Inoculation with enterococci does not affect colon inflammation in the multi-drug resistance 1a-deficient mouse model of IBD

Abstract

Background: Intestinal bacteria are thought to play a role in the pathogenesis of human inflammatory bowel disease (IBD). We investigated whether oral inoculation with specific intestinal bacteria increased colon inflammation in the multi-drug resistance 1a-deficient (Mdr1a-/-) mouse model of IBD. Methods: Five-week-old Mdr1a-/- mice (FVB background) and FVB mice were randomly assigned to one of two treatment groups (Control or Inoculation, n = 12 per group). All mice were fed AIN-76A rodent diet, and mice in the Inoculation groups also received a single oral bacterial inoculation consisting of twelve cultured Enterococcus species combined with conventional intestinal flora obtained from the gastrointestinal tract of healthy mice (EF.CIF). Body weight, food intake, and disease activity index (DAI) were assessed throughout the study, and at 21 or 24 weeks of age, inflammation was assessed post-mortem by determining colon length and histological injury score (HIS), and plasma serum amyloid A (SAA). Results: Mdr1a-/- mice consumed more food than FVB mice at 13 weeks of age (P < 0.05). There was also a significant effect of genotype on body weight, with Mdr1a-/- mice weighing less than FVB mice throughout the study (P < 0.05) regardless of treatment, but there was no effect of inoculation on body weight (P > 0.25). Colon HIS of Mdr1a-/- mice was significantly higher than that of FVB mice in the Control (9.3 ± 4.7 (mean ± SD) vs. 0.58 ± 0.51; P < 0.001) and Inoculation (6.7 ± 5.1 vs. 0.92 ± 0.39; P < 0.001) groups. There was no difference in colon HIS of Mdr1a-/- mice in the Control group compared with Mdr1a-/- mice in the Inoculation group (P = 0.25), nor was there any difference in within-group variation of colon HIS in these two Mdr1a-/- groups. DAI was higher in Mdr1a-/- mice than in FVB mice, but there was no effect of treatment in either strain, nor were there any differences in colon length or plasma SAA. Conclusions: Inoculation of Mdr1a-/- mice with the EF.CIF inoculum described here does not increase colon inflammation or reduce the observed variability of inflammation.