Food-Based Interventions as Therapy for Inflammatory Bowel Disease: Important Steps in Diet Trial Design and Reporting of Outcomes.

Diet therapy for inflammatory bowel disease (IBD) is an international research priority but guidance for IBD-specific diet trial design is lacking. This review critically evaluates key elements of prospective IBD food-based intervention trials and identifies gaps. Electronic databases were searched for interventional IBD diet studies. Prospective primary studies/trials were included if used food-based dietary strategies. Forty studies/trials evaluating 29 food-based strategies as therapy for IBD were identified. Considerable heterogeneity in diets, trial design, and methodology exists. Thirty-one trials (78%) intended the diet to modulate inflammation but 14/31 (46%) did not have a primary endpoint measuring an objective change in inflammatory activity and 20/31 (65%) controlled for medication stability prior to application of diet at baseline. Higher-quality IBD diet trials used symptom-based assessment tools coupled with an objective evaluation of inflammatory activity. Dietary advice trials are the most common. One-third of trials developed and administered diet education without a dietitian. Evaluation and reporting on adherence to diet therapy occurred in <60% of trials. Failure to include or report on key elements of trial design reduced the interpretability and validity of the results. This is a considerable limitation to advancing scientific knowledge in this area. Diet therapy trials should adhere to similar rigorous quality standards used to develop other IBD therapies. Therefore, a set of practical recommendations was generated to provide the authors' perspective to help inform the future design of high-quality IBD diet trials.

High-quality inflammatory bowel disease (IBD) diet trials are lacking and existing trials are fraught with methodological flaws. This review is intended to assist clinician-researchers in the design and conduct of future food-based intervention trials to raise the quality of IBD diet research.

Acceptance and Commitment Therapy for Adults Living With Inflammatory Bowel Disease and Distress: A Randomized Controlled Trial.

INTRODUCTION: The bidirectional relationship between disease activity and mental health in inflammatory bowel disease (IBD) has prompted investigations into the efficacy of psychotherapeutic interventions such as acceptance and commitment therapy (ACT) on biopsychosocial outcomes. We aimed to examine the efficacy of an ACT program (intervention) in comparison with a cognitive behavioral therapy-informed psychoeducation program (active control) for individuals with IBD and coexistent psychological distress. Both programs were delivered online through a hybrid format (i.e., therapist-led and participant-led sessions). METHODS: A total of 120 adults with IBD were randomized to either the intervention (N = 61) or active control groups (N = 59). Efficacy was determined using linear mixed models for group differences, in rate of changes in study outcomes, between baseline, postintervention, and 3-month follow-up. RESULTS: The primary outcome health-related quality of life significantly improved in the intervention group when compared with the active control group, with a significantly different rate of change observed from baseline to postintervention ( t [190] = 2.15, P = 0.033) in favor of the intervention group with a medium effect size (ß = 0.41, mean difference = 0.07, 95% confidence interval 0.01-0.12, P = 0.014). Similarly, the secondary outcome Crohn's disease activity significantly reduced in the intervention group when compared with the active control group, with a significantly different rate of change observed from baseline to 3-month follow-up ( t [90] = -2.40, P = 0.018) in favor of the intervention group with a large effect size (ß = -0.77, mean difference = -9.43, 95% confidence interval -13.72 to -5.13, P < 0.001) ( P = 0.014). Furthermore, when observing the rate of change in outcomes over time for the groups separately, anxiety symptoms and pain significantly improved in the intervention group only, and conversely, ulcerative colitis activity and stress symptoms significantly improved in the active control group only. All other outcomes (N = 14) significantly improved over time in both groups including IBD activity, gastrointestinal unhelpful thinking patterns, visceral anxiety, fatigue interference, fatigue severity, fatigue frequency, psychological inflexibility, self-efficacy, resilience, current health status, depression symptoms, IBD control, and pain catastrophizing; however, these changes were not significantly different between the groups. DISCUSSION: Both programs were of benefit to people with IBD and distress. However, ACT offers a significant added benefit for health-related quality of life and self-reported Crohn's disease activity and may be a useful adjuvant therapy in integrated IBD care.

Review article: Evidence-based dietary management of inflammatory bowel disease.

