Dataset Information

Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study.

ABSTRACT: Development of potentially life-threatening enterocolitis is the most frequent complication in children with Hirschsprung disease (HSCR), even after definitive corrective surgery. Intestinal microbiota likely contribute to the etiology of enterocolitis, so the aim of this study was to compare the fecal bacterial and fungal communities of children who developed Hirschsprung-associated enterocolitis (HAEC) with HSCR patients who had never had enterocolitis. Eighteen Hirschsprung patients who had completed definitive surgery were enrolled: 9 had a history of HAEC and 9 did not. Fecal DNA was isolated and 16S and ITS-1 regions sequenced using Next Generation Sequencing and data analysis for species identification. The HAEC group bacterial composition showed a modest reduction in Firmicutes and Verrucomicrobia with increased Bacteroidetes and Proteobacteria compared with the HSCR group. In contrast, the fecal fungi composition of the HAEC group showed marked reduction in diversity with increased Candida sp., and reduced Malassezia and Saccharomyces sp. compared with the HSCR group. The most striking finding within the HAEC group is that the Candida genus segregated into "high burden" patients with 97.8% C. albicans and 2.2% C. tropicalis compared with "low burden" patients 26.8% C. albicans and 73% C. tropicalis. Interestingly even the low burden HAEC group had altered Candida community structure with just two species compared to more diverse Candida populations in the HSCR patients. This is the first study to identify Candida sp. as potentially playing a role in HAEC either as expanded commensal species as a consequence of enterocolitis (or treatment), or possibly as pathobioants contributing to the pathogenesis of HAEC. These findings suggest a dysbiosis in the gut microbial ecosystem of HAEC patients, such that there may be dominance of fungi and bacteria predisposing patients to development of HAEC.

SUBMITTER: Frykman PK

PROVIDER: S-EPMC4409062 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study.

Frykman Philip K PK Nordenskjöld Agneta A Kawaguchi Akemi A Hui Thomas T TT Granström Anna L AL Cheng Zhi Z Tang Jie J Underhill David M DM Iliev Iliyan I Funari Vince A VA Wester Tomas T

PloS one 20150424 4

Development of potentially life-threatening enterocolitis is the most frequent complication in children with Hirschsprung disease (HSCR), even after definitive corrective surgery. Intestinal microbiota likely contribute to the etiology of enterocolitis, so the aim of this study was to compare the fecal bacterial and fungal communities of children who developed Hirschsprung-associated enterocolitis (HAEC) with HSCR patients who had never had enterocolitis. Eighteen Hirschsprung patients who had c ...[more]

PMID: 25909773

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Project description:Purpose:Hirschsprung-associated enterocolitis (HAEC) is the most frequent potentially life-threatening complication in children with Hirschsprung disease (HSCR) even after definitive corrective surgery. Mounting evidence suggests that intestinal microbiota likely contribute to the etiology of enterocolitis, so the aim of this study was to use a mouse model of post pull-through HAEC to compare the fecal bacterial communities of animals which developed HAEC to those free of enterocolitis. Methods:Ten Ednrb -/- and 8wild type mice underwent the microsurgical pull-through surgery, and stool was collected at the time of surgery, and then either at 2 and 4 weeks after the operation, or when the mice developed enterocolitis. The mid-colon of all animals was collected, prepared and histologically graded for enterocolitis. Fecal DNA was isolated and bacterial 16S rRNA genes analyzed using Illumina sequencing. Results:Six Ednrb-/- mice developed HAEC with a mean enterocolitis score of 5.7, while the remaining 4 mutant and 8 WT mice remained free of enterocolitis by 4 weeks. The HAEC group had lower alpha diversity by Chao1 analysis compared with WT group, while the Ednrb-/- mice demonstrated distinct bacterial communities from WT mice on beta diversity analysis. The most striking finding was increased proportion of Akkermansia and reduced Bacteroidetes compared with the NO HAEC and WT groups, suggesting Akkermansia may contribute to development of enterocolitis while Bacteroidetes may be protective. Less abundant genera that were reduced in HAEC were Dysgonomas and Clostridium XIVa which may play a protective role. Conclusions:This is the first study to identify Akkermansia as potentially playing a role in HAEC, either as a pathobiont taxa contributing to pathogenesis of enterocolitis, or possibly a protective commensal taxa expanded in response to inflammation. These findings characterized the dynamic shifts in the gut microbial communities through the onset of post pull-through HAEC, and suggests that there may be identifiable bacterial community differences in HSCR patients that are high risk for developing HAEC.

Project description:Environmental microbes have been associated with both protective and adverse health effects in children and adults. Epidemiological studies often rely on broad biomarkers of microbial exposure (i.e. endotoxin, 1 → 3-beta-d-glucan), but fail to identify the taxonomic composition of the microbial community. Our aim was to characterize the bacterial and fungal microbiome in different types of environmental samples collected in studies of human health effects. We determined the composition of microbial communities present in home, school and outdoor air samples by amplifying and sequencing regions of rRNA genes from bacteria (16S) and fungi (18S and ITS). Samples for this pilot study included indoor settled dust (from both a Boston area birth cohort study on Home Allergens and Asthma (HAA) (n = 12) and a study of school exposures and asthma symptoms (SICAS) (n = 1)), as well as fine and coarse concentrated outdoor ambient particulate (CAP) samples (n = 9). Sequencing of amplified 16S, 18S, and ITS regions was performed on the Roche-454 Life Sciences Titanium pyrosequencing platform. Indoor dust samples were dominated by Gram-positive bacteria (Firmicutes and Actinobacteria); the most abundant bacterial genera were those related to human flora (Streptococcus, Staphylococcus, Corynebacterium and Lactobacillus). Outdoor CAPs were dominated by Gram-negative Proteobacteria from water and soil sources, in particular the genera Acidovorax, and Brevundimonas (which were present at very low levels or entirely absent in indoor dust). Phylum-level fungal distributions identified by 18S or ITS regions showed very similar findings: a predominance of Ascomycota in indoor dust and Basidiomycota in outdoor CAPs. ITS sequencing of fungal genera in indoor dust showed significant proportions of Aureobasidium and Leptosphaerulina along with some contribution from Cryptococcus, Epicoccum, Aspergillus and the human commensal Malassezia. ITS sequencing detected more than 70 fungal genera in indoor dust not observed by culture. Microbiome sequencing is feasible for different types of archived environmental samples (indoor dust, and low biomass air particulate samples), and offers the potential to study how whole communities of microbes (including unculturable taxa) influence human health.

