title: Diet-induced alterations in gut microflora contribute to lethal pulmonary damage in TLR2/TLR4-deficient mice.
abstract: Chronic intake of Western diet has driven an epidemic of obesity and metabolic syndrome, but how it induces mortality remains unclear. Here, we show that chronic intake of a high-fat diet (HFD), not a low-fat diet, leads to severe pulmonary damage and mortality in mice deficient in Toll-like receptors 2 and 4 (DKO). Diet-induced pulmonary lesions are blocked by antibiotic treatment and are transmissible to wild-type mice upon either cohousing or fecal transplantation, pointing to the existence of bacterial pathogens. Indeed, diet and innate deficiency exert significant impact on gut microbiota composition. Thus, chronic intake of HFD promotes severe pulmonary damage and mortality in DKO mice in part via gut dysbiosis, a finding that may be important for immunodeficient patients, particularly those on chemotherapy or radiotherapy, where gut-microbiota-caused conditions are often life threatening.
authors: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA.
authors: Yewei
authors: Y
authors: Ji
authors: Graduate Program in Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853, USA.
authors: Shengyi
authors: S
authors: Sun
authors: Graduate Program in Genetics, Genomics and Development, Cornell University, Ithaca, NY 14853, USA.
authors: Julia K
authors: JK
authors: Goodrich
authors: Graduate Program in Immunology, Cornell University, Ithaca, NY 14853, USA.
authors: Hana
authors: H
authors: Kim
authors: Department of Microbiology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors: Angela C
authors: AC
authors: Poole
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors: Gerald E
authors: GE
authors: Duhamel
authors: Graduate Program in Genetics, Genomics and Development, Cornell University, Ithaca, NY 14853, USA; Department of Microbiology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors: Ruth E
authors: RE
authors: Ley
authors: Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA; Graduate Program in Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853, USA; Graduate Program in Genetics, Genomics and Development, Cornell University, Ithaca, NY 14853, USA. Electronic address: lq35@cornell.edu.
authors: Ling
authors: L
authors: Qi
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D064806:Dysbiosis / Q000150:complications* / Q000209:etiology / Q000276:immunology; D007113:Immunity, Innate; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008171:Lung Diseases / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D051195:Toll-Like Receptor 2 / Q000172:deficiency* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000172:deficiency* / Q000235:genetics
chemical_list: C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4