BACKGROUND: Dietary management of patients with inflammatory bowel disease (IBD) involves more than defining a therapeutic diet. The profusion of 'expert advice' is not necessarily built on evidence. AIMS: To provide evidence-based guidance on all clinically relevant aspects of nutritional and dietary management of patients with IBD. METHODS: A comprehensive review of the published literature was made. RESULTS: Four pillars of management should be considered in all patients. First, nutritional status should be optimised, since myopenia and visceral obesity are associated with poorer outcomes, which can be improved with attention to their correction. Accurate point-of-care measurement of body composition is advocated to identify problems, guide interventions and monitor outcomes. Second, exclusive enteral nutrition and the Crohn's Disease Exclusion Diet with partial enteral nutrition in reducing intestinal inflammation in patients with Crohn's disease have sufficient evidence to be advocated. Multiple other dietary approaches, while promising, have insufficient evidence to be recommended. Third, dietary approaches are important in symptomatic control in many non-inflammatory scenarios. Finally, guidance on following a healthy diet is fundamental to the general health of patients. Multiple approaches are advocated, but the optimal strategy is unclear. The precarious nutritional status of patients with IBD together with the risks of nutritional inadequacy and maladaptive eating behaviours associated with restrictive diets dictate involvement of expert dietitians in assessment and personalised delivery of dietary interventions. CONCLUSIONS: Four pillars of nutritional management require specific assessment and interventional strategies that should be chosen by evidence. Optimal delivery requires the skills of a specialised dietitian.

Recent advances in measuring the effects of diet on gastrointestinal physiology: Probing the "leaky gut" and application of real-time ultrasound.

There is a large pool of ideas in both mainstream and non-mainstream medicine on how diet can be manipulated in order to treat or prevent illnesses. Despite this, our understanding of how specific changes in diet influence the structure and function of the gastrointestinal tract is limited. This review aims to describe two areas that might provide key information on the integrity and function of the gastrointestinal tract. First, demystifying the "leaky gut syndrome" requires rational application and interpretation of tests of intestinal barrier function. Multiple ways of measuring barrier function have been described, but the inherent difficulties in translation from animal studies to humans have created misinterpretations and misconceptions. The intrinsic nature of intestinal barrier function is dynamic. This is seldom considered in studies of intestinal barrier assessment. To adequately understand the effects of dietary interventions on intestinal barrier function, background barrier function in different regions of the gut and the dynamic responses to stressors (such as psychological stress) should be assessed as a minimum. Second, intestinal ultrasound, which is now established in the assessment and monitoring of inflammatory bowel disease, has hitherto been poorly evaluated in assessing real-time intestinal function and novel aspects of structure in patients with disorders of gut-brain interaction. In conclusion, a more complete functional and structural profile that these investigations enable should permit a greater understanding of the effects of dietary manipulation on the gastrointestinal tract and provide clinically relevant information that, amongst other advantages, might permit opportunities for personalized health care delivery.

Recent advances in measuring the effects of diet on gastrointestinal physiology: Sniffing luminal gases and fecal volatile organic compounds.

Despite the huge pool of ideas on how diet can be manipulated to ameliorate or prevent illnesses, our understanding of how specific changes in diet influence the gastrointestinal tract is limited. This review aims to describe two innovative investigative techniques that are helping lift the veil of mystery about the workings of the gut. First, the gas-sensing capsule is a telemetric swallowable device that provides unique information on gastric physiology, small intestinal microbial activity, and fermentative patterns in the colon. Its ability to accurately measure regional and whole-gut transit times in ambulant humans has been confirmed. Luminal concentrations of hydrogen and carbon dioxide are measured by sampling through the gastrointestinal tract, and such application has enabled mapping of the relative amounts of fermentation of carbohydrates in proximal-versus-distal colon after manipulation of the types and amounts of dietary fiber. Second, changes in the smell of feces, via analysis of volatile organic compounds, occur in response to the diet, and by the presence and therapy of irritable bowel syndrome and inflammatory bowel disease. Such information is likely to aid our understanding of what dietary change can do to the colonic luminal microenvironment, and may value-add to diagnosis and therapeutic design. In conclusion, such methodologies enable a more complete physiological profile of the gastrointestinal tract to be created. Systematic description in various cohorts and effects of dietary interventions, particularly when co-ordinated with the analysis of microbiome, are needed.

