Combined probiotic bacteria promotes intestinal epithelial barrier function in interleukin-10-gene-deficient mice.
OBJECTIVE
To investigate the protective effects of combinations of probiotic (Bifico) on interleukin (IL)-10-gene-deficient (IL-10 KO) mice and Caco-2 cell monolayers.


METHODS
IL-10 KO mice were used to assess the benefits of Bifico in vivo. IL-10 KO and control mice received approximately 1.5 × 10(8) cfu/d of Bifico for 4 wk. Colons were then removed and analyzed for epithelial barrier function by Ussing Chamber, while an ELISA was used to evaluate proinflammatory cytokines. The colon epithelial cell line, Caco-2, was used to test the benefit of Bifico in vitro. Enteroinvasive Escherichia coli (EIEC) and the probiotic mixture Bifico, or single probiotic strains, were applied to cultured Caco-2 monolayers. Barrier function was determined by measuring transepithelial electrical resistance and tight junction protein expression.


RESULTS
Treatment of IL-10 KO mice with Bifico partially restored body weight, colon length, and epithelial barrier integrity to wild-type levels. In addition, IL-10 KO mice receiving Bifico treatment had reduced mucosal secretion of tumor necrosis factor-α and interferon-γ, and attenuated colonic disease. Moreover, treatment of Caco-2 monolayers with Bifico or single-strain probiotics in vitro inhibited EIEC invasion and reduced the secretion of proinflammatory cytokines.


CONCLUSIONS
Bifico reduced colon inflammation in IL-10 KO mice, and promoted and improved epithelial-barrier function, enhanced resistance to EIEC invasion, and decreased proinflammatory cytokine secretion.
Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
Chen-Zhang
CZ
Shi
Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
Hong-Qi
HQ
Chen
Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
Yong
Y
Liang
Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
Yang
Y
Xia
Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
Yong-Zhi
YZ
Yang
Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
Jun
J
Yang
Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
Jun-Dong
JD
Zhang
Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
Shu-Hai
SH
Wang
Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
Jing
J
Liu
Chen-Zhang Shi, Hong-Qi Chen, Yong Liang, Yang Xia, Yong-Zhi Yang, Jun Yang, Huan-Long Qin, Department of Surgery, Affiliated Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China.
Huan-Long
HL
Qin
D000818:Animals; D001835:Body Weight; D018938:Caco-2 Cells; D003092:Colitis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000628:therapy*; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D017097:Electric Impedance; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology* / Q000648:ultrastructure; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D010539:Permeability; D019936:Probiotics; D062725:Tight Junction Proteins / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism / Q000382:microbiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C573415:IFNG protein, human; C556062:IL10 protein, mouse; D018836:Inflammation Mediators; D062725:Tight Junction Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
Caco-2 monolayers; Interleukin-10 gene-deficient mice; Intestinal barrier function; Probiotic bacteria; Tight junction proteins