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Study of the gut metabolome in postoperative Hirschsprung's disease patients hints at increased glycosaminoglycan breakdown and dysbiosis

Vera Plekhova (UGent) , Ellen De Paepe (UGent) , Katrien Van Renterghem (UGent) , Myriam Van Winckel (UGent) , Lieselot Hemeryck (UGent) and Lynn Vanhaecke (UGent)
(2021)
Author
Abstract
Hirschsprung's disease (HD) is a neurological intestinal birth defect seen in approximately 1 to 5000 newborns. Despite surgical treatment shortly after presentation, up to 60% of patients will express long-term gastrointestinal complaints, including recurring and potentially life-threatening Hirschsprung-associated enterocolitis (HAEC). The aim of this study was to unravel chronic post-operative gastrointestinal disturbances, furthermore looking into predisposing differences between patients with and without a history of HAEC. Faecal samples from postoperative HD patients (n = 38) and their healthy siblings (n = 21) were subjected to targeted and untargeted metabolomic analysis using high resolution Q-Orbitrap MS. Targeted analysis identified pipecolic acid, N-acetylneuraminic acid, N-acetylglucosamine, glutamic acid, isovaleric acid, ethyl pentyl ketone, fructose and serine as significantly (p < 0.05) decreased in HD patients, whereas dopamine was significantly (p < 0.05) increased. The HAEC subgroup expressed decreased concentrations of trans-4-hydroxy-L-proline and 4-methyl-3-penten-2-one, but increased ethyl pentyl ketone. Validated multivariate OPLS-DA regression models (based on 42760 untargeted metabolite features) of the comprehensive gut metabolome allowed differentiation of HD patients versus healthy controls, as well as between patients with and without a HAEC. Pathway analysis revealed impact on amino sugar, lysine, sialic acid and heparan sulfate metabolism in HD, as well as impaired tyrosine metabolism in patients with a history of HAEC. These changes imply disruption of the intestinal mucosa due to glycosaminoglycan breakdown and dysbiosis, furthermore revealing promising diagnostic and/or prognostic candidate biomarkers. Parallels between HAEC biomarkers with pediatric celiac disease markers hint towards similarities in pathophysiology, warranting further investigation.
Keywords
Hirschsprung's disease, Metabolomics, Gut Metabolome

Citation

Please use this url to cite or link to this publication:

MLA
Plekhova, Vera, et al. Study of the Gut Metabolome in Postoperative Hirschsprung’s Disease Patients Hints at Increased Glycosaminoglycan Breakdown and Dysbiosis. 2021.
APA
Plekhova, V., De Paepe, E., Van Renterghem, K., Van Winckel, M., Hemeryck, L., & Vanhaecke, L. (2021). Study of the gut metabolome in postoperative Hirschsprung’s disease patients hints at increased glycosaminoglycan breakdown and dysbiosis. Presented at the Metabolomics 2021, online.
Chicago author-date
Plekhova, Vera, Ellen De Paepe, Katrien Van Renterghem, Myriam Van Winckel, Lieselot Hemeryck, and Lynn Vanhaecke. 2021. “Study of the Gut Metabolome in Postoperative Hirschsprung’s Disease Patients Hints at Increased Glycosaminoglycan Breakdown and Dysbiosis.” In .
Chicago author-date (all authors)
Plekhova, Vera, Ellen De Paepe, Katrien Van Renterghem, Myriam Van Winckel, Lieselot Hemeryck, and Lynn Vanhaecke. 2021. “Study of the Gut Metabolome in Postoperative Hirschsprung’s Disease Patients Hints at Increased Glycosaminoglycan Breakdown and Dysbiosis.” In .
Vancouver
1.
Plekhova V, De Paepe E, Van Renterghem K, Van Winckel M, Hemeryck L, Vanhaecke L. Study of the gut metabolome in postoperative Hirschsprung’s disease patients hints at increased glycosaminoglycan breakdown and dysbiosis. In 2021.
IEEE
[1]
V. Plekhova, E. De Paepe, K. Van Renterghem, M. Van Winckel, L. Hemeryck, and L. Vanhaecke, “Study of the gut metabolome in postoperative Hirschsprung’s disease patients hints at increased glycosaminoglycan breakdown and dysbiosis,” presented at the Metabolomics 2021, online, 2021.
@inproceedings{8722941,
  abstract     = {{Hirschsprung's disease (HD) is a neurological intestinal birth defect seen in approximately 1 to 5000 newborns. Despite surgical treatment shortly after presentation, up to 60% of patients will express long-term gastrointestinal complaints, including recurring and potentially life-threatening Hirschsprung-associated enterocolitis (HAEC). 
The aim of this study was to unravel chronic post-operative gastrointestinal disturbances, furthermore looking into predisposing differences between patients with and without a history of HAEC. Faecal samples from postoperative HD patients (n = 38) and their healthy siblings (n = 21) were subjected to targeted and untargeted metabolomic analysis using high resolution Q-Orbitrap MS.
Targeted analysis identified pipecolic acid, N-acetylneuraminic acid, N-acetylglucosamine, glutamic acid, isovaleric acid, ethyl pentyl ketone, fructose and serine as significantly (p < 0.05) decreased in HD patients, whereas dopamine was significantly (p < 0.05) increased. The HAEC subgroup expressed decreased concentrations of trans-4-hydroxy-L-proline and 4-methyl-3-penten-2-one, but increased ethyl pentyl ketone. Validated multivariate OPLS-DA regression models (based on 42760 untargeted metabolite features) of the comprehensive gut metabolome allowed differentiation of HD patients versus healthy controls, as well as between patients with and without a HAEC. Pathway analysis revealed impact on amino sugar, lysine, sialic acid and heparan sulfate metabolism in HD, as well as impaired tyrosine metabolism in patients with a history of HAEC. These changes imply disruption of the intestinal mucosa due to glycosaminoglycan breakdown and dysbiosis, furthermore revealing promising diagnostic and/or prognostic candidate biomarkers. Parallels between HAEC biomarkers with pediatric celiac disease markers hint towards similarities in pathophysiology, warranting further investigation.}},
  author       = {{Plekhova, Vera and De Paepe, Ellen and Van Renterghem, Katrien and Van Winckel, Myriam and Hemeryck, Lieselot and Vanhaecke, Lynn}},
  keywords     = {{Hirschsprung's disease,Metabolomics,Gut Metabolome}},
  language     = {{und}},
  location     = {{online}},
  title        = {{Study of the gut metabolome in postoperative Hirschsprung's disease patients hints at increased glycosaminoglycan breakdown and dysbiosis}},
  year         = {{2021}},
}