Abstract
Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care. Many patients exhibit incomplete responses to ulcerative colitis (UC) therapy. Schirmer et al. investigate the gut microbiome's role in pediatric UC treated with two conventional therapies. Baseline and longitudinal microbial trends are implicated in disease severity and progression, including remission and colectomy requirement. These insights may motivate new therapeutic approaches.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 600-610.e4 |
| Journal | Cell Host and Microbe |
| Volume | 24 |
| Issue number | 4 |
| DOIs | |
| State | Published - Oct 10 2018 |
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Keywords
- 5ASA
- colectomy
- corticosteroids
- disease course
- gut microbiome
- host-microbial interactions
- pediatric ulcerative colitis
- response to therapy
- serological markers
- treatment-naive
ASJC Scopus subject areas
- Parasitology
- Microbiology
- Virology
Cite this
Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course. / Schirmer, Melanie; Denson, Lee; Vlamakis, Hera; Franzosa, Eric A.; Thomas, Sonia; Gotman, Nathan M.; Rufo, Paul; Baker, Susan S.; Sauer, Cary; Markowitz, James; Pfefferkorn, Marian; Oliva-Hemker, Maria; Rosh, Joel; Otley, Anthony; Boyle, Brendan; Mack, David; Baldassano, Robert; Keljo, David; LeLeiko, Neal; Heyman, Melvin; Griffiths, Anne; Patel, Ashish S.; Noe, Joshua; Kugathasan, Subra; Walters, Thomas; Huttenhower, Curtis; Hyams, Jeffrey; Xavier, Ramnik J.
In: Cell Host and Microbe, Vol. 24, No. 4, 10.10.2018, p. 600-610.e4.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course
AU - Schirmer, Melanie
AU - Denson, Lee
AU - Vlamakis, Hera
AU - Franzosa, Eric A.
AU - Thomas, Sonia
AU - Gotman, Nathan M.
AU - Rufo, Paul
AU - Baker, Susan S.
AU - Sauer, Cary
AU - Markowitz, James
AU - Pfefferkorn, Marian
AU - Oliva-Hemker, Maria
AU - Rosh, Joel
AU - Otley, Anthony
AU - Boyle, Brendan
AU - Mack, David
AU - Baldassano, Robert
AU - Keljo, David
AU - LeLeiko, Neal
AU - Heyman, Melvin
AU - Griffiths, Anne
AU - Patel, Ashish S.
AU - Noe, Joshua
AU - Kugathasan, Subra
AU - Walters, Thomas
AU - Huttenhower, Curtis
AU - Hyams, Jeffrey
AU - Xavier, Ramnik J.
PY - 2018/10/10
Y1 - 2018/10/10
N2 - Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care. Many patients exhibit incomplete responses to ulcerative colitis (UC) therapy. Schirmer et al. investigate the gut microbiome's role in pediatric UC treated with two conventional therapies. Baseline and longitudinal microbial trends are implicated in disease severity and progression, including remission and colectomy requirement. These insights may motivate new therapeutic approaches.
AB - Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care. Many patients exhibit incomplete responses to ulcerative colitis (UC) therapy. Schirmer et al. investigate the gut microbiome's role in pediatric UC treated with two conventional therapies. Baseline and longitudinal microbial trends are implicated in disease severity and progression, including remission and colectomy requirement. These insights may motivate new therapeutic approaches.
KW - 5ASA
KW - colectomy
KW - corticosteroids
KW - disease course
KW - gut microbiome
KW - host-microbial interactions
KW - pediatric ulcerative colitis
KW - response to therapy
KW - serological markers
KW - treatment-naive
UR - http://www.scopus.com/inward/record.url?scp=85054102370&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054102370&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2018.09.009
DO - 10.1016/j.chom.2018.09.009
M3 - Article
C2 - 30308161
AN - SCOPUS:85054102370
VL - 24
SP - 600-610.e4
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 4
ER -