title: Antibiotic-Induced Depletion of Murine Microbiota Induces Mild Inflammation and Changes in Toll-Like Receptor Patterns and Intestinal Motility.
abstract: We examine the impact of changes in microbiota induced by antibiotics on intestinal motility, gut inflammatory response, and the function and expression of toll-like receptors (TLRs). Alterations in mice intestinal microbiota were induced by antibiotics and evaluated by q-PCR and DGGE analysis. Macroscopic and microscopic assessments of the intestine were performed in control and antibiotic-treated mice. TLR expression was determined in the intestine by q-RT-PCR. Fecal parameter measurements, intestinal transit, and muscle contractility studies were performed to evaluate alterations in intestinal motility. Antibiotics reduced the total bacterial quantity 1000-fold, and diversity was highly affected by treatment. Mice with microbiota depletion had less Peyer's patches, enlarged ceca, and mild gut inflammation. Treatment with antibiotics increased the expression of TLR4, TLR5, and TLR9 in the ileum and TLR3, TLR4, TLR6, TLR7, and TLR8 in the colon, and it reduced the expression of TLR2, TLR3, and TLR6 in the ileum and TLR2 and TLR9 in the colon. Antibiotics decreased fecal output, delayed the whole gut and colonic transit, and reduced the spontaneous contractions and the response to acetylcholine (ACh) in the ileum and colon. Activation of TLR4 by lipopolysaccharide (LPS) reverted the reduction of the spontaneous contractions induced by antibiotics in the ileum. Activation of TLR4 by LPS and TLR5 by flagellin reduced the response to ACh in the ileum in control mice. Our results confirm the role of the microbiota in the regulation of TLRs expression and shed light on the microbiota connection to motor intestinal alterations.
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Miguel Servet, 177, 50013, Zaragoza, Spain. lgralo@unizar.es.
authors.forename: Laura
authors.initials: L
authors.lastname: Grasa
authors.affiliation: Department of Physiology and Biochemistry of Animal Nutrition, Estación Experimental del Zaidín (CSIC), Granada, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Abecia
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Miguel Servet, 177, 50013, Zaragoza, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Forcén
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Miguel Servet, 177, 50013, Zaragoza, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Castro
authors.affiliation: Department of Anatomical Pathology, Faculty of Veterinary Sciences, University of Zaragoza, Zaragoza, Spain.
authors.forename: José Antonio García
authors.initials: JA
authors.lastname: de Jalón
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Miguel Servet, 177, 50013, Zaragoza, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Latorre
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Miguel Servet, 177, 50013, Zaragoza, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Alcalde
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Veterinary Sciences, University of Zaragoza, Miguel Servet, 177, 50013, Zaragoza, Spain.
authors.forename: María Divina
authors.initials: MD
authors.lastname: Murillo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D005769:Gastrointestinal Motility; D005786:Gene Expression Regulation; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D051193:Toll-Like Receptors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors
keywords: Antibiotics; Intestinal microbiota; Intestinal motility; Toll-like receptors