Breaking down silos: The Gastroenterology Immunology Neuroscience (GIN) Discovery Program - a new model for research.

The Gastroenterology Immunology Neuroscience (GIN) Discovery Program represents a new model for research that overcomes the limitations imposed by traditional "research silos" in science. By uniting these three fields, the GIN Program aims to enhance the understanding and treatment of chronic conditions through a system-wide perspective focusing on the gut-immune-brain axis. Key initiatives include monthly interdisciplinary seminars, an annual symposium, and GINnovate, a commercialization and entrepreneurship event. Additionally, the program offers a seed grant competition for early and mid-career researchers, promoting advancements in gut-immune-brain axis research through the power of collaboration. The GIN Program in a short period of time has facilitated the formation of a vibrant community, captivating attention from both national and international institutions. This effort to break down barriers in research aims to inspire similar models that prioritize open communication, mutual respect and a commitment to impactful science.

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.

Diet as a therapeutic tool in chronic gastrointestinal disorders: Lessons from the FODMAP journey.

BACKGROUND AND AIM: Diet is a powerful tool in the management of gastrointestinal disorders, but developing diet therapies is fraught with challenge. This review discusses key lessons from the FODMAP diet journey. METHODS: Published literature and clinical experience were reviewed. RESULTS: Key to designing a varied, nutritionally adequate low-FODMAP diet was our accurate and comprehensive database of FODMAP composition, made universally accessible via our user-friendly, digital application. Our discovery that FODMAPs coexist with gluten in cereal products and subsequent gluten/fructan challenge studies in nonceliac gluten-sensitive populations highlighted issues of collinearity in the nutrient composition of food and confirmation bias in the interpretation of dietary studies. Despite numerous challenges in designing, funding, and executing dietary randomized controlled trials, efficacy of the low-FODMAP diet has been repeatedly demonstrated, and confirmed by real-world experience, giving this therapy credibility in the eyes of clinicians and researchers. Furthermore, real-world application of this diet saw the evolution of a safe and effective three-phased approach. Specialist dietitians must deliver this diet to optimize outcomes as they can target and tailor the therapy and to mitigate the key risks of compromising nutritional adequacy and precipitating disordered eating behaviors, skills outside the gastroenterologist's standard tool kit. While concurrent probiotics are ineffective, specific fiber supplements may improve short-term and long-term outcomes. CONCLUSIONS: The FODMAP diet is highly effective, but optimal outcomes are contingent on the involvement of a gastroenterological dietitian who can assess, educate, and monitor patients and manage risks associated with implementation of this restrictive diet.

Controversies and reality of the FODMAP diet for patients with irritable bowel syndrome.

Since its first trial showing evidence of efficacy for managing symptoms of irritable bowel syndrome, the fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet has been gaining popularity but not without criticism. Application of the diet has changed from a rigid list of "allowed" and "not allowed" foods to a structured program of initial FODMAP restriction followed by food reintroduction and finally personalization so that patients are empowered to adjust their diet themselves to achieve good predictability of symptoms. Safety concerns of the diet have centered around its initial elimination leading to compromise of nutritional and psychological health, but careful patient assessment and management, preferably through a FODMAP-trained dietitian, will reduce the risk of such negative health outcomes. Most negative attention for the FODMAP diet has been the notion that it will ruin the microbiota. Controlled studies have indicated that reducing FODMAP intake has no effects on bacterial diversity but will reduce total bacterial abundance, and higher FODMAP intakes will increase health-promoting bacteria, supporting the concept of the full FODMAP program, including attaining a minimal "maintenance" level of FODMAP restriction. This review addresses all these concerns in detail and how to overcome them, including the use of a "FODMAP-gentle" diet, describing restriction of a select few foods very concentrated in FODMAPs. This version of the diet is commonly applied in practice by experienced FODMAP-trained dietitians but is not clearly described in literature. Careful direction and assessment of response or nonresponse will decrease the risks of over-restriction and under-restriction of diet.

