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Randomized Controlled Trial
. 2017 Sep 3;8(5):451-466.
doi: 10.1080/19490976.2017.1334754. Epub 2017 Jul 5.

Randomized, controlled trial evaluating the effect of multi-strain probiotic on the mucosal microbiota in canine idiopathic inflammatory bowel disease

Robin White  1 , Todd Atherly  2 , Blake Guard  3 , Giacomo Rossi  4 , Chong Wang  5 , Curtis Mosher  6 , Craig Webb  7 , Steve Hill  8 , Mark Ackermann  9 , Peter Sciabarra  1 , Karin Allenspach  1 , Jan Suchodolski  3 , Albert E Jergens  1
Affiliations
Randomized Controlled Trial

Randomized, controlled trial evaluating the effect of multi-strain probiotic on the mucosal microbiota in canine idiopathic inflammatory bowel disease

Robin White et al. Gut Microbes. .

Abstract

The intestinal microbiota is increasingly linked to the pathogenesis of idiopathic inflammatory bowel disease (IBD) in dogs. While studies have reported alterations in fecal (luminal) microbial populations, only limited information is available about the mucosal microbiota of IBD dogs at diagnosis and following medical therapy. Our aim was to characterize the mucosal microbiota and determine the clinical, microbiological, and mucosal homeostatic effects of probiotic treatment in dogs with IBD. Thirty four IBD dogs were randomized to receive standard therapy (ST = diet + prednisone) with or without probiotic. Tissue sections from endoscopic biopsies were evaluated by fluorescence in situ hybridization (FISH) on a quantifiable basis. Disease activity and changes in mucosal microbiota and tight junction protein (TJP) expression were assessed before and after 8 weeks of IBD therapy. ST and ST/probiotic therapy modulated the number of mucosal bacteria of IBD dogs in a similar fashion. Both treatments increased the numbers of total bacteria and individual species residing within adherent mucus, with ST therapy increasing Bifidobacterium spp. and ST/probiotic therapy increasing Lactobacillus spp (P < 0.05 for both), respectively. Both treatments were associated with rapid clinical remission but not improvement in histopathologic inflammation. Probiotic therapy was associated with upregulated (P < 0.05) expression of TJPs E-cadherin, occludin, and zonulin versus ST. The probiotic effect on mucosal bacteria is similar to that of IBD dogs receiving ST. IBD dogs fed probiotic had increased TJP expression suggesting that probiotic may have beneficial effects on mucosal homeostasis.

Keywords: CIBDAI; FISH; IBD; microbiota; probiotic; randomized controlled trial; tight junction protein.

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Figures

Figure 1.
Figure 1.
Trial design and flow of IBD dogs. ST = standard therapy.
Figure 2.
Figure 2.
Dog enrollment and disposition.
Figure 3.
Figure 3.
FISH of canine IBD endoscopic biopsies. Triple color FISH identifies colonic microbiota within mucosal compartments of endoscopic biopsies. Panels A-C = ST/probiotic group and panels D-F = ST group. Panel A = tissue hybridized with probe Cy3-Strc493- Panel B = tissue hybridized with probe Cy3-Ebac; Panel C = tissue hybridized with probe Cy3-Faecal698; Panel D = tissue hybridized with probe Cy3-Ebac; Panel E = tissue hybridized with probe Cy3-Bif164; Panel F = issue hybridized with probe Cy3-Strc493. All other bacteria that hybridize exclusively with the universal probe (Eub338-FITC) appear green. DAPI-stained colonic mucosa with goblet cells appears blue. All images at 600x magnification. a = attaching bacteria; am = adherent mucus compartment; fm = free mucus compartment.
Figure 4.
Figure 4.
Box plots showing the effect of treatment on the number of colonic microbiota within adherent mucus of IBD dogs treated with ST or ST/probiotic. Figures A- F show the number of mucosal bacteria which hybridize against each probe: Bif164 → Bifidobacterium spp, Ebac1790 → Enterobacteriaceae, Eub338 → all bacteria, Faecali698 → Faecalibacterium spp, Lab158 → Lactobacillus spp, and Strc493 → Streptococcus spp Differences (P < 0.05) in the numbers of bacteria between treatment groups are indicated by the letters A, B, C, and D. Groups with the same letter are not statistically different.
Figure 5.
Figure 5.
Temporal evaluation of clinical (CIBDAI) scores by IBD treatment group. CIBDAI = canine IBD activity index; ST = standard therapy; V = visit.
Figure 6.
Figure 6.
Tight junction protein (TJP) expression in intestinal epithelia of canine IBD endoscopic biopsies. (Top 2 rows): Panel shows IHC staining for TJP in colonic biopsies of dogs treated with ST. (Bottom row): Panel shows immunohistochemical (IHC) staining for TJPs in duodenal biopsies of ST/probiotic treated dogs as compared with H&E (control) tissue. IHC protein expression was defined by the number of epithelial cells within the mucosa expressing a select TJP. See Table 4 for additional information.
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