Postprandial symptoms in disorders of gut-brain interaction and their potential as a treatment target.

Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.

Utilizing technology for diet and exercise change in complex chronic conditions across diverse environments (U-DECIDE): feasibility randomised controlled trial.

BACKGROUND: Diet and exercise are important components of treatment for complex chronic conditions, however access to allied health support is limited. When available, support is often siloed and fragmented. Digital health incorporating patient choice may help to align health care services with preferences and goals. This study evaluated the implementation of a ubiquitously accessible patient-centred digital health diet and exercise service. METHODS: U-DECIDE was a single-centre, 26-week randomised controlled trial set in kidney and liver disease clinics in a tertiary hospital in Brisbane, Australia. Participants were adults with a complex chronic condition referred for dietetic consultation with at least one feature of the metabolic syndrome. All participants received a dietary consultation, an activity monitor and usual care. Intervention participants were offered one text message per week and access to additional digital health options (increased text message frequency, nutrition app, exercise app, group-based diet and/or exercise video consultations). The primary outcome of feasibility was determined by safety (study-related serious adverse events: SRSAEs), recruitment (≥ 50% eligible patients), retention (≥ 70%), exposure uptake (≥ 75% of intervention group had greater access to health professional contact than comparator) and video consultation adherence (≥ 80% attendance). Secondary outcomes included process evaluation metrics and clinical outcomes. RESULTS: Of 67 participants (intervention n = 33, comparator n = 34), 37 (55%) were men, median (IQR) age was 51 (41-58) years. The most chosen digital health options were the nutrition app (n = 29, 88%) and exercise video consultations (n = 26, 79%). Only one participant chose no additional digital health options. The intervention group had no SRSAEs. The study exceeded targets for recruitment (52%), retention (81%) and exposure uptake (94%). Video consultation adherence was 42%. Engagement across digital health options was inconsistent. CONCLUSIONS: Digital health options incorporating patient choice were feasible and can be offered to people with complex chronic disease as a service model option. TRIAL REGISTRATION: Australia and New Zealand Trials Register: Trial Registration Number: ACTRN12620001282976. Registered 27th November 2020.

Alterations to the duodenal microbiota are linked to gastric emptying and symptoms in functional dyspepsia.

OBJECTIVE: Functional dyspepsia (FD) is a complex disorder, with debilitating epigastric symptoms. Evidence suggests alterations in gastrointestinal (GI) motility, visceral hypersensitivity, permeability and low-level immune activation in the duodenum may play a role. However, we still have a relatively poor understanding of how these factors interact to precipitate the onset of FD symptoms which are frequently meal related. The duodenal microbiota, in combination with specific dietary substrates, may be important mediators in disease pathophysiology; however, these interlinked factors have not been thoroughly investigated in FD. DESIGN: Eighty-six individuals (56 FD, 30 controls) undergoing endoscopy were consecutively recruited and underwent detailed clinical assessment, including upper GI symptoms, gastric emptying and dietary assessment. Duodenal biopsies were obtained aseptically, and the mucosa-associated microbiota (MAM) analysed via 16S rRNA gene amplicon sequencing. RESULTS: The relative abundances of predominant members of the Firmicutes, Bacteroidota and Fusobacteriota phyla were linked to symptom burden in FD. Inverse relationships between the relative abundances of Streptococcus and Prevotella, and the relative abundance of Veillonella spp with gastric emptying time, were also observed. No significant differences in long-term nutrient intake or diet quality were found between FD and controls, and there appeared to be limited association between habitual diet and duodenal MAM profiles. CONCLUSION: This study suggests a link between the duodenal MAM, gastric emptying and FD symptoms, and this is largely independent of long-term dietary intake.

Challenges and priorities for researching the gut microbiota in individuals living with anorexia nervosa.

OBJECTIVE: The gut microbiota is implicated in several symptoms and biological pathways relevant to anorexia nervosa (AN). Investigations into the role of the gut microbiota in AN are growing, with a specific interest in the changes that occur in response to treatment. Findings suggest that microbial species may be associated with some of the symptoms common in AN, such as depression and gastrointestinal disturbances (GID). Therefore, researchers believe the gut microbiota may have therapeutic relevance. Whilst research in this field is rapidly expanding, the unique considerations relevant to conducting gut microbiota research in individuals with AN must be addressed. METHOD: We provide an overview of the published literature investigating the relationship between the gut microbiota and symptoms and behaviors present in AN, discuss important challenges in gut microbiota research, and offer recommendations for addressing these. We conclude by summarizing research design priorities for the field to move forward. RESULTS: Several ways exist to reduce participant burden and accommodate challenges when researching the gut microbiota in individuals with AN. DISCUSSION: Recommendations from this article are foreseen to encourage scientific rigor and thoughtful protocol planning for microbiota research in AN, including ways to reduce participant burden. Employing such methods will contribute to a better understanding of the role of the gut microbiota in AN pathophysiology and treatment. PUBLIC SIGNIFICANCE: The field of gut microbiota research is rapidly expanding, including the role of the gut microbiota in anorexia nervosa. Thoughtful planning of future research will ensure appropriate data collection for meaningful interpretation while providing a positive experience for the participant. We present current challenges, recommendations for research design and priorities to facilitate the advancement of research in this field.

