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Efficacy of diet restriction with or without probiotic for treatment of patients with IBS-D: Phase I-II clinical trial.
Zhao, XS, Shi, LJ, Ning, BL, Zhao, ZM, Li, XX, Zhu, MH, Zhang, YB, Fu, J
Immunity, inflammation and disease. 2023;11(5):e857
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Irritable bowel syndrome (IBS) is a functional intestinal disorder that can significantly affect quality of life. IBS patients suffer from intermittent abdominal pain/ discomfort, altered bowel habits, and abdominal bloating/distension. The aim of this study was to assess the effects of dietary restriction and probiotic use on IBS‐D patients. This study was a 2 × 2 factorial design, single‐centre, randomised trial. Phase 1 was a 12‐week dietary intervention, with 214 participants randomised to an IgG positive restricted diet (IgG res diet) or a control diet (cold/spicy/fried restricted). In Phase 2, 167 participants were randomised into either an IgG res diet + placebo or an IgG res diet + probiotic for 12 weeks. Symptom Severity Scale (IBS‐D‐SSS) and IgG titer were assessed at the beginning and the end of the study. Results showed that both diets reduced IBS‐D symptom severity scores and decreased immunoglobulin (IgG) antibody titer, although the IgG res diet had a greater impact. IBS symptom scores decreased with the addition of a Bifidobacterium probiotic along with dietary exclusion, however, IgG titers did not change with the probiotic compared to placebo. Authors concluded that diet restriction with appropriate and effective probiotics, provides greater symptom reductions for patients with IBS-D.
Expert Review
Conflicts of interest:
None
Take Home Message:
For individuals with IBDS-D:
- Establish IgG intolerances to foods and ensure an elimination diet remains nutritionally balanced
- Consider combining elimination diet with a Bifidobacterium supplement.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Irritable bowel syndrome (IBS) is a common functional intestinal disorder, affecting 5-20% of the population and diet is likely a major factor in its development as well as in its management. The aim of this study was to compare 3 dietary interventions and the use of a probiotic supplement in patients with IBS-diarrhoea dominant (IBS-D).
Methods
The study was conducted in 2 phases. The first was a 12-week 2 × 2 factorial design, randomised dietary intervention and included 224 patients (214 completed) with IBS-D. The diets were an Eastern/Chinese restriction diet, avoiding cold/raw, spicy and fried foods (CSF), the second avoided common allergens as determined by an IgG test (IgG diet, 14 foods tested), the third a combination of the two, whilst the control group continued their usual (Eastern/Chinese) diet.
The second phase was a 12-week randomised, double-blind, placebo-controlled trial comparing the CSF + IgG diet plus placebo with the CSF + IgG diet plus a 2 billion Bifidobacterium adolescentis supplement; this part included 202 patients of whom 169 completed the study.
The primary outcomes under observation were a reduction in IBS-D symptom severity Score (IBS-D-SSS) and IgG antibody titre (TigG).
Results
Phase 1: The IBS-D-SSS improved in all four groups from baseline (p<0.001), with the intervention groups improving significantly more than the control group (p<0.001). There was no statistically significant difference between the IgG and the IgG + CSF groups, although the authors considered there to be a synergistic effect. Statistically significant (p<0.001) reductions in TIgG were seen in all interventions, but not the control group.
Part 2: Significant (p<0.001) improvements in IBS-D-SSS were seen with both placebo and Bifidobacterium, although this was greater in the probiotic group (p<0.001). Improvements in TIgG were seen in both groups (p<0.001), with no difference between groups.
Conclusion
The authors concluded that the best intervention for patients with IBD-D is an IgG food elimination diet together with a Bifidobacterium probiotic supplement.
Clinical practice applications:
- Consider an elimination diet based on IgG testing for clients with IBS-D
- Consider combining elimination diet with a Bifidobacterium supplement. The dose used in this study was 4x 0.5 billion capsules of Bifidobacterium adolescentis
- Eliminating cold/raw, spicy and fried food could be an alternative to IgG elimination if the latter is not suitable for the client.