Project description:Dysbiosis in the gut microbiome has been implicated in several diseases including auto-immune diseases, inflammatory diseases, cancers and mental disorders. Keratitis is an inflammatory disease of the eye significantly contributing to corneal blindness in the developing world. It would be worthwhile to investigate the possibility of dysbiosis in the gut microbiome being associated with Keratitis. Here, we have analyzed fungal and bacterial populations in stool samples through high-throughput sequencing of the ITS2 region for fungi and V3-V4 region of 16S rRNA gene for bacteria in healthy controls (HC, n = 31) and patients with fungal keratitis (FK, n = 32). Candida albicans (2 OTUs), Aspergillus (1 OTU) and 3 other denovo-OTUs were enriched in FK samples and an unclassified denovo-OTU was enriched in HC samples. However, the overall abundances of these 'discriminatory' OTUs were very low (< 0.001%) and not indicative of significant dysbiosis in the fungal community inhabiting the gut of FK patients. In contrast, the gut bacterial richness and diversity in FK patients was significantly decreased when compared to HC. 52 OTUs were significantly enriched in HC samples whereas only 5 OTUs in FK. The OTUs prominently enriched in HC were identified as Faecalibacterium prausnitzii, Bifidobacterium adolescentis, Lachnospira, Mitsuokella multacida, Bacteroides plebeius, Megasphaera and Lachnospiraceae. In FK samples, 5 OTUs affiliated to Bacteroides fragilis, Dorea, Treponema, Fusobacteriaceae, and Acidimicrobiales were significantly higher in abundance. The functional implications are that Faecalibacterium prausnitzii, an anti-inflammatory bacterium and Megasphaera, Mitsuokella multacida and Lachnospira are butyrate producers, which were enriched in HC patients, whereas Treponema and Bacteroides fragilis, which are pathogenic were abundant in FK patients, playing a potential pro-inflammatory role. Heatmap, PCoA plots and functional profiles further confirm the distinct patterns of gut bacterial composition in FK and HC samples. Our study demonstrates dysbiosis in the gut bacterial microbiomes of FK patients compared to HC. Further, based on inferred functions, it appears that dysbiosis in the gut of FK subjects is strongly associated with the disease phenotype with decrease in abundance of beneficial bacteria and increase in abundance of pro-inflammatory and pathogenic bacteria.

Project description:BackgroundThe Coronavirus Disease 2019 pandemic provided a natural experiment to study the effect of social distancing on the risk of developing Hirschsprung's Associated Enterocolitis (HAEC).MethodsUsing the Pediatric Health Information System (PHIS), a retrospective cohort study of children (<18 years) with Hirschsprung's Disease (HSCR) across 47 United States children's hospitals was performed. The primary outcome was HAEC admissions per 10,000 patient-days. The exposure (COVID-19) was defined as April 2020-December 2021. The unexposed (historical control) period was April 2018-December 2019. Secondary outcomes included sepsis, bowel perforation, intensive care unit (ICU) admission, mortality, and length of stay.ResultsOverall, we included 5707 patients with HSCR during the study period. There were 984 and 834 HAEC admissions during the pre-pandemic and pandemic periods, respectively (2.6 vs. 1.9 HAEC admissions per 10,000 patient-days, incident rate ratio [95% confidence interval]: 0.74 [0.67, 0.81], p < 0.001). Compared to pre-pandemic, those with HAEC during the pandemic were younger (median [IQR]: 566 [162, 1430] days pandemic vs. 746 [259, 1609] days pre-pandemic, p < 0.001) and more likely to live in the lowest quartile of median household income zip codes (24% pandemic vs. 19% pre-pandemic, p = 0.02). There were no significant differences in rates of sepsis (6.1% pandemic vs. 6.1% pre-pandemic, p > 0.9), bowel perforation (1.3% pandemic vs. 1.2% pre-pandemic, p = 0.8), ICU admissions (9.6% pandemic vs. 12% pre-pandemic, p = 0.2), mortality (0.5% pandemic vs. 0.6% pre-pandemic, p = 0.8), or length of stay (median [interquartile range]: 4 [(Pastor et al., 2009; Gosain and Brinkman, 2015) 2,112,11 days pandemic vs. 5 [(Pastor et al., 2009; Tang et al., 2020) 2,102,10 days pre-pandemic, p = 0.4).ConclusionsThe COVID-19 pandemic was associated with significantly decreased incidence of HAEC admissions across US children's hospitals. Possible etiologies such as social distancing should be explored.Level of evidenceII.

Dataset Information

Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study.

Publications

Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study.

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