Papers of the Month
By Megan Avakian
Changes in gut, liver may contribute to Alzheimer’s disease susceptibility
NIEHS-funded researchers determined how changes in the gut and liver may contribute to cadmium-induced Alzheimer’s disease (AD). They previously showed that male mice with a genetic variant called apolipoprotein E4 (ApoE4), a known risk factor for AD, were most susceptible to the disease following cadmium exposure. Here, they shed light on how cadmium and ApoE4 alter the gut and liver in ways that may promote AD.
The study included one group of mice genetically altered to have the human ApoE4 gene and another group with the more common human ApoE3 gene variant, which is not implicated in AD. For 14 weeks, the researchers exposed mice to cadmium in drinking water. Then they used genetic sequencing to characterize changes in the gut microbiome and quantified changes in serum metabolite levels and gene expression in the liver.
ApoE4 males exposed to cadmium had the most prominent changes in the gut microbiome, serum metabolites, and gene expression in the liver. Specifically, they had an increase in gut microbial species common in patients with AD. They also had lower lactate-producing bacteria and decreased serum lactate, a molecule essential for neuron function. These animals also showed a positive correlation between inflammation genes in the liver and pro-inflammatory bacteria in the gut.
Study results suggested that cadmium induced changes in the gut and liver of mice most susceptible to AD, notably males with the ApoE4 genetic risk factor. According to the authors, these gut-liver changes may contribute to differences in susceptibility to cadmium-induced AD.
Citation: Zhang A, Matsushita M, Zhang L, Wang H, Shi X, Gu H, Xia Z, Cui JY. 2021. Cadmium exposure modulates the gut-liver axis in an Alzheimer's disease mouse model. Commun Biol 4(1):1398.
Air pollution exposure affects populations disproportionately
Certain racial and ethnic groups and low-income populations in the U.S. are exposed to higher levels of fine particulate matter air pollution (PM2.5) compared with other groups, according to a new NIEHS-funded study.
The researchers linked demographic data from the U.S. Census Bureau and American Community Survey for 2000-2016 with publicly available PM2.5 data from across the U.S. They analyzed relative exposure disparities across income and racial and ethnic groups for each of the nation’s 32,000 zip code tabulation areas.
Areas where white and Native American populations were overrepresented were consistently exposed to lower average PM2.5 than areas where Black, Asian, and Hispanic or Latino populations were overrepresented. For example, in 2016, the average PM2.5 concentration for the Black population was 13.7% higher than that of the white population and 36.3% higher than that of the Native American population. As the Black population increased in an area, so did PM2.5, with a steep increase for areas where more than 85% of the population was Black. Similar trends held for Hispanic and Latino populations, whereas the opposite was true for areas with high-density white populations. From 2004-2016, areas with low-income groups were consistently exposed to higher average PM2.5 levels than areas with high-income groups. In addition, disparities in exposure to PM2.5 at levels above health protective standards increased over time.
According to the authors, study results highlighted the importance of targeted air pollution reduction strategies to provide all people protection from environmental hazards.
Citation: Jbaily A, Zhou X, Liu J, Lee TH, Kamareddine L, Verguet S, Dominici F. 2022. Air pollution exposure disparities across US population and income groups. Nature 601(7892):228–233.
High levels of PFAS detected in anti-fogging sprays, cloths
NIEHS-funded researchers found high levels of per- and polyfluoroalkyl substances (PFAS) in the sprays and cloths many people use to prevent their glasses from fogging up while wearing a face mask.
The researchers tested four anti-fogging sprays and five anti-fogging cloths for PFAS. Several different PFAS were present in all products, including two understudied PFAS compounds — fluorotelomer alcohols and fluorotelomer ethoxylates. PFAS concentrations varied in samples, reaching levels up to 185,000 micrograms per gram in cloth products and 25,000 micrograms per milliliter in sprays. For context, exposure to just 1% of the total PFAS from each use of the spray equals an exposure 14-500 times greater than drinking 1 liter of water at the U.S. Environmental Protection Agency’s health advisory level for PFAS.
To characterize how the products may affect health, the researchers exposed a mouse cell line to the sprays. They assessed cell toxicity and measures of adipogenic activity, like fat accumulation and the formation of fat cells from stem cells. All anti-fog sprays induced significant cell toxicity and adipogenic activity compared with controls. These effects occurred at a dose of less than one pump of the spray.
These results suggested that understudied PFAS compounds are present in commercial anti-fogging products at levels that may harm health. More research is needed to fully understand the health risks from using these PFAS-containing products, according to the authors.
Citation: Herkert NJ, Kassotis CD, Zhang S, Han Y, Pulikkal VF, Sun M, Ferguson PL, Stapleton HM. 2022. Characterization of per- and polyfluorinated alkyl substances present in commercial anti-fog products and their in vitro adipogenic activity. Environ Sci Technol 56(2):1162–1173.
Leveraging unused samples to predict metal exposures
NIEHS-funded researchers demonstrated a robust approach for predicting exposure to arsenic and manganese using a commonly stored but often unused biological sample. As an alternative to using whole blood, their method used only the clotted erythrocyte fraction to track metal exposures.
The research included whole blood and clotted erythrocyte fraction samples previously collected from 84 participants enrolled in a mother-child cohort study in Chicago. Using mass spectrometry, the scientists measured arsenic and manganese levels in both sample types. They used a linear regression model to predict whole blood exposures from clotted erythrocyte fraction and assessed whether the model could identify participants falling above or below potential public health–based cutoff values for unsafe exposure.
Both arsenic and manganese levels were strongly correlated between sample types. The linear regression model accurately predicted whole blood levels from clotted erythrocyte fraction. Further evaluation showed that whole blood levels predicted from the model could sufficiently discriminate between potential clinical and public health–based cutoffs for both metals.
To confirm that arsenic binds to clotted erythrocyte fraction at a range of exposures, the researchers exposed rats to arsenic at 0.01, 0.1, 1.0, or 10.0 milligrams per kilogram body weight. Arsenic in both sample types was strongly correlated, with whole blood levels ranging from 15-95 milligrams per liter and clotted erythrocyte fraction levels from 17-123 milligrams per liter.
According to the authors, this study provides a validated method for retrospective assessments of metal exposures in previously unused samples.
Citation: Haque E, Moran ME, Wang H, Adamcakova-Dodd A, Thorne PS. 2022. Validation of blood arsenic and manganese assessment from archived clotted erythrocyte fraction in an urban cohort of mother-child dyads. Sci Total Environ 810:152320.
(Megan Avakian is a science writer for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)