Disparities in the gut metabolome of post-operative Hirschsprung's disease patients

Vera Plekhova,Lieselot Y Hemeryck,Myriam Van Winckel,Ellen De Paepe,Lynn Vanhaecke,Katrien Van Renterghem

doi:10.1038/s41598-021-95589-0

Vera Plekhova, Lieselot Y Hemeryck + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-95589-0

Copy DOI

Abstract

Hirschsprung's disease (HD) is a congenital structural abnormality of the colon seen in approximately 1 to 5000 live births. Despite surgical correction shortly after presentation, up to 60% of patients will express long-term gastrointestinal complaints, including potentially life-threatening Hirschsprung-associated enterocolitis (HAEC). In this study fecal samples from postoperative HD patients (n = 38) and their healthy siblings (n = 21) were analysed using high-resolution liquid chromatography—mass spectrometry aiming to further unravel the nature of the chronic gastrointestinal disturbances. Furthermore, within the patient group, we compared the faecal metabolome between patients with and without a history of HAEC as well as those diagnosed with short or long aganglionic segment. Targeted analysis identified several individual metabolites characteristic for all HD patients as well as those with a history of HAEC and long segment HD. Moreover, multivariate models based on untargeted data established statistically significant (p < 0.05) differences in comprehensive faecal metabolome in the patients’ cohort as a whole and in patients with a history of HAEC. Pathway analysis revealed the most impact on amino sugar, lysine, sialic acid, hyaluronan and heparan sulphate metabolism in HD, as well as impaired tyrosine metabolism in HAEC group. Those changes imply disruption of intestinal mucosal barrier due to glycosaminoglycan breakdown and dysbiosis as major metabolic changes in patients’ group and should be further explored for potential diagnostic or treatment targets.

Highlights

Hirschsprung’s disease (HD) is a congenital structural abnormality of the colon seen in approximately 1 to 5000 live births
Several gut microbiome derived metabolites and fermentation pathways, as a direct reflection of gut microbiome functionality, were established to be discriminating for the fecal metabolome of HD patients compared to their healthy siblings
Lysine catabolism was upregulated in HD patients and has previously been associated with inadequate bacterial butyrate production in the large bowel, in which lysine represents alternative to carbohydrates as the main substrates for short-chain fatty acid (SCFA) production[31,32]

Summary

Introduction

Hirschsprung’s disease (HD) is a congenital structural abnormality of the colon seen in approximately 1 to 5000 live births. Several microbiome-derived inflammatory markers (including ASCA IgA and OmpC antibodies) were retrieved in serum of both Chrohn’s disease and HD patients with HAEC e pisodes[20] The latter suggests similarities between the two pathologies at the level of chronic intestinal inflammation, provoked and maintained by intestinal dysbiosis, and points towards host-microbiome interaction playing an essential role in triggering and sustaining gut inflammation in HD patients susceptible to H AEC20. None of those markers, allow to fully explain or predict HAEC episodes and long-term surgery outcomes in HD patients, pointing towards interference from multiple and some yet unknown factors in the manifestation of this p athology[21]. Non-invasive sampling of feces is more favorable to conventional invasive sampling of blood, in young children[25,26]

Methods

Results

Conclusion