RESUMEN
The human gut microbiome, the host, and the environment are inextricably linked across the life course with significant health impacts. Consisting of trillions of bacteria, fungi, viruses, and other micro-organisms, microbiota living within our gut are particularly dynamic and responsible for digestion and metabolism of diverse classes of ingested chemical pollutants. Exposure to chemical pollutants not only in early life but throughout growth and into adulthood can alter human hosts' ability to absorb and metabolize xenobiotics, nutrients, and other components critical to health and longevity. Inflammation is a common mechanism underlying multiple environmentally related chronic conditions, including cardiovascular disease, multiple cancer types, and mental health. While growing research supports complex interactions between pollutants and the gut microbiome, significant gaps exist. Few reviews provide descriptions of the complex mechanisms by which chemical pollutants interact with the host microbiome through either direct or indirect pathways to alter disease risk, with a particular focus on inflammatory pathways. This review focuses on examples of several classes of pollutants commonly ingested by humans, including (i) heavy metals, (ii) persistent organic pollutants (POPs), and (iii) nitrates. Digestive enzymes and gut microbes are the first line of absorption and metabolism of these chemicals, and gut microbes have been shown to alter compounds from a less to more toxic state influencing subsequent distribution and excretion. In addition, chemical pollutants may interact with or alter the selection of more harmful and less commensal microbiota, leading to gut dysbiosis, and changes in receptor-mediated signaling pathways that alter the integrity and function of the gut intestinal tract. Arsenic, cadmium, and lead (heavy metals), influence the microbiome directly by altering different classes of bacteria, and subsequently driving inflammation through metabolite production and different signaling pathways (LPS/TLR4 or proteoglycan/TLR2 pathways). POPs can alter gut microbial composition either directly or indirectly depending on their ability to activate key signaling pathways within the intestine (e.g., PCB-126 and AHR). Nitrates and nitrites' effect on the gut and host may depend on their ability to be transformed to secondary and tertiary metabolites by gut bacteria. Future research should continue to support foundational research both in vitro, in vivo, and longitudinal population-based research to better identify opportunities for prevention, gain additional mechanistic insights into the complex interactions between environmental pollutants and the microbiome and support additional translational science.
RESUMEN
Supplemental oxygen is a life-saving intervention administered to individuals suffering from respiratory distress, including adults with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Despite the clinical benefit, supplemental oxygen can create a hyperoxic environment that increases reactive oxygen species, oxidative stress, and lung injury. We have previously shown that cytochrome P450 (CYP)1A enzymes decrease susceptibility to hyperoxia-induced lung injury. In this investigation, we determined the role of CYP1B1 in hyperoxic lung injury in vivo. Eight- to ten-week old C57BL/6 wild type (WT) and Cyp1b1-/- mice were exposed to hyperoxia (>95% O2) for 24-72 h or maintained in room air (21% O2). Lung injury was assessed by histology and lung weight to body weight (LW/BW) ratios. Extent of inflammation was determined by assessing pulmonary neutrophil infiltration and cytokine levels. Lipid peroxidation markers were quantified by gas chromatography mass spectrometry, and oxidative DNA adducts were quantified by 32P-postlabeling as markers of oxidative stress. We found that Cyp1b1-/- mice displayed attenuation of lung weight and pulmonary edema, particularly after 48-72 h of hyperoxia compared with WT controls. Further, Cyp1b1-/- mice displayed decreased levels of pulmonary oxidative DNA adducts and pulmonary isofurans after 24 h of hyperoxia. Cyp1b1-/- mice also showed increased pulmonary CYP1A1 and 1A2 and mRNA expression. In summary, our results support the hypothesis that Cyp1b1-/- mice display decreased hyperoxic lung injury than wild type counterparts and that CYP1B1 may act as a pro-oxidant during hyperoxia exposure, contributing to increases in oxidative DNA damage and accumulation of lipid hydroperoxides.