Healthy Cotwins Share Gut Microbiome Signatures With Their Inflammatory Bowel Disease Twins and Unrelated Patients
Eelco C. Brand, Marjolein A. Y. Klaassen, Ranko Gaćeša, 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, Bas Oldenburg, Femke van Wijk, Eelco C. Brand, Pieter Honkoop, Rutger J. Jacobs, Cyriel Y. Ponsioen, Nanne K.H. de Boer, Yasser A. Alderlieste, Margot A. van Herwaarden, Sebastiaan A.C. van Tuyl, Maurice Lutgens, C. Janneke van der Woude, Wout Mares, D.B. de Koning, J Bosman, J. van der Vecht, A. M. P. De Schryver, Andrea E. van der Meulen‐de Jong, Marieke Pierik, Paul J. Boekema, Robert J. Verburg, Bindia Jharap, Gonneke Willemsen, Dorret I. Boomsma, Jeroen M. Jansen, Pieter Stokkers, Frank Hoentjen, Rutger Quispel, Carmen S. Horjus Talabur Horje, Paul C. van de Meeberg, Nofel Mahmmod, Rachel West, Marleen Willems, Itta M. Minderhoud, Herma H. Fidder, Fiona D M van Schaik, Meike M. Hirdes, Nynke Boontje, Bart L.M. Müskens, Rinse K. Weersma, Mariëlle Romberg‐Camps
Abstract
Background & aimsIt 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.MethodsFecal 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.ResultsNo 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.ConclusionsThe 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. 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.