title: Longitudinal analysis of inflammation and microbiota dynamics in a model of mild chronic dextran sulfate sodium-induced colitis in mice.
abstract: OBJECTIVE
  To characterize longitudinally the inflammation and the gut microbiota dynamics in a mouse model of dextran sulfate sodium (DSS)-induced colitis.
  
  
  METHODS
  In animal models, the most common method used to trigger colitis is based on the oral administration of the sulfated polysaccharides DSS. The murine DSS colitis model has been widely adopted to induce severe acute, chronic or semi-chronic colitis, and has been validated as an important model for the translation of mice data to human inflammatory bowel disease (IBD). However, it is now clear that models characterized by mild intestinal damage are more accurate for studying the effects of therapeutic agents. For this reason, we have developed a murine model of mild colitis to study longitudinally the inflammation and microbiota dynamics during the intestinal repair processes, and to obtain data suitable to support the recovery of gut microbiota-host homeostasis.
  
  
  RESULTS
  All plasma cytokines evaluated, except IL-17, began to increase (P < 0.05), after 7 d of DSS administration. IL-17 only began to increase 4 d after DSS withdrawal. IL-1β and IL-17 continue to increase during the recovery phase, even when clinical signs of colitis had disappeared. IL-6, IL-10 and IFN-γ reached their maxima 4 d after DSS withdrawal and decreased during the late recovery phase. TNFα reached a peak (a three- fold increase, P < 0.05), after which it slightly decreased, only to increase again close to the end of the recovery phase. DSS administration induced profound and rapid changes in the mice gut microbiota. After 3 d of DSS administration, we observed a major reduction in Bacteroidetes/Prevotella and a corresponding increase in Bacillaceae, with respect to control mice. In particular, Bacteroidetes/Prevotella decreased from a relative abundance of 59.42%-33.05%, while Bacillaceae showed a concomitant increase from 2.77% to 10.52%. Gut microbiota rapidly shifted toward a healthy profile during the recovery phase and returned normal 4 d after DSS withdrawal. Cyclooxygenase 2 expression started to increase 4 d after DSS withdrawal (P < 0.05), when dysbiosis had recovered, and continued to increase during the recovery phase. Taken together, these data indicated that a chronic phase of intestinal inflammation, characterized by the absence of dysbiosis, could be obtained in mice using a single DSS cycle.
  
  
  CONCLUSIONS
  Dysbiosis contributes to the local and systemic inflammation that occurs in the DSS model of colitis; however, chronic bowel inflammation is maintained even after recovery from dysbiosis.
authors.affiliation: Luigia De Fazio, Elena Cavazza, Enzo Spisni, Antonio Strillacci, Maria Chiara Valerii, Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: De Fazio
authors.affiliation: Luigia De Fazio, Elena Cavazza, Enzo Spisni, Antonio Strillacci, Maria Chiara Valerii, Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cavazza
authors.affiliation: Luigia De Fazio, Elena Cavazza, Enzo Spisni, Antonio Strillacci, Maria Chiara Valerii, Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Spisni
authors.affiliation: Luigia De Fazio, Elena Cavazza, Enzo Spisni, Antonio Strillacci, Maria Chiara Valerii, Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Strillacci
authors.affiliation: Luigia De Fazio, Elena Cavazza, Enzo Spisni, Antonio Strillacci, Maria Chiara Valerii, Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Centanni
authors.affiliation: Luigia De Fazio, Elena Cavazza, Enzo Spisni, Antonio Strillacci, Maria Chiara Valerii, Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Candela
authors.affiliation: Luigia De Fazio, Elena Cavazza, Enzo Spisni, Antonio Strillacci, Maria Chiara Valerii, Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Praticò
authors.affiliation: Luigia De Fazio, Elena Cavazza, Enzo Spisni, Antonio Strillacci, Maria Chiara Valerii, Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Campieri
authors.affiliation: Luigia De Fazio, Elena Cavazza, Enzo Spisni, Antonio Strillacci, Maria Chiara Valerii, Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ricci
authors.affiliation: Luigia De Fazio, Elena Cavazza, Enzo Spisni, Antonio Strillacci, Maria Chiara Valerii, Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Valerii
mesh_terms: D000818:Animals; D003092:Colitis / Q000097:blood* / Q000139:chemically induced / Q000382:microbiology; D003106:Colon / Q000166:cytology; D016207:Cytokines / Q000097:blood; D016264:Dextran Sulfate / Q000737:chemistry*; D006706:Homeostasis; D007249:Inflammation / Q000628:therapy*; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D012313:RNA / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; C556062:IL10 protein, mouse; D020381:Interleukin-17; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D016753:Interleukin-10; D012313:RNA; D016264:Dextran Sulfate
keywords: Colitis, Dysbiosis; Cyclooxygenase 2; Dextran sulfate sodium; Inflammation