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Intestinal Microbiota in Hirschsprung Disease

Neuvonen, Malla I.*,†; Korpela, Katri*,†; Kyrklund, Kristiina*,†; Salonen, Anne; de Vos, Willem‡,§,#; Rintala, Risto J.*,†; Pakarinen, Mikko P.*,†

Journal of Pediatric Gastroenterology and Nutrition: November 2018 - Volume 67 - Issue 5 - p 594–600
doi: 10.1097/MPG.0000000000001999
Original Article: Gastroenterology

Objectives: The aim of the study was to characterize the microbiota profiles of patients with Hirschsprung disease (HD) and to evaluate this in relation to postoperative bowel function and the incidence of Hirschsprung-associated enterocolitis (HAEC).

Methods: All patients operated on for HD at our center between 1987 and 2011 were invited to answer questionnaires on bowel function and to participate in a clinical follow-up for laboratory investigations, including fecal DNA extraction, fecal calprotectin (FC), and brush border lactase (LCT) genotyping. The microbiota compositions of patients with HD were compared with those of healthy controls aged between 2 and 7 years.

Results: The microbiota composition of eligible patients with HD (n = 34; median age 12 [range, 3–25] years) differed from the healthy controls (n = 141), showing decreased overall microbial richness (P < 0.005). Seventy-seven percent had experienced HAEC. Normal maturation of the intestinal flora was not observed, but patients had a significantly increased abundance of Proteobacteria among other taxa (P < 0.005) resulting in a reduced carbohydrate degradation potential, as predicted by the taxonomic composition. Genetic lactase deficiency was present in 17% and did not correlate with bowel symptoms. No patients reported active HAEC at the time of sampling and FC was within the normal range in all samples.

Conclusions: Patients with HD and HAEC had a significantly altered intestinal microbiome compared to healthy individuals, characterized by a lack of richness and pathologic expansions of taxa, particularly Enterobacteria and Bacilli. Further evaluation is needed to identify whether these observations are intrinsic to HD or secondary to the recurrent use of antibiotics during early childhood.

*Department of Pediatric Surgery, Children's Hospital, Helsinki University Central Hospital

Immunobiology Research Program, Faculty of Medicine

Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland

§Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands

#Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.

Address correspondence and reprint requests to Malla I. Neuvonen, LMS, Department of Pediatric Surgery, Hospital for Children and Adolescents, University of Helsinki, PL 281, 00029 HUS, Helsinki, Finland (e-mail:

Received 14 January, 2018

Accepted 25 March, 2018

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This research was supported by grants from the Finnish Pediatric Research Foundation, Päivikki and Sakari Sohlberg Foundation, the Helsinki University Central Hospital research funds, and the Sigrid Juselius Foundation. Academy of Finland grant to K.K.

The authors report no conflicts of interest.

© 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,