Gut as the target tissue of mercury and the extraintestinal effects Original paper

What was reviewed?

This paper reviewed evidence that the gut is a primary target tissue for mercury, including inorganic mercury (IHg) and methylmercury (MeHg), and that gut injury helps explain “extraintestinal” toxicity in organs such as the liver and brain. The authors synthesized mechanistic and animal-model findings showing that mercury can be absorbed and chemically transformed in the gut, while mercury exposure also disrupts gut barrier functions (biological, chemical, mechanical, and immune), creating downstream systemic inflammation and organ-specific injury through gut–liver and gut–brain pathways.

Who was reviewed?

The review focused on experimental evidence across multiple animal models and in vitro intestinal systems rather than a single clinical cohort. It drew heavily from rodent studies (including Sprague Dawley rats and mice), fish models, and poultry models to describe conserved gut microbiome shifts, barrier damage, and metabolomic changes after oral IHg or MeHg exposure, and it used intestinal epithelial models (e.g., Caco-2) to support direct effects on permeability and tight junction biology.

What were the most important findings?

The authors concluded that both IHg and MeHg reliably trigger gut dysbiosis and metabolomic disruption that track with barrier injury and systemic effects. As major microbial associations, IHg exposure often enriches Proteobacteria and Firmicutes and alters families linked to inflammation and pathogenic potential while reducing diversity at higher doses; reported shifts include increases in taxa such as Desulfovibrionaceae and Pseudomonas in fish and expansions of pathobiont-associated groups in poisoned rodents, alongside reductions in beneficial taxa in some settings. MeHg similarly perturbs community structure and can reduce Lactobacillaceae while increasing Porphyromonadaceae and Prevotellaceae in intestinal regions, and it links to neuroactive metabolite changes in feces, including elevated glutamate and GABA with reductions in amino acids tied to neurotransmitter synthesis. Mechanistically, the paper emphasized mercury-driven tight junction and cytoskeletal disruption (including altered ZO1/F-actin patterns), increased intestinal permeability, and higher pro-inflammatory cytokine signaling (notably IL-6 and TNF-α), supporting a model where gut damage amplifies hepatotoxicity for IHg and neurotoxicity for MeHg via gut–liver and gut–brain axes.

What are the greatest implications of this review?

For clinicians and microbiome-signature work, this review argues that mercury toxicity is not only a direct organ-deposition problem; it is also a gut-mediated disease process where dysbiosis, inflammatory signaling, and barrier breakdown act upstream of liver and brain outcomes. This framing supports using gut microbial and fecal metabolite readouts as early indicators of mercury-related risk and suggests that microbiome-directed strategies could plausibly reduce harm, including approaches that restore barrier integrity, reduce inflammatory signaling, and shift microbial metabolism toward reduced mercury bioactivation. The authors also cautioned that many animal studies use relatively high exposures, so translating signatures to environmentally relevant doses remains a priority for future work and database annotation.