Is pollen‐food syndrome a frequent comorbidity in adults with irritable bowel syndrome?
Authors: Kirtika Patel, Gemma Vila‐Nadal, Jasmit Shah, Mohamed H. Shamji, Lorna Swan, Stephen R. Durham, Kinesh Patel, Isabel J. Skypala
Journal: Allergy (2020)

Irritable bowel syndrome (IBS) affects up to 10% of UK adults, 50% of whom may also have seasonal allergic rhinitis (SAR) and thus an increased risk of developing pollen-food syndrome (PFS) if sensitized to birch tree pollen.1-3 In an exploratory prospective controlled cohort study, we compared the prevalence of PFS in IBS subjects from a secondary care clinic diagnosed using the Rome IV criteria,4 with that of an age and gender-matched control group with another chronic health condition (congenital heart disease). The control group were chosen as they had a chronic health condition and a younger age demographic which matched the IBS group. The study received ethical and HRA approval (REC 17/NW0577, IRAS Reference: 229644), and all subjects gave written informed consent to take part. Both groups self-completed a validated PFS diagnostic questionnaire.3 The IBS case group alone also self-completed a food and symptom questionnaire, validated IBS and SAR questionnaires (Appendix S1), underwent skin prick testing (SPT) to aeroallergens, food reagents and fresh foods (ALK Abelló) (Appendix S1) and had a 10-mL blood sample collected and analysed for ImmunoCAP 112 ISAC (Thermo Fisher Scientific). Twenty-two of the 35 subjects in the IBS group (63%) reported hay fever; 10/22 (29%) were diagnosed with PFS. Ten control group subjects (29%) reported hay fever, none of whom were diagnosed with PFS (P = .008, Fisher's exact test). The IBS + PFS group had a significantly higher score for IBS severity, SAR and symptom severity compared to those with IBS alone (Appendix S2 and S3). There were no differences in IBS or SAR severity between those with IBS + SAR and IBS + SAR+PFS. When reporting symptoms and foods suspected, the most frequent foods to trigger symptoms in the whole IBS cohort were milk and wheat, predominantly provoking typical IBS symptoms of abdominal pain, bloating, vomiting and diarrhoea (Figure 1, Appendix S4). The IBS + PFS group were significantly more likely to report oropharyngeal symptoms such as tingle and numbness or itchy throat (P = .001), and reactions to kiwi, peach/nectarine and plum/apricot (Figure 1). None of the IBS subjects had a positive SPT to milk, and those with IBS alone were also not sensitized to wheat or the wheat allergens Tri a 14 and Tri a 19 (Appendix S5 and S6). However, 7/10 of the IBS + PFS cohort had a positive SPT to semolina (P > .001), six of whom also reported symptoms to wheat. The majority (86%) of IBS + PFS patients with a positive SPT to wheat reported symptoms to pasta rather than bread, with a modest correlation between a positive SPT to wheat and reported reactions to pasta but not bread (Spearman Rank r = 0.433, P = .009). The IBS + PFS cohort was also more likely to have positive SPT to raw potato (P = .001), hazelnut (P = .003), tomato (P = .017), cooked potato (P = .018), Timothy grass (P = .004), mixed grass (P = .007) and silver birch (P = .007, Fisher's exact test) (Appendix S5). Those with IBS + SAR+PFS were also significantly more likely to have positive SPT to the same foods (Appendix S5). The ISAC results showed that the majority (60%) of the IBS + PFS group were sensitized to PR10 allergens compared to 4% of those with IBS alone (Table 1). Of the four IBS + PFS subjects not sensitized to PR10 allergens, two were sensitized to thaumatin-like proteins (TLP), one of whom was also sensitized to profilins. Sensitization to other allergens was rare (Appendix S6). These data suggest individuals with IBS have a greater prevalence of PFS than the UK population level of 2%5 but larger studies are needed. Others have reported atopic subgroups in IBS populations, but it is unknown whether symptoms experienced by those with IBS and PFS are due to underlying immune responses.2, 6 The onset or exacerbation of IBS during the birch pollen season has been demonstrated to occur together with an increase in inflammatory cells in the duodenal mucosa of individuals with birch pollen allergy, which might explain increased severity of IBS symptoms in individuals with IBS and SAR.7 It is unclear what triggered the reported hay fever in the control group as no allergy tests were performed in this group, given their inclusion was solely to determine the prevalence of PFS. There was no selection bias as control subjects were recruited purely based on age and gender. Adults in the UK usually have PFS due to cross-reactivity between Bet v 1 in birch pollen and PR10 allergens; grass sensitization is linked to allergy to profilins, which are a common cause of PFS in other countries.2, 8 Out of the whole IBS cohort, only 3 IBS + PFS subjects had low level sensitization to profilins but not Phl p 12 (Timothy grass profilin). The 2 IBS + PFS subjects who had positive tests to the Kiwi TLP Act d 2 were not sensitized to Bet v 1 or PR10 proteins. The significance of these sensitization patterns is unclear. Cross-reactivity due to grass sensitization might explain why such a large percentage of this group had a positive test to semolina. However, only 4/7 IBS + PFS group had a positive SPT to both semolina and grass, and none of the IBS alone group had a positive semolina SPT despite 6/25 being grass sensitized. Thus, although not sensitized to Tri a 19, the wheat allergen most usually implicated in wheat allergy, the positive SPT to semolina suggests potential sensitization to other wheat allergens in some individuals with IBS + PFS, which might indicate an allergic component to symptoms. This finding might explain why wheat exclusion is an effective intervention for some patients with IBS.9 The strengths of this study were the use of validated questionnaires, and a matched control group, but it was underpowered to compare differences within the IBS group. In conclusion, our results suggest individuals with IBS have a high incidence of SAR and consequent PFS, with an increase in IBS severity in those with SAR as a comorbidity. Whether this association is causal could be tested by exploring whether dietary avoidance measures directed against PFS might have an impact on IBS symptoms, and/or test the impact of anti-allergic medication on IBS symptoms. The authors declare that they have no conflicts of interest. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.