Healthy cotwins share gut microbiome signatures with their inflammatory bowel disease twins and unrelated patients

Eelco C Brand, Marjolein A Y Klaassen, Ranko Gacesa, Arnau Vich Vila, Hiren Ghosh, Marcel R de Zoete, Dorret I Boomsma, Frank Hoentjen, Carmen S Horjus Talabur Horje, Paul C van de Meeberg, Gonneke Willemsen, Jingyuan Fu, Cisca Wijmenga, Femke van Wijk, Alexandra Zhernakova, Bas Oldenburg*, Rinse K Weersma*, Dutch TWIN-IBD consortium and the Dutch Initiative on Crohn and Colitis

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Downloads (Pure)

Abstract

BACKGROUND & AIMS: It is currently unclear whether reported changes in the gut microbiome are cause or consequence of inflammatory bowel disease (IBD). Therefore, we studied the gut microbiome of IBD-discordant and -concordant twin pairs, which offers the unique opportunity to assess individuals at increased risk of developing IBD, namely healthy cotwins from IBD-discordant twin pairs.

METHODS: Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex- and BMI-matched controls, and 99 unrelated IBD patients. Whole-genome metagenomic shotgun sequencing was performed. Taxonomic and functional (pathways) composition was compared between healthy-cotwins, IBD-twins, unrelated IBD patients, and healthy controls with multivariable, i.e. adjusted for potential confounding, generalized linear models.

RESULTS: No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins (false discovery rate (FDR)<0.10). Compared to healthy controls, 13, 19, and 18 species, and 78, 105, and 153 pathways were found to be differentially abundant in healthy-cotwins, IBD-twins and unrelated IBD patients, respectively (FDR<0.10). Of these, 8/19 (42.1%) and 1/18 (5.6%) species, and 37/105 (35.2%) and 30/153 (19.6%) pathways overlapped between healthy cotwins and IBD-twins, and healthy cotwins and unrelated IBD patients respectively. Many of the shared species and pathways have previously been associated with IBD. The shared pathways include potentially inflammation-related pathways, for example: an increase in propionate degradation and L-arginine degradation pathways.

CONCLUSIONS: The gut microbiome of healthy cotwins from IBD-discordant twin pairs displays IBD-like signatures. These IBD-like microbiome signatures might precede the onset of IBD. However, longitudinal follow up studies are needed to infer a causal relationship.

Original languageEnglish
Pages (from-to)1970-1985
Number of pages16
JournalGastroenterology
Volume160
Issue number6
Early online date18-Jan-2021
DOIs
Publication statusPublished - May-2021

Cite this