Inhaling ultrafine particles causes shifts in gut microbiome

Exposure to ultrafine particulate matter — the smallest particles of air pollution — can alter the composition of microorganisms living in the gut, according to an NIEHS-funded study using mice. The changes occurred independent of intestinal inflammation, a sign of disease.

Research suggests that shifts in the gut microbiome, or microbial community, factor into many diseases also tied to particulate matter exposure, such as cardiovascular and metabolic disorders. Although exposure to ultrafine particles has been associated with intestinal inflammation and changes in the gut microbiome, it is unclear whether inflammation causes the changes or vice versa.

To investigate, the researchers periodically exposed two groups of mice to ultrafine particles at concentrations typical of human exposure levels in Los Angeles and other U.S. urban areas over the course of a year. One group of mice had high lipid, or fat, levels characteristic of cardiovascular disease, whereas the other had normal lipid levels. During the exposure period, the researchers periodically sequenced DNA from microbes in mouse fecal samples. At the end of the period, they sequenced microbial DNA from the intestines and looked for signs of intestinal inflammation.

Genetic analysis of fecal samples showed changes in microbial diversity or abundance over time, depending on mouse lipid levels. Analysis of the intestinal microbiome at week 10 showed significant changes in microbial composition in the mice with high lipid levels. Intestinal inflammation did not accompany any of the observed changes.

The results show that breathing in ultrafine particles leads to microbial changes that cannot be attributed to increased intestinal inflammation, according to the authors. They also noted future studies should investigate whether microbiome shifts contribute to the health effects induced by particulate matter exposure. (JL)

Citation: Chang C, Gupta R, Sedighian F, Louie A, Gonzalez DM, Le C, Cho JM, Park S, Castellanos J, Ting T, Dong TS, Arias-Jayo N, Lagishetty V, Navab M, Reddy S, Sioutas C, Hsiai T, Jacobs JP, Araujo JA. 2024. Subchronic inhalation exposure to ultrafine particulate matter alters the intestinal microbiome in various mouse models. Environ Res 248:118242.

Microplastics detected in testicular tissue may affect male fertility

NIEHS-funded researchers found significant levels of microplastics in the testicular tissue of humans and dogs. In canines, higher levels of plastic in the testes were associated with reduced reproductive function.

The researchers compared dog and human tissues because people share environments with their pets, resulting in similar environmental exposures across species. In addition, canine and human reproductive systems share many biological features.

The study included 23 human testis tissues, obtained during autopsies, and 47 canine testis samples, obtained from clinics that perform neuter surgeries. The researchers used advanced mass spectrometry to look for 12 different types of plastic in the samples. They used statistical tests to examine the association between microplastics and reproductive function in canine samples. They did not examine this relationship in the human samples, because they had been chemically preserved.

The team detected microplastics in all samples. On average, dog samples had 122.63 micrograms of plastic per gram of tissue and human samples contained 328.44 micrograms of plastic per gram. Samples from both species contained relatively equal proportions of the 12 different plastics. Polyethylene, used in plastic bottles and bags, was the most common type of plastic in both species, accounting for 36.4% and 35.2% of total microplastics in dogs and humans, respectively. In dogs, higher levels of two plastics, polyvinyl chloride and polyethylene terephthalate, were significantly related to lower testes weight, a measure of reduced sperm production.

According to the authors, the study results highlight the pervasive presence of microplastics in the male reproductive system across species, with potential adverse effects on male fertility. (MA)

Citation: Hu CJ, Garcia MA, Nihart A, Liu R, Yin L, Adolphi N, Gallego DF, Kang H, Campen MJ, Yu X. 2024. Microplastic presence in dog and human testis and its potential association with sperm count and weights of testis and epididymis. Toxicol Sci kfae060.

Fluoride exposure during pregnancy may increase neurobehavioral problems in children

Prenatal fluoride exposure may increase the risk of neurobehavioral problems among U.S. children, according to NIEHS-funded researchers. This is the first U.S.-based study to examine the relationship between fluoride exposure during pregnancy and neurobehavioral outcomes in childhood.

Nearly three-quarters of the U.S. population receives drinking water containing fluoride at levels of approximately 0.7 milligrams per liter. This is thought to be the optimal level for preventing tooth decay while minimizing adverse health effects for fluoride exposure. However, recent research suggests that exposure at this level may harm neurodevelopment.

The study included 229 predominately Hispanic pregnant women and their children living in Los Angeles. The researchers measured fluoride exposures in urine samples collected from the mothers during the third trimester of pregnancy. The team quantified the children’s neurobehavioral outcomes at age three using the Preschool Child Behavior Checklist, which relies on reports from parents to assess behavioral and emotional problems in children.

Mothers had a median fluoride exposure of 0.76 milligrams per liter. Children exposed to an additional 0.68 milligrams per liter of fluoride in utero were nearly twice as likely to exhibit behaviors at a level close to or meeting the standard for a clinical diagnosis. For example, children exposed to more fluoride had more anxiety, emotional regulation issues, traits associated with autism spectrum disorder, and physical problems, such as headaches. There was no relationship between fluoride and externalizing behaviors, such as aggression.

According to the authors, study findings suggest that prenatal fluoride exposure at levels common across the U.S. may increase the risk of neurobehavioral problems among children. They noted the results may support recommendations for limiting fluoride exposure during the prenatal period. (MA)

Citation: Malin AJ, Eckel SP, Hu H, Martinez-Mier EA, Hernandez-Castro I, Yang T, Farzan SF, Habre R, Breton CV, Bastain TM. 2024. Maternal urinary fluoride and child neurobehavior at age 36 months. JAMA Netw Open 7(5):e2411987.

Developmental exposures altered epigenetic signatures across tissues in offspring

Early life exposure to lead and phthalates altered epigenetic signatures in brain, blood, and liver tissues, according to an NIEHS-funded study in mice. Epigenetic signatures reflect the chemical marks on genes that affect gene function, but do not change the DNA sequence. The research may help advance studies in humans by providing insight into whether epigenetic signatures in more accessible tissues, such as blood, can help predict effects in harder-to-access tissues, like the brain.

The researchers orally exposed female mice to either lead or phthalates throughout gestation and weaning. Then, they examined changes in DNA methylation, a type of epigenetic modification, in the offspring’s brain, blood, and liver tissues at five months of age. They compared the epigenetic signatures in exposed and unexposed mice to identify differentially methylated regions (DMR) of genes. The researchers were particularly interested in DMRs on imprinted genes, which are important for healthy growth and development. Precise DNA methylation is critical for the proper expression of imprinted genes, and early disruption of this process can result in developmental disorders.

Brain tissues contained the majority of DMRs for both lead and phthalate exposure. Across all tissues, DMRs appeared in gene regions responsible for regulation of gene expression. DMRs were most prevalent on imprinted genes in exposed mice. Two imprinted genes, which have been associated with developmental disorders, contained a significant number of exposure-associated DMRs and displayed similar signatures across tissues.

According to the authors, these results suggest that epigenetic signatures on imprinted genes in blood may be useful biomarkers of exposures in brain and liver tissues, two commonly studied organs that are mostly inaccessible in human population studies. (MA)

Citation: Morgan RK, Wang K, Svoboda LK, Rygiel CA, Lalancette C, Cavalcante R, Bartolomei MS, Prasasya R, Neier K, Perera BPU, Jones TR, Colacino JA, Sartor MA, Dolinoy DC. 2024. Effects of developmental lead and phthalate exposures on DNA methylation in adult mouse blood, brain, and liver: a focus on genomic imprinting by tissue and sex. Environ Health Perspect 132(6):67003.