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

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.

Untargeted Maternal Plasma Metabolomics in Hirschsprung Disease: A Pilot Study

“…In 38 postoperative HSCR patients, fecal metabolome revealed that glutamic acid was significantly reduced, in comparison to 21 healthy siblings ( P = 0.030). [ 16 ] Furthermore, strong expression of glutamate synthetase has been reported in the normal human gut and ganglionic segments of HSCR colon; however, this is absent in the aganglionic segments of HSCR colonic tissue. [ 17 ] Our study reports similar lower concentrations of glutamic acid in postnatal plasma of mothers of HSCR children.…”

Serum Metabolomic Signatures of Hirschsprung’s Disease Based on GC–MS and LC–MS

“…The abundance of short-chain fatty acids in the stools of children with Hirschsprung-associated enterocolitis (HAEC), as analyzed by gas chromatography−mass spectrometry (GC−MS), was significantly reduced, especially decreased acetate and increased butyrate. 9 Plekhova et al 10 observed significant differences in fecal metabolites, such as pipecolinic acid, Nacetylneuraminic acid, and glutamic acid, between HSCR patients and the control group. These studies indicate that there is a significant correlation between metabolite imbalance and HSCR, but serum samples have not been explored.…”

Faecal metabolome responses to an altered dietary protein:carbohydrate ratio in adult dogs

“…Metabolomics is a holistic approach used to map all small molecules present in a biological matrix, thereby accurately reflecting an individual’s (patho)physiological state (Plekhova et al. 2021 ). Fecal metabolomics more specifically provides functional readouts of gut microbial metabolism and its interaction with host and environmental factors, including dietary intake (Han et al.…”