The Overlap of Irritable Bowel Syndrome and Noncoeliac Gluten Sensitivity

Anupam Rej; David S. Sanders


Curr Opin Gastroenterol. 2019;35(3):199-205. 

In This Article

The Overlap of Noncoeliac Gluten Sensitivity and Irritable Bowel Syndrome

There appears to be a significant overlap between individuals with NCGS and IBS. It appears that a large proportion of individuals presenting with IBS have sensitivity to wheat. This was highlighted in a large study of 920 patients with IBS, fulfilling the Rome II criteria. 276 of these patients (30%) were noted to be asymptomatic on an elimination diet, followed by symptoms on DBPC challenge.[16] Interestingly, individuals who were noted to be wheat sensitive were noted to have a higher frequency of anaemia, weight loss, co-existing atopy and food allergy in infancy versus IBS controls. These findings may help to distinguish between IBS and NCGS. However, caution must be taken when interpreting this, as findings such as weight loss and anaemia may be a result of self-implemented restrictive diets by patients with NCGS, rather than NCGS itself.[16]

As a result of a lack of biomarkers for NCGS, the Salerno experts' criteria[36] have set out a diagnostic protocol to formalise the diagnosis of NCGS, as seen in Figure 2. This involves performing a double-blind placebo-controlled (DBPC) gluten (8 g/day) challenge to make the diagnosis. The first DBPC trial assessing the performance of the Salerno experts' criteria was by Elli et al..[37] This study, evaluating 98 patients with functional gastrointestinal symptoms identified 14% of patients to have NCGS, responding to gluten withdrawal and relapse during re-challenge. A systematic review and meta-analysis[38] of 11 studies of NCGS demonstrated an overall pooled percentage of relapsing after a gluten challenge at 30%. Interestingly, the percentage of relapse was not significantly different between placebo and gluten. This would suggest that responses seen to a gluten re-challenge may be a nocebo response. However, when the gluten challenge was applied via the Salerno experts' criteria, there were a higher number of patients relapsing on gluten versus placebo (40 versus 24%, P = 0.003).[38] This may suggest that individuals with NCGS are likely to be identified in patients presenting with IBS-type symptoms via the use of the Salerno experts' criteria.

Figure 2.

Overview of Salerno experts' criteria. CD, coeliac disease; GCD, gluten-containing diet; GFD, gluten free diet; WA, wheat allergy. Adapted from [36].

Whilst the Salerno experts' criteria have enabled NCGS to be formally diagnosed, this may not be practical to implement in clinical practice. Many individuals who note that gluten causes symptoms are unlikely to undergo a gluten challenge. Also, issues remain with diagnosis, as several different study designs are used, as well as individuals having an anticipatory nocebo response, which may affect the reported prevalence. Further research is required to understand the pathophysiological basis of NCGS and identification of biomarkers to help aid diagnosis and distinguish between IBS.

There is now emerging evidence that individuals with IBS also may have sensitivity to gluten, with evidence to support a GFD in these patients. A RCT in 45 patients with IBS-D,[23] where patients were placed on a 4-week GFD or GCD, demonstrated an increased number of bowel movements per day on a GCD versus GFD (P = 0.04). A prospective study in 41 patients with IBS-D,[39] evaluating a 6-week GFD demonstrated a reduction in IBS Symptom Severity Score (IBS-SSS) from 286 to 131 on a GFD (P < 0.001). There have been several trials evaluating gluten in IBS and NCGS, as seen in Table 1.

A double-blind crossover trial in 59 individuals with self-reported NCGS,[40] noted a significant increase in gastrointestinal symptom rating scale (GSRS) score in those consuming fructans versus gluten (P = 0.049). This may suggest that fructans is the causal agent for symptoms rather than gluten. However, it has also been highlighted in the literature[5] that FODMAPs as a whole are unlikely to be purely responsible for symptoms experienced by NCGS patients, as individuals improve on a GFD, despite receiving FODMAPs from other sources outside wheat, such as legumes. Also, extraintestinal manifestations of NCGS cannot be explained by the mechanism of action of FODMAPs.

Currently, trials evaluating gluten in NCGS and IBS are heterogeneous, with different gluten amounts used for studies, different study durations, different end points, as well as different geographical locations. Robust study designs are required to help identify which components of wheat are responsible for symptom generation in IBS and NCGS. However, designing dietary trials remains challenging,[41] although recommendations have been set out to help aid this.[41,42]