Evaluation of the Impact of BaP Exposure on the Gut Microbiota and Allergic Responses in an OVA-Sensitized Mouse Model

Background: Exposure to environmental pollutants, including benzo[a]pyrene (BaP), has been implicated in allergic diseases and intestinal microbiota homeostasis, but the environment–microbiota–immunity triangular relationship and to what extent BaP-induced remodeling of the gut microbiota contributes to intestinal allergic inflammation remain to be established. Objectives: We investigated the impact of BaP on intestinal allergic inflammation and examined the relationship between this effect and gut microbiota dysbiosis. We explored the potential ability of intestinal bacteria to degrade BaP and alleviate cytotoxicity as a detoxification strategy to counteract the effects of BaP exposure. Methods: We combined microbiome shotgun metagenomics with animal histological and intestinal allergic inflammatory responses to assess the effects of BaP (50μg/mouse per day) in a 23-d toxicity test in antigen-induced allergic female mice. In addition, genome annotation, quantitative analysis of BaP, and in vitro cytotoxicity-tests using CaCo-2 cells were conducted to infer the role of intestinal bacteria in BaP detoxification. Results: BaP exposure impacted the taxonomic composition and the functional potential of the gut microbiota and aggravated antigen-induced intestinal allergic inflammatory responses. The level of inflammatory cytokines correlated with the abundance of specific bacterial taxa, including Lachnospiraceae bacterium 28-4 and Alistipes inops. We identified 614 bacteria harboring genes implicated in the degradation of BaP, and 4 of these bacterial strains were shown to significantly reduce the cytotoxicity of BaP to CaCo-2 cells in vitro. Discussion: Using allergic female mice as a model, we investigated the relationship between BaP, microbiota, and host immune reactions, highlighting the role of gut bacteria in BaP-aggravated allergic reactions. Our findings offer novel insight toward establishing the causal relationship between BaP exposure and the occurrence of allergic disorders. Identifying gut bacteria that degrade BaP may provide new strategies for ameliorating BaP cytotoxicity. https://doi.org/10.1289/EHP11874

[1]  Manoj Kumar,et al.  Microbial Dysbiosis Tunes the Immune Response Towards Allergic Disease Outcomes , 2022, Clinical Reviews in Allergy & Immunology.

[2]  K. Patil,et al.  Multimodal interactions of drugs, natural compounds and pollutants with the gut microbiota , 2022, Nature Reviews Microbiology.

[3]  K. Whitehead,et al.  Intestinal permeation enhancers enable oral delivery of macromolecules up to 70 kDa in size , 2021, European Journal of Pharmaceutics and Biopharmaceutics.

[4]  G. Barbara,et al.  Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier , 2021, Frontiers in Nutrition.

[5]  Lingyu Zhang,et al.  The Protection of Lactiplantibacillus plantarum CCFM8661 Against Benzopyrene-Induced Toxicity via Regulation of the Gut Microbiota , 2021, Frontiers in Immunology.

[6]  Qidong Ren,et al.  Organ and tissue-specific distribution of selected polycyclic aromatic hydrocarbons (PAHs) in ApoE-KO mouse. , 2021, Environmental pollution.

[7]  B. León,et al.  Modulating Th2 Cell Immunity for the Treatment of Asthma , 2021, Frontiers in Immunology.

[8]  P. Watnick,et al.  The Interplay of Sex Steroids, the Immune Response, and the Intestinal Microbiota. , 2020, Trends in microbiology.

[9]  A. Neish,et al.  Gut Microbiota in Intestinal and Liver Disease. , 2020, Annual review of pathology.

[10]  Feng Xu,et al.  Study on the regulatory effects and mechanisms of action of bifidobacterial exopolysaccharides on anaphylaxes in mice. , 2020, International journal of biological macromolecules.

[11]  L. Biancone,et al.  Histological scores in inflammatory bowel disease , 2020, Journal of digestive diseases.

[12]  Junhua Li,et al.  Assessment of fecal DNA extraction protocols for metagenomic studies , 2020, GigaScience.

[13]  P. Pandey,et al.  Difference in the rhizosphere microbiome of Melia azedarach during removal of benzo(a)pyrene from cadmium co-contaminated soil. , 2020, Chemosphere.

[14]  P. Pandey,et al.  Rhizosphere assisted biodegradation of benzo(a)pyrene by cadmium resistant plant-probiotic Serratia marcescens S2I7, and its genomic traits , 2020, Scientific Reports.

