Metformin exposure altered intestinal microbiota composition and metabolites in amphibian larvae

Ecotoxicol Environ Saf. 2023 Nov 15:267:115617. doi: 10.1016/j.ecoenv.2023.115617. Epub 2023 Oct 21.

Abstract

The antidiabetic pharmaceutical metformin (MET) is largely unmetabolized by the human body. Its residues are readily detectable in various aquatic environments and may have adverse impacts on the growth and survival of aquatic species. To date, its toxicological effects have scarcely been explored in non-fish species. Here, we exposed the tadpoles of black-spotted pond frog (Pelophylax nigromaculatus) to different concentrations (0, 1, 10 and 100 μg/L) of MET for 30 days and measured the body size, intestinal microbiota and metabolites to evaluate potential effects of MET exposure in amphibian larvae. MET exposure did not affect the growth and intestinal microbial diversity of tadpoles. However, intestinal microbial composition changed significantly, with some pathogenic bacteria (e.g., bacterial genera Salmonella, Comamonas, Stenotrophomonas, Trichococcus) increasing and some beneficial bacteria (e.g., Blautia, Prevotella) decreasing in MET-exposed tadpoles. The levels of some intestinal metabolites associated with growth and immune performance also changed significantly following MET exposure. Overall, our results indicated that exposure to MET, even at environmentally relevant concentrations, would cause intestinal microbiota dysbiosis and metabolite alteration, thereby influencing the health status of non-target aquatic organisms, such as amphibians.

Keywords: Antidiabetic pharmaceutical; Immune performance; Intestinal microbiota dysbiosis; Metabolic perturbation; Pelophylax nigromaculatus tadpole.

MeSH terms

  • Animals
  • Anura
  • Dysbiosis
  • Gastrointestinal Microbiome*
  • Humans
  • Hypoglycemic Agents
  • Larva
  • Metformin* / toxicity

Substances

  • Metformin
  • Hypoglycemic Agents