Original Article
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World J Gastroenterol. Dec 28, 2014; 20(48): 18316-18329
Published online Dec 28, 2014. doi: 10.3748/wjg.v20.i48.18316
Bifidobacterium infantis attenuates colitis by regulating T cell subset responses
Li Zuo, Kai-Tao Yuan, Li Yu, Qing-Hong Meng, Peter Chee-Keung Chung, Ding-Hua Yang
Li Zuo, Qing-Hong Meng, Peter Chee-Keung Chung, Department of Immunology, Guiyang Medical College, Guiyang 550004, Guizhou Province, China
Kai-Tao Yuan, Department of Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China
Li Yu, Department of Paediatrics, Guangzhou First Municipal People’s Hospital, Guangzhou 510180, Guangdong Province, China
Ding-Hua Yang, Department of Hepatobiliary Surgery, Nan Fang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Author contributions: Zuo L and Yuan KT contributed equally to this work; Zuo L and Yang DH designed the research; Zuo L, Yuan KT, Yu L and Meng QH performed the research; Chung PCK and Yang DH contributed to the new reagents and analytic tools; Zuo L, Yuan KT and Yang DH analyzed the data; Zuo L and Yuan KT wrote the paper.
Supported by Guangzhou Baoxing Biotechnology Company
Correspondence to: Ding-Hua Yang, MD, PhD, Professor, Department of Hepatobiliary Surgery, Nan Fang Hospital, Southern Medical University, 1838 North Guangzhou Dadao, Guangzhou 510515, Guangdong Province, China. dhyang5810@yahoo.com
Telephone: +86-20-61641706 Fax: +86-20-61641706
Received: October 30, 2013
Revised: May 24, 2014
Accepted: July 22, 2014
Published online: December 28, 2014
Processing time: 223 Days and 11.5 Hours
Abstract

AIM: to investigate the effect of Bifidobacterium infantis (B. infantis) on the T cell subsets and in attenuating the severity of experimental colitis in mice.

METHODS: Normal BALB/c mice were fed different doses of B. infantis for 3 wk, and T cell subsets and related cytokine profiles in mesenteric lymph nodes (MLNs) were detected by flow cytometry and real-time RT-PCR. Colitis was induced by administration of trinitrobenzene sulfonic acid (TNBS) in mice. Before colitis induction, mice were fed high dose B. infantis for 3 wk. Cytokine profiles in MLNs and histological changes of colonic tissue were examined 6 d after colitis induction.

RESULTS: No significant change in cytokine profiles was observed in normal mice fed low dose B. infantis. However, Th1-related cytokines (IL-2, IFN-γ, IL-12p40), Th17-related transcription factor and cytokines (RORγt, IL-21, IL-23), regulatory T cell (Treg)-related transcription factor and cytokines (Foxp3, IL-10) were increased in normal mice fed high dose B. infantis. Furthermore, flow cytometry assay showed B. infantis increased the numbers of CD4+Foxp3+ Tregs and Th17 cells in MLNs. Colitis was successfully induced by TNBS in mice, characterized by colonic inflammation and aberrant Th1 and Th17 responses. Feeding high dose B. infantis for 3 wk before colitis induction decreased the inflammatory cell infiltration and goblet cell depletion and restored the intestinal epithelium. In addition, B. infantis feeding reduced Th1-related cytokines (T-bet, IL-2 and IFN-γ) and Th17-related cytokines (IL-12p40, RORγt, IL-17A, IL-21 and IL-23), and increased Treg-related molecules (Foxp3, IL-10 and TGF-β) in colitis mice.

CONCLUSION: B. infantis effectively attenuates TNBS-induced colitis by decreasing Th1 and Th17 responses and increasing Foxp3+ Treg response in the colonic mucosa.

Keywords: Bifidobacterium; Colitis; Cytokines; Th17; Regulatory T cells

Core tip: Inflammatory bowel disease is a common autoimmune disorder characterized by chronic inflammation of the gastrointestinal tract. Abnormal immune cell responses contribute to the pathogenesis of the colitis. Probiotics are found to regulate the intestinal immune system and play a beneficial role in treating colitis. In our study, we showed that Bifidobacterium infantis (B. infantis) reduced the intestinal inflammation in TNBS-induced colitis mice though decreasing the Th1 and Th17 responses and promoting the Foxp3+ Treg response in mesenteric lymph nodes. This mechanism underlying the regulatory effect of B. infantis on the immune system may have significant clinical implications in treating inflammatory bowel disease and preventing colorectal cancer.