High concentrate diet induced mucosal injuries by enhancing epithelial apoptosis and inflammatory response in the hindgut of goats

PLoS One. 2014 Oct 30;9(10):e111596. doi: 10.1371/journal.pone.0111596. eCollection 2014.

Abstract

Purpose: It is widely accepted that lipopolysaccharide and volatile fatty acids (VFA) accumulate in the digestive tract of ruminants fed diets containing high portions of grain. Compared to the ruminal epithelium, the hindgut epithelium is composed of a monolayer structure that is more "leaky" for lipopolysaccharide and susceptible to organic acid-induced damage. The aim of this study was to investigate changes in epithelial structure, apoptosis and inflammatory response in the hindgut of goats fed a high-concentrate diet for 6 weeks.

Experimental design: Eight local Chinese goats with rumen cannulas were randomly assigned to two groups: one group was fed a high-concentrate diet (65% concentrate of dry matter, HC) and the other group was fed a low-concentrate diet (35% concentrate of dry matter, LC) for 6 wks. Ruminal fluid, plasma, and hindgut mucosa tissues were collected. Histological techniques, real-time PCR and western blotting were used to evaluate the tissues structure, cell apoptosis and local inflammation in the hindguts.

Results: Feeding HC diet for 6 wks resulted in a significant decrease of ruminal pH (p<0.01), and ruminal lipopolysaccharide concentrations were significantly increased in HC goats (p<0.05). Obvious damage was observed to mucosal epithelium of the hindgut and the intercellular tight junctions in HC, but not in LC, goats. The expression of MyD88 and caspase-8 mRNA was increased in colonic epithelium of HC goats compared to LC (p<0.05), and the expression of TLR-4 and caspase-3 showed a tendency to increase. In the cecum, interleukin-1β mRNA expression was decreased (p<0.05), and caspase-3 showed a potential increase (p = 0.07) in HC goats. The level of NF-κB protein was increased in colonic epithelium of HC goats. Caspase-3 activity was elevated in both colon and cecum, whereas caspase-8 activity was statistically increased only in colon.

Conclusions: Feeding a high-concentrate diet to goats for 6 wks led to hindgut mucosal injuries via activating epithelial cells apoptosis and local inflammatory response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Diet / adverse effects*
  • Epithelium / pathology*
  • Feeding Behavior
  • Gene Expression Regulation
  • Goats
  • Hydrogen-Ion Concentration
  • Inflammation / blood
  • Inflammation / pathology*
  • Intestinal Mucosa / injuries*
  • Intestinal Mucosa / pathology
  • Lipopolysaccharides / blood
  • NF-kappa B / metabolism
  • Rumen / metabolism
  • Tight Junctions / metabolism

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Caspase 3
  • Caspase 8

Grants and funding

This work was supported by National Basic Research Program of China (Project No. 2011CB100802) and National Nature Science Foundation of China (Project No. 31272470) and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.