Papers of the Month
Extramural
By Julie Leibach
Exposure to harmful algal bloom toxin alters gut microbiome, antibiotic resistance
Exposure to microcystin — a toxin commonly released during harmful algal blooms — can change the gut’s collection of microorganisms, or microbiome, and the associated abundance of antibiotic resistance genes, according to an NIEHS-funded study in mice.
Harmful algal blooms occur in water where nutrient runoff fuels the growth of toxin-producing organisms, such as microbes called cyanobacteria. Among the variety of toxins released by cyanobacteria, microcystin is the most prevalent. Routes of exposure include drinking or eating contaminated water or food, as well as skin contact.
For their study, the researchers exposed young mice to microcystin for two weeks. Then, they analyzed fecal and blood samples for the types of microbes and antibiotic resistance genes present. They found that exposure to microcystin caused a pronounced change in microbiome makeup and a notable decline in several beneficial gut bacteria compared with unexposed mice. That change correlated with an increase in the number and diversity of genes related to resistance to common antibiotics, such as tetracycline and macrolides. (Research has shown that antibiotic-resistance genes can be transferred from bacteria to host.)
Microcystin exposure also increased immune dysfunction in adult mice. Specifically, the team measured an increase in biological markers associated with immune system deterioration. They reported similar effects in mice designed to elicit human-like immune responses that typical lab mice might not reflect.
According to the authors, their study is the first to characterize the effect of microcystin on the immune system and on antimicrobial resistance. The findings have implications for which treatments are offered to people with other conditions who have also been exposed to the toxin.
Citation: Saha P, Bose D, Stebliankin V, Cickovski T, Seth RK, Porter DE, Brooks BW, Mathee K, Narasimhan G, Colwell R, Scott GI, Chatterjee S. 2022. Prior exposure to microcystin alters host gut resistome and is associated with dysregulated immune homeostasis in translatable mouse models. Sci Rep 12(1):11516.
Prioritizing understudied compounds in chemical mixtures could offer insight into breast cancer risk
Researchers funded by NIEHS identified understudied chemicals that frequently occur in the same products as those linked to breast cancer. These findings could inform studies looking at how exposure to chemical mixtures influences disease risk. The team focused on common exposure pathways, including food, pesticides, and personal care products, among others.
Breast cancer is the leading cause of cancer-related death among women worldwide. Only 10% of cases are attributed to genetic predisposition; the remainder stem from other risk factors, such as environmental exposures. However, data are scant regarding the role of chemical mixtures on breast cancer development.
The researchers first turned to a vast federal database that inventories chemicals used globally. For various compounds, they manually assigned key words related to 32 types of exposure pathways that people might encounter daily. Next, the team divided chemicals in the database into three categories: those with known breast cancer associations, those with no known association, and chemicals whose association with breast cancer had not been studied.
In total, the team assessed more than 6,300 understudied chemicals for co-occurrence with cancer-related compounds as well as for similarities between structure and chemical properties. Of those, they identified 50 understudied substances with chemical properties like those of cancer-linked agents that should be prioritized for additional toxicological and human studies.
The results highlight a need to consider chemical co-occurrence in mixtures — especially when compounds share certain features — when examining how everyday exposures influence breast cancer risk, according to the authors.
Citation: Koval LE, Dionisio KL, Friedman KP, Isaacs KK, Rager JE. 2022. Environmental mixtures and breast cancer: Identifying co-exposure patterns between understudied vs breast cancer-associated chemicals using chemical inventory informatics. J Expo Sci Environ Epidemiol; doi:10.1038/s41370-022-00451-8 [Online 16 June 2022].
Future flooding may exacerbate disparities in exposure to hazardous pollution
Increased flooding from climate change in the U.S. will likely expose more people to legacy waste from former industrial sites, according to an NIEHS-funded study. Populations that face inequality stemming from racial, economic, and housing status are more likely to live in the areas that could be affected.
The researchers chose six urban centers located near coasts or along rivers that have experienced major industrial development and where legacy contamination has been documented. Those sites included populous areas in Rhode Island, Texas, Pennsylvania, Louisiana, Minnesota, and Oregon.
By examining state manufacturing directories spanning nearly 60 years, the team identified nearly 15,500 former industrial sites in certain sectors — such as coal, petroleum, and rubber — that were highly likely to be contaminated with waste considered harmful to humans. The researchers then estimated the future flood risk of those sites, drawing on data from the First Street Foundation, which makes projections based on multiple flood models.
All told, they identified 6,636 sites facing an elevated flood risk by 2050, and thousands to hundreds of thousands of people at risk of local exposure to contaminated floodwaters. Using data from the U.S. Census Bureau and guidance from the Centers for Disease Control and Prevention, the team also discovered that groups with higher measures of social vulnerability were overall more likely to live in those flood-prone areas.
The findings suggest that urban planning efforts should include strategies for remediation and engagement with residents of historically marginalized communities, the authors noted.
Citation: Marlow T, Elliot JR, Frickel S. 2022. Future flooding increases unequal exposure risks to relic industrial pollution. Environ Res Lett 17(7):074021.
COVID-19 virus hijacks lipid metabolism in the body to cause disease
The coronavirus that causes COVID-19 establishes infection by rewiring how cells make and process lipids, or fats, according to researchers funded in part by NIEHS. They also found that preventing cells from making certain fats stopped several coronavirus strains from proliferating.
First, the team explored how SARS-CoV-2 influences fat composition by exposing cells to live virus, as well as by altering cells to express individual virus proteins. Of hundreds of lipids analyzed, most revealed significant changes in structural and chemical properties after cells were exposed to the virus compared with unexposed cells. The researchers observed similar results in cells expressing virus proteins compared with cells without proteins.
Fats called triacylglycerols (TAGs) — the most abundant fats in animal cells — increased most substantially in response to infection. Further investigation showed a dramatic increase in TAG-related lipid droplets, which store fats, in cells expressing certain viral proteins. The researchers noted that those proteins may play a direct role in stimulating TAG production.
The team also evaluated the ability of fat-targeting compounds, such as weight-loss drugs, to stop infection. Drugs that inhibited pathways involved in TAG synthesis and breakdown successfully blocked viral proliferation. They were also effective against four coronavirus variants of concern, in addition to the original strain.
The array of lipid changes that occurred after infection indicates that SARS-CoV-2 affects fat metabolism in diverse ways, through multiple molecular mechanisms, according to the authors. Understanding cellular pathways that the virus needs for survival is a critical step toward developing targeted treatments.
Citation: Farley SE, Kyle JE, Leier HC, Bramer LM, Weinstein JB, Bates TA, Lee JY, Metz TO, Schultz C, Tafesse FG. 2022. A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants. Nat Commun 13(1):3487.
(Julie Leibach is a senior science writer at MDB, Inc., a contractor for the NIEHS Division of Extramural Research and Training.)
