The Composition of the Fecal and Mucosa-adherent Microbiota Varies Based on Age and Disease Activity in Ulcerative Colitis

Mikkel Malham; Marie V. Vestergaard; Thomas Bataillon; Palle Villesen; Astrid Dempfle; Corinna Bang; Anne Line Engsbro; Christian Jakobsen; Andre Franke; Vibeke Wewer; Louise B. Thingholm; Andreas M. Petersen

doi:10.1093/ibd/izae179

The Composition of the Fecal and Mucosa-adherent Microbiota Varies Based on Age and Disease Activity in Ulcerative Colitis

Mikkel Malham^*, Marie V. Vestergaard, Thomas Bataillon, Palle Villesen, Astrid Dempfle, Corinna Bang, Anne Line Engsbro, Christian Jakobsen, Andre Franke, Vibeke Wewer, Louise B. Thingholm, Andreas M. Petersen

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

2 Citations (Scopus)

Abstract

Background: Pediatric-onset ulcerative colitis (pUC) represents a more aggressive disease phenotype compared with adult-onset UC. We hypothesized that this difference can, in part, be explained by the composition of the microbiota. Methods: In a prospective, longitudinal study, we included pediatric (N=30) and adult (N=30) patients with newly or previously (>1 year) diagnosed UC. We analyzed the microbiota composition in the mucosa-adherent microbiota at baseline, using 16S rRNA gene sequencing, and the fecal microbiota at baseline and at 3-month intervals, using shotgun metagenomics. Results: For fecal samples, the bacterial composition differed between pUC and aUC in newly diagnosed patients (β-diversity, Bray Curtis: R²=0.08, P=.02). In colon biopsies, microbial diversity was higher in aUC compared with pUC (α-diversity, Shannon: estimated difference 0.54, P=.006). In the mucosa-adherent microbiota, Alistipes finegoldii was negatively associated with disease activity in pUC while being positively associated in aUC (estimate: -0.255 and 0.098, P=.003 and P=.02 in pUC and aUC, respectively). Finally, we showed reduced stability of the fecal microbiota in pediatric patients, evidenced by a different composition of the fecal microbiota in newly and previously diagnosed pUC, a pattern not found in adults. Conclusions: Our results indicate that pediatric UC patients have a more unstable fecal microbiota and a lower α diversity than adult patients and that the microbiota composition differs between aUC and pUC patients. These findings offer some explanation for the observed differences between pUC and aUC and indicate that individualized approaches are needed if microbiota modifications are to be used in the future treatment of UC.

Original language	English
Journal	Inflammatory Bowel Diseases
Volume	31
Issue	2
Pages (from-to)	501-513
Number of pages	13
ISSN	1078-0998
DOIs	https://doi.org/10.1093/ibd/izae179
Publication status	Published - Feb 2025

Keywords

histology
inflammatory bowel disease
microbiome
pediatrics

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10.1093/ibd/izae179

Cite this

Malham, M., Vestergaard, M. V., Bataillon, T., Villesen, P., Dempfle, A., Bang, C., Engsbro, A. L., Jakobsen, C., Franke, A., Wewer, V., Thingholm, L. B., & Petersen, A. M. (2025). The Composition of the Fecal and Mucosa-adherent Microbiota Varies Based on Age and Disease Activity in Ulcerative Colitis. Inflammatory Bowel Diseases, 31(2), 501-513. https://doi.org/10.1093/ibd/izae179

@article{77789b4f44b4449eb31959f0aaf493bb,

title = "The Composition of the Fecal and Mucosa-adherent Microbiota Varies Based on Age and Disease Activity in Ulcerative Colitis",

abstract = "Background: Pediatric-onset ulcerative colitis (pUC) represents a more aggressive disease phenotype compared with adult-onset UC. We hypothesized that this difference can, in part, be explained by the composition of the microbiota. Methods: In a prospective, longitudinal study, we included pediatric (N=30) and adult (N=30) patients with newly or previously (>1 year) diagnosed UC. We analyzed the microbiota composition in the mucosa-adherent microbiota at baseline, using 16S rRNA gene sequencing, and the fecal microbiota at baseline and at 3-month intervals, using shotgun metagenomics. Results: For fecal samples, the bacterial composition differed between pUC and aUC in newly diagnosed patients (β-diversity, Bray Curtis: R2=0.08, P=.02). In colon biopsies, microbial diversity was higher in aUC compared with pUC (α-diversity, Shannon: estimated difference 0.54, P=.006). In the mucosa-adherent microbiota, Alistipes finegoldii was negatively associated with disease activity in pUC while being positively associated in aUC (estimate: -0.255 and 0.098, P=.003 and P=.02 in pUC and aUC, respectively). Finally, we showed reduced stability of the fecal microbiota in pediatric patients, evidenced by a different composition of the fecal microbiota in newly and previously diagnosed pUC, a pattern not found in adults. Conclusions: Our results indicate that pediatric UC patients have a more unstable fecal microbiota and a lower α diversity than adult patients and that the microbiota composition differs between aUC and pUC patients. These findings offer some explanation for the observed differences between pUC and aUC and indicate that individualized approaches are needed if microbiota modifications are to be used in the future treatment of UC.",

keywords = "histology, inflammatory bowel disease, microbiome, pediatrics",

author = "Mikkel Malham and Vestergaard, {Marie V.} and Thomas Bataillon and Palle Villesen and Astrid Dempfle and Corinna Bang and Engsbro, {Anne Line} and Christian Jakobsen and Andre Franke and Vibeke Wewer and Thingholm, {Louise B.} and Petersen, {Andreas M.}",

year = "2025",

month = feb,

doi = "10.1093/ibd/izae179",

language = "English",

volume = "31",

pages = "501--513",

journal = "Inflammatory Bowel Diseases",

issn = "1078-0998",

publisher = "Oxford University Press",

number = "2",

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Malham, M, Vestergaard, MV, Bataillon, T , Villesen, P, Dempfle, A, Bang, C, Engsbro, AL, Jakobsen, C, Franke, A, Wewer, V, Thingholm, LB & Petersen, AM 2025, 'The Composition of the Fecal and Mucosa-adherent Microbiota Varies Based on Age and Disease Activity in Ulcerative Colitis', Inflammatory Bowel Diseases, vol. 31, no. 2, pp. 501-513. https://doi.org/10.1093/ibd/izae179