[15]  H. Chiba,et al.  Determination of polycyclic aromatic hydrocarbon content in heat-treated meat retailed in Egypt: Health risk assessment, benzo[a]pyrene induced mutagenicity and oxidative stress in human colon (CaCo-2) cells and protection using rosmarinic and ascorbic acids. , 2019, Food chemistry.

[16]  Y. Shao,et al.  Isoorientin attenuates benzo[a]pyrene-induced colonic injury and gut microbiota disorders in mice. , 2019, Food research international.

[17]  B. O. Ajayi,et al.  6-Gingerol abates benzo[a]pyrene-induced colonic injury via suppression of oxido-inflammatory stress responses in BALB/c mice. , 2019, Chemico-biological interactions.

[18]  T. Fukuyama,et al.  Direct activation of aryl hydrocarbon receptor by benzo[a]pyrene elicits T‐helper 2‐driven proinflammatory responses in a mouse model of allergic dermatitis , 2019, Journal of applied toxicology : JAT.

[19]  Shau-ku Huang,et al.  Benzo(a)pyrene facilitates dermatophagoides group 1 (Der f 1)‐induced epithelial cytokine release through aryl hydrocarbon receptor in asthma , 2019, Allergy.

[20]  Jinshao Ye,et al.  Metabolic and proteomic mechanism of benzo[a]pyrene degradation by Brevibacillus brevis. , 2019, Ecotoxicology and environmental safety.

[21]  Xujun Liang,et al.  Benzo(a)pyrene degradation by cytochrome P450 hydroxylase and the functional metabolism network of Bacillus thuringiensis. , 2019, Journal of hazardous materials.

[22]  Hsi-en Ho,et al.  The gut microbiome in food allergy. , 2019, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[23]  Qianhua Peng,et al.  Biosynthesis of gold nanoparticles using Caffeoylxanthiazonoside, chemical isolated from Xanthium strumarium L. fruit and their Anti-allergic rhinitis effect- a traditional Chinese medicine. , 2019, Journal of photochemistry and photobiology. B, Biology.

[24]  Suisha Liang,et al.  1,520 reference genomes from cultivated human gut bacteria enable functional microbiome analyses , 2019, Nature Biotechnology.

[25]  D. Antonopoulos,et al.  Healthy infants harbor intestinal bacteria that protect against food allergy , 2018, Nature Medicine.

[26]  J. Köhl,et al.  C5a receptor 1−/− mice are protected from the development of IgE‐mediated experimental food allergy , 2018, Allergy.

[27]  Luke R. Thompson,et al.  Species-level functional profiling of metagenomes and metatranscriptomes , 2018, Nature Methods.

[28]  M. Pérez-Gordo,et al.  Microbiome and Allergic Diseases , 2018, Front. Immunol..

[29]  Jian Wang,et al.  Assessment of the cPAS-based BGISEQ-500 platform for metagenomic sequencing , 2017, GigaScience.

[30]  J. Ratel,et al.  Environmental Pollutant Benzo[a]Pyrene Impacts the Volatile Metabolome and Transcriptome of the Human Gut Microbiota , 2017, Front. Microbiol..

[31]  P. de Vos,et al.  The Impact of Gut Microbiota on Gender-Specific Differences in Immunity , 2017, Front. Immunol..

[32]  S. Vermeire,et al.  The intestinal barrier: a fundamental role in health and disease , 2017, Expert review of gastroenterology & hepatology.

[33]  E. Balskus,et al.  Chemical transformation of xenobiotics by the human gut microbiota , 2017, Science.

[34]  M. Kawanishi,et al.  Modulation of benzo[a]pyrene–DNA adduct formation by CYP1 inducer and inhibitor , 2017, Genes and Environment.

[35]  Hui Jiang,et al.  A reference human genome dataset of the BGISEQ-500 sequencer , 2017, GigaScience.

[36]  H. Takano,et al.  Low‐dose benzo[a]pyrene aggravates allergic airway inflammation in mice , 2016, Journal of applied toxicology : JAT.

[37]  X. Geng,et al.  Induction of colitis in mice with food allergen-specific immune response , 2016, Scientific Reports.

[38]  N. Barnich,et al.  Oral exposure to environmental pollutant benzo[a]pyrene impacts the intestinal epithelium and induces gut microbial shifts in murine model , 2016, Scientific Reports.

