Healthy Cotwins Share Gut Microbiome Signatures With Their Inflammatory Bowel Disease Twins and Unrelated Patients

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 160; no. 6; pp. 1970 - 1985
• Main Authors: Brand, Eelco C., Klaassen, Marjolein A.Y., Gacesa, Ranko, Vich Vila, Arnau, Ghosh, Hiren, de Zoete, Marcel R., Boomsma, Dorret I., Hoentjen, Frank, Horjus Talabur Horje, Carmen S., van de Meeberg, Paul C., Willemsen, Gonneke, Fu, Jingyuan, Wijmenga, Cisca, van Wijk, Femke, Zhernakova, Alexandra, Oldenburg, Bas, Weersma, Rinse K., Honkoop, Pieter, Jacobs, Rutger J., Ponsioen, Cyriel Y., de Boer, Nanne K.H., Alderlieste, Yasser A., van Herwaarden, Margot A., van Tuyl, Sebastiaan A.C., Lutgens, Maurice W., Janneke van der Woude, C., Mares, Wout G.M., de Koning, Daan B., Bosman, Joukje H., Vecht, Juda, de Schryver, Anneke M.P., van der Meulen-de Jong, Andrea E., Pierik, Marieke J., Boekema, Paul J., Verburg, Robert J., Jharap, Bindia, Jansen, Jeroen M., Stokkers, Pieter C.F., Quispel, Rutger, Mahmmod, Nofel, West, Rachel L., Willems, Marleen, Minderhoud, Itta M., Fidder, Herma H., van Schaik, Fiona D.M., Hirdes, Meike M.C., Boontje, Nynke A., Müskens, Bart L.M., Romberg-Camps, Marielle J.L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2021
• Subjects: Crohn’s Disease; Discordant Twin Design; Family Studies; Microbiota; Preclinical; Prediagnostic; Prediction; Ulcerative Colitis; Crohn’s Disease; PCoA; 16S rRNA; CD; Discordant Twin Design; Family Studies; Prediction; IBDU; PPI; IBD; UMC; NTR; PERMANOVA; SCFA; UC; Prediagnostic; TWIN-study; Microbiota; PALGA; FDR; Ulcerative Colitis; Preclinical; BMI
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2021.01.030

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.
Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex-, and body mass index–matched controls, and 99 unrelated patients with IBD. Whole-genome metagenomic shotgun sequencing was performed. Taxonomic and functional (pathways) composition was compared among healthy cotwins, IBD-twins, unrelated patients with IBD, and healthy controls with multivariable (ie, adjusted for potential confounding) generalized linear models.
No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins (false discovery rate <0.10). Compared with 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 patients with IBD, respectively (false discovery rate <0.10). Of these, 8 (42.1%) of 19 and 1 (5.6%) of 18 species, and 37 (35.2%) of 105 and 30 (19.6%) of 153 pathways overlapped between healthy cotwins and IBD-twins, and healthy cotwins and unrelated patients with IBD, 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.
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.
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