3rd meeting of the federation of neurogastroenterology

Gut microbiota dysbiosis in IBS

Microbiota dysbiosis and its relation to irritable bowel syndrome (IBS) was discussed during various sessions of the conference. In particular, Pr. Magnus Simrén and Pr. Uday Ghoshal highlighted some features related to microbiota composition of IBS patients. Based on several studies, IBS patients have been shown to have a low microbial richness compared to healthy individuals, and Methanobacteriales may be undetected and methane production low in such patients [1].

Furthermore, a subset of IBS patients present dysbiosis with increased Firmicutes and Bacteroides enterotypes compared to healthy individuals with enriched Clostridiales and Prevotella enterotypes. However, an important question is not only which bacteria are associated with IBS but what they do in the gut and how they are involved in mechanisms of visceral hypersensitivity, neuro-motor dysfunction, increased permeability, and low-grade inflammation. Small intestine bacterial overgrowth (SIBO) may be the cause of IBS in some patients and a current challenge is to improve screening for these patients as upper gut aspirate culture is difficult to perform and not always available. The glucose hydrogen breath test may be used to identify such patients, and this would appear to be more accurate than the lactulose hydrogen breath test [2].

Gut microbiota modulation in IBS

Can the gut microbiome be changed for therapeutic purposes and could it relieve IBS symptoms? Options to modulate gut microbiota include antibiotics, probiotics, synbiotics, altering gut motility, dietary manipulation, fecal transplantation, and use of bacteriophages. These therapies were discussed in the presentations of Pr. Uday Ghoshal and Pr. Giovanni Barbara. A role for antibiotics is most apparent in IBS-patients with SIBO. Both norfloxacin and rifaximin are significantly more effective in reducing IBS symptoms in SIBO- positive than SIBO-negative patients.

In IBS patients without constipation, according to Target 1 and 2 studies, rifaximin relieves global IBS-symptoms, and bloating. Target 3 and further studies have shown that rifaximin can be used repeatedly in relapsing IBS-D without loss of effect or appearance of bacterial resistance [3, 4]. Moreover, rifaximin transiently reduces bacterial counts in the feces but it also seems to have an eubiotic effect increasing Lactobacillaceae abundance.

The low FODMAP diet seems to reduce symptoms in some IBS patients but it also results in lower Bifidobacterium counts in the feces. In IBS patients responding to a low FODMAP diet the dysbiosis index increases, thus responsiveness to the diet may be predicted by faecal bacterial profiles. The efficacy of fecal microbial transplantation in IBS remains controversial as this was demonstrated in only one of the two large randomized controlled studies [5, 6]. As stated by Pr. Giovanni Barbara, the American College of Gastroenterology, based on a meta-analysis of 53 randomized controlled trials, concluded that probiotics reduce global IBS symptoms as well as bloating and flatulence [7]. To be consolidated, this recommendation should be founded on new, high-quality data.

However, not all probiotics are similar. Bifidobacterium infantis was shown by prof. Eamonn Quigley to relieve abdominal pain, bloating, and bowel function and improve quality of life in patients with all IBS-subtypes, and this appears to have anti-inflammatory and immunomodulating properties reducing CRP and TNFα in conditions like psoriasis, chronic fatigue syndrome, and ulcerative colitis. Furthermore, preliminary results suggest that in combination with Bifidobacterium longum it might also relieve depression in patients with IBS.

The microbiome and gut-brain axis

Based on preclinical studies, products of gut bacteria have been shown to change brain responses to stimuli, however the challenge is to translate these studies to clinical relevance. Huiying Wang showed in her recent study that Bifidobacterium longum strain modulates brain activity during social stress (associated with a cyberball game) in healthy volunteers based on evaluation using magnetoencephalography and QOL questionnaires. Besides an effect on neural oscillations, the strain also enhances a feeling of vitality and reduces mental fatigue compared to placebo over a four-week follow-up period. Pr. Paul Enck described the relationship between stress or anxiety and IBS as two-way as the symptoms can be both the cause and result of IBS. Based on a study of patients with IBS, Bifidobacterium longum was shown to correlate with a decrease in depression and anxiety scores, but at onset, these scores were insufficiently high to establish a diagnosis of depression or anxiety [8]. Thus, it is more appropriate to state that this probiotic affects mood rather than depression or anxiety. Similar to Bifidobacterium longum, rifaximin has also been shown to modulate brain activity and increase relaxation and reduce anxiety during social stress based on a double blindedrandomized trial of healthy volunteers evaluated by magnetoencephalography [9].