title: Ambient Ultrafine Particle Ingestion Alters Gut Microbiota in Association with Increased Atherogenic Lipid Metabolites.
abstract: Ambient particulate matter (PM) exposure is associated with atherosclerosis and inflammatory bowel disease. Ultrafine particles (UFP, dp< 0.1-0.2 μm) are redox active components of PM. We hypothesized that orally ingested UFP promoted atherogenic lipid metabolites in both the intestine and plasma via altered gut microbiota composition. Low density lipoprotein receptor-null (Ldlr-/-) mice on a high-fat diet were orally administered with vehicle control or UFP (40 μg/mouse/day) for 3 days a week. After 10 weeks, UFP ingested mice developed macrophage and neutrophil infiltration in the intestinal villi, accompanied by elevated cholesterol but reduced coprostanol levels in the cecum, as well as elevated atherogenic lysophosphatidylcholine (LPC 18:1) and lysophosphatidic acids (LPAs) in the intestine and plasma. At the phylum level, Principle Component Analysis revealed significant segregation of microbiota compositions which was validated by Beta diversity analysis. UFP-exposed mice developed increased abundance in Verrocomicrobia but decreased Actinobacteria, Cyanobacteria, and Firmicutes as well as a reduced diversity in microbiome. Spearman's analysis negatively correlated Actinobacteria with cecal cholesterol, intestinal and plasma LPC18:1, and Firmicutes and Cyanobacteria with plasma LPC 18:1. Thus, ultrafine particles ingestion alters gut microbiota composition, accompanied by increased atherogenic lipid metabolites. These findings implicate the gut-vascular axis in a atherosclerosis model.
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Rongsong
authors.initials: R
authors.lastname: Li
authors.affiliation: Division of Clinical Nutrition, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Jieping
authors.initials: J
authors.lastname: Yang
authors.affiliation: Civil and Environmental Engineering, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Arian
authors.initials: A
authors.lastname: Saffari
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Jacobs
authors.affiliation: Department of Bioengineering, School of Engineering &Applied Science, University of California, Los Angeles, CA 90095, USA.
authors.forename: Kyung In
authors.initials: KI
authors.lastname: Baek
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Hough
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Muriel H
authors.initials: MH
authors.lastname: Larauche
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.|Department of Bioengineering, School of Engineering &Applied Science, University of California, Los Angeles, CA 90095, USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Ma
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.|Department of Bioengineering, School of Engineering &Applied Science, University of California, Los Angeles, CA 90095, USA.
authors.forename: Nelson
authors.initials: N
authors.lastname: Jen
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Nabila
authors.initials: N
authors.lastname: Moussaoui
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Bill
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Hanul
authors.initials: H
authors.lastname: Kang
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Reddy
authors.affiliation: Division of Clinical Nutrition, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Henning
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Campen
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pisegna
authors.affiliation: Division of Clinical Nutrition, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fogelman
authors.affiliation: Civil and Environmental Engineering, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.affiliation: Division of Cardiology, Department of Medicine, School of Medicine, University of California, Los Angeles, CA 90095, USA.|Department of Bioengineering, School of Engineering &Applied Science, University of California, Los Angeles, CA 90095, USA.
authors.forename: Tzung K
authors.initials: TK
authors.lastname: Hsiai
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification; D002432:Cecum / Q000378:metabolism; D004083:Cholestanol / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D050356:Lipid Metabolism / Q000187:drug effects*; D008244:Lysophosphatidylcholines / Q000032:analysis / Q000097:blood; D008246:Lysophospholipids / Q000032:analysis / Q000097:blood; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D052638:Particulate Matter / Q000737:chemistry / Q000494:pharmacology*; D025341:Principal Component Analysis; D012336:RNA, Ribosomal, 16S / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics
chemical_list: D016207:Cytokines; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D052638:Particulate Matter; D012336:RNA, Ribosomal, 16S; D011973:Receptors, LDL; D004083:Cholestanol; D002784:Cholesterol