-Differences in uptake seen for four metals during intrauterine and early postnatal life in those who eventually developed IBD vs controls
by Zeena Nackerdien PhD, CME Writer, MedPage Today 2020-04-15

Study Authors: Nilendra Nair, Christine Austin, et al.

Target Audience and Goal Statement: Gastroenterologists, pediatricians

The goal of this study was to determine an association between early-life exposures to environmental metallic toxins and inflammatory bowel disease (IBD), based on analyses of deciduous teeth.

Question Addressed:

• What was the association between early-life exposures to metals and the future risk of IBD?

Study Synopsis and Perspective:

IBD describes chronic inflammatory disorders of the digestive tract, including ulcerative colitis (UC) and Crohn’s disease (CD). According to the Crohn’s and Colitis Foundation of America, the number of people with IBD continues to rise in the U.S. Their 2020 estimate of 1.6 million Americans currently living with IBD represents a growth of about 200,000 since they first reported the figure in 2011.

These chronic inflammatory conditions are also diseases of industrialized nations. IBD is known to arise from a complex interplay between genes and the environment. Smoking, appendicitis, oral contraceptive pills, diet, breastfeeding, infections/vaccinations, antibiotics, helminths, and childhood hygiene are among the specific environmental risk factors that have been implicated in the increased worldwide incidence of IBD. However, even smoking, a well-known environmental risk factor, contributes only partially to disease pathogenesis (i.e., most smokers do not have CD and most CD patients do not smoke).

Despite numerous studies that have examined environmental factors and IBD, robust evidence about harmful or protective factors to inform IBD prevention is lacking. Tracking environmental exposures early in life, when risk factors could modulate the immune system, potentially conferring long-lasting health consequences, constitutes a particular challenge.

In a study published in Gastroenterology, Joana Torres, MD, PhD, of Icahn School of Medicine’s Mount Sinai Road to Prevention Group in New York City, and colleagues compared 28 baby teeth — preserved by parents at natural shedding according to Portuguese custom and provided by 12 adult IBD patients and 16 unaffected controls — and found significant differences in uptake of four metals in the primary teeth of those who eventually developed IBD versus controls.

While blood tests can detect a metal of interest, such as lead, at any given time, they cannot reveal past exposures or time-stamp when they happened. However, baby teeth, like the growth rings of trees, retain information incrementally, storing evidence of environmental exposure, from their initial development in the womb until they are shed.

Of the 12 IBD patients, seven were diagnosed with CD and five with UC. Most of the participants were women (79%), and the average age at recruitment was 26.6 years.

The researchers were able to analyze teeth that had been stored for years because elemental deposits in teeth are stable at ambient temperatures. They looked at four metals — lead, copper, zinc, and chromium — and the developmental time periods during which exposures took place going back to the 25th week of pregnancy. Metals were analyzed using laser ablation-inductively coupled plasma-mass spectrometry analysis. They collected metal profiles from the second trimester of pregnancy through the first 6 months after birth in weekly increments.

Distribution lag models were used to estimate time-varying differences in metal exposures between IBD patients and controls at discrete timepoints. Metal uptake in the teeth of individuals who eventually developed IBD diverged from controls in a time-dependent manner and at different developmental time periods for each metal. IBD patients absorbed more of all four metals compared with controls.

Exposure to lead is known to be an inflammatory toxicant that has been shown to predispose to murine colitis, as well as alter the gut microbiome and affect metabolic functions. Lead exposure was higher in IBD patients from 15 weeks before birth to at least 35 weeks postnatally, with the strongest association observed around the sixth month after birth.

Similarly, zinc and copper levels were positively associated with IBD status from intrauterine development to birth or 18 weeks postnatally. Chromium levels were also positively associated with IBD status from 9 to 15 weeks before birth.

Study limitations, the researchers said, included the small and homogeneous sample size, as well as the inability of the associative findings to determine if increased metal uptake is driven by genetic susceptibility or other factors, and what the consequences of metal exposure might be for the inchoate immune system, gut barrier, and microbiome.

Source Reference: Gastroenterology 2020; DOI: 10.1053/j.gastro.2020.03.040

Study Highlights and Explanation of Findings:

Concern over environmental pollutants and their adverse health consequences continues to grow. In this innovative study, Torres and colleagues examined the associations between early-life metal exposures and future risk of IBD.

To accomplish this, they used the same tooth analysis “road-tested” in earlier studies. In 2018, researchers from the Icahn School of Medicine at Mount Sinai showed that cycles involved in zinc and copper metabolism are dysregulated in autism spectrum disorder (ASD), and can be used to predict who will later develop disease. Subsequently, a small study suggested that how a child metabolizes nutrients and toxins may play a role in attention deficit-hyperactivity disorder (ADHD) and autism.

Current study findings showed differences in the uptake of lead, copper, zinc, and chromium during intrauterine and early postnatal life in individuals who eventually developed IBD compared with controls.

“The data suggests that metal exposure during a critical window in early life may be a risk factor for IBD,” said co-author Manish Arora, PhD, also of the Icahn School of Medicine at Mount Sinai, in a press release. The team added that their findings might provide an opportunity to reconcile epidemiological data with quantitative and objective exposure data, which may help explain the rising incidence of disease in an increasingly urbanized world.

“We know that IBD develops because of a combination of genetic and environmental factors,” Lindsey G. Albenberg, DO, of the Children’s Hospital of Philadelphia, told MedPage Today, when asked for her perspective on the findings. “In terms of the environment, we know patients with IBD have an altered composition of the gut microbiota, and studies in animals show that metals can have profound effects on the composition of the gut microbiota. Thus, it is possible that exposure to certain metals can cause gut microbiota changes that predispose to the development of IBD.”

She cautioned, however, that individual metals have different effects on the gut microbiota and most of these studies have been done in animals only. “It is also likely that a person’s genetic background can interact with environmental metals to induce unique microbiota changes,” she added.

“If environmental metals are found to be a significant risk factor for the development of IBD and other immune-mediated diseases, there may be ways to mitigate these exposures through diet or even supplements that alleviate toxicity. However, global efforts to address water and soil contamination will also be required,” Albenberg said.