Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was reviewed?
This systematic review examined the association between exposure to major heavy metals, arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd) and alterations in human gut microbiota composition. The review systematically identified and synthesized data from human observational studies. Through extensive database searches and rigorous inclusion criteria, the review consolidated evidence on gut microbiota changes linked to heavy metal exposure, with an emphasis on the nutritional approach to mitigate such impacts. The review explored how these toxicants, commonly encountered through environmental pollution, food, and water, may disturb the delicate balance of gut microbial communities (dysbiosis), and outlined possible nutritional and probiotic strategies for prevention and remediation.
Who was reviewed?
The review encompassed 12 human observational studies, including cross-sectional, cohort, longitudinal, and case-control designs. Study participants varied widely: infants, children, adults, and pregnant women from diverse geographic regions, mainly the USA, China, Nepal, and Bangladesh. Sample sizes ranged from 17 to 724 per study. Heavy metal exposure was measured in various biological specimens (urine, blood, feces, teeth, toenails, hair) and environmental sources (water), predominantly using inductively coupled plasma mass spectrometry (ICP-MS). Gut microbiota composition was assessed mainly via 16S rRNA gene sequencing, PCR, and metagenomics on fecal samples. The quality of included studies was assessed using the Newcastle Ottawa Scale, with most studies deemed high quality.
Most important findings
| Critical Points | Details |
|---|---|
| Gut microbiota disturbance | Exposure to As, Pb, and Hg consistently led to changes in gut microbiota composition, often resulting in dysbiosis. Dysbiosis is characterized by an imbalance in microbial communities, which has been linked to inflammation, increased gut permeability (“leaky gut”), and heightened risk of diseases such as inflammatory bowel disease, metabolic disorders, and cancers. |
| Pathobiont increase | High levels of As, Pb, and Hg exposure were associated with increased abundance of Collinsella, a pro-inflammatory pathobiont genus implicated in metabolic and inflammatory diseases and in the reduction of gut barrier integrity. |
| Shifts in microbial phyla | As and Pb exposure were linked to increased Proteobacteria and Enterobacteriaceae (potentially pathogenic), and decreased beneficial genera such as Bifidobacterium and Ruminococcus. These shifts may exacerbate inflammation and metabolic dysfunction. |
| Metal-specific findings | As reduced beneficial Bifidobacterium (except in the presence of high zinc), and increased pathogenic taxa. Pb exposure in utero and postnatally decreased both beneficial and harmful bacteria, but also increased pathogenic fungi such as Malassezia. Hg exposure data were less consistent, but included associations with increased pathobionts and, in some cases, beneficial taxa. Cd exposure was only assessed in one study, which found a positive association with Bifidobacterium. |
| Nutritional modulation | Observational evidence indicated that higher dietary fiber intake is inversely correlated with blood HM concentrations and may reduce Collinsella abundance, suggesting fiber can help mitigate HM-induced dysbiosis. Probiotic and antioxidant-rich diets were also recommended as protective strategies. |
| Exposure pathways and heterogeneity | Differences in specimen type, age, location, and baseline microbiota contributed to heterogeneous findings. Pb exposure primarily occurred via air, Hg via soil, and As via water, reflecting varied environmental and dietary risks. |
| Research limitations | Many studies were cross-sectional, limiting causal inference. Confounding factors such as co-exposure to multiple metals and nutritional status were often inadequately controlled. The number of studies per metal was limited, especially for Cd and Hg. |
Key implications
For heavy metal certification programs, this review demonstrates that even low to moderate HM exposures can drive significant shifts in gut microbiota, particularly increasing pathobionts and reducing beneficial bacteria. This reinforces the need for stringent HM limits in food and water. It also underscores the value of dietary fiber and probiotic-rich foods as part of preventive strategies in populations at risk of HM exposure. Certification should consider not only direct toxicity, but also impacts on gut microbial health. Ongoing monitoring and further human studies are essential to refine exposure thresholds and recommendations.
Citation
Rezazadegan M, Forootani B, Hoveyda Y, Rezazadegan N, Amani R. Major heavy metals and human gut microbiota composition: a systematic review with nutritional approach. J Health Popul Nutr. 2025;44:21. https://doi.org/10.1186/s41043-025-00750-4
Heavy metals are high-density elements that accumulate in the body and environment, disrupting biological processes. Lead, cadmium, arsenic, mercury, nickel, tin, aluminum, and chromium are of greatest concern due to persistence, bioaccumulation, and health risks, making them central to the HMTC program’s safety standards.
Lead is a neurotoxic heavy metal with no safe exposure level. It contaminates food, consumer goods and drinking water, causing cognitive deficits, birth defects and cardiovascular disease. HMTC’s rigorous lead testing applies ALARA principles to protect infants and consumers and to prepare brands for tightening regulations.
Cadmium is a persistent heavy metal that accumulates in kidneys and bones. Dietary sources include cereals, cocoa, shellfish and vegetables, while smokers and industrial workers receive higher exposures. Studies link cadmium to kidney dysfunction, bone fractures and cancer.