Maintenance of a gluten free diet in coeliac disease: The roles of self-regulation, habit, psychological resources, motivation, support, and goal priority.

INTRODUCTION: A strict lifelong gluten free diet (GFD) is the only treatment for coeliac disease (CD). Theory-based research has focused predominantly on initiation, rational, and motivational processes in predicting adherence. The aim of this study was to evaluate an expanded collection of theoretical constructs specifically relevant to the maintenance of behaviour change, in the understanding and prediction of GFD adherence. METHODS: Respondents with CD (N = 5573) completed measures of GFD adherence, psychological distress, intentions, self-efficacy, and the maintenance-relevant constructs of self-regulation, habit, temptation and intentional and unintentional lapses (cognitive and behavioural consequences of lowered or fluctuating psychological resources and self-control), motivation, social and environmental support, and goal priority, conflict, and facilitation. Correlations and multiple regression were used to determine their influence on adherence, over and above intention and self-efficacy, and how relationships changed in the presence of distress. RESULTS: Better adherence was associated with greater self-regulation, habit, self-efficacy, priority, facilitation, and support; and lower psychological distress, conflict, and fewer self-control lapses (e.g., when busy/stressed). Autonomous and wellbeing-based, but not controlled motivations, were related to adherence. In the presence of distress, the influence of self-regulation and intentional lapses on adherence were increased, while temptation and unintentional lapses were decreased. DISCUSSION: The findings point to the importance of considering intentional, volitional, automatic, and emotional processes in the understanding and prediction of GFD adherence. Behaviour change interventions and psychological support are now needed so that theoretical knowledge can be translated into evidence-based care, including a role for psychologists within the multi-disciplinary treatment team.

When the low FODMAP diet does not work.

Irritable bowel syndrome (IBS) is heterogeneous. Patients need proper assessment and explanation of IBS pathophysiology and appropriate therapies. A low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet effectively reduces symptoms in 75% of patients. Best treatment for those nonresponsive will depend on the pathophysiological basis for symptom genesis, with the following possible abnormalities: (i) Visceral hypersensitivity and/or enhanced gut-brain communication: a low FODMAP diet is mainly targeted for this patient group. A dietitian may also recommend antispasmodic agents, including peppermint oil. Another dietary treatment is a low food chemical diet, although this diet is often extremely limited, and therefore, not suited for some populations. Psychological therapies are also clinically beneficial. (ii) Altered motility: in patients with fast transit, a dietitian may recommend a reduction in all FODMAPs or targeted monosaccharides and disaccharides, which are more osmotic in nature. If not effective, patients may benefit from psyllium, which has an exceptional water-holding capacity aimed to promote more formed stools. Patients with slow or uncoordinated transit are often more difficult to treat. Dietary interventions have some success and usually comprise a combination of adequate fiber and fluid, osmotic laxatives, and stimulating agents such as caffeine, senna, and exercise. (iii) Altered microbiome: supplementary probiotics and prebiotics have weak evidence of efficacy with some notable exceptions. A dietitian may trial supplementary Bifidobacterium infantis or oligosaccharides, usually as an adjunct therapy. Guidance from a dietitian will encompass dietary methods to treat IBS but additionally identify where dietary treatment is not indicated to ensure that diet is correctly used and patients are not nutritionally or psychologically compromised.

Diets that differ in their FODMAP content alter the colonic luminal microenvironment.

