Microbiota-Derived Metabolic Factors Reduce Campylobacteriosis in Mice
| Autor: | Xiaolun Sun, Kathryn Winglee, Zhen He, Dorina Avram, Christian Jobin, Steven D. Bruner, Anthony A. Fodor, Prabhanshu Tripathi, Josee Gauthier, Raad Z. Gharaibeh |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cholagogues and Choleretics Lithocholic acid medicine.drug_class Colon 030106 microbiology Campylobacter jejuni digestive system Article Microbiology Bile Acids and Salts 03 medical and health sciences chemistry.chemical_compound Feces Mice fluids and secretions Lactobacillus Culture Techniques Campylobacter Infections medicine Animals Anaerobiosis Colitis Bifidobacterium Hepatology biology Bile acid Chemistry Deoxycholic acid Ursodeoxycholic Acid Gastroenterology Fecal Microbiota Transplantation medicine.disease biology.organism_classification Gastroenteritis Gastrointestinal Microbiome Intestines Mice Inbred C57BL Disease Models Animal 030104 developmental biology Lithocholic Acid Anaerobic bacteria Deoxycholic Acid |
| Zdroj: | Gastroenterology. 154(6) |
| ISSN: | 1528-0012 |
| Popis: | Background & Aims Campylobacter jejuni, a prevalent foodborne bacterial pathogen, exploits the host innate response to induce colitis. Little is known about the roles of microbiota in C jejuni–induced intestinal inflammation. We investigated interactions between microbiota and intestinal cells during C jejuni infection of mice. Methods Germ-free C57BL/6 Il10−/− mice were colonized with conventional microbiota and infected with a single dose of C jejuni (109 colony-forming units/mouse) via gavage. Conventional microbiota were cultured under aerobic, microaerobic, or anaerobic conditions and orally transplanted into germ-free Il10−/− mice. Colon tissues were collected from mice and analyzed by histology, real-time polymerase chain reaction, and immunoblotting. Fecal microbiota and bile acids were analyzed with 16S sequencing and high-performance liquid chromatography with mass spectrometry, respectively. Results Introduction of conventional microbiota reduced C jejuni–induced colitis in previously germ-free Il10−/− mice, independent of fecal load of C jejuni, accompanied by reduced activation of mammalian target of rapamycin. Microbiota transplantation and 16S ribosomal DNA sequencing experiments showed that Clostridium XI, Bifidobacterium, and Lactobacillus were enriched in fecal samples from mice colonized with microbiota cultured in anaerobic conditions (which reduce colitis) compared with mice fed microbiota cultured under aerobic conditions (susceptible to colitis). Oral administration to mice of microbiota-derived secondary bile acid sodium deoxycholate, but not ursodeoxycholic acid or lithocholic acid, reduced C jejuni–induced colitis. Depletion of secondary bile acid–producing bacteria with antibiotics that kill anaerobic bacteria (clindamycin) promoted C jejuni–induced colitis in specific pathogen-free Il10−/− mice compared with the nonspecific antibiotic nalidixic acid; colitis induction by antibiotics was associated with reduced level of luminal deoxycholate. Conclusions We identified a mechanism by which the microbiota controls susceptibility to C jejuni infection in mice, via bacteria-derived secondary bile acids. |
| Databáze: | OpenAIRE |
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