from typical short-chain-fatty-acid producers. In the fecal metabolome, 370 molecular features changed (224 decreased; 146 increased), and principal component analysis cleanly discriminated exposed from control mice.

Indole-pathway metabolites shifted markedly: indolelactic acid fell more than ten-fold, while indoxyl and 3-indolepropionic acid rose, each correlating with specific Firmicutes or Tenericutes families. Bile acid homeostasis also shifted, with reduced glycocholic acid in feces and increased excretion of 7-α-hydroxy-3-oxo-4-cholestenoate and a related degradation product, suggesting altered bile acid synthesis or enterohepatic cycling. Isoflavone metabolism signatures changed in parallel; fecal daidzein and dihydrodaidzein decreased, while O-desmethylangolensin increased and tracked with Bacilli-affiliated taxa. Correlation matrices linked these metabolite changes to the altered bacterial families, supporting a functional coupling between taxonomic and metabolic shifts under arsenic stress.

Key implications

For clinicians and translational researchers, these results define a coherent exposure signature: loss of multiple Firmicutes families commonly associated with butyrate production, broad remodeling of tryptophan-derived indoles that shape epithelial integrity and immune signaling, and disturbed bile acid handling that can influence glucose–lipid homeostasis and inflammation. Because the study observed no weight or histopathology differences, the microbiome and metabolome shifts likely precede overt tissue injury and may serve as early indicators of risk. For microbiome signature databases, the paired taxa–metabolite links (for example, depressed indolelactic acid with Firmicutes losses and increased O-desmethylangolensin with Bacilli) offer concrete features to catalog in arsenic-exposure panels.