Fibre intake and supplementation during treatment for haematological malignancies: A scoping review.

BACKGROUND: Gastrointestinal microbiome diversity decreases rapidly during haematological cancer treatment with low diversity associated with poorer clinical outcomes. Therefore, factors that may benefit the microbiome require evaluation. This scoping review aimed to identify and describe the available research on fibre intake and supplementation during haematological cancer treatment. METHODS: This scoping review included observational studies of usual fibre intake and intervention fibre supplementation trials with patients undergoing chemotherapy, immunotherapy or stem cell transplantation for haematological malignancy. Comprehensive searching of four databases plus grey literature was conducted. Study design, type of fibre (for fibre supplementation trials) and evaluated outcomes were recorded. The review was registered on Open Science Framework and completed in three stages. There were no date restrictions in the search and only studies in English were included. RESULTS: Five studies met the inclusion criteria for the review including two observational studies and three supplementation trials. No randomised control trials were identified. The interventional studies provided either a single fibre supplement (fructo-oligosaccharide) or a combination of fibres (polydextrose, lactosucrose, resistant starch or oligosaccharides plus fibre) during stem cell transplantation. The most frequently evaluated outcomes included tolerability of the fibre supplement, clinical outcomes (infection, graft versus host disease, survival) and the impact on the gastrointestinal microbiome. CONCLUSIONS: Further research, including randomised controlled trials, is needed to investigate the role of fibre during haematological cancer treatment, including the pathways in which it might improve disease outcome.

Efficacy of a low FODMAP diet in irritable bowel syndrome: systematic review and network meta-analysis.

OBJECTIVE: A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is recommended for irritable bowel syndrome (IBS), if general lifestyle and dietary advice fails. However, although the impact of a low FODMAP diet on individual IBS symptoms has been examined in some randomised controlled trials (RCTs), there has been no recent systematic assessment, and individual trials have studied numerous alternative or control interventions, meaning the best comparator is unclear. We performed a network meta-analysis addressing these uncertainties. DESIGN: We searched the medical literature through to 2 April 2021 to identify RCTs of a low FODMAP diet in IBS. Efficacy was judged using dichotomous assessment of improvement in global IBS symptoms or improvement in individual IBS symptoms, including abdominal pain, abdominal bloating or distension, and bowel habit. Data were pooled using a random effects model, with efficacy reported as pooled relative risks (RRs) with 95% CIs, and interventions ranked according to their P-score. RESULTS: We identified 13 eligible RCTs (944 patients). Based on failure to achieve an improvement in global IBS symptoms, a low FODMAP diet ranked first vs habitual diet (RR of symptoms not improving=0.67; 95% CI 0.48 to 0.91, P-score=0.99), and was superior to all other interventions. Low FODMAP diet ranked first for abdominal pain severity, abdominal bloating or distension severity and bowel habit, although for the latter it was not superior to any other intervention. A low FODMAP diet was superior to British Dietetic Association (BDA)/National Institute for Health and Care Excellence (NICE) dietary advice for abdominal bloating or distension (RR=0.72; 95% CI 0.55 to 0.94). BDA/NICE dietary advice was not superior to any other intervention in any analysis. CONCLUSION: In a network analysis, low FODMAP diet ranked first for all endpoints studied. However, most trials were based in secondary or tertiary care and did not study effects of FODMAP reintroduction and personalisation on symptoms.

Optimal Design of Clinical Trials of Dietary Interventions in Disorders of Gut-Brain Interaction.

There is accumulating evidence for the fundamental role of diet in the integrated care of disorders of gut-brain interaction. Food is a complex mixture of components with individual, synergistic, and antagonistic effects, compared with the relative purity of a pharmaceutical. Food is also an inherent part of individuals' daily lives, and food choice is strongly tied to food preferences, personal beliefs, cultural and religious practices, and economic status, which can influence its ability to function as a therapeutic intervention. Hence, randomized controlled trials of dietary interventions carry unique methodological complexities that are not applicable to pharmaceutical trials that if disregarded can pose significant risk to trial quality. The challenges of designing and delivering the dietary intervention depend on the type of intervention (i.e., nutrient vs food supplementation or whole-diet intervention). Furthermore, there are multiple modes of delivery of dietary interventions, each with their own advantages (e.g., the high precision of feeding trials and the strong clinical applicability of dietary counseling trials). Randomized placebo-controlled trials of dietary interventions are possible with sufficient attention to their design and methodological nuances. Collaboration with experts in nutrition and dietetics is essential for the planning phase; however, even with expert input, not all challenges can be overcome. Researchers undertaking future dietary trials must be transparent in reporting these challenges and approaches for overcoming them. This review aims to provide guiding principles and recommendations for addressing these challenges to facilitate the conduct and reporting of high-quality trials that inform and improve clinical practice.