The Composition of the Fecal and Mucosa-adherent Microbiota Varies Based on Age and Disease Activity in Ulcerative Colitis. / Malham, Mikkel; Vestergaard, Marie V.; Bataillon, Thomas et al.
In: Inflammatory Bowel Diseases, Vol. 31, No. 2, 02.2025, p. 501-513.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The Composition of the Fecal and Mucosa-adherent Microbiota Varies Based on Age and Disease Activity in Ulcerative Colitis

AU - Malham, Mikkel

AU - Vestergaard, Marie V.

AU - Bataillon, Thomas

AU - Villesen, Palle

AU - Dempfle, Astrid

AU - Bang, Corinna

AU - Engsbro, Anne Line

AU - Jakobsen, Christian

AU - Franke, Andre

AU - Wewer, Vibeke

AU - Thingholm, Louise B.

AU - Petersen, Andreas M.

PY - 2025/2

Y1 - 2025/2

N2 - Background: Pediatric-onset ulcerative colitis (pUC) represents a more aggressive disease phenotype compared with adult-onset UC. We hypothesized that this difference can, in part, be explained by the composition of the microbiota. Methods: In a prospective, longitudinal study, we included pediatric (N=30) and adult (N=30) patients with newly or previously (>1 year) diagnosed UC. We analyzed the microbiota composition in the mucosa-adherent microbiota at baseline, using 16S rRNA gene sequencing, and the fecal microbiota at baseline and at 3-month intervals, using shotgun metagenomics. Results: For fecal samples, the bacterial composition differed between pUC and aUC in newly diagnosed patients (β-diversity, Bray Curtis: R2=0.08, P=.02). In colon biopsies, microbial diversity was higher in aUC compared with pUC (α-diversity, Shannon: estimated difference 0.54, P=.006). In the mucosa-adherent microbiota, Alistipes finegoldii was negatively associated with disease activity in pUC while being positively associated in aUC (estimate: -0.255 and 0.098, P=.003 and P=.02 in pUC and aUC, respectively). Finally, we showed reduced stability of the fecal microbiota in pediatric patients, evidenced by a different composition of the fecal microbiota in newly and previously diagnosed pUC, a pattern not found in adults. Conclusions: Our results indicate that pediatric UC patients have a more unstable fecal microbiota and a lower α diversity than adult patients and that the microbiota composition differs between aUC and pUC patients. These findings offer some explanation for the observed differences between pUC and aUC and indicate that individualized approaches are needed if microbiota modifications are to be used in the future treatment of UC.

AB - Background: Pediatric-onset ulcerative colitis (pUC) represents a more aggressive disease phenotype compared with adult-onset UC. We hypothesized that this difference can, in part, be explained by the composition of the microbiota. Methods: In a prospective, longitudinal study, we included pediatric (N=30) and adult (N=30) patients with newly or previously (>1 year) diagnosed UC. We analyzed the microbiota composition in the mucosa-adherent microbiota at baseline, using 16S rRNA gene sequencing, and the fecal microbiota at baseline and at 3-month intervals, using shotgun metagenomics. Results: For fecal samples, the bacterial composition differed between pUC and aUC in newly diagnosed patients (β-diversity, Bray Curtis: R2=0.08, P=.02). In colon biopsies, microbial diversity was higher in aUC compared with pUC (α-diversity, Shannon: estimated difference 0.54, P=.006). In the mucosa-adherent microbiota, Alistipes finegoldii was negatively associated with disease activity in pUC while being positively associated in aUC (estimate: -0.255 and 0.098, P=.003 and P=.02 in pUC and aUC, respectively). Finally, we showed reduced stability of the fecal microbiota in pediatric patients, evidenced by a different composition of the fecal microbiota in newly and previously diagnosed pUC, a pattern not found in adults. Conclusions: Our results indicate that pediatric UC patients have a more unstable fecal microbiota and a lower α diversity than adult patients and that the microbiota composition differs between aUC and pUC patients. These findings offer some explanation for the observed differences between pUC and aUC and indicate that individualized approaches are needed if microbiota modifications are to be used in the future treatment of UC.

KW - histology

KW - inflammatory bowel disease

KW - microbiome

KW - pediatrics

UR - http://www.scopus.com/inward/record.url?scp=85206593688&partnerID=8YFLogxK

U2 - 10.1093/ibd/izae179

DO - 10.1093/ibd/izae179

M3 - Journal article

C2 - 39150994

AN - SCOPUS:85206593688

SN - 1078-0998

VL - 31

SP - 501

EP - 513

JO - Inflammatory Bowel Diseases

JF - Inflammatory Bowel Diseases

IS - 2

ER -

The Composition of the Fecal and Mucosa-adherent Microbiota Varies Based on Age and Disease Activity in Ulcerative Colitis

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