OBJECTIVE: A low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) diet reduces symptoms of IBS, but reduction of potential prebiotic and fermentative effects might adversely affect the colonic microenvironment. The effects of a low FODMAP diet with a typical Australian diet on biomarkers of colonic health were compared in a single-blinded, randomised, cross-over trial. DESIGN: Twenty-seven IBS and six healthy subjects were randomly allocated one of two 21-day provided diets, differing only in FODMAP content (mean (95% CI) low 3.05 (1.86 to 4.25) g/day vs Australian 23.7 (16.9 to 30.6) g/day), and then crossed over to the other diet with ≥21-day washout period. Faeces passed over a 5-day run-in on their habitual diet and from day 17 to day 21 of the interventional diets were pooled, and pH, short-chain fatty acid concentrations and bacterial abundance and diversity were assessed. RESULTS: Faecal indices were similar in IBS and healthy subjects during habitual diets. The low FODMAP diet was associated with higher faecal pH (7.37 (7.23 to 7.51) vs. 7.16 (7.02 to 7.30); p=0.001), similar short-chain fatty acid concentrations, greater microbial diversity and reduced total bacterial abundance (9.63 (9.53 to 9.73) vs. 9.83 (9.72 to 9.93) log10 copies/g; p<0.001) compared with the Australian diet. To indicate direction of change, in comparison with the habitual diet the low FODMAP diet reduced total bacterial abundance and the typical Australian diet increased relative abundance for butyrate-producing Clostridium cluster XIVa (median ratio 6.62; p<0.001) and mucus-associated Akkermansia muciniphila (19.3; p<0.001), and reduced Ruminococcus torques. CONCLUSIONS: Diets differing in FODMAP content have marked effects on gut microbiota composition. The implications of long-term reduction of intake of FODMAPs require elucidation. TRIAL REGISTRATION NUMBER: ACTRN12612001185853.

A diet low in FODMAPs reduces symptoms of irritable bowel syndrome.

BACKGROUND & AIMS: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) often is used to manage functional gastrointestinal symptoms in patients with irritable bowel syndrome (IBS), yet there is limited evidence of its efficacy, compared with a normal Western diet. We investigated the effects of a diet low in FODMAPs compared with an Australian diet, in a randomized, controlled, single-blind, cross-over trial of patients with IBS. METHODS: In a study of 30 patients with IBS and 8 healthy individuals (controls, matched for demographics and diet), we collected dietary data from subjects for 1 habitual week. Participants then randomly were assigned to groups that received 21 days of either a diet low in FODMAPs or a typical Australian diet, followed by a washout period of at least 21 days, before crossing over to the alternate diet. Daily symptoms were rated using a 0- to 100-mm visual analogue scale. Almost all food was provided during the interventional diet periods, with a goal of less than 0.5 g intake of FODMAPs per meal for the low-FODMAP diet. All stools were collected from days 17-21 and assessed for frequency, weight, water content, and King's Stool Chart rating. RESULTS: Subjects with IBS had lower overall gastrointestinal symptom scores (22.8; 95% confidence interval, 16.7-28.8 mm) while on a diet low in FODMAPs, compared with the Australian diet (44.9; 95% confidence interval, 36.6-53.1 mm; P < .001) and the subjects' habitual diet. Bloating, pain, and passage of wind also were reduced while IBS patients were on the low-FODMAP diet. Symptoms were minimal and unaltered by either diet among controls. Patients of all IBS subtypes had greater satisfaction with stool consistency while on the low-FODMAP diet, but diarrhea-predominant IBS was the only subtype with altered fecal frequency and King's Stool Chart scores. CONCLUSIONS: In a controlled, cross-over study of patients with IBS, a diet low in FODMAPs effectively reduced functional gastrointestinal symptoms. This high-quality evidence supports its use as a first-line therapy. CLINICAL TRIAL NUMBER: ACTRN12612001185853.

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.

Role of diet in prevention versus treatment of Crohn's disease and ulcerative colitis.

Diet is a modifiable risk factor for disease course and data over the past decade have emerged to indicate its role in Crohn's disease (CD) and ulcerative colitis (UC). However, literature is riddled with misinterpretation of data, often leading to unexpected or conflicting results. The key understanding is that causative factors in disease development do not always proceed to an opportunity to change disease course, once established. Here, we discuss the data on dietary influences in three distinct disease states for CD and UC-predisease, active disease and quiescent disease. We appraise the literature for how our dietary recommendations should be shaped to prevent disease development and if or how that differs for CD and UC induction therapy and maintenance therapy. In UC, principles of healthy eating are likely to play a role in all states of disease. Conversely, data linking dietary factors to CD prevention and treatment are paradoxical with the highest quality evidence for CD treatment being exclusive enteral nutrition, a lactose, gluten and fibre-free diet comprising solely of ultraprocessed food-all dietary factors that are not associated or inversely associated with CD prevention. High-quality evidence from dietary trials is much awaited to expand our understanding and ultimately lead our dietary recommendations for targeted patient populations.

