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

doi:10.1053/j.gastro.2021.01.030

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 journal › Article › Academic › peer-review

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 language	English
Number of pages	16
Journal	Gastroenterology
DOIs	https://doi.org/10.1053/j.gastro.2021.01.030
Publication status	E-pub ahead of print - 18-Jan-2021

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Brand, E. C., Klaassen, M. A. Y., Gacesa, R., Vila, A. V., Ghosh, H., de Zoete, M. R., Boomsma, D. I., Hoentjen, F., Horjus Talabur Horje, C. S., van de Meeberg, P. C., Willemsen, G., Fu, J., Wijmenga, C., van Wijk, F., Zhernakova, A., Oldenburg, B., Weersma, R. K., & Dutch TWIN-IBD consortium and the Dutch Initiative on Crohn and Colitis (2021). Healthy cotwins share gut microbiome signatures with their inflammatory bowel disease twins and unrelated patients. Gastroenterology. https://doi.org/10.1053/j.gastro.2021.01.030

Brand, Eelco C ; Klaassen, Marjolein A Y ; Gacesa, Ranko ; Vila, Arnau Vich ; 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 ; Dutch TWIN-IBD consortium and the Dutch Initiative on Crohn and Colitis. / Healthy cotwins share gut microbiome signatures with their inflammatory bowel disease twins and unrelated patients. In: Gastroenterology. 2021.

@article{c45a527ea5cf4111bb6c515882dc22df,

title = "Healthy cotwins share gut microbiome signatures with their inflammatory bowel disease twins and unrelated patients",

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.",

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

year = "2021",

month = jan,

day = "18",

doi = "10.1053/j.gastro.2021.01.030",

language = "English",

journal = "Gastroenterology",

issn = "0016-5085",

publisher = "W B SAUNDERS CO-ELSEVIER INC",

}

Brand, EC, Klaassen, MAY, Gacesa, R , Vila, AV, Ghosh, H, de Zoete, MR, Boomsma, DI, Hoentjen, F, Horjus Talabur Horje, CS, van de Meeberg, PC, Willemsen, G, Fu, J , Wijmenga, C, van Wijk, F, Zhernakova, A, Oldenburg, B, Weersma, RK & Dutch TWIN-IBD consortium and the Dutch Initiative on Crohn and Colitis 2021, 'Healthy cotwins share gut microbiome signatures with their inflammatory bowel disease twins and unrelated patients', Gastroenterology. https://doi.org/10.1053/j.gastro.2021.01.030

Healthy cotwins share gut microbiome signatures with their inflammatory bowel disease twins and unrelated patients. / Brand, Eelco C; Klaassen, Marjolein A Y; Gacesa, Ranko ; Vila, Arnau Vich; 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; Dutch TWIN-IBD consortium and the Dutch Initiative on Crohn and Colitis.

In: Gastroenterology, 18.01.2021.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Healthy cotwins share gut microbiome signatures with their inflammatory bowel disease twins and unrelated patients

AU - Brand, Eelco C

AU - Klaassen, Marjolein A Y

AU - Gacesa, Ranko

AU - Vila, Arnau Vich

AU - Ghosh, Hiren

AU - de Zoete, Marcel R

AU - Boomsma, Dorret I

AU - Hoentjen, Frank

AU - Horjus Talabur Horje, Carmen S

AU - van de Meeberg, Paul C

AU - Willemsen, Gonneke

AU - Fu, Jingyuan

AU - Wijmenga, Cisca

AU - van Wijk, Femke

AU - Zhernakova, Alexandra

AU - Oldenburg, Bas

AU - Weersma, Rinse K

AU - Dutch TWIN-IBD consortium and the Dutch Initiative on Crohn and Colitis

PY - 2021/1/18

Y1 - 2021/1/18

N2 - 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.

AB - 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.

U2 - 10.1053/j.gastro.2021.01.030

DO - 10.1053/j.gastro.2021.01.030

M3 - Article

C2 - 33476671

JO - Gastroenterology

JF - Gastroenterology

SN - 0016-5085

ER -