IL23R-Protective Coding Variant Promotes Beneficial Bacteria and Diversity in the Ileal Microbiome in Healthy Individuals Without Inflammatory Bowel Disease

J Crohns Colitis. 2019 Mar 30;13(4):451-461. doi: 10.1093/ecco-jcc/jjy188.

Abstract

Background and aims: This study aimed to characterize the mucosa-associated microbiota in ileal Crohn's disease [CD] patients and in healthy controls in terms of host genotype and inflammation status.

Methods: The mucosa-associated microbiotas of intestinal pinch biopsies from 15 ileal CD patients with mild and moderate disease and from 58 healthy controls were analysed based on 16S ribosomal sequencing to determine microbial profile differences between [1] IL23R, NOD2 and ATG16L1 genotypes in healthy subjects, [2] ileal CD patients and control subjects, and [3] inflamed and non-inflamed mucosal tissue in CD patients.

Results: The protective variant of the IL23R gene [rs11209026] significantly impacted the microbial composition in the ileum of healthy subjects and was associated with an increased abundance of phylotypes within the family Christensenellaceae as well as increases in diversity and richness. Comparative analysis of healthy and non-inflamed CD microbiome samples indicated a notable decrease in the abundance of Faecalibacterium prausnitzii as well as Shannon diversity and richness. Inflamed and non-inflamed ileal samples of CD subjects had high intra-individual stability and inter-individual variability, but no significant alterations in diversity, richness or taxa were identified. Calprotectin correlated positively with the abundance of Proteobacteria and negatively with diversity in the samples from healthy subjects.

Conclusions: The observation of low diversity and low abundance of beneficial bacteria in healthy control subjects carrying the IL23R [rs11209026] wild-type GG genotype indicates that the gut microbiome is influenced by host genetics and is altered prior to disease diagnosis. Faecal calprotectin may be a potential non-invasive screening tool for dysbiosis in subjects without disorders of intestinal inflammation.

Keywords: IL23R; Oscillaspira; 16S rRNA gene sequencing; Christensenellaceae; Crohn’s disease; Interleukin 23 receptor; Proteobacteria; calprotectin; ileum; inflammation; inflammatory bowel disease.

MeSH terms

  • Adult
  • Autophagy-Related Proteins / genetics
  • Case-Control Studies
  • Crohn Disease / genetics
  • Crohn Disease / microbiology*
  • Crohn Disease / pathology
  • Feces / chemistry
  • Female
  • Gastrointestinal Microbiome / genetics*
  • Genetic Variation
  • Genotype
  • Healthy Volunteers
  • Humans
  • Ileitis / genetics
  • Ileitis / microbiology*
  • Ileitis / pathology
  • Ileum / microbiology
  • Ileum / pathology
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Leukocyte L1 Antigen Complex / analysis
  • Male
  • Middle Aged
  • Nod2 Signaling Adaptor Protein / genetics
  • Receptors, Interleukin / genetics*
  • Severity of Illness Index

Substances

  • ATG16L1 protein, human
  • Autophagy-Related Proteins
  • IL23R protein, human
  • Leukocyte L1 Antigen Complex
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • Receptors, Interleukin