Limits...
Fish oil enhances recovery of intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplant.

Li Q, Zhang Q, Wang C, Tang C, Zhang Y, Li N, Li J - PLoS ONE (2011)

Bottom Line: Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp.In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function.Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

ABSTRACT

Background: The intestinal chronic rejection (CR) is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity.

Methods/principal findings: The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions.

Conclusions/significance: Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation.

Show MeSH

Related in: MedlinePlus

Fish oil prevented the alteration of TJ ultrastructure and redistribution of TJ proteins in intestinal transplant rats.(A): Transmission electron microscopic analysis was performed to investigate changes in the ultrastructure of TJ during chronic rejection. Arrows indicated apical TJ and arrows heads depicted desmosomes. In PBS and CO groups, the electron dense materials decreased significantly, indicating disruption of TJ ultrastructure both in the allograft. In addition, desmosomes disappeared in the two groups. In contrast, fish oil preserved the ultrastructure of TJs. In FO group, TJs and desmosomes displayed intact structure as those in syngeneic group. Bars in the images were 0.5 µm. (B): Examination of the tight junction protein occludin by immunofluorescency. The allograft intestine was subjected to immunostaining with the corresponding antibody. And the distribution of TJ proteins in the epithelium was examined by immunofluorecency. (C): Immunolocalization of claudin-1 in the allograft intestine in intestinal transplant rats. The allograft intestine was subjected to immunostaining with the claudin-1 antibody, and images were captured with a confocal scanning microscope. (D): Immunofluorescence staining for claudin-3. Fish oil prevented redistribution of claudin-3 in the allograft intestine.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3117781&req=5

pone-0020460-g007: Fish oil prevented the alteration of TJ ultrastructure and redistribution of TJ proteins in intestinal transplant rats.(A): Transmission electron microscopic analysis was performed to investigate changes in the ultrastructure of TJ during chronic rejection. Arrows indicated apical TJ and arrows heads depicted desmosomes. In PBS and CO groups, the electron dense materials decreased significantly, indicating disruption of TJ ultrastructure both in the allograft. In addition, desmosomes disappeared in the two groups. In contrast, fish oil preserved the ultrastructure of TJs. In FO group, TJs and desmosomes displayed intact structure as those in syngeneic group. Bars in the images were 0.5 µm. (B): Examination of the tight junction protein occludin by immunofluorescency. The allograft intestine was subjected to immunostaining with the corresponding antibody. And the distribution of TJ proteins in the epithelium was examined by immunofluorecency. (C): Immunolocalization of claudin-1 in the allograft intestine in intestinal transplant rats. The allograft intestine was subjected to immunostaining with the claudin-1 antibody, and images were captured with a confocal scanning microscope. (D): Immunofluorescence staining for claudin-3. Fish oil prevented redistribution of claudin-3 in the allograft intestine.

Mentions: In this study, we observed significant alterations in the composition of intestinal microbiota and disruption of epithelial integrity in CR. Furthermore, exogenous administration of fish oil promotes restoration of the normal gut microbiota and intestinal tight junction in CR rats. The intestinal transplanted rats displayed major historical characteristics of chronic rejection. Tissue damage was most pronounced in the allografts and recipients' native ileum. Our data suggested the histological characteristics of intestinal epithelial injury and chronic inflammation in chronic rejection. Besides, here we found that administration of fish oil to intestinal transplant rats was associated with an improvement of the mucosal structure and the intestinal epithelial integrity was well protected. Moreover, inflammatory cells infiltration was markedly reduced by fish oil. It is well known that enteric pathogenic bacteria compete with the endogenous microbiota and that infections are more common when the normal intestinal microbiota is lost. We examined the status of the gut microbiota in the graft, recipients' native ileum and colon in CR rats and found dramatic differences in CR rats (Figures 1–7) compared with syngeneic transplanted animals and normal rats. The rats of chronic rejection were accompanied by the shifts of gut microbiota towards Escherichia coli, Bacteroides and Clostridium groups. Meanwhile, the relative abundance of Lactobacillales bacteria in the intestines had a significant decrease in CR rats. Similar changes were showed in experimental models of intestinal inflammation [32], [33] and in patients with IBD [34], [35], which indicated that these alterations are caused by inflammation.