The effect of dietary emulsifiers and thickeners on intestinal barrier function and its response to acute stress in healthy adult humans: A randomised controlled feeding study.

BACKGROUND: Although dietary emulsifiers are implicated in the pathogenesis of Crohn's disease, their effect has not been studied in humans. AIM: To determine the effects of high- and low-emulsifier diets (HED, LED) on intestinal barrier function in healthy subjects in unstressed and acutely stressed states. METHODS: We conducted a single-blinded, cross-over, controlled feeding trial in 22 healthy adults. After recording 7 days of their habitual diet, we randomised participants to HED or LED with ≥3-week washout between diets. On dietary completion, acute stress was induced via intravenous corticotrophin-releasing hormone. We assessed dietary adherence, effects on 2-h urinary lactulose: rhamnose ratio (LRR), serum concentrations of lipopolysaccharide-binding protein, soluble-CD14 and markers of epithelial injury and inflammation. RESULTS: Dietary adherence was excellent. In an unstressed state, median (interquartile range) LRR during HED was 0.030 (0.018-0.042); on LED, this was 0.042 (0.029-0.078; p = 0.04). LPB concentrations were lower on HED than LED (p = 0.026), but no differences were observed for epithelial injury or inflammation. Under acute stress, LRR increased by 89% (-1% to 486%) on HED (p = 0.004), differing (p = 0.001) from 39% (1%-90%) decrease on LED (p = 0.009). Soluble-CD14 also increased (p < 0.001). The LED had a prolonged carry-over effect on suppressing HED-induced changes during stress. Similar changes in LRR and soluble-CD14 were observed when HED was used as the first diet (both p < 0.01). CONCLUSION: High intake of emulsifiers improved barrier function in the unstressed state, but increased intestinal permeability to stress, without evidence of inflammation. A LED was protective of the stress effect.

Comparison of Gas-sensing Capsule With Wireless Motility Capsule in Motility Disorder Patients.

Background/Aims: Motility disorders are prevalent, often leading to disrupted regional or whole gut transit times. In this study, we conducted a comparative analysis between the wireless motility capsule and an innovative gas-sensing capsule to evaluate regional and whole gut transit times in individuals with diagnosed motility disorders. Methods: We prospectively enrolled 48 patients (34 women) diagnosed with functional dyspepsia and/or functional constipation according to Rome IV criteria. Patients ingested the capsules in tandem. We assessed the agreement between transit times recorded by both devices using Spearman correlation and Bland-Altman analysis. Additionally, diagnostic concordance between the capsules were evaluated using confusion matrices. Results: We observed a significant correlation between the wireless motility capsule and the gas-sensing capsule for gastric emptying time (r = 0.79, P < 0.001) and colonic transit time (r = 0.66, P < 0.001). The gas-sensing capsule exhibited a sensitivity of 0.83, specificity of 0.96, and accuracy of 0.94 when using the standard cutoff for delayed gastric emptying (5 hours). Similarly, when applying the cutoff value for delayed colonic transit (> 59 hours), the gas-sensing capsule demonstrated a sensitivity of 0.79, specificity of 0.84, and accuracy of 0.82. Importantly, the gas-sensing capsule was well-tolerated, and no serious adverse events were reported during the study. Conclusions: Our findings underscore the gas-sensing capsule's suitability as a dependable tool for assessing regional and whole gut transit times. It represents a promising alternative to the wireless motility capsule for evaluating patients with suspected motility disorders.

Development of Novel High and Low Emulsifier Diets Based upon Emulsifier Distribution in the Australian Food Supply for Intervention Studies in Crohn's Disease.

