Toward a porcine in vivo model to analyze the pathogenesis of TLR5-dependent enteropathies

Gut Microbes. 2020 Nov 9;12(1):1782163. doi: 10.1080/19490976.2020.1782163. Epub 2020 Jul 25.

Abstract

Non-communicable diseases, such as the metabolic syndrome and inflammatory bowel disease, constitute serious public health threats in developed countries. Besides environmental factors, genetic predispositions contribute to the onset and progression of the disease. State-of-the-art mouse models recently highlight the involvement of Toll-like receptor 5 (TLR5)-driven microbiota composition in the development of metabolic disorders. Here, we discuss the causes and consequences of an altered enteric microbiota and provide information on a similar mechanism in another species, the pig. We show for the first time that a single nucleotide polymorphism in the porcine TLR5 gene conferring impaired functionality is associated with changes in the intestinal microbiota in adult sows and neonatal piglets. Changes in the developing adaptive cellular immune response support the concept of TLR5-driven changes of the microbe-host interplay also in the pig. Together, these findings suggest that pigs with impaired TLR-functionality might represent a model for TLR5-driven diseases in humans.

Keywords: Toll-like receptor 5; inflammatory bowel disease; metabolic syndrome; microbiota; pig model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Disease Models, Animal*
  • Feces / microbiology
  • Gastrointestinal Microbiome
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Inflammatory Bowel Diseases / genetics*
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / immunology
  • Metabolic Syndrome / microbiology
  • Polymorphism, Single Nucleotide
  • Swine
  • Toll-Like Receptor 5 / genetics*

Substances

  • Toll-Like Receptor 5

Grants and funding

M.F. and K.v.V. were supported by the German Federal Ministry of Education and Research (BMBF) within the consortium InfectControl 2020 (Project NeoBiom, grant ID 03ZZ0829C). M.F. was also supported by the national platform for zoonosis research (Project NAMPatIn, grant ID 01KI1906). M.F. was supported by the Freie Universität Berlin within the Excellence Initiative of the DFG. R.P. and M.W.H. were supported by the German Research Foundation (DFG, grant Pi 946/2-1, Ho 2236/14-1 and HO2236/17-1, the priority program SPP1656, Ho 2236/9-2, as well as the Collaborative Research Center CRC1382, project-ID 403224013 – SFB 1382, projects B1, respectively).