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.

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.

Revolution in diet therapy for inflammatory bowel disease.

Until recently, diet as a therapeutic tool to treat inflammatory bowel disease (IBD) has not been proven effective. Nearly a century in the making we are in the grips of a revolution in diet therapies for IBD, driven by emerging data revealing diet as a key environmental factor associated with IBD susceptibility, and observational studies suggesting that dietary intake may play a role in the disease course of established IBD. This review summarizes the current evidence for diets trialed as induction and maintenance therapy for IBD. For Crohn's disease, exclusive enteral nutrition and the Crohn's disease exclusion diet with partial enteral nutrition are supported by emerging high-quality evidence as induction therapy, but are short-term approaches that are not feasible for prolonged use. Data on diet as maintenance therapy for Crohn's disease are conflicting, with some studies supporting fortification, and others suppression, of certain food components. For ulcerative colitis, data are not as robust for diet as induction and maintenance therapy; however, consistent themes are emerging, suggesting benefits for diets that are plant-based, high in fiber and low in animal protein. Further studies for both Crohn's disease and ulcerative colitis are eagerly awaited, which will allow specific recommendations to be made. Until this time, recommendations default to population based healthy eating guidelines.

Evolution, adaptation, and new applications of the FODMAP diet.

The FODMAP diet has been a treatment of irritable bowel syndrome (IBS) for many years. Rigorous scientific evaluation and clinical application of the FODMAP diet have generated deep understanding regarding clinical efficacy, mechanisms of action, and potential adverse effects of this dietary approach. In turn, this knowledge has allowed fine-tuning of the diet to optimize treatment benefits and minimize risks, in the form of the traditional three-phase diet; the FODMAP-gentle approach, which is a less restrictive iteration; and a proposed FODMAP-modified, Mediterranean-style diet which endeavours to optimise both gastrointestinal symptoms and other health parameters. Furthermore, recognition that IBS-like symptoms feature in other conditions has seen the FODMAP diet tested in non-IBS populations, including in older adults with diarrhea and women with endometriosis. These areas represent new frontiers for the FODMAP diet and a space to watch as future research evaluates the validity of these novel clinical applications.

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.

Review article: Current status and future directions of ingestible electronic devices in gastroenterology.

BACKGROUND: Advances in microelectronics have greatly expanded the capabilities and clinical potential of ingestible electronic devices. AIM: To provide an overview of the structure and potential impact of ingestible devices in development that are relevant to the gastrointestinal tract. METHODS: We performed a detailed literature search to inform this narrative review. RESULTS: Technical success of ingestible electronic devices relies on the ability to miniaturise the microelectronic circuits, sensors and components for interventional functions while being sufficiently powered to fulfil the intended function. These devices offer the advantages of being convenient and minimally invasive, with real-time assessment often possible and with minimal interference to normal physiology. Safety has not been a limitation, but defining and controlling device location in the gastrointestinal tract remains challenging. The success of capsule endoscopy has buoyed enthusiasm for the concepts, but few ingestible devices have reached clinical practice to date, partly due to the novelty of the information they provide and also due to the challenges of adding this novel technology to established clinical paradigms. Nonetheless, with ongoing technological advancement and as understanding of their potential impact emerges, acceptance of such technology will grow. These devices have the capacity to provide unique insight into gastrointestinal physiology and pathophysiology. Interventional functions, such as sampling of tissue or luminal contents and delivery of therapies, may further enhance their ability to sharpen gastroenterological diagnoses, monitoring and treatment. CONCLUSIONS: The development of miniaturised ingestible microelectronic-based devices offers exciting prospects for enhancing gastroenterological research and the delivery of personalised, point-of-care medicine.