Considerations for future research:
- 45% and 35% of screened patients, respectively in the 2 phases of the study, were IgG negative. Screening for more potential food intolerances may extend the suitability of the approach to more patients
- Only a single strain probiotic was tested. Further research could evaluate other or combinations of Bifidobacteria strains in combination with an IgG elimination diet
- The mechanism(s) by which probiotics may affect symptoms of IBS-D are unknown. Adding stool microbiome analyses may shed further light on the effect of the intervention on the composition and function of the microbiome.
Abstract
BACKGROUND AND AIM Diet is a major contributor to irritable bowel syndrome (IBS) and is also a powerful tool for treatment of IBS. This study compared two diets and explored the effectiveness of the diets when combined with a probiotic for treatment of IBS-D patients. METHODS Phase I, patients were randomized into groups; control, cold/spicy/fried restricted diet (CSF res diet), IgG positive restricted diet (IgG res diet), and a combination both diets (CSF + IgG res diet). Phase II, patients were randomized into IgG res diet + placebo and IgG res diet + probiotic. Both interventions were 12 weeks in duration. Symptom Severity Scale (IBS-D-SSS) and IgG titer were assessed at the beginning and the end of the study. RESULTS Totals of 214 and 167 patients completed the two parts of the study, respectively. After intervention, IBS-D-SSS and TIgG grade were significantly improved compared to baseline, with results similar to the control group. In general, there were decreases in IBS-D-SSS and TIgG grade that were significantly different among the groups. There were exceptions; no differences were observed for IBS-D-SSS between the IgG res diet and CSF + IgG res diet, or TIgG grade between the CSF res diet, IgG res diet, and CSF + IgG res diet. However, the CSF res diet and IgG res diet had a synergistic effect that decreased IBS-D-SSS and TIgG titer, with a greater contribution by the IgG res diet. Therefore, we evaluated the IgG res diet with either placebo or probiotic and found that IBS-D-SSS and TIgG grade decreased from baseline. There was a significant decrease in IBS-D-SSS with the probiotic but TIgG grade was not significantly different between the IgG diet + placebo and IgG diet + probiotic diet. CONCLUSIONS Both the CSF res diet and IgG res diet improved IBS symptoms and demonstrated synergy, although the IgG res diet had a greater contribution. Further, when intolerant foods cannot be eliminated from a diet, avoiding uncooked, cold, spicy, fried, and alcoholic foods is a superior choice. The IgG res diet combined with Bifidobacteria was the best dietary choice and may function though a non-IgG pathway.
2.
Chronic Food Antigen-specific IgG-mediated Hypersensitivity Reaction as A Risk Factor for Adolescent Depressive Disorder.
Tao, R, Fu, Z, Xiao, L
Genomics, proteomics & bioinformatics. 2019;17(2):183-189
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The prevalence of major depressive disorder (MDD) among adolescents has been on the rise recently. A high level of systemic low-grade inflammation is found in the serum of MDD adults, which is believed to interfere with neurotransmitter metabolism, resulting in symptoms of depression. Furthermore, disruption of the blood-brain barrier may inhibit neurotransmitter metabolism. One hundred and eighty-four adolescents with moderate MDD were evaluated against the same number of healthy controls to determine their serum levels of markers of inflammation, homocysteine, food sensitivity, histamine, and histamine metabolism. The study found that histamine levels and food antigen-specific antibodies in MDD adolescent patients were significantly higher than those in the control group. Increasing histamine levels, food-specific IgG levels, and S100 calcium-binding protein B levels suggest blood-brain barrier leakage may contribute to adolescent depression. There is still much to be learned about the pathophysiology of MDD, and further studies are needed to elucidate the mechanisms involved. The results of this study can be used by healthcare professionals to understand the role of histamine and food sensitivities in the development of adolescent depression rather than low-grade inflammation.
