Τίτλος:
Neutralization of IL-1α ameliorates Crohn's diseaselike ileitis by functional alterations of the gut microbiome
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Crohn's disease and ulcerative colitis are chronic and progressive inflammatory bowel diseases (IBDs) that are attributed to dysregulated interactions between the gut microbiome and the intestinal mucosaassociated immune system. There are limited studies investigating the role of either IL-1α or IL-1β in mouse models of colitis, and no clinical trials blocking either IL-1 have yet to be performed. In the present study, we show that neutralization of IL-1α by a specific monoclonal antibody against murine IL-1α was highly effective in reducing inflammation and damage in SAMP mice, mice that spontaneously develop a Crohn's-like ileitis. Anti-mouse IL-1α significantly ameliorated the established, chronic ileitis and also protected mice from developing acute DSS-induced colitis. Both were associated with taxonomic divergence of the fecal gut microbiome, which was treatment-specific and not dependent on inflammation. Anti-IL-1α administration led to a decreased ratio of Proteobacteria to Bacteroidetes, decreased presence of Helicobacter species, and elevated representation of Mucispirillum schaedleri and Lactobacillus salivarius. Such modification in flora was functionally linked to the antiinflammatory effects of IL-1α neutralization, as blockade of IL-1α was not effective in germfree SAMP mice. Furthermore, preemptive dexamethasone treatment of DSS-challenged SAMP mice led to changes in flora composition without preventing the development of colitis. Thus, neutralization of IL-1α changes specific bacterial species of the intestinal microbiome, which is linked to its antiinflammatory effects. These functional findings may be of significant value for patients with IBD, who may benefit from targeted IL-1α-based therapies. © 2019 National Academy of Sciences. All rights reserved.
Συγγραφείς:
Menghini, P.
Corridoni, D.
Buttó, L.F.
Osme, A.
Shivaswamy, S.
Lam, M.
Bamias, G.
Pizarro, T.T.
Rodriguez-Palacios, A.
Dinarello, C.A.
Cominelli, F.
Περιοδικό:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
Εκδότης:
National Academy of Sciences
Λέξεις-κλειδιά:
interleukin 1alpha; monoclonal antibody, animal experiment; animal model; Article; Bacteroidetes; controlled study; Crohn disease; cytokine production; disease severity; dysbiosis; Helicobacter; ileitis; inflammation; intestine flora; Lactobacillus salivarius; mouse; nonhuman; priority journal; protein expression; protein function; Proteobacteria; regulatory mechanism; species composition; upregulation
DOI:
10.1073/pnas.1915043116
