Gut Microbiota as a Mediator of Essential and Toxic Effects of Zinc in the Intestines and Other Tissues Original paper

What was reviewed?

This review comprehensively examined the bidirectional relationship between zinc (Zn) status—both deficiency and excess—and gut microbiota composition across multiple species, including poultry, pigs, rodents, and humans. It also explored how these microbiota changes modulate local (intestinal) and systemic (extraintestinal) physiological and pathological effects of zinc, including inflammation, metabolic disorders, and neurodevelopmental conditions.

Who was reviewed?

The review drew from both in vivo and in vitro studies involving chicks, piglets, mice, and human subjects, including genetic studies on human Zn transporters. It considered experimental Zn deficiency and supplementation using various Zn formulations (oxide, sulfate, nanoparticles) and reviewed probiotic co-supplementation studies.

Most Important Findings

Zinc plays a critical, dose-dependent role in shaping gut microbiota composition and function, with downstream effects on intestinal and systemic health. Zinc deficiency is consistently associated with gut dysbiosis, which is marked by decreased microbial diversity, shifts in phyla proportions (notably reduced Firmicutes and increased Proteobacteria), and compromised intestinal barrier function. Physiological zinc supplementation, in contrast, supports gut integrity by enhancing tight junction protein expression, reducing pathogen abundance, and promoting beneficial microbial metabolite production such as short-chain fatty acids (SCFAs).

However, zinc overexposure induces microbial shifts favoring pathogenic taxa, impairs gut barrier function, and promotes systemic inflammation and endotoxemia. Beyond the gut, zinc–microbiota interactions have been implicated in extraintestinal disorders including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), severe acute pancreatitis, fetal alcohol syndrome, endometriosis, and obesity. Notably, co-supplementation with probiotics enhances zinc bioavailability and supports microbial-host homeostasis, with some probiotic strains (e.g., E. coli Nissle 1917) exploiting zinc-binding mechanisms to competitively inhibit pathogens. The review highlights a nuanced, dose-dependent role of zinc in gut microbiota regulation:

Greatest Implications

This review underscores the critical role of microbial context in modulating zinc’s biological effects. While physiological zinc supports microbial homeostasis and host immunity, excess zinc undermines nutritional immunity, selects for virulence traits in pathogens, and disrupts host–microbe symbiosis. Importantly, the work highlights the importance of considering microbial responses to Zn when designing supplementation strategies, especially in vulnerable populations (e.g., children, ASD, chronic inflammation). It also opens avenues for microbiota-targeted zinc therapeutics in metabolic and neurodevelopmental diseases.