Non-Invasive Mapping of the Gastrointestinal Microbiota Identifies Children with Inflammatory Bowel Disease

Abstract

BackgroundPediatric inflammatory bowel disease (IBD) is challenging to diagnose because of the non-specificity of symptoms; an unequivocal diagnosis can only be made using colonoscopy, which clinicians are reluctant to recommend for children. Diagnosis of pediatric IBD is therefore frequently delayed, leading to inappropriate treatment plans and poor outcomes. We investigated the use of 16S rRNA sequencing of fecal samples and new analytical methods to assess differences in the microbiota of children with IBD and other gastrointestinal disorders.Methodology/Principal FindingsWe applied synthetic learning in microbial ecology (SLiME) analysis to 16S sequencing data obtained from i) published surveys of microbiota diversity in IBD and ii) fecal samples from 91 children and young adults who were treated in the gastroenterology program of Children’s Hospital (Boston, USA). The developed method accurately distinguished control samples from those of patients with IBD; the area under the receiver-operating-characteristic curve (AUC) value was 0.83 (corresponding to 80.3% sensitivity and 69.7% specificity at a set threshold). The accuracy was maintained among data sets collected by different sampling and sequencing methods. The method identified taxa associated with disease states and distinguished patients with Crohn’s disease from those with ulcerative colitis with reasonable accuracy. The findings were validated using samples from an additional group of 68 patients; the validation test identified patients with IBD with an AUC value of 0.84 (e.g. 92% sensitivity, 58.5% specificity).Conclusions/SignificanceMicrobiome-based diagnostics can distinguish pediatric patients with IBD from patients with similar symptoms. Although this test can not replace endoscopy and histological examination as diagnostic tools, classification based on microbial diversity is an effective complementary technique for IBD detection in pediatric patients.

Robust Microbiota-Based Diagnostics for Inflammatory Bowel Disease

“…These predictions remained valid when a subset of samples was reprocessed and reanalyzed in a different hospital. While Papa et al (12) achieved similar accuracy for pediatric IBD predictions, their results indicated that an important factor in diagnostic accuracy was the sequencing depth, which allows low-abundance but highly informative groups to be sampled. This might lead to increased costs, as fewer samples can be analyzed in every run.…”

Early-Life Sugar Consumption Affects the Rat Microbiome Independently of Obesity

“…Oscillibacter and Lachnospiracea incertae sedis, which are both genera of the Firmicutes phylum and the Clostridia class, were also reduced by sugar. Oscillibacter is negatively correlated with Crohn disease (65,66) and is implicated as a potential treatment for ulcerative colitis after fecal transfer (67). Lachnospiracea incertae sedis are involved in the fermentation of starches to produce SCFAs (68).…”

The role of the human gut microbiome in ankylosing spondylitits

“…Consistent with this hypothesis, 16S community profiling revealed that the gut microbiome in ERAP-/-did shift, however it was surprisingly towards a more inflammatory profile, with increases of bacteria such as Rikenellaceae, Lachnospiraceae and Ruminococcus which are not only known to elicit a strong immune response, but are also key bacteria in the TI of AS patients (102)(103)(104). The shift in the ERAP-/-mouse microbiome was further explored to determine if it was the overall structure or simply the presence or absence of bacteria that was driving the signature.…”

“…Of the seven families of microbes with differences in abundance within the AS microbiome, Lachnospiraceae, Ruminococcaceae and Prevotellaceace are strongly associated with colitis and CD (102)(103)(104) with Prevotellaceace especially known to elicit a strong inflammatory response in the gut (104). Further investigations showed that correlations between these families of bacteria further shape the AS microbial signature, and that these microbes are present in all AS samples studied suggesting that they are not only driving the microbial signature, but they are at the core of the AS microbial signature.…”

“…(27,101) Restoration of SFB in these mice increased the number of gut-resident IL-17-producing cells and enhanced resistance to infection through induction of specific epithelia cell-specific genes, as well as inflammatory response host genes, which were found to be up regulated by the bacteria leading to an inflammatory environment (27). Lachnospiraceae, Ruminococcaceae and Prevotellaceace are families of bacteria that have been observed in IBD gut microbiomes and are strongly associated with colitis and CD (102)(103)(104), with…”