enterocolitis

Short chain fatty acid composition in the gut is associated with Hirschsprung associated enterocolitis

Ball and stick representation of an acetate molecule, CH3COO-

Ball and stick representation of an acetate molecule, CH3COO-

Hirschsprung disease is a disorder in which a baby is born without nerves in part or all of the large intestines, rendering them functionless. Hirschsprung-associated enterocolitis (HAEC) is a complication of Hirschsprung disease (HD), in which the intestines become inflamed due to infection. HAEC is a common cause of death in children with Hirschsprung disease, but the real cause of infection in not very well understood yet. Poor immunity, poor intestinal wall function, and an altered gut microbiome are thought to contribute to the issue. An important role of the gut microbiome is to produce short chain fatty acids (SCFAs) from complex and indigestible fiber. The short chain fatty acids contribute to bacterial homeostasis of the gut, and so they may be associated with intestinal issues observed in HAEC. Scientists from California, Michigan, and Sweden set out to test this possible connection by measuring the SCFA, and SCFA-producing bacterial composition in HD children who have HAEC.  The study was published by the Journal of Pediatric Surgery

The study population consisted of 18 children with HD, with ages ranging from 3 months to 8 years, and a median age of 2.7 years. Nine participants had a history of HAEC, while nine did not. Fecal samples were collected from the children and analyzed for SCFAs and bacterial composition. Among the children involved in the study, there were no significant differences in early feeding type, probiotic use, complications unrelated to HAEC, and length of HD diagnosis. One patient in the HD group and two in the HAEC group had trisomy 21, better known as Down Syndrome.

Total fecal SCFA composition in children with a history of HAEC was four-fold lower than that of HD patients who did not have a history of HAEC.  When broken into individual SCFAs, the children with HAEC had substantially less acetate in their stools, but actually slightly higher butyrate levels compared to non-HAEC.  Interestingly, the HAEC patients actually had higher levels of butyrate and acetate producing bacteria, despite the dramatically lower acetate levels.  The authors suggest that perhaps the butyrate producing bacteria are actually converting acetate to butyrate, resulting in higher levels of both butyrate and butyrate producing bacteria, along with lower levels of acetate.

While we still don’t know a cause for Hirschsprung-associated enterocolitis, this study does provide an association between HAEC episodes and alteration of short chain fatty acid composition of the large intestines. This study is limited by its small sample size and other factors that are difficult to account for, but the results still do help scientists identify possible causes of the disease.

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The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.

Fungi associated with enterocolitis for those with Hirschsprung's disease

Plot of the fungal populations in the stool of children without enterocolitis (left), and those with enterocolitis (right).  Notice the substantially larger population of Candida, and Candida albicans in the population with enter…

Plot of the fungal populations in the stool of children without enterocolitis (left), and those with enterocolitis (right).  Notice the substantially larger population of Candida, and Candida albicans in the population with enterocolitis.

Hirschsprung's disease (HD) occurs when an infant is born without ganglion cells in their colon.  The result is that the portion of the colon that lacks these cells cannot relax and pass stool.  It is normally treated surgically by bypassing this portion of the colon with a normally functioning part of the colon.  Unfortunately, around 25% of patients that undergo this procedure eventually get enterocolitis (i.e. colon infection), which can be life threatening. 

Researchers have long believed there to be a bacterial cause for this type of Hirschsprung's associated enterocolitis (HAEC), however the connection has remained elusive.  Researchers, primarily from Cedars-Sinai, published the results of a study this week that suggests fungi, not bacteria, are primarily responsible for causing HAEC.  They published their results in the journal PLoS ONE.

The researchers developed a cohort of seventeen children that suffered from HD as an infant, and who had surgery to correct it.  Eight of these children developed HAEC, while the other nine remained healthy.  The researchers took stool samples from each of the children and measured their bacterial and fungal populations.  Surprisingly to the researchers, there was no statistical difference in the abundance of various bacteria between the two groups.  However, there was a much different story with the fungi.  The normal HD patients had a higher diversity of fungi than the HAEC patients.  In addition, HAEC patients were dominated by Candida species, while the others were not.  Moreover, an average of 90% of the Candida was Candida albicans, a pathogenic fungus that we have written about on the blog in the past.

The scientists were not able to say whether or not Candida albicans was responsible for causing the enterocolitis in these patients, however they do suggest it as a possibility.  To that end, they suggest that perhaps antifungals, rather than antibiotics, should be used to combat HAEC, especially given the fact that antibiotics can lead to ‘blooms’ in fungal species.  We often discuss the importance of all the aspects of the microbiome beyond just the bacteriome (bacteria), such as the virome (viruses), and mycobiome (fungi), and this paper shows another example of why these various ‘omes’ should not be neglected during microbiome research.

Please email blog@MicrobiomeInstitute.org for any comments, news, or ideas for new blog posts.

The views expressed in the blog are solely those of the author of the blog and not necessarily the American Microbiome Institute or any of our scientists, sponsors, donors, or affiliates.