Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli

Abstract

Resident bacteria play an important role in initiating and perpetuating gastrointestinal inflammation. We previously demonstrated that six commensal bacteria including Bacteroides vulgatus caused more aggressive colitis and gastritis in HLA-B27 transgenic rats than did the other five bacteria without B. vulgatus. This study compared the degree of gastrointestinal inflammation in gnotobiotic HLA-B27 transgenic rats monoassociated with either B. vulgatus or Escherichia coli. Gnotobiotic transgenic rats raised in Trexler isolators were selectively colonized with either B. vulgatus or E. coli. Control rats were either germfree or colonized with six common commensal bacteria (Streptococcus faecium, E. coli, Streptococcus avium, Eubacterium contortum, Peptostreptococcus productus, and B. vulgatus [DESEP-B]). After 1 month, all the rats were killed and tissues were prepared for histologic and biochemical evaluation. Colitis induced by B. vulgatus monoassociation was almost equal to that in DESEP-B-colonized rats and was significantly more severe than E. coli-induced colitis, which was absent by histological testing and mild by colonic myeloperoxidase and interleukin-1beta concentration determinations. However, gastritis was detectable only in DESEP-B-associated rats. These studies suggest that not all resident bacteria have equal proinflammatory capabilities, since B. vulgatus alone is more active than E. coli alone in inducing colitis, and that colitis and gastritis result from different luminal bacterial stimuli.

FIG. 1

Histological features of colons from gnotobiotic HLA-B27/β₂-microglobulin transgenic rats monoassociated with B. vulgatus or E. coli for 1 month. (A) Cecal histological section from a transgenic rat monoassociated with E. coli. There is almost no sign of inflammation. (B) Cecal tissue from a transgenic rat monoassociated with B. vulgatus. There is mononuclear cell infiltration of the lamina propria, mucosal thickening, crypt hyperplasia, and focal goblet cell depletion. Magnification, ×40.

FIG. 2

Blinded histological inflammatory scores of the cecum and antrum in gnotobiotic HLA-B27 transgenic rats. GF transgenic rats, 2 months old, were colonized with DESEP-B, B. vulgatus alone, or E. coli alone or kept GF (negative control). The rats were killed 1 month after bacterial colonization. ∗, P = 0.001 with respect to E. coli and GF rats. §, P < 0.05 with respect to all three other groups.

FIG. 3

As a marker of neutrophilic infiltration, colonic MPO activity was increased in all colonized rats with respect to GF controls. Homogenized cecal tissues collected 1 month after bacterial colonization were assayed by a colorimetric biochemical assay for MPO (see Materials and Methods). ∗, P < 0.03 with respect to E. coli and P < 0.0001 with respect to GF rats. §, P < 0.0001 with respect to GF rats and P < 0.01 with respect to DESEP-B.