Microbiome alterations are related to an imbalance of immune response and bacterial translocation in BDL-rats

Document Type : Original Article


1 Instituto de Investigación en Enfermedades Crónico Degenerativas, Departamento de Biología Molecular y Genómica. Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara. CP 44340, Guadalajara, Jalisco, México

2 Instituto de Investigación en Inmunodeficiencias y VIH. Departamento de Clínicas Médicas. Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara. CP 44340, Guadalajara, Jalisco, México

3 FISABIO Fundación para el fomento de la Investigación Sanitaria y Biomédica de la comunidad de Valencia. CP 46015, España

4 División de Inmunología, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social. CP 44340, Guadalajara, Jalisco, México

5 Departamento de Ciencias Biomédicas, Centro Universitario de Tonalá, Universidad de Guadalajara. CP 45425, Tonalá, Jalisco, México

6 Unidad de VIH, Antiguo Hospital Civil de Guadalajara “Fray Antonio Alcalde”. CP 44280, Guadalajara, Jalisco, México

7 Departamento de Microbiología y Patología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara. CP 44340, Guadalajara, Jalisco, México

8 Laboratorio de Inmunología, Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara. CP 44600, Guadalajara, Jalisco, México

9 Departamento de Ciencias de la Salud, Centro Universitario de los Valles, Universidad de Guadalajara. CP 46600, Ameca, Jalisco, México


Objective(s): Bacterial translocation in patients with cirrhosis is an important triggering factor for infections and mortality. In the bile duct ligation (BDL) model, crucial players of bacterial translocation are still unknown. This study aims to determine the interrelation between microbiome composition in the colon, mesenteric lymph nodes, and liver, as well as the local inflammatory microenvironment in the BDL model.
Materials and Methods: Liver damage was assayed by Masson trichrome staining, and hepatic enzymes. The diversity of microbiota in colon stools, mesenteric lymph nodes, and liver was determined by 16S rRNA pyrosequencing. Cytokine expression in mesenteric lymph nodes was analyzed by qRT-PCR.
Results: Our results show that Proteobacteria was the predominant phylum found to translocate to mesenteric lymph nodes and liver in cirrhotic rats. Bile duct ligation induces a drastic intestinal dysbiosis, revealed by an increased relative abundance of Sarcina, Clostridium, Helicobacter, Turicibacter, and Streptococcus genera. However, beneficial bacteria, such as Lactobacillus, Prevotella and Ruminococcus were found to be notably decreased in BDL groups. Mesenteric pro-inflammatory (TNF-α, IL-1β, IL-6, TLR-4) and regulatory (TGF-β, Foxp3, and IL-10) molecules at 30 days post-BDL were significantly increased. Conversely, TGF-β and Foxp3 were significantly augmented at 8 days post-BDL.
Conclusion: Dysbiosis in the colon and mesenteric lymph nodes is linked to an imbalance in the immune response; therefore, this may be an important trigger for bacterial translocation in the BDL model.


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