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THE EXPOSOME IN HUMAN EVOLUTION: FROM DUST TO DIESEL.

ABSTRACT: Global exposures to air pollution and cigarette smoke are novel in human evolutionary history and are associated with about 16 million premature deaths per year. We investigate the history of the human exposome for relationships between novel environmental toxins and genetic changes during human evolution in six phases. Phase I: With increased walking on savannas, early human ancestors inhaled crustal dust, fecal aerosols, and spores; carrion scavenging introduced new infectious pathogens. Phase II: Domestic fire exposed early Homo to novel toxins from smoke and cooking. Phases III and IV: Neolithic to preindustrial Homo sapiens incurred infectious pathogens from domestic animals and dense communities with limited sanitation. Phase V: Industrialization introduced novel toxins from fossil fuels, industrial chemicals, and tobacco at the same time infectious pathogens were diminishing. Thereby, pathogen-driven causes of mortality were replaced by chronic diseases driven by sterile inflammogens, exogenous and endogenous. Phase VI: Considers future health during global warming with increased air pollution and infections. We hypothesize that adaptation to some ancient toxins persists in genetic variations associated with inflammation and longevity.

SUBMITTER: Trumble BC

PROVIDER: S-EPMC7141577 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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THE EXPOSOME IN HUMAN EVOLUTION: FROM DUST TO DIESEL.

Trumble Benjamin C BC Finch Caleb E CE

The Quarterly review of biology 20191201 4

Global exposures to air pollution and cigarette smoke are novel in human evolutionary history and are associated with about 16 million premature deaths per year. We investigate the history of the human <i>exposome</i> for relationships between novel environmental toxins and genetic changes during human evolution in six phases. Phase I: With increased walking on savannas, early human ancestors inhaled crustal dust, fecal aerosols, and spores; carrion scavenging introduced new infectious pathogens ...[more]

PMID: 32269391

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Project description:Air pollution, especially emissions derived from traffic sources, is associated with adverse cardiovascular outcomes. However, it remains unclear how inhaled factors drive an extrapulmonary pathology, as the lung is an effective barrier for solid particulates and many gases. Previously, using plasma from healthy human subjects exposed to diesel exhaust under controlled conditions, we found that canonical inflammatory response transcripts of interleukin-8 (IL-8), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were elevated in endothelial cells treated wih plasma obtained after exposure compared with pre-exposure samples or filtered air (sham) exposures. While the findings confirmed the presence of bioactive factor(s) in the plasma after diesel inhalation, we wanted to better examine the complete genomic response to investigate 1) major responsive transcripts and 2) collected response pathways and ontogeny that may help to refine this method. Thus, we assayed previousy collected RNA with microarray chips, examining the responses of cultured endothelial cells to plasma obtained from 6 healthy human subjects exposed to 100 μg/m3 diesel exhaust or filtered air for 2 h on separate occasions. In addition to pre-exposure baseline samples, we investigated samples obtained immediately post and 24h post exposure. Primary human coronary artery endothelial cells were grown to confluence and treated with 10% plasma for 24 h, followed by isolation of RNA for microarrays. Microarray analysis of the coronary artery endothelial cells challenged with plasma identified 855 probes that change over time following diesel exhaust exposure. Over-representation analysis identified inflammatory cytokine pathways were upregulated both at the 2 and 24 h condition. These outcomes are consistent with our recent findings that plasma contains bioactive and inflammatory factors following pollutant inhalation and provide a novel pathway to explain the well-reported extrapulmonary toxicity of ambient air pollutants.

Project description:Metabolites produced by the gut microbiota play an important role in the cross-talk with the human host. Many microbial metabolites are biologically active and can pass the gut barrier and make it into the systemic circulation, where they form the gut microbial exposome, i.e. the totality of gut microbial metabolites in body fluids or tissues of the host. A major difficulty faced when studying the microbial exposome and its role in health and diseases is to differentiate metabolites solely or partially derived from microbial metabolism from those produced by the host or coming from the diet. Our objective was to collect data from the scientific literature and build a database on gut microbial metabolites and on evidence of their microbial origin. Three types of evidence on the microbial origin of the gut microbial exposome were defined: (1) metabolites are produced in vitro by human faecal bacteria; (2) metabolites show reduced concentrations in humans or experimental animals upon treatment with antibiotics; (3) metabolites show reduced concentrations in germ-free animals when compared with conventional animals. Data was manually collected from peer-reviewed publications and inserted in the Exposome-Explorer database. Furthermore, to explore the chemical space of the microbial exposome and predict metabolites uniquely formed by the microbiota, genome-scale metabolic models (GSMMs) of gut bacterial strains and humans were compared. A total of 1848 records on one or more types of evidence on the gut microbial origin of 457 metabolites was collected in Exposome-Explorer. Data on their known precursors and concentrations in human blood, urine and faeces was also collected. About 66% of the predicted gut microbial metabolites (n = 1543) were found to be unique microbial metabolites not found in the human GSMM, neither in the list of 457 metabolites curated in Exposome-Explorer, and can be targets for new experimental studies. This new data on the gut microbial exposome, freely available in Exposome-Explorer ( http://exposome-explorer.iarc.fr/ ), will help researchers to identify poorly studied microbial metabolites to be considered in future studies on the gut microbiota, and study their functionalities and role in health and diseases.

Dataset Information

THE EXPOSOME IN HUMAN EVOLUTION: FROM DUST TO DIESEL.

Publications

THE EXPOSOME IN HUMAN EVOLUTION: FROM DUST TO DIESEL.

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