Enterobacteriaceae act in concert with the gut microbiota to induce spontaneous and maternally transmitted colitis.
Disruption of homeostasis between the host immune system and the intestinal microbiota leads to inflammatory bowel disease (IBD). Whether IBD is instigated by individual species or disruptions of entire microbial communities remains controversial. We characterized the fecal microbial communities in the recently described T-bet(-/-) ×Rag2(-/-) ulcerative colitis (TRUC) model driven by T-bet deficiency in the innate immune system. 16S rRNA-based analysis of TRUC and Rag2(-/-) mice revealed distinctive communities that correlate with host genotype. The presence of Klebsiella pneumoniae and Proteus mirabilis correlates with colitis in TRUC animals, and these TRUC-derived strains can elicit colitis in Rag2(-/-) and WT adults but require a maternally transmitted endogenous microbial community for maximal intestinal inflammation. Cross-fostering experiments indicated a role for these organisms in maternal transmission of disease. Our findings illustrate how gut microbial communities work in concert with specific culturable colitogenic agents to cause IBD.
Garrett
Wendy S
WS
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Gallini
Carey A
CA
Yatsunenko
Tanya
T
Michaud
Monia
M
DuBois
Andrea
A
Delaney
Mary L
ML
Punit
Shivesh
S
Karlsson
Maria
M
Bry
Lynn
L
Glickman
Jonathan N
JN
Gordon
Jeffrey I
JI
Onderdonk
Andrew B
AB
Glimcher
Laurie H
LH
D000818:Animals; D003093:Colitis, Ulcerative / Q000382:microbiology* / Q000473:pathology* / Q000628:therapy; D003106:Colon / Q000382:microbiology / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004755:Enterobacteriaceae / Q000302:isolation & purification / Q000502:physiology*; D005243:Feces / Q000382:microbiology; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D007413:Intestinal Mucosa / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000302:isolation & purification*; D008297:Male; D051379:Mice; D056265:Microbial Interactions; D011513:Proteus mirabilis / Q000302:isolation & purification*; D020825:T-Box Domain Proteins / Q000235:genetics
D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D020825:T-Box Domain Proteins