Introduction
Gut microbiome alterations are known to be one of the pathogenic pathways of irritable bowel syndrome (IBS), mainly in its post-infectious form (PI-IBS) 1. To date, untargeted therapeutic approaches have obtained conflicting results in patients with PI-IBS 2,3
Gut microbiome testing are emerging as a promising diagnostic tool to target microbiota and offer a personalized therapeutic strategy, but their real value is still unknown.
Aims & Methods
Our aim is to evaluate whether a personalized approach based on gut microbiome testing is an effective strategy for PI-IBS.
In this pilot study, we included consecutive patients with PI-IBS, diagnosed according to the Rome IV guidelines4, referring at our outpatient microbiome clinic in 2022.
All patients underwent a commercially available stool microbiome testing (XMICROGem from XBIOGem) based on 16S rRNA analysis and performed as already described5. Then, patients received a targeted therapy based on results of the gut microbiome testing, with the aim of restoring balance among the bacterial subpopulations of the gut microbiota. Non-adsorbable antibiotics were used to downregulate the abundance of pathobionts, while prebiotics and probiotics were given to boost the abundance of specific taxa and/or to compete with gut pathobionts. Patients were followed up to 12 weeks after the end of therapy.
We collected the following data of patients: age, gender, presence of gastrointestinal (GI) symptoms (assessed with the GSRS); specific characteristics of gut microbiome (alpha diversity, abundance of Proteobacteria, Firmicutes, Bacteroidetes, Bifidobacteria, Lactobacilli, Akkermansia, and short-chain fatty acid producers including Lachnospiraceae, Faecalibacterium, Roseburia, Butyrivibrio); specific therapy given after testing, including non-adsorbable antibiotics, prebiotics, and probiotic strains. The primary outcome was the resolution of at list one symptom, while secondary outcomes were the resolution of more than one (if present) and all of them at 12 weeks.
Results
Thirteen patients were enrolled in the study period (8 males, 5 females, mean age 31 years-old). Of them, 9 (69%) had IBS-D and 4 (31%) IBS-C. Nine patients (69%) had bloating, and 10 (71%) had abdominal pain at baseline. At gut microbiome testing: three (23%) patients presented with low alpha diversity, three (23%) with high abundance of Proteobacteria, five (38%) of Firmicutes. Seven (54%) patients presented with low abundance of SCFA-producing bacteria, eight (62%) of Akkermansia and nine (69%) of Bifidobacteria.
Patients were treated with the following non-adsorbable antibiotics: rifaximin in nine (69%) patients, and paromomicin in four (31%) patients. The following prebiotics and probiotic strains were used after antibiotics: multispecies probiotics in five patients (38%), Bifidobacterium-based probiotics in five patients (38%), Lactobacillus-based probiotics in eight patients (54%), and Escherichia coli Nissle 1917 in 2 (15%) patients; inulin and psyllium were used in nine (69%) patients.
At 12-week follow-up, 12 patients (93%) experienced an improvement of symptoms, with five of them (38%) experiencing a total remission of symptoms.
Conclusion
A precision medicine approach based on gut microbiome testing may be a promising strategy to treat PI-IBS. Well designed, randomized and larger studies are needed to confirm our preliminary findings.
References
1. Downs, I. A., Aroniadis, O. C., Kelly, L. & Brandt, L. J. Postinfection Irritable Bowel Syndrome: The Links Between Gastroenteritis, Inflammation, the Microbiome, and Functional Disease. J Clin Gastroenterol 51, 869–877 (2017).
2. Lee, Y. Y., Annamalai, C. & Rao, S. S. C. Post-Infectious Irritable Bowel Syndrome. Curr Gastroenterol Rep 19, 56 (2017).
3. Jin, Y. et al. Beneficial effects of Rifaximin in post-infectious irritable bowel syndrome mouse model beyond gut microbiota. J Gastroenterol Hepatol 33, 443–452 (2018).
4. Drossman, D. A. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features, and Rome IV. Gastroenterology 150, 1262-1279.e2 (2016).
5. De Maio, F. et al. Characterization of gut microbiota in patients with metabolic syndrome candidates for bariatric/metabolic surgery: Preliminary findings of a multi-center prospective study. Diabetes Res Clin Pract 180, 109079 (2021).
Disclosure
G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma.
A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai.
G.C. has received personal fees for acting as advisor for Ferring Therapeutics.
All other authors have no conflicts of interest to disclose.
