Lactobacillus rhamnosus GG on Rotavirus-Induced Injury of Ileal Epithelium in Gnotobiotic Pigs

Liu, Fangning*; Li, Guohua*; Wen, Ke*; Wu, Shaoping; Zhang, Yongguo; Bui, Tammy*; Yang, Xingdong*; Kocher, Jacob*; Sun, Jun; Jortner, Bernard*; Yuan, Lijuan*

Journal of Pediatric Gastroenterology & Nutrition: December 2013 - Volume 57 - Issue 6 - p 750–758
doi: 10.1097/MPG.0b013e3182a356e1
Original Articles: Gastroenterology

Objective: The aim of this study was to study the effect of continued Lactobacillus rhamnosus GG strain (LGG) feeding on rotavirus gastroenteritis in the gnotobiotic (Gn) pig model of virulent human rotavirus (HRV) infection.

Methods: Gn pigs were assigned to treatment groups: mock control, LGG only, HRV only, or LGG plus HRV. Nine days before HRV inoculation (3 days of age), pigs were fed LGG with a daily dose increase of 10-fold from 103 to 1012 colony-forming units (CFU). The 1012 CFU/dose of LGG feeding continued until post-HRV inoculation day (PID) 6. Clinical sign (diarrhea), rotavirus fecal shedding, histopathology of the ileum, adherent junction and tight junction protein expression in the ileal epithelial cells, mucin production in the large and small intestinal contents, and serum cytokine responses from PID 2 to 6 were examined and compared among the treatment groups.

Results: Clinically, the percentage of pigs developing diarrhea, the mean duration of diarrhea, and the mean cumulative fecal scores were lower in the LGG fed pigs compared to the nonfed pigs after HRV inoculation. LGG partially protected ileal epithelium against HRV-induced compensatory increases of the adherent junction protein α-catenin and β-catenin, tight junction protein occludin, claudin-3 and claudin-4, and leak protein claudin-2. LGG promoted mucin production because the mucin levels in the large intestinal contents of the LGG+HRV pigs were significantly higher than the HRV-only pigs on PID 2. Additionally, LGG maintained the anti-inflammatory cytokine transforming growth factor-β level in serum after HRV infection.

Conclusions: LGG is moderately effective for ameliorating rotavirus diarrhea by partially preventing injuries to the epithelium.

*Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA

Department of Biochemistry, Rush University, Chicago, IL.

Address correspondence and reprint requests to Lijuan Yuan, Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Integrated Life Science Building (0913), 1981 Kraft Dr, Blacksburg, VA 24061 (e-mail: lyuan@vt.edu).

Received 5 March, 2013

Accepted 1 July, 2013

This work was partially financially supported by a grant from the NCCAM, National Institutes of Health (R01AT004789), and the start-up fund from Virginia Tech to L.Y.

The authors report no conflicts of interest.

© 2013 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,