Low FODMAP diet in irritable bowel syndrome: a review of recent clinical trials and meta-analyses.

PURPOSE OF REVIEW: The low fermentable oligosaccharides, disaccharides, monosaccharides and polyol (FODMAP) diet is widely used in the dietary management of irritable bowel syndrome (IBS). The aim of this review is to summarize recent evidence regarding the use of the low FODMAP diet in IBS and other gastrointestinal disorders from recent clinical trials and meta-analyses. RECENT FINDINGS: Several recent systematic reviews and meta-analyses support the use of low FODMAP restriction for global symptoms in IBS in the short term. Uncontrolled follow-up studies show that at least 50% of individuals experience symptom relief following restriction, reintroduction and personalization in the long term. Although evidence from comparative trials in IBS suggests potential benefit of less burdensome approaches (e.g. standard IBS diet and low lactose diet) many studies are insufficiently powered. One established mechanism is colonic gas production that may induce pain signalling measurable in the brain, however altered gastrointestinal epithelial integrity and shifts in microbiome composition and function may also be involved. SUMMARY: Quality trials of the low FODMAP diet are emerging and have been transformational in supporting the widespread application to IBS management in some areas (e.g. short-term effectiveness), whereas other areas still require considerable improvements in research evidence (e.g. long-term effectiveness, mechanisms and educational delivery).

Nonfermented Dairy Intake, but Not Fermented Dairy Intake, Associated with a Higher Risk of Depression in Middle-Age and Older Finnish Men.

BACKGROUND: Despite the putative health benefits of fermented dairy products, evidence on the association between fermented dairy and nonfermented dairy intake, and depression incidence is limited. OBJECTIVES: This study examined cross-sectional and prospective associations between total dairy, fermented dairy, and nonfermented dairy intake with 1) the presence of elevated depressive symptoms and 2) the risk of a future hospital discharge or outpatient diagnosis of depression. METHODS: Data from 2603 Finnish men (aged 42-60 y), recruited as part of the Kuopio Ischaemic Heart Disease Risk Factor Study, were included. Multivariable logistic regression models were used to examine ORs and 95% CIs for elevated depressive symptoms (Human Population Laboratory scale ≥5 points) at baseline. Cox proportional hazards regression models were used to estimate HRs and 95% CIs between dairy categories and risk of depression diagnoses. RESULTS: In cross-sectional analyses, fermented dairy intake in the highest (compared with lowest) tertile was associated with lower odds of having elevated depressive symptoms (adjusted OR: 0.70; 95% CI: 0.52, 0.96). Each 100-g increase in nonfermented dairy intake was associated with higher odds of having elevated depressive symptoms (adjusted OR: 1.06; 95% CI: 1.01, 1.10). During a mean follow-up time of 24 y, 113 males received a diagnosis of depression. After excluding cheese intake, higher fermented dairy intake was associated with a lower risk of depression diagnosis (adjusted HR: 0.62; 95% CI: 0.38, 1.03), which was strengthened after excluding those with elevated depressive symptoms at baseline (adjusted HR: 0.55; 95% CI: 0.31, 0.99), whereas nonfermented dairy intake in the highest tertile was associated with a 2-fold higher risk of depression (adjusted HR: 2.02; 95% CI: 1.20, 3.42). CONCLUSIONS: Fermented dairy and nonfermented dairy intake were differentially associated with depression outcomes when examined cross-sectionally and over a mean period of 24 y. These findings suggest that dairy fermentation status may influence the association between dairy intake and depression in Finnish men. The KIHD study was registered at clinicaltrials.gov as NCT03221127.

Diet and depression: exploring the biological mechanisms of action.

The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression onset and symptom management. To guide future clinical trials and targeted dietary therapies, this review provides an overview of what is currently known regarding underlying mechanisms of action by which diet may influence mental and brain health. The mechanisms of action associating diet with health outcomes are complex, multifaceted, interacting, and not restricted to any one biological pathway. Numerous pathways were identified through which diet could plausibly affect mental health. These include modulation of pathways involved in inflammation, oxidative stress, epigenetics, mitochondrial dysfunction, the gut microbiota, tryptophan-kynurenine metabolism, the HPA axis, neurogenesis and BDNF, epigenetics, and obesity. However, the nascent nature of the nutritional psychiatry field to date means that the existing literature identified in this review is largely comprised of preclinical animal studies. To fully identify and elucidate complex mechanisms of action, intervention studies that assess markers related to these pathways within clinically diagnosed human populations are needed.

Gastrointestinal symptoms following treatment for anorexia nervosa: A systematic literature review.

OBJECTIVE: Gastrointestinal (GI) disturbances are a frequent and burdensome experience for patients with anorexia nervosa (AN). How GI symptoms respond to current interventions is not well characterized, yet is critical to facilitate treatment success, and to