Bacterial Translocation Is Linked to Increased Intestinal IFN-γ, IL-4, IL-17, and mucin-2 in Cholestatic Rats.
Background and rationale for the study. Bacterial translocation is an important triggering factor of infection and mortality in cirrhosis. In a rat model using bile duct ligation (BDL), bacterial translocation appears within 24 h after ligation. The dynamic between TH1/TH2/TH17 cytokines and the integrity of the colonic mucosa in the context of cirrhosis is little known. This study aims to determine the link between bacterial translocation and intestinal inflammation in a cholestasis model. Additionally, alterations of the colonic mucus layer and the bacterial load were also addressed.


RESULTS
Bacterial translocation detected by microbiological cultures and MALDI-TOF showed that Escherichia coli predominates in mesenteric lymph nodes of BDL rats. Intestinal bacterial load analyzed by qPCR indicates a dramatic Escherichia/Shigella overgrowth at 8 and 30 days post-BDL. IFN-γ, IL-4, and IL-17 evaluated by Western blotting were increased at 8 and 30 days in the small intestine. In the colon, in contrast, only IFN-γ was significantly increased. The colonic mucus layer and mucin-2 expression determined by Alcian blue staining and immunohistochemistry surprisingly showed an increase in the mucus layer thickness related to increased mucin-2 expression during the entire process of liver damage. Hepatic enzymes, as well as collagen I, collagen III, TNF-α, and IL-6 liver gene expression were increased. In conclusion, bacterial overgrowth associated with bacterial translocation is linked to the over-expression of IFN-γ, IL-4, IL-17 and mucin-2. These molecules might facilitate the intestinal permeability through exacerbating the inflammatory process and disturbing tight junctions, leading to the perpetuation of the liver damage.
['Vega-Magaña|Natali|N|', 'Delgado-Rizo|Vidal|V|', 'García-Benavides|Leonel|L|', 'Del Toro-Arreola|Susana|S|', 'Segura-Ortega|Jorge|J|', 'Morales|Adelaida Sara M Zepeda|ASMZ|', 'Zepeda-Nuño|José Sergio|JS|', 'Escarra-Senmarti|Marta|M|', 'Gutiérrez-Franco|Jorge|J|', 'Haramati|Jesse|J|', 'Bueno-Topete|Miriam R|MR|']
D000818:Animals D018988:Bacterial Translocation D002779:Cholestasis D004195:Disease Models, Animal D000069196:Gastrointestinal Microbiome D006505:Hepatitis D007371:Interferon-gamma D020381:Interleukin-17 D015847:Interleukin-4 D007413:Intestinal Mucosa D007422:Intestines D008099:Liver D008103:Liver Cirrhosis D008198:Lymph Nodes D008297:Male D055262:Mucin-2 D010539:Permeability D017208:Rats, Wistar D013997:Time Factors D015854:Up-Regulation
Bile duct ligation Inflammation Mucus layer