Yoshifumi Watanabe1, Tsunekazu Mizushima2,3,4, Ryu Okumura5,6, Shiki Fujino1, Takayuki Ogino1, Norikatsu Miyoshi1, Hidekazu Takahashi1, Mamoru Uemura1, Chu Matsuda1, Hirofumi Yamamoto1, Kiyoshi Takeda7,5,6, Yuichiro Doki1, Hidetoshi Eguchi1. 1. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. 2. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan. tmizushima@gesurg.med.osaka-u.ac.jp. 3. Department of Therapeutics for Inflammatory Bowel Diseases, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan. tmizushima@gesurg.med.osaka-u.ac.jp. 4. Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, 1-1 Yamadaoka, Suita, Osaka, Japan. tmizushima@gesurg.med.osaka-u.ac.jp. 5. Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan. 6. Immunology Frontier Research Center, Osaka University, 2-2 Yamadaoka, Suita, Osaka, Japan. 7. Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, 1-1 Yamadaoka, Suita, Osaka, Japan.
Abstract
BACKGROUND: The intestinal environment plays important roles in mucosal barrier homeostasis and intestinal inflammation, as clarified in studies using experimental animals but not in humans. AIMS: We investigated whether environmental changes in the fecal stream cause phenotypic changes in the human mucosal barrier. METHODS: We obtained human ileal samples after fecal stream diversions in patients with rectal cancer or Crohn's disease. We investigated the bacterial load and diversity in the human defunctioned ileum, defined as the anal side of the ileum relative to the ileostomy. We also examined the epithelium and lamina propria cell phenotypes in the defunctioned ileum. RESULTS: After fecal stream diversion, bacterial loads decreased significantly in the defunctioned ileum. Based on the Chao1, Shannon, and observed species indices, the diversity of mucosa-associated microbiota was lower in the defunctioned ileum than in the functional ileum. Moreover, the healthy defunctioned ileum showed reductions in villous height, goblet cell numbers, and Ki-67+ cell numbers. Additionally, interferon-γ+, interleukin-17+, and immunoglobulin A+ cell abundance in the lamina propria decreased. After the intestinal environment was restored with an ileostomy closure, the impaired ileal homeostasis recovered. The defunctioned ileum samples from patients with Crohn's disease also showed reductions in interferon-γ+ and interleukin-17+ cell numbers. CONCLUSIONS: Fecal stream diversion reduced the abundance and diversity of intestinal bacteria. It also altered the intestinal mucosal barrier, similar to the alterations observed in germ-free animals. In patients with Crohn's disease, Th1 and Th17 cell numbers were attenuated, which suggests that the host-microbiome interaction is important in disease pathogenesis.
BACKGROUND: The intestinal environment plays important roles in mucosal barrier homeostasis and intestinal inflammation, as clarified in studies using experimental animals but not in humans. AIMS: We investigated whether environmental changes in the fecal stream cause phenotypic changes in the human mucosal barrier. METHODS: We obtained human ileal samples after fecal stream diversions in patients with rectal cancer or Crohn's disease. We investigated the bacterial load and diversity in the human defunctioned ileum, defined as the anal side of the ileum relative to the ileostomy. We also examined the epithelium and lamina propria cell phenotypes in the defunctioned ileum. RESULTS: After fecal stream diversion, bacterial loads decreased significantly in the defunctioned ileum. Based on the Chao1, Shannon, and observed species indices, the diversity of mucosa-associated microbiota was lower in the defunctioned ileum than in the functional ileum. Moreover, the healthy defunctioned ileum showed reductions in villous height, goblet cell numbers, and Ki-67+ cell numbers. Additionally, interferon-γ+, interleukin-17+, and immunoglobulin A+ cell abundance in the lamina propria decreased. After the intestinal environment was restored with an ileostomy closure, the impaired ileal homeostasis recovered. The defunctioned ileum samples from patients with Crohn's disease also showed reductions in interferon-γ+ and interleukin-17+ cell numbers. CONCLUSIONS: Fecal stream diversion reduced the abundance and diversity of intestinal bacteria. It also altered the intestinal mucosal barrier, similar to the alterations observed in germ-free animals. In patients with Crohn's disease, Th1 and Th17 cell numbers were attenuated, which suggests that the host-microbiome interaction is important in disease pathogenesis.
Authors: Marie Joossens; Geert Huys; Margo Cnockaert; Vicky De Preter; Kristin Verbeke; Paul Rutgeerts; Peter Vandamme; Severine Vermeire Journal: Gut Date: 2011-01-05 Impact factor: 23.059