Abstract
Major depressive disorder (MDD) is the most common nonfatal disease burden worldwide. Systemic chronic low-grade inflammation has been reported to be associated with MDD progression by affecting monoaminergic and glutamatergic neurotransmission. However, whether various proinflammatory cytokines are abnormally elevated before the first episode of depression is still largely unclear. Here, we evaluated 184 adolescent patients who were experiencing their first episode of depressive disorder, and the same number of healthy individuals was included as controls. We tested the serum levels of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), IgE, 14 different types of food antigen-specific IgG, histamine, homocysteine, S100 calcium-binding protein B, and diamine oxidase. We were not able to find any significant differences in the serum levels of hs-CRP or TNF-α between the two groups. However, the histamine level of the patients (12.35 μM) was significantly higher than that of the controls (9.73 μM, P < 0.001, Mann-Whitney U test). Moreover, significantly higher serum food antigen-specific IgG positive rates were also found in the patient group. Furthermore, over 80% of patients exhibited prolonged food intolerance with elevated levels of serum histamine, leading to hyperpermeability of the blood-brain barrier, which has previously been implicated in the pathogenesis of MDD. Hence, prolonged high levels of serum histamine could be a risk factor for depressive disorders, and antihistamine release might represent a novel therapeutic strategy for depression treatment.
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Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches.
Mitchell, N, Hewitt, CE, Jayakody, S, Islam, M, Adamson, J, Watt, I, Torgerson, DJ
Nutrition journal. 2011;10:85
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The exact causes of migraine are unknown, but it is thought that it may be a culmination of several different factors, such as stress, altered sleep patterns, weather and hypersensitivity to foods. Testing for food intolerances is a challenging process and several methods can be employed to test. This study aimed to determine the effectiveness of using a type of testing known as the enzyme linked immune-sorbent assay (ELISA), which tests the body’s delayed immune reaction to foods, and whether eliminating foods based on results from this test would help migraine sufferers. The results showed that 4 weeks of eliminating foods based on the ELISA test decreased migraines, however this was not sustained to 12 weeks of food elimination. It was concluded that in the short-term, eliminating foods based on results from the ELISA decreased headache frequency, but this could not be sustained long-term. This study could be used by healthcare professionals to understand that diet elimination based on measuring the body’s delayed immune response may have limited effects on migraines.
Abstract
BACKGROUND Research suggests that food intolerance may be a precipitating factor for migraine like headaches. AIM: To evaluate the effectiveness of the ELISA (Enzyme Linked Immuno-Sorbent Assay) Test and subsequent dietary elimination advice for the prevention of migraine like headaches. DESIGN Randomised controlled trial. SETTING Community based volunteers in the UK. PARTICIPANTS Volunteers who met the inclusion criteria for migraine like headaches and had one or more food intolerance were included in the study. Participants received either a true diet (n = 84) or a sham diet (n = 83) sheet. Participants were advised to remove the intolerant foods from their diet for 12 weeks. MAIN OUTCOME MEASURES Number of headache days over a 12 week period (item A MIDAS questionnaire). Other measures includes the total MIDAS score and total HIT-6 score. RESULTS The results indicated a small decrease in the number of migraine like headaches over 12 weeks, although this difference was not statistically significant (IRR 1.15 95% CI 0.94 to 1.41, p = 0.18). At the 4 week assessment, use of the ELISA test with subsequent diet elimination advice significantly reduced the number of migraine like headaches (IRR 1.23 95%CI 1.01 to 1.50, p = 0.04). The disability and impact on daily life of migraines were not significantly different between the true and sham diet groups. CONCLUSIONS Use of the ELISA test with subsequent diet elimination advice did not reduce the disability or impact on daily life of migraine like headaches or the number of migraine like headaches at 12 weeks but it did significantly reduce the number of migraine like headaches at 4 weeks.
4.
Clinical relevance of IgG antibodies against food antigens in Crohn's disease: a double-blind cross-over diet intervention study.
