The bi-annual meeting “IBS days 2022”, organized by Dr. Giovanni Barbara and Dr. Vincenzo Stanghellini (University of Bologna) took place June 20-22nd. Leading experts of one of the most common and elusive disorders of the gastrointestinal tract, the Irritable Bowel Syndrome (IBS), got together under the scorching sun of Bologna. Within the beauty of the frescoed walls at the medieval Palazzo Re Enzo, we forgot about the last two years of pandemic, and fully immersed into the latest clinical diagnostic tools, therapeutic algorithms, and discovery research on Disorders of Gut-Brain Interaction (DGBI), including IBS.
From emphasizing proper patient-physician communication (Dr. Douglas Drossman, University of North Carolina, USA), reviewing the available and potential future biomarkers (Dr. Giovanni Barbara), to raising the intriguing hypothesis of a continuum between functional and organic disease (Dr. Eamon Quigley, Houston Methodist Hospital and Weill Cornell Medical College, USA), this meeting was packed with concepts useful to both the researcher and the clinician. Here are some of the topics discussed in this interesting meeting.
Food for thought on the underlying mechanisms of gut pain
Emerging evidence has started to elucidate the underlying drivers of gut pain. For instance, recent findings in mice and in humans revealed that a bacterial gut infection can change local immune responses in the gut, leading to certain foods being perceived as harmful and causing persistent gut pain driven by histamine release by mast cells. But there could also be a role for microbial histamine in inducing visceral hyperalgesia seen in IBS patients. I had the pleasure to present our work performed at McMaster University which discovered a novel interaction of microbes with fermentable carbohydrates leading to bacterial production of a key pain mediator, histamine. The findings may open the way to microbiome-directed therapies, either through a direct specific probiotic therapy or indirectly through dietary modifications, for this subset of IBS patients.
The role of intestinal and non-intestinal infections as triggers of IBS, had a prominent role in the discussions. Post-Infectious IBS (PI-IBS) was described decades ago as a very defined subset of IBS occurring after a gastrointestinal infection. Dr. Stephen Collins (McMaster University, Canada) presented data on Clostridioides difficile infection and onset of severe constipation. Dr. Giovanni Marasco (University of Bologna, Italy) showed extensive data on persistent gastrointestinal symptoms after COVID-19 infection and a potential rise of DGBI after the COVID-19 pandemic.
Extraintestinal comorbidities of IBS
Another central theme in the meeting was that of comorbidities and symptoms beyond the gastrointestinal tract in DGBI. Dr. Magnus Simren (University of Gothenburg, Sweden) reminded us of the significant impact that anxiety, depression, and somatic symptoms have in DGBI. Dr. Javier Santos (Vall d’Hebron University Hospital, Barcelona) explained the ambitious goals of the DISCOvERIE project: to study the link between anxiety and depression and IBS while identifying biomarkers for accurate and earlier diagnosis, prognosis, and management of patients. Dr. Premysl Bercik (McMaster University) presented novel data demonstrating that the initial gut microbiota-brain signalling is mediated by the innate immune system. Dr. Barbara reported that psychological and abdominal symptoms correlate with increased gut permeability in IBS patients with diarrhea (IBS-D), suggesting the lactulose/mannitol ratio could help discriminate between IBS-D patients and asymptomatic controls.
Diet and other available interventions for managing IBS-related symptoms
Dr. Elena Verdu (McMaster University, Canada) alerted about the widespread use of restrictive diets, such as the low FODMAP diet and the gluten-free diet, raising the importance of biomarker discovery for a more tailored use of these diets. To this end, she presented data on the use of non-specific IgG anti-gliadin antibodies which, after ruling out celiac disease and wheat allergy, could identify IBS patients that preferentially benefit from a reduction of gluten containing foods.
Dr. Robin Spiller (NIHR, Nottingham, UK) guided us through the impact of dietary fibers and fermentable carbohydrates on the gut microbiota, proposing that changes in microbial fermentation pathways to reduce gas production could potentially help patients with IBS.
Fecal microbiota transplantation (FMT) seems to be a topic of great interest in many meetings and given the importance of the microbiome and of infections in IBS, we heard an update on the many trials performed to date by Dr. Colleen Kelly (Alpert Medical School of Brown University, USA). While for C. difficile infections FMT does not seem to require donor selection or specific mode of delivery, for IBS, the data are not so clear. Moreover, long-COVID and the recent report that the virus can linger in our gut for longer than expected, remind us that donor screening is essential.
Why the traditional advice of “restricting diet according to digestive tolerance” needs to be revisited
One of the central themes was the role of diet, as a driver of symptoms in DGBI but also as part of its management. Dr. Francisco Guarner (Teknon Medical Center, Barcelona) cautioned that strict exclusion diets can destabilize our microbiome. For instance, a recent randomised cross-over small study showed that the number of anal gas evacuations and sensation of flatulence secondary to following the Mediterranean diet were less evident in individuals with a robust gut microbiome (higher stability). These findings suggest that the traditional advice of “restricting diet according to digestive tolerance” does not always work for everybody, as a more stable gut microbiome driven by a diet that usually includes plant-based foods leads to a better tolerance of digestive symptoms.
After two intense days of learning and deliberation, we return renewed to our laboratories and clinical practice with an increased knowledge and awareness of this debilitating condition, with the hope to make a difference for our patients. We look forward to the updates in next edition of the IBS days!
References for further reading:
Savarino E, Zingone F, Barberio B, et al. Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J. 2022. doi: 10.1002/ueg2.12259.
Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology. 2021; 160(1):99-114.e3. doi: 10.1053/j.gastro.2020.04.014.
Van den Houte K, Bercik P, Simren M, et al. Mechanisms Underlying Food-Triggered Symptoms in Disorders of Gut-Brain Interactions. Am J Gastroenterol. 2022; 117(6):937-946. doi: 10.14309/ajg.0000000000001812.