IBS is prevalent in 12% of the global population, but factors contributing to the condition are not well known. Some widely accepted triggers include diet, environment, genetics, and one’s gut microflora. Several studies show strong evidence that the gut microflora composition is one contributing factor. Therefore, investigating the microbial signatures that may contribute to IBS through a gut health test may inform targeted treatments. However, symptoms of IBS are heterogeneous and have been categorized into different subtypes. Individuals may indicate chronic episodes of diarrhea (IBS-D), constipation (IBS-C), an alternating or a mix of both (IBS-A or IBS-M), or other symptoms that lead to discomfort (IBS-U).

Due to symptom heterogeneity, it is essential to investigate the unique and common microflora signatures that contribute to each IBS subtype to inform targeted treatments for symptom relief and improved quality of life.

 Metagenomic Sequencing to Uncover Microflora Composition

For our paper published in mSystems, our team aimed to determine the microflora signatures between healthy control subjects and people with IBS. Our secondary goal was to identify the longitudinal effects of daily custom probiotic and prebiotic supplementation on the gut microflora among those with IBS.

We conducted a prospective study of 490 subjects with IBS and 122 healthy control subjects. In addition, a subset of people with IBS (134 subjects) had longitudinal samples with daily synbiotic supplementation. The study utilized whole-genome metagenomic sequencing, a technique that can resolve down to the strain level of microbes, to investigate baseline and longitudinal gut microbiome composition and functional potential.

Genomic DNA was sequenced to identify microflora and potential functional pathways. The synbiotics were individually formulated and tailored for each person’s microbiome results and symptom concerns. Longitudinal stool samples were assessed, on average, every 5 months.

 IBS and Shigella

Our findings demonstrate the significant differences in the gut microflora between healthy controls and those with IBS (Figure). The IBS gut microflora had significantly lower microbial diversity (P<0.0001) and a reduction in the abundance of anti-inflammatory microbes, including Faecalibacterium prausnitzii (P<0.0001) and Roseburia intestinalis (P<0.01), while there was an increased abundance of inflammatory microbes Shigella (P<0.0001). The association between Shigella and IBS may be driven by dysbiosis or inflammation in the gut microbiome. Post-infectious IBS is also a possible association with Shigella or the use of antibiotics.

Microflora that contribute to inflammation may influence the phenotype. Individuals with IBS had microbiomes with reduced short-chain fatty acid and vitamin synthesis from the functional potential pathway analysis. In the longitudinal IBS dataset, we detected a significant increase in the microbial abundance of probiotics provided in the formulations across the three timepoints.

Probiotics, Prebiotics, and Synbiotics

Our findings indicate that IBS is a heterogeneous condition and there is no one-size-fits-all approach to treating the syndrome. For example, antibiotics may help relieve symptoms of diarrhea or small intestinal bacterial overgrowth (SIBO) associated with IBS but may also contribute to exacerbating the symptoms and dysbiosis. In addition, symptoms of leaky gut may manifest as IBS, but a leaky gut has more severe implications with intestinal integrity and permeability.

There are alternative solutions to treating IBS as demonstrated by clinical studies showing the effectiveness of probiotics and prebiotics in alleviating symptoms. Rather than risking the overuse of antibiotics, which can have severe implications in the microbiome and contributes to the rise in antibiotic-resistant microbes, careful examination and changes in diet, lifestyle, and alternative strategies such as probiotics, prebiotics, or synbiotics could have more of a beneficial impact on symptoms.

Our research clearly shows the differences in the gut microflora between healthy controls and those with IBS. Further research should investigate functional potential changes to the gut microflora in response to probiotic treatment and whether the changes result in symptom alleviation. Carefully monitoring phenotypic changes in IBS symptoms with treatment will help inform and improve future treatment strategies.