[39]  F. Hildebrand,et al.  Species–function relationships shape ecological properties of the human gut microbiome , 2016, Nature Microbiology.

[40]  H. Guillou,et al.  The gut microbiota: a major player in the toxicity of environmental pollutants? , 2016, npj Biofilms and Microbiomes.

[41]  K. Nadeau,et al.  Gut Microbiome and the Development of Food Allergy and Allergic Disease. , 2015, Pediatric clinics of North America.

[42]  T. R. Licht,et al.  A catalog of the mouse gut metagenome , 2015, Nature Biotechnology.

[43]  Xiaoli Xie,et al.  KEGG-PATH: Kyoto encyclopedia of genes and genomes-based pathway analysis using a path analysis model. , 2014, Molecular bioSystems.

[44]  Judith A. Blake,et al.  The Mouse Genome Database: integration of and access to knowledge about the laboratory mouse , 2013, Nucleic Acids Res..

[45]  Ki-Hyun Kim,et al.  A review of airborne polycyclic aromatic hydrocarbons (PAHs) and their human health effects. , 2013, Environment international.

[46]  B. Yang,et al.  Food Allergen–Induced Mast Cell Degranulation is Dependent on PI3K‐Mediated Reactive Oxygen Species Production and Upregulation of Store‐Operated Calcium Channel Subunits , 2013, Scandinavian journal of immunology.

[47]  Hui Peng,et al.  Effect of copper(II) on biodegradation of benzo[a]pyrene by Stenotrophomonas maltophilia. , 2013, Chemosphere.

[48]  V. Tremaroli,et al.  Functional interactions between the gut microbiota and host metabolism , 2012, Nature.

[49]  M. Ramya,et al.  Efficiency of the intestinal bacteria in the degradation of the toxic pesticide, chlorpyrifos , 2012, 3 Biotech.

[50]  T. Fukatsu,et al.  Symbiont-mediated insecticide resistance , 2012, Proceedings of the National Academy of Sciences.

[51]  D. B. Min,et al.  Effects of grilling and roasting on the levels of polycyclic aromatic hydrocarbons in beef and pork , 2011 .

[52]  C. Huttenhower,et al.  Metagenomic biomarker discovery and explanation , 2011, Genome Biology.

[53]  A. Okoh,et al.  Benzo[a]pyrene removal by axenic- and co-cultures of some bacterial and fungal strains. , 2010 .

[54]  Siu-Ming Yiu,et al.  SOAP2: an improved ultrafast tool for short read alignment , 2009, Bioinform..

[55]  A. V. van Herwaarden,et al.  How important is intestinal cytochrome P450 3A metabolism? , 2009, Trends in pharmacological sciences.

[56]  Natsuko Kageyama-Yahara,et al.  Therapeutic Effect of Kakkonto in a Mouse Model of Food Allergy with Gastrointestinal Symptoms , 2008, International Archives of Allergy and Immunology.

[57]  W. Verstraete,et al.  Human Colon Microbiota Transform Polycyclic Aromatic Hydrocarbons to Estrogenic Metabolites , 2004, Environmental health perspectives.

[58]  Célia Regina Pesquero,et al.  Emission of polycyclic aromatic hydrocarbons from light-duty diesel vehicles exhaust , 2004 .

[59]  Sergio Romagnani,et al.  Immunologic influences on allergy and the TH1/TH2 balance. , 2004, The Journal of allergy and clinical immunology.

[60]  P J Lioy,et al.  Analysis of human exposure to benzo(a)pyrene via inhalation and food ingestion in the Total Human Environmental Exposure Study (THEES). , 1991, Journal of exposure analysis and environmental epidemiology.

[61]  S. Wise,et al.  Determination of polycyclic aromatic hydrocarbons in a coal tar standard reference material , 1988 .

[62]  M. Apte,et al.  Indoor air pollution due to emissions from wood-burning stoves. , 1987, Environmental science & technology.

[63]  A. Guz,et al.  Small Bowel Tonometry : Assessment of Small Gut Mucosal Oxygen Tension in Dog and Man , 1965, Nature.

[64]  Y. Ni,et al.  Intestinal Dysbiosis Featuring Abundance of Ruminococcus gnavus Associates With Allergic Diseases in Infants. , 2018, Gastroenterology.

[65]  M. Fujii,et al.  Polycyclic aromatic hydrocarbons aggravate antigen-induced nasal blockage in experimental allergic rhinitis. , 2007, Journal of pharmacological sciences.