Bentz, S, Hausmann, M, Piberger, H, Kellermeier, S, Paul, S, Held, L, Falk, W, Obermeier, F, Fried, M, Schölmerich, J, et al
Digestion. 2010;81(4):252-64
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Environmental factors are thought to play a part in the development of or exacerbation of symptoms in Crohn's disease (CD), and patients often implicate food as a contributing factor. Immunoglobulin E (IgE) food reactions can be rare in IBD and immunoglobulin G (IgG) testing can be controversial, this study set out to compare IgG antibody reactions in 79 CD patients and 20 healthy individuals. The pilot study measured IgG levels against 271 foods in the blood. It then went on to measure stool frequency, abdominal pain and general well-being following a 6 week specific elimination diet (based on foods identified by the IgG testing) or a 6 week sham diet. 23 participants were included in the follow on 12 week, cross-over double blinded study. Eosinophil-derived neurotoxin (EDN) in stool was also measured to evaluate disease activity. The pilot study showed a significantly higher IgG reaction in the CD patients. In the follow-up study there was a decrease in stool frequency, abdominal pain and general well-being during the specific diet compared to the sham diet. EDN was found to decrease in both the specific and sham diet. It was concluded that IgG antibodies may contribute to CD but the mechanism is still not clear.
Abstract
BACKGROUND Environmental factors are thought to play an important role in the development of Crohn's disease (CD). Immune responses against auto-antigens or food antigens may be a reason for the perpetuation of inflammation. METHODS In a pilot study, 79 CD patients and 20 healthy controls were examined for food immunoglobulin G (IgG). Thereafter, the clinical relevance of these food IgG antibodies was assessed in a double-blind cross-over study with 40 patients. Based on the IgG antibodies, a nutritional intervention was planned. The interferon (IFN)gamma secretion of T cells was measured. Eosinophil-derived neurotoxin was quantified in stool. RESULTS The pilot study resulted in a significant difference of IgG antibodies in serum between CD patients and healthy controls. In 84 and 83% of the patients, respectively, IgG antibodies against processed cheese and yeast were detected. The daily stool frequency significantly decreased by 11% during a specific diet compared with a sham diet. Abdominal pain reduced and general well-being improved. IFNgamma secretion of T cells increased. No difference for eosinophil-derived neurotoxin in stool was detected. CONCLUSION A nutritional intervention based on circulating IgG antibodies against food antigens showed effects with respect to stool frequency. The mechanisms by which IgG antibodies might contribute to disease activity remain to be elucidated.
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Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics.
Drisko, J, Bischoff, B, Hall, M, McCallum, R
Journal of the American College of Nutrition. 2006;25(6):514-22
Abstract
OBJECTIVE In Irritable Bowel Syndrome, the gut-associated immune system may be up-regulated resulting in immune complex production, low-grade inflammation, loss of Class I bacteria, and translocation of inflammatory mediators and macromolecules outside of the GI lumen. Since food intolerance may be one of the reasons for this upregulation, our goal was to investigate the role of food intolerance in IBS patients. METHODS In this open label pilot study, we enrolled 20 patients with IBS by Rome II criteria (15 women, ages 24-81) who had failed standard medical therapies in a tertiary care GI clinic. Baseline serum IgE and IgG food and mold panels, and comprehensive stool analysis (CSA) were performed. Breath-hydrogen testing and IBS Quality-of-Life (QOL) questionnaires were obtained. Patients underwent food elimination diets based on the results of food and mold panels followed by controlled food challenge. Probiotics were also introduced. Repeat testing was performed at 6-months. We followed up with this cohort at 1 year after trial completion to assess the reported intervention and for placebo effect. RESULTS Baseline abnormalities were identified on serum IgG food and mold panels in 100% of the study subjects with significant improvement after food elimination and rotation diet (p < 0.05). Significant improvements were seen in stool frequency (p < 0.05), pain (p < 0.05), and IBS-QOL scores (p < 0.0001). Imbalances of beneficial flora and dysbiotic flora were identified in 100% of subjects by CSA. There was a trend to improvement of beneficial flora after treatment but no change in dysbiotic flora. The 1-year follow up demonstrated significant continued adherence to the food rotation diet (4.00 +/- 1.45), minimal symptomatic problems with IBS (4.00 +/- 1.17), and perception of control over IBS (4.15 +/- 1.23). The continued use of probiotics was considered less helpful (3.40 +/- 1.60). CONCLUSION These data demonstrate that identifying and appropriately addressing food sensitivity in IBS patients not previously responding to standard therapy results in a sustained clinical response and impacts on overall well being and quality of life in this challenging entity.