Abstract

Short bowel syndrome (SBS) presents an increasing problem in pediatrics. SBS often results from surgical resection of necrotic bowel following necrotizing enterocolitis or treatment of anatomic gastrointestinal defects. SBS is associated with significant morbidity and mortality, and creates substantial burdens for patients, families, and the health system. Recent reports have demonstrated that the fecal microbiome of children with SBS is significantly different from healthy control and severe intestinal microbial imbalances is associated with poor growth. We hypothesized that children with SBS and adverse clinical features such as PN dependent, shorter bowel length and lack of ileocecal valve would demonstrate more gut dysbiosis compare with the SBS non-PN dependent. An improved understanding of SBS pathogenesis would enhance management and potentially suggest new interventions. We studied microbial communities of SBS and control non-SBS patients from the jejunum, obtained endoscopically or by ostomy aspiration, and stool. We enrolled SBS patients who did and did not require parenteral nutrition (PN), as a surrogate marker for the seriousness of their disease. We studied the microbiota using high-throughput DNA sequencing of 16S rRNA genes and statistical analyses. We found that microbial diversity was significantly greater in jejunal aspirate than in stool samples in SBS patients, unlike non-SBS patients; that SBS patients receiving enteral feeds had greater diversity, and that SBS patients on PN and enteral feeds had lower differences in diversity in jejunal vs. stool samples. We found a trend toward increased diversity in patients with an intact ileocecal valve, and found that certain taxa were more abundant in the certain sample types, and in SBS patients vs. non-SBS patients. SBS patients have lower microbial diversity, especially patients with more severe disease, patients requiring PN, and those lacking an ileocecal valve. SBS patients, particularly those with more complex characteristics, exhibit differences in their intestinal microbiota. Particular individual taxa were over- and under-represented in patients with more unfavorable disease. While diminished diversity and alterations in microbiota composition are likely consequences of SBS, future efforts aimed at increasing microbial diversity and interventions targeting specific microbiota characteristics might constitute a testable approach to ameliorate some clinical SBS clinical consequences.

Highlights

  • Short Bowel Syndrome (SBS) is characterized by a loss of intestinal length, resulting in malabsorption of nutrients, fluids and/or electrolytes

  • We examined the data for bacterial taxa, defined at the Genus level, that were significantly different in the different clinical states, per the Wald test with Benjamini-Hochberg adjustment for false discovery, as implemented in DESeq2 [42] (Fig 4, data presented in tabular form in S1 Table)

  • We found that in the jejunal aspirate (JA) samples (Fig 4D) an unclassified Enterobacteriaceae, two unclassified Lactobacillales, and an unclassified Enterococcaceae were significantly overabundant in the SBS patients, and in the SS samples (Fig 4E) we found that Phasocolarctobacterium, Ruminococcus, an unclassified Erysipelotrichaceae, Oscillospira, SMB53, Turicibacter, Sutterella, Odoribacteria, two unclassified Peptostreptococcaceae, an unclassified Lachnospiraceae, 5 Bacteroides, and 2 Bifidobacterium were overabundant in the SBS patients; and that Granulicatella, Staphylococcus, an unclassified Bacillus, Citrobacter, Fusobacterium, 4 Klebsiella, 5 Enterococcus, 3 unclassified Lactobacillales, 3 unclassified Bacteria, 4 unclassified Enterobacteriaceae, Streptococcus, and 2 unclassified Enterococcaceae were overabundant in the normal SS samples

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Summary

Introduction

Short Bowel Syndrome (SBS) is characterized by a loss of intestinal length, resulting in malabsorption of nutrients, fluids and/or electrolytes. Small bowel bacterial overgrowth (SBBO) is a common complication associated with SBS and SBBO predicts increased morbidity and mortality in these patients. Cut-offs have not been validated or well-studied, and depend on the managing clinician [13], and culture methods are not standardized among microbiology labs. For these reasons, a variety of non-invasive diagnostic tests have been suggested for the diagnosis of SBBO; these are based largely on the excretion of hydrogen in exhaled breath generated by the metabolism of carbohydrate by the luminal bacteria. The hydrogen breath test is the most common alternative method to diagnoses SBBO It uses carbohydrate (glucose, lactulose and xylose) as a substrate [12]. Both the glucose and lactulose hydrogen breath tests have shown unsatisfactory abilities to predict SBBO [12, 14]

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