• IRRITABLE BOWEL SYNDROME
• INTESTINAL BACTERIA
• INTESTINAL MICROBIOLOGY
• INTESTINAL BARRIER FUNCTION
• IMMUNOLOGY

Symptoms compatible with IBS, that is, abdominal pain and discomfort, bloating, abdominal distention and an erratic bowel function, are very common reasons for GI consultations in primary care1 and patients with IBS are one of the most frequent patient categories in gastroenterology outpatient clinics.2 Despite being very common and in spite of considerable research effort during the last decades, the pathophysiology of IBS is still considered to be complex and incompletely understood3 ,4 and even though our understanding of this disabling condition arguably has increased tremendously, we still cannot use knowledge from pathophysiology studies to subgroup IBS patients in a clinically meaningful way. In everyday clinical work, we still rely on subgrouping patients based on the predominant bowel habit when we decide how to manage and treat the patients.5 Even though we have new pharmacological treatment options targeting specific molecules in the GI tract,6–9 only a subset of patients will respond favourably when we choose patients based on the current imperfect system to subgroup patients, that is, into patients with predominant diarrhoea, constipation or mixed bowel habit.5 Ideally, clinical subgrouping based on the underlying pathophysiology should have the potential to lead to targeted therapy to the right patient groups, thereby improving treatment results. However, this has so far proven to be difficult to accomplish in IBS and other functional GI disorders.

Altered gut microbiota composition has recently been put forward as an important pathogenetic and pathophysiological factor in functional bowel disorders in general, and IBS in particular, and there are now several studies that demonstrate abnormal gut microbiota composition in IBS patients compared with controls10 by using modern culture-independent techniques.11 However, several of the earlier studies have included relatively small and heterogeneous groups of patients, and have not characterised the phenotype of the patients in great detail10 thereby making it impossible to define relevant subgroups. Recently, some studies have linked the gut microbiota characteristics of the patient with the clinical phenotype and the symptom pattern in larger groups of IBS patients12 ,13 providing hope that faecal microbial profiling may lead to the development of clinically useful IBS subgroups in the future. Jalanka-Tuovinen et al 14 provide further evidence supporting that determination of gut microbiota composition in faecal samples from well-characterised patients with IBS may be a better way to subgroup patients. In their elegant and comprehensive study, they included patients who were diagnosed with postinfectious IBS, that is, patients who had their IBS onset after a bout of gastroenteritis, the best characterised risk factor to develop IBS to date15 ,16 and compared their faecal microbiota composition with four other groups of subjects—healthy controls, diarrhoea-predominant IBS, and two groups of subjects with or without persisting bowel dysfunction 6 months after a gastroenteritis. The main finding was that they could identify a bacterial profile of 27 genus-like groups, providing an Index of Microbial Dysbiosis (IMD), which reliably could separate patient groups and controls, and the faecal microbiota of the postinfectious IBS patients resembled that of the IBS patients with diarrhoea predominance, suggesting a common pathophysiology. What is even more interesting is that the IMD correlated with intestinal symptoms, increased inflammation markers and compromised intestinal barrier, further implicating that the findings are of clinical and pathophysiological relevance. However, in line with another recent study,12 no association between the IMD and anxiety or depression could be demonstrated, which makes it tempting to speculate that future studies should try to stratify patients into those with a predominantly peripheral cause of their symptoms, such as microbe–host immune interactions, as opposed to those with a stronger central nervous system basis for their symptoms.

Several recent studies have demonstrated abnormal intestinal barrier function17 and a low-grade gut inflammation or immune dysfunction4 in IBS patients. In the current study by Jalanka-Tuovinen et al,14 several interesting associations between the faecal microbial profile of the patients and different immune markers were demonstrated, as well as with amino acids that are important for gut integrity, as they are important components of mucin18 and also with pathways regulating epithelial cell junctions. Based on these associations between the microbiota composition and the host expression pathways, the authors propose that the compromised intestinal barrier in IBS may underlie both immunological and microbiological abnormalities in postinfectious IBS and diarrhoea-predominant IBS, the two IBS subgroups included in this study. Moreover, the association between the microbial profile and the intestinal symptoms supports the relevance of these findings for the generation of symptoms in these patients. Furthermore, based on the current study14 and previous findings,12 psychological symptoms seem to be of importance for symptom generation in IBS by other pathways independent of gut microbiota composition (figure 1).

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Figure 1

Proposed model for symptom generation in postinfectious IBS and diarrhoea-predominant IBS based on the study by Jalanka-Tuovinen et al.14

To conclude, several lines of evidence, including the present study by Jalanka-Tuovinen et al,14 now support that gut microbiota alterations are of importance for at least some subgroups of IBS patients.10 Future studies should evaluate if we can use faecal microbial profiling in IBS patients together with other pathogenetic and pathophysiological measures to define clinically relevant subgroups to optimise management and treatment outcome in this large group of patients, where current treatment strategies are suboptimal. Whether a subgroup based on the IMD will constitute such a clinically meaningful subgroup remains to be proven, but based on the current study in Gut 14 it is tempting to speculate that this might be the case.