New approach enables better characterization of the human exposome

NIEHS-funded researchers developed a scalable workflow that maximizes the information captured about unidentified chemicals in human samples to better characterize the exposome. The exposome refers to the totality of environmental exposures, potentially in the millions, experienced throughout a person’s life.

The team developed a new technique called express liquid extraction (XLE) that prevents loss of chemicals, common with current sample extraction approaches, thereby allowing for better identification of a wider array of substances. XLE is used with traditional gas chromatography-high resolution mass spectrometry and is then paired with sophisticated computational tools. The workflow allows researchers to quantify known environmental chemicals and potentially identify thousands of unknown chemicals in diverse biological samples, such as plasma, lung, and stool.

According to the researchers, the automated workflow integrates computational methods for data extraction, preprocessing, and spectral annotation to quantify environmental chemicals based on reference standards. Because the approach captures more information about chemicals and leverages sophisticated computational tools, scientists may be better able to predict structures of unknown chemicals in human samples. The workflow also improves the interoperability of data collected using different mass spectrometry techniques. Interoperability means data use similar formats and vocabularies, which is critical for increasing confidence in compound identification in exposome research.

A critical need for high-throughput, low-cost, omics-scale biomonitoring data for exposome research in human population studies is addressed through this workflow, according to the team. The approach also will help to harmonize exposome analyses, thus enabling development of human exposome databases to include information on tens of thousands of chemical exposures in tens of thousands of individuals.

Citation: Hu X, Walker DI, Liang Y, Smith MR, Orr ML, Juran BD, Ma C, Uppal K, Koval M, Martin GS, Neujahr DC, Marsit CJ, Go YM, Pennell KD, Miller GW, Lazaridis KN, Jones DP. 2021. A scalable workflow to characterize the human exposome. Nat Commun 12(1):5575.

Greenness may reduce effects of air pollution on mortality in cancer patients

Greenness — vegetation, green spaces, and so forth — is associated with lower mortality risk in cancer patients, even in the presence of air pollution, according to a new NIEHS-funded study. This is the first study to evaluate associations between greenness and particulate matter (PM2.5) on causes of death in a large, U.S.-based cohort of cancer patients and survivors. Previous studies have independently linked greenness with better health and exposure to outdoor air pollution with worsened health. However, it was not known how these factors may interact to affect mortality risk until now.

Using advanced statistical models, the team estimated the association between county-level PM2.5 concentrations, greenness, and cancer mortality in a cohort of more than 5.5 million cancer patients and survivors using integrated data from 1999 to 2016.

Higher PM2.5 levels were associated with increased cardiopulmonary mortality but not cancer mortality. Increased greenness was associated with lower cancer mortality for all cancer patients. However, greenness only lowered cardiopulmonary mortality among individuals with high survivable cancers. Individuals with high survivability cancers seemed to benefit more from greenness than those with low survivability cancers, as did those in urban rather than rural locations.

Regarding the interaction between PM2.5 and greenness on mortality, higher greenness was associated with lower cancer mortality risk for all levels of PM2.5. In contrast, higher PM2.5 was associated with an increased risk of cardiopulmonary mortality only for areas with low greenness.

According to the authors, this work highlights the potential benefits of greenness for patients diagnosed with cancer and other diseases.

Citation: Coleman CJ, Yeager RA, Riggs DW, Coleman NC, Garcia GR, Bhatnagar A and Pope CA. 2021. Greenness, air pollution, and mortality risk: A U.S. cohort study of cancer patients and survivors. Environ Int 157:106797.

Untargeted analysis sheds light on thousands of chemicals in e-cigarettes

According to an NIEHS-funded study, e-cigarettes contain thousands of unknown chemicals, some of which may harm human health. The researchers also found evidence of chemicals related to combustion, a process not typically associated with vaping because it involves lower temperatures than combustible cigarette smoking. E-cigarettes often include flavoring agents, undisclosed additives, chemicals formed during the vaping process, and contaminants from packaging and device components, but most of these are not known or characterized. For consistency in their analysis, the team looked at only tobacco-flavored e-liquids.

Using several different types of popular e-cigarette products, the researchers applied chemical fingerprinting techniques to characterize both e-liquids before vaping and aerosols produced from the vaping process. They used quantitative and nontargeted analyses, which measure both known and unknown compounds in a sample.

In general, the team reported that the total number of detected compounds increased from before to after vaping. Many of the nearly 2,000 chemicals were unidentified. They found a large number of condensed-hydrocarbon–like compounds associated with combustion. They also identified lipid-like compounds, previously linked to a type of lung disease, and six other potentially hazardous additives and contaminants, including tributylphosphine oxide, isophorone, and caffeine.

According to the authors, this study highlights the presence of unexpected, potentially hazardous compounds in e-cigarette products, such as those derived from combustion, and the need for toxicological assessments of compounds prioritized using a nontargeted approach.

Citation: Tehrani MW, Newmeyer MN, Rule AM, Prasse C. 2021. Characterizing the chemical landscape in commercial e-cigarette liquids and aerosols by liquid chromatography-high-resolution mass spectrometry. Chem Res Toxicol 34(10):2216–2226.

Metabolomics shed light on the microbiota-brain link

The gut microbiome may control conditions in the brain that could lead to altered brain function, according to an NIEHS-funded study. The gut harbors hundreds of trillions of microbes, collectively called the microbiome. Although emerging studies support that the microbiome may be linked to neurological disorders, whether and how microbes control brain function remains largely unclear.

Researchers developed a new methodology using high-coverage metabolomics to map the biochemical landscape in the feces, blood, and brain tissues of mice lacking microbes and compared them to mice with normal microbiomes. They combined targeted and untargeted approaches to identify known and unknown metabolites and leveraged statistical and data visualization tools to compare findings between the two groups.

The researchers found metabolomic signatures from microbiota in all sample types for normal mice. They reported 533 altered metabolites for feces, 231 for blood, and 58 for brain, which they explained were related to several important molecular pathways, such as oxidative stress and inflammation in the brain.

They also found mice lacking microbes were missing many neurotransmitters — brain signaling molecules — that were present in the gut of normal mice. The team reported that microbiota may regulate the production and transport of neurotransmitters in the gut. Their analysis also revealed microbiota may regulate gut metabolism and energy harvest and could have a similar effect on blood circulation and the nervous system.

According to the authors, high-coverage metabolomics may be valuable for future research to reveal how microbes influence metabolism and gut-brain communication pathways.

Citation: Lai Y, Liu CW, Yang Y, Hsiao YC, Ru H, Lu K. 2021. High-coverage metabolomics uncovers microbiota-driven biochemical landscape of interorgan transport and gut-brain communication in mice. Nat Commun 12(1):6000.