Previous research has shown that differences in the gut microbiomes of adult patients with irritable bowel syndrome (IBS) -both in structure and in the levels of metabolites produced or modified by gut microbes- often accompany abdominal pain. An association between gastrointestinal microbes and IBS in children has been also reported and is characterized by shifts in the abundances of members of the phyla Bacteroidetes, Proteobacteria, and Firmicutes.
However, in the clinical setting, an accurate diagnosis of patients with IBS remains a challenge because it is based largely on clinical criteria. Microbiome data could help in this regard.
In collaboration with other scientists from Baylor College of Medicine, Texas Children’s Hospital, Diversigen, and the University of Washington, we have developed an improved disease classification technique that enables personalized diagnosis of pediatric patients with IBS based on their gut microbiome.
We sought to explore the associations between abdominal pain and the gut microbiome by using a multiomics approach in 23 preadolescent children with IBS—diagnosed according to the validated Rome III questionnaire and daily pain and stool diaries for 2 weeks—and 22 healthy controls.
A battery of tests meant children with IBS could be distinguished from healthy children in terms of bacterial species composition, bacterial genes, and fecal metabolite abundances. The stool communities of children with IBS were enriched in Gammaproteobacteria, unclassified Clostridiales, metabolic pathways related to amino acid metabolism and phospholipid synthesis, together with higher levels of sterols, steroids (sulfated steroids), bile acids, and phenylalanine and tyrosine metabolites.
Moreover, correlations were found between abdominal pain and the relative abundances of different bacterial species, metagenomic functions and metabolites. Pain frequency and severity assessed by a validated numerical rating scale showed positive correlations with the relative abundances of Flavonifractor plautii, Lachnospiraceae bacterium and unclassified Eggerthella, fucose and rhamnose degradation and phospholipid biosynthesis, and protein-degradation products, among others.
A battery of tests meant children with IBS could be distinguished from healthy children in terms of bacterial species composition, bacterial genes, and fecal metabolite abundances.
The clinical relevance of the gut microbiome in IBS was also supported by a previous study led by Professor Magnus Simrén that found that IBS symptom severity in adults is linked to a specific fecal microbiota signature characterized by low microbial richness, low CH4 exhaled, an enriched Bacteroides enterotype and the absence of Methanobacteriales.
By using a set of only 10 bacterial features (species, functional pathways and metabolites) that differed the most between IBS cases and healthy controls, we generated a disease classifier that helped distinguish cases from healthy controls with an area under the curve of 0.93 and an accuracy around 80%. As such, our microbiome-based classifier could pave the way towards more effective and personalized diagnosis and treatment of children with IBS based not only on microbial features, but on biochemical and molecular characteristics as well. This study also provides a foundation for future improvements in building disease classifier models for the diagnosis and monitoring of chronic gastrointestinal diseases.
Our study is the first to combine deep microbiome analysis with developing new diagnostic strategies to tailor the diagnosis of children with IBS. Through non-invasive gut microbiome-related data, we are closer to delivering tailored diagnoses for individuals with IBS, which may help identify the subset of patients more likely to benefit from nutritional interventions.
Saulnier DM, Riehle K, Mistretta TA, et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology. 2011; 141(5):1782-91. doi: 10.1053/j.gastro.2011.06.072.
Hollister EB, Oezguen N, Chumpitazi BP, et al. Leveraging human microbiome features to diagnose and stratify children with irritable bowel syndrome. J Mol Diagn. 2019; 21(3):449-61. doi: 10.1016/j.moldx.2019.01.006.