Active Vitamin D 3 Treatment Attenuated Bacterial Translocation via Improving Intestinal Barriers in Cirrhotic Rats

Mol Nutr Food Res. 2021 Feb;65(3):e2000937. doi: 10.1002/mnfr.202000937. Epub 2020 Dec 10.

Abstract

Scope: Pathological bacterial translocation from the disrupted intestinal barrier leads to substantial complications and mortality in liver cirrhosis. Vitamin D is reported as beneficial to gut barriers in some animal models. However, its effect on cirrhotic bacterial translocation is unknown. The authors aim to investigate the effects of calcitriol on bacterial translocation in cirrhotic rats.

Methods and results: Cirrhotic rats are administrated with a 2-week course of active vitamin D3 (calcitriol, 0.1 μg kg-1 per day) or vehicle by oral gavage after thioacetamide (TAA) injection for 16 weeks. Bacterial translocation, gut permeability, gut microbiota, and associated mechanisms are investigated. Calcitriol treatment significantly attenuates bacterial translocation and reduces intestinal permeability in TAA-induced cirrhotic rats. It upregulates the expressions of occludin in the small intestine and claudin-1 in the colon of cirrhotic rats directly independent of intrahepatic status. Even when a short period of calcitriol treatment do not reduce intestinal bacterial overgrowth, it induces a remarkable change of bacterial diversities and enrichment of Muribaculaceae, Bacteroidales, Allobaculum, Anaerovorax, and Ruminococcaceae.

Conclusion: Calcitriol treatment attenuates intestinal permeability, reduces bacterial translocation, and enriches potentially beneficial gut microbiota in cirrhotic rats that may enable it as a potential therapeutic agent to prevent cirrhotic complications.

Keywords: calcitriol; cirrhotic bacterial translocations; gut barriers; gut microbiota; vitamin D3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / drug effects
  • Calcitriol / pharmacology
  • Cholecalciferol / pharmacology*
  • Colon / drug effects
  • Colon / metabolism
  • Cytochrome P-450 CYP3A / genetics
  • Cytokines / blood
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects*
  • Gene Expression Regulation / drug effects
  • Hydroxyproline / metabolism
  • Intestines / drug effects*
  • Intestines / microbiology
  • Intestines / physiology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / microbiology*
  • Liver Cirrhosis / pathology
  • Male
  • Rats, Sprague-Dawley
  • Thioacetamide / toxicity
  • Tight Junction Proteins / metabolism

Substances

  • Cytokines
  • Tight Junction Proteins
  • Thioacetamide
  • Cholecalciferol
  • Cytochrome P-450 CYP3A
  • Calcitriol
  • Hydroxyproline