Fish oil enhances recovery of intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplant.

Li Q, Zhang Q, Wang C, Tang C, Zhang Y, Li N, Li J - PLoS ONE (2011)

Fish oil prevented the alteration of TJ ultrastructure and redistribution of TJ proteins in intestinal transplant rats.(A): Transmission electron microscopic analysis was performed to investigate changes in the ultrastructure of TJ during chronic rejection. Arrows indicated apical TJ and arrows heads depicted desmosomes. In PBS and CO groups, the electron dense materials decreased significantly, indicating disruption of TJ ultrastructure both in the allograft. In addition, desmosomes disappeared in the two groups. In contrast, fish oil preserved the ultrastructure of TJs. In FO group, TJs and desmosomes displayed intact structure as those in syngeneic group. Bars in the images were 0.5 µm. (B): Examination of the tight junction protein occludin by immunofluorescency. The allograft intestine was subjected to immunostaining with the corresponding antibody. And the distribution of TJ proteins in the epithelium was examined by immunofluorecency. (C): Immunolocalization of claudin-1 in the allograft intestine in intestinal transplant rats. The allograft intestine was subjected to immunostaining with the claudin-1 antibody, and images were captured with a confocal scanning microscope. (D): Immunofluorescence staining for claudin-3. Fish oil prevented redistribution of claudin-3 in the allograft intestine.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3117781&req=5

pone-0020460-g007: Fish oil prevented the alteration of TJ ultrastructure and redistribution of TJ proteins in intestinal transplant rats.(A): Transmission electron microscopic analysis was performed to investigate changes in the ultrastructure of TJ during chronic rejection. Arrows indicated apical TJ and arrows heads depicted desmosomes. In PBS and CO groups, the electron dense materials decreased significantly, indicating disruption of TJ ultrastructure both in the allograft. In addition, desmosomes disappeared in the two groups. In contrast, fish oil preserved the ultrastructure of TJs. In FO group, TJs and desmosomes displayed intact structure as those in syngeneic group. Bars in the images were 0.5 µm. (B): Examination of the tight junction protein occludin by immunofluorescency. The allograft intestine was subjected to immunostaining with the corresponding antibody. And the distribution of TJ proteins in the epithelium was examined by immunofluorecency. (C): Immunolocalization of claudin-1 in the allograft intestine in intestinal transplant rats. The allograft intestine was subjected to immunostaining with the claudin-1 antibody, and images were captured with a confocal scanning microscope. (D): Immunofluorescence staining for claudin-3. Fish oil prevented redistribution of claudin-3 in the allograft intestine.
Mentions: In this study, we observed significant alterations in the composition of intestinal microbiota and disruption of epithelial integrity in CR. Furthermore, exogenous administration of fish oil promotes restoration of the normal gut microbiota and intestinal tight junction in CR rats. The intestinal transplanted rats displayed major historical characteristics of chronic rejection. Tissue damage was most pronounced in the allografts and recipients' native ileum. Our data suggested the histological characteristics of intestinal epithelial injury and chronic inflammation in chronic rejection. Besides, here we found that administration of fish oil to intestinal transplant rats was associated with an improvement of the mucosal structure and the intestinal epithelial integrity was well protected. Moreover, inflammatory cells infiltration was markedly reduced by fish oil. It is well known that enteric pathogenic bacteria compete with the endogenous microbiota and that infections are more common when the normal intestinal microbiota is lost. We examined the status of the gut microbiota in the graft, recipients' native ileum and colon in CR rats and found dramatic differences in CR rats (Figures 1–7) compared with syngeneic transplanted animals and normal rats. The rats of chronic rejection were accompanied by the shifts of gut microbiota towards Escherichia coli, Bacteroides and Clostridium groups. Meanwhile, the relative abundance of Lactobacillales bacteria in the intestines had a significant decrease in CR rats. Similar changes were showed in experimental models of intestinal inflammation [32], [33] and in patients with IBD [34], [35], which indicated that these alterations are caused by inflammation.

Bottom Line: Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp.In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function.Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

ABSTRACT

Background: The intestinal chronic rejection (CR) is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity.

Methods/principal findings: The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions.

Conclusions/significance: Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation.

Show MeSH
Related in: MedlinePlus