BACKGROUND: The aims of this study were to develop and evaluate a high/low-emulsifier diet and compare emulsifier content with preclinical studies that have associated Crohn's disease with emulsifiers. METHODS: Supermarkets were audited with a seven-day high- (HED) and low-emulsifier diet (LED) meal plan developed. The emulsifier content of food was sought from food manufacturers, compared to acceptable daily intake (ADI), and doses were provided in trials. Nutritional composition analysis was completed. Healthy adults ate these diets for seven days in a randomized single-blinded cross-over feeding study to assess palatability, tolerability, satiety, food variety, dietary adherence, blinding and the ease of following the meal plan via visual analogue scale. RESULTS: A database of 1680 foods was created. There was no difference in nutritional content between the HED and LED, except HED had a higher ultra-processed food content (p < 0.001). The HED contained 41 emulsifiers, with 53% of the products able to be quantified for emulsifiers (2.8 g/d), which did not exceed the ADI, was similar to that in observational studies, and was exceeded by doses used in experimental studies. In ten participants, diets were rated similarly in palatability-HED mean 62 (5% CI 37-86) mm vs. LED 68 (54-82) mm-in tolerability-HED 41 (20-61) mm vs. LED 55 (37-73) mm-and in satiety HED 57 (32-81) mm vs. LED 49 (24-73) mm. The combined diets were easy to follow (82 (67-97) mm) with good variety (65 (47-81)) and excellent adherence. CONCLUSION: Nutritionally well-matched HED and LED were successfully developed, palatable and well tolerated.

Comparison of Digitally Delivered Gut-Directed Hypnotherapy Program With an Active Control for Irritable Bowel Syndrome.

INTRODUCTION: Gut-directed hypnotherapy (GDH) treats irritable bowel syndrome (IBS), but its accessibility is limited. This problem may be overcome by digital delivery. The aim of this study was to perform a randomized control trial comparing the efficacy of a digitally delivered program with and without GDH in IBS. METHODS: Adults with IBS were randomized to a 42-session daily digital program with the GDH Program (Nerva) or without (Active Control). Questionnaires were completed to assess gastrointestinal symptoms through IBS Symptom Severity Scale (IBS-SSS), quality of life, and psychological symptoms (Depression Anxiety and Stress Scale-21) at regular intervals during the program and 6 months following the conclusion on the intervention. The primary end point was the proportion of participants with ≥50-point decrease in IBS-SSS between the interventions at the end of the program. RESULTS: Of 240/244 randomized participants, 121 received GDH Program-the median age 38 (range 20-65) years, 90% female, IBS-SSS 321 (interquartile range 273-367)-and 119 Active Control-36 (21-65), 91% female, IBS-SSS 303 (255-360). At program completion, 81% met the primary end point with GDH Program vs 63% Active Control ( P = 0.002). IBS-SSS was median 208 (interquartile range 154-265) with GDH and 244 (190-308) with control ( P = 0.004), 30% reduction in pain was reported by 71% compared with 35% ( P < 0.001), and IBS quality of life improved by 14 (6-25) compared with 7 (1-15), respectively ( P < 0.001). Psychological status improved similarly in both groups. DISCUSSION: A digitally delivered GDH Program provided to patients with IBS was superior to the active control, with greater improvement in both gastrointestinal symptoms and quality of life and provides an equitable alternative to face-to-face behavioral strategies.

People with Inflammatory Bowel Disease Prefer Cognitive Behavioral Therapy for Fatigue Management: A Conjoint Analysis.

BACKGROUND: Psychological interventions are a promising area for fatigue management in patients with inflammatory bowel disease (IBD). However, most interventions trialled to date have been pilots with limited direct input from patients about the type of intervention they want. Thus, this study aimed to explore patient preferences for a psychological IBD fatigue intervention. METHODS: An international online cross-sectional survey was conducted with adults with self-reported IBD. A conjoint analysis was employed to elicit, through a series of forced-choice scenarios, patient preferences for a fatigue intervention. For this study, the attributes manipulated across these forced-choice scenarios were type of intervention, modality of delivery, and duration of intervention. RESULTS: Overall, 834 people with IBD were included in analysis. Respondents ranked the type of psychological intervention as most important for overall preference (with cognitive-behavioral therapy (CBT) preferred over the other approaches), followed by modality of delivery, but placed very little importance on how long the intervention runs for. Patients with IBD appear to most strongly preference a short online CBT intervention for managing their IBD-related fatigue. CONCLUSION: This study helps provide therapists and program developers clear direction on patient preferences when it comes to developing new psychological programs that address fatigue in IBD.

Probiotics: are they beneficial?

There are wide-ranging probiotic choices in Australasia. We reviewed the efficacy of probiotics for the management of gastrointestinal (GI) conditions in adults and assessed relevance to clinical practice. The benefits of probiotics were inconsistent, with a strong consensus reached for only a few of the indications. As different species/strains and combinations differ in efficacy, results cannot be extrapolated from one to another. This review endorses specific probiotics for limited indications. Efficacy of most marketed probiotic formulations remains unstudied and unproven, warranting further research.

Nutrition Assessment and Management in Celiac Disease.

Celiac disease (CeD) is the most common immune condition affecting the gastrointestinal tract; it is triggered by gluten and the only available treatment is a strict gluten-free diet (GFD). Therefore, for patients with CeD, adopting a GFD is not a lifestyle choice. The major problem is that a GFD is restrictive and, like all restrictive diets, it has the potential for adverse nutritional outcomes, especially if adopted for a long term. It is well known that GFD can be nutritionally inadequate and is frequently associated with vitamin and mineral deficiencies; it is also associated with excessive sugar and fat intake, particularly when gluten-free substitutes are consumed. Consequently, people with CeD are affected by higher rates of overweight and obesity and metabolic complications, such as fatty liver and cardiovascular disease. Therefore, assessment of nutritional status and diet quality at diagnosis and while on a long-term GFD is key in the management of CeD. This narrative review addresses nutritional considerations in CeD and management of common challenges associated with a GFD.

Clinical utility of C-reactive protein-to-albumin ratio in the management of patients with inflammatory bowel disease.

Background and Aim: C-reactive protein (CRP)-to-albumin ratio (CAR) is a novel score with prognostic value in inflammatory conditions. This study assessed the performance of CAR as an objective marker of disease activity and prediction of subtherapeutic infliximab trough levels in patients with inflammatory bowel disease (IBD). Methods: A retrospective study was conducted on three different patient cohorts with IBD: patients who had (i) fecal calprotectin (FC) measurements; (ii) Mayo Endoscopic Scores; and (iii) infliximab trough levels available. The relative performances of CAR, albumin, and CRP were compared in predicting disease activity (based on FC or Mayo Endoscopic Score) and infliximab trough levels. Results: In both the FC (n = 289) and endoscopy (n = 65) cohorts, albumin and CAR correlated with objective disease activity. CAR (area under the curve [AUC] 0.70) was only marginally better at detecting active disease, measured by FC, compared to CRP (AUC 0.68). A CAR >0.15 was able to detect Mayo 3 disease (AUC 0.83, sensitivity 81%, specificity 89%). Albumin (r = 0.38) and CAR (r = -0.42) correlated with infliximab trough levels (n = 204). The optimal CAR for detecting subtherapeutic infliximab trough levels was >0.08 (AUC 0.70, sensitivity 66%, specificity 64%). Both albumin and CAR were independent predictors of subtherapeutic infliximab trough levels but correlated poorly with infliximab trough levels longitudinally in the same patient. Conclusion: CAR was only a modest discriminator of subtherapeutic infliximab levels and offers little more than CRP in detecting active disease. CAR has potential to detect severe Mayo 3 disease and could be calculated in patients admitted with suspected acute severe ulcerative colitis.

Vedolizumab and Ustekinumab Levels in Pregnant Women With Inflammatory Bowel Disease and Infants Exposed In Utero.

BACKGROUND & AIMS: Vedolizumab and ustekinumab pharmacokinetics in pregnancy and the infant after in utero exposure remain incompletely defined. We aim to define the antenatal stability of ustekinumab and vedolizumab levels and the time at which infant drug levels become undetectable. METHODS: This multicenter prospective observational cohort study recruited pregnant or preconception women with inflammatory bowel disease receiving vedolizumab or ustekinumab. Trough drug levels, clinical data, and biochemical data were documented preconception, during each trimester of pregnancy, and postpartum. Maternal and cord blood drug levels were measured at delivery and in infants until undetectable. Infant outcomes were assessed until 2 years of age. RESULTS: A total of 102 participants (vedolizumab, n = 58) were included. The majority of mothers were, and remained, in clinical and biochemical remission. Maternal vedolizumab levels decreased over the course of pregnancy in association with increasing weight, rather than increasing gestation. Maternal ustekinumab levels remained stable. The median time to drug becoming undetectable in the infant was shorter for vedolizumab (11 wk; range, 5-19 wk; n = 32) than ustekinumab (14 wk; range, 9-36 wk; n = 17) and correlated positively with infant delivery level. Thirty-two of 41 (88%) and 17 of 30 (67%) vedolizumab- and ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age, respectively. Pregnancy and infant outcomes were favorable. Twenty infants with undetectable drug levels received the rotavirus vaccine, with no adverse reactions reported. CONCLUSIONS: Maternal vedolizumab levels decreased, whereas ustekinumab levels remained stable over the course of pregnancy. Most vedolizumab- and approximately half of ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age. No concerning maternal or infant safety signals were identified.

Characterisation of biomarkers of intestinal barrier function in response to a high fat/high carbohydrate meal and corticotropin releasing hormone.

BACKGROUND: Variation of circulating concentrations of putative biomarkers of intestinal barrier function over the day and after acute physiological interventions are poorly documented on humans. This study aimed to examine the stability and pharmacokinetics of changes in plasma concentrations of intestinal Fatty-acid -binding -protein (IFABP), Lipopolysaccharide-binging-protein (LBP), soluble CD14, and Syndecan-1 after acute stress and high fat-high-carbohydrate meal. METHODS: In a single-blinded, cross-over, randomised study, healthy volunteers received on separate days corticotropin-releasing hormone (CRH, 100 µg) or normal saline (as placebo) intravenously in random order, then a HFHC meal. Participants were allowed low caloric food. Markers of intestinal barrier function were measured at set timed intervals from 30 minutes before to 24 hours after interventions. RESULTS: 10 participants (50% female) completed all three arms of the study. IFABP decreased by median 3.6 (IQR 1.4-10)% from -30 minutes to zero time (p = 0.001) and further reduced by 25 (20-52)% at 24 hours (p = 0.01) on the low caloric diet, but did not change in response to the meal. Syndecan-1, LBP and sCD14 were stable over a 24-hour period and not affected acutely by food intake. LBP levels 2 hours after CRH reduced by 0.61 (-0.95 to 0.05) µg/ml compared with 0.16 (-0.3 to 0.5) µg/ml post placebo injection (p = 0.05), but other markers did not change. CONCLUSION: Concentrations of IFABP, but not other markers, are unstable over 24 hours and should be measured fasting. A HFHC meal does not change intestinal permeability. Transient reduction of LPB after CRH confirms acute barrier dysfunction during stress.

Intestinal barrier biomarkers in clinical evaluation of patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with chronic intestinal barrier dysfunction, though its non-invasive assessment remains challenging. This study aimed to determine how four putative circulating markers vary across differing states of intestinal inflammation and with therapy in patients with IBD. METHODS: Plasma samples from one prospective cross-sectional and four longitudinal studies, including healthy controls, were analysed for markers of lipopolysaccharide translocation, lipopolysaccharide-binding protein (LBP) and soluble-CD14 (sCD14), and markers of epithelial injury, syndecan-1 and intestinal-type fatty acid-binding protein (IFABP). Inflammatory activity was determined using objective measures. RESULTS: Compared with healthy subjects, concentrations of LBP and sCD14 were higher in patients with active (P < 0.001) and severe ulcerative colitis (UC) (P < 0.0001) and active Crohn's disease (CD) (P < 0.001). In UC in remission, LBP was less than in active disease (P = 0.011) LBP levels decreased longitudinally before and after induction of medical therapy in patients with IBD (P = 0.030) and as severe UC was brought into remission at weeks 2 and 12 (P ≤ 0.022). Response to treatment was associated with higher baseline levels of LBP (P = 0.019) and soluble-CD14 (P = 0.014). Concentrations of syndecan-1 and IFABP were or tended to be lower in UC and CD in active disease and did not change with successful therapy. CONCLUSION: While markers of epithelial injury were subnormal with active disease and did not change with therapy, markers of lipopolysaccharide translocation directly reflected intestinal inflammation, reduced with successful therapy and predicted treatment response.