TY - JOUR
T1 - A Synbiotic with Tumor Necrosis Factor- α Inhibitory Activity Ameliorates Experimental Jejunoileal Mucosal Injury
AU - Takahashi, Ryoki
AU - Noguchi, Takayasu
AU - Mizoguchi, Yoko
AU - Shimoyama, Tadashi
AU - Nakazawa, Teruko
AU - Ikuta, Tohru
N1 - Funding Information:
The authors thank Dr. Tao for his contribution to this study and the Sagami Research Laboratory for allowing them to perform the animal studies. The Sagami Research Laboratory was supported in part by Wakamoto Pharmaceutical Co. Ltd. (WPCL). T he authors also thank Nadine Odo for critical reading and editing of the manuscript. Tohru Ikuta was supported in part by a grant from the National Institutes of Health (P20 MD003383) and the American Heart Association, USA (15GRNT25710387).
Publisher Copyright:
© 2018 Ryoki Takahashi et al.
PY - 2018
Y1 - 2018
N2 - Despite the recent development of biological modifiers for inflammatory bowel diseases (IBD), there continues to be considerable interest in fermented medicines because of its negligible adverse effects. We previously showed that the synbiotic Gut Working Tablet (GWT) alleviates experimental colitis. Here we show that GWT is capable of ameliorating jejunoileal mucosal injury, which is frequently seen with IBD. We created experimental jejunoileal mucositis in rats by injection of methotrexate (MTX) which increases intestinal permeability, a hallmark finding of IBD. Administering GWT to MTX-injected rats restored intestinal integrity by reversing villi shortening, crypt loss, and goblet cell depletion in the mucosa. Also GWT reduced activities of myeloperoxidase and lipid peroxidase and increased superoxide dismutase activity, which is critical for maintaining intestinal function. We further found that GWT suppressed mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) in macrophage and reduced TNF-α mRNA expression in specimens with experimental colitis, which is in contrast to VSL#3 that enhanced TNF-α production. Together, the current and previous animal studies clearly demonstrate the protective role of GWT in chemically induced enterocolitis. Crohn's disease, a well-known IBD, can affect any portion of the intestine, and these results suggest that GWT may be useful as a novel therapeutic or maintenance therapy for IBD.
AB - Despite the recent development of biological modifiers for inflammatory bowel diseases (IBD), there continues to be considerable interest in fermented medicines because of its negligible adverse effects. We previously showed that the synbiotic Gut Working Tablet (GWT) alleviates experimental colitis. Here we show that GWT is capable of ameliorating jejunoileal mucosal injury, which is frequently seen with IBD. We created experimental jejunoileal mucositis in rats by injection of methotrexate (MTX) which increases intestinal permeability, a hallmark finding of IBD. Administering GWT to MTX-injected rats restored intestinal integrity by reversing villi shortening, crypt loss, and goblet cell depletion in the mucosa. Also GWT reduced activities of myeloperoxidase and lipid peroxidase and increased superoxide dismutase activity, which is critical for maintaining intestinal function. We further found that GWT suppressed mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) in macrophage and reduced TNF-α mRNA expression in specimens with experimental colitis, which is in contrast to VSL#3 that enhanced TNF-α production. Together, the current and previous animal studies clearly demonstrate the protective role of GWT in chemically induced enterocolitis. Crohn's disease, a well-known IBD, can affect any portion of the intestine, and these results suggest that GWT may be useful as a novel therapeutic or maintenance therapy for IBD.
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U2 - 10.1155/2018/9184093
DO - 10.1155/2018/9184093
M3 - Article
C2 - 29862296
AN - SCOPUS:85047604576
SN - 2314-6133
VL - 2018
JO - BioMed Research International
JF - BioMed Research International
M1 - 9184093
ER -