Long-term response to gluten-free diet as evidence for non-celiac wheat sensitivity in one third of patients with diarrhea-dominant and mixed-type irritable bowel syndrome
Barmeyer C, Schumann M, Meyer T et al.
Int J Colorectal Dis. 2016. DOI 10/1007/s00384-016-2663-x
Irritable bowel syndrome (IBS) is a common functional bowel disorder with a recognized social and economic impact due to the associated reduced quality of life and high rates of IBS-related non-productive time.
Int J Colorectal Dis. 2016. DOI 10/1007/s00384-016-2663-x
Irritable bowel syndrome (IBS) is a common functional bowel disorder with a recognized social and economic impact due to the associated reduced quality of life and high rates of IBS-related non-productive time.
New evidence finds that subgroups of IBS patients may be “gluten sensitive” and could therefore respond to a gluten-free diet (GFD) even in the absence of the histological abnormalities characteristic of celiac disease (CD). This led to the concept of two new disorders called “non-celiac gluten sensitivity” (NCGS) and “non-celiac wheat sensitivity” (NCWS).
The authors previously reported patients with IBS-D (mostly diarrhea), carrying HLA-DQ2/8 allele (HLA class II genes associated with CD), benefited from being on a GFD for 6 months in an open-uncontrolled trial. The authors therefore speculated that HLA-DQ2 could be a useful marker to identify a subgroup of gluten-sensitive IBS patients who benefit from a GFD.
The aim of this study was to analyse if HLA-DQ2 and DQ8 are suitable markers for the diagnosis of wheat sensitivity (WS) and to evaluate the long-term clinical response to a GFD in a defined cohort of patients with IBS-D and IBS-M (mixed type with diarrhea and constipation).
91 subjects (>18 years of age) fulfilled the primary inclusion criteria (ROME III criteria—reflecting current understanding of IBS, and self-reported weekly symptoms) for IBS-D or IBS-M and were eligible to enter a 4-week observation period without any intervention. At the end of each week, the “Subject’s Global Assessment” (SGA) of relief was determined. The SGA asks the subject to rate the relief from their symptoms during the past week compared to the way they felt prior to entering the study. Five different answers were available and subjects who answered “unchanged” or “worse” at all four time points, underwent diagnostic tests to exclude other medical conditions. 45 subjects did not finish the observation period; 15 of these were due to “significant improvement” or “symptoms less than once a week”; 30 due to other reasons; and, 11 dropped out due to a new diagnosis: CD (n=3), lactose intolerance (n=3), pregnancy (n=1), erosive duodenitis (n=1), giardiasis (n=1), and mastocytosis (n=1).
35 subjects (15 IBS-D and 20 IBS-M) entered the study and received two dietary consultations from registered dietitians at an interval of two weeks; the first to educate subjects on a GFD and the second to ascertain adherence to a GFD. Subjects were then monitored for 4 months by a weekly assessment of the SGA of relief via phone calls. For the SGA, those who answered “considerably relieved” or “completely relieved’’ on at least 75% of the weeks over the 4 month dietary intervention were defined as responders (R75), taking into account both magnitude and persistence of effect. The stricter requirement of 75% of time (vs 50% of time commonly used) was used as it was assumed symptoms would disappear with a GFD when WS was their primary cause. However, the weaker response criterion of 50% of the time (R50) was used as a secondary outcome measure. Other secondary outcomes measures included changes in the score of the IBS-QOL, IBS-SSS, and EQ-5D questionnaires and changes in pain intensity, stool consistency, and stool frequency before and at the end of the study. Prior to the dietary intervention, blood was collected for genotyping and determination of HLA-DQ2/8 status followed dietary intervention to avoid bias. At the end of the study period, subjects were followed up at 1 year to determine their long-term dietary habits and ongoing symptom relief.
Patient Characteristics
The study found that 40% of the study population was positive for HLA-DQ2 or DQ8; a slightly higher proportion than in the general population. A significantly higher proportion of HLA-DQ2/8 positive subjects was observed in the IBS-M group compared with the IBS-D group (n=10 (50%) vs n=4 (27%). 94% (33/35 subjects) adhered to a GFD for the study period; two IBS-M subjects dropped out between 4-6 weeks, one due to increased symptom severity (HLA-DQ2 +ve) and one due to commencement of treatment for another condition (HLA-DQ 2/8 –ve). Both were classed as non-responders.
The authors previously reported patients with IBS-D (mostly diarrhea), carrying HLA-DQ2/8 allele (HLA class II genes associated with CD), benefited from being on a GFD for 6 months in an open-uncontrolled trial. The authors therefore speculated that HLA-DQ2 could be a useful marker to identify a subgroup of gluten-sensitive IBS patients who benefit from a GFD.
The aim of this study was to analyse if HLA-DQ2 and DQ8 are suitable markers for the diagnosis of wheat sensitivity (WS) and to evaluate the long-term clinical response to a GFD in a defined cohort of patients with IBS-D and IBS-M (mixed type with diarrhea and constipation).
91 subjects (>18 years of age) fulfilled the primary inclusion criteria (ROME III criteria—reflecting current understanding of IBS, and self-reported weekly symptoms) for IBS-D or IBS-M and were eligible to enter a 4-week observation period without any intervention. At the end of each week, the “Subject’s Global Assessment” (SGA) of relief was determined. The SGA asks the subject to rate the relief from their symptoms during the past week compared to the way they felt prior to entering the study. Five different answers were available and subjects who answered “unchanged” or “worse” at all four time points, underwent diagnostic tests to exclude other medical conditions. 45 subjects did not finish the observation period; 15 of these were due to “significant improvement” or “symptoms less than once a week”; 30 due to other reasons; and, 11 dropped out due to a new diagnosis: CD (n=3), lactose intolerance (n=3), pregnancy (n=1), erosive duodenitis (n=1), giardiasis (n=1), and mastocytosis (n=1).
35 subjects (15 IBS-D and 20 IBS-M) entered the study and received two dietary consultations from registered dietitians at an interval of two weeks; the first to educate subjects on a GFD and the second to ascertain adherence to a GFD. Subjects were then monitored for 4 months by a weekly assessment of the SGA of relief via phone calls. For the SGA, those who answered “considerably relieved” or “completely relieved’’ on at least 75% of the weeks over the 4 month dietary intervention were defined as responders (R75), taking into account both magnitude and persistence of effect. The stricter requirement of 75% of time (vs 50% of time commonly used) was used as it was assumed symptoms would disappear with a GFD when WS was their primary cause. However, the weaker response criterion of 50% of the time (R50) was used as a secondary outcome measure. Other secondary outcomes measures included changes in the score of the IBS-QOL, IBS-SSS, and EQ-5D questionnaires and changes in pain intensity, stool consistency, and stool frequency before and at the end of the study. Prior to the dietary intervention, blood was collected for genotyping and determination of HLA-DQ2/8 status followed dietary intervention to avoid bias. At the end of the study period, subjects were followed up at 1 year to determine their long-term dietary habits and ongoing symptom relief.
Patient Characteristics
The study found that 40% of the study population was positive for HLA-DQ2 or DQ8; a slightly higher proportion than in the general population. A significantly higher proportion of HLA-DQ2/8 positive subjects was observed in the IBS-M group compared with the IBS-D group (n=10 (50%) vs n=4 (27%). 94% (33/35 subjects) adhered to a GFD for the study period; two IBS-M subjects dropped out between 4-6 weeks, one due to increased symptom severity (HLA-DQ2 +ve) and one due to commencement of treatment for another condition (HLA-DQ 2/8 –ve). Both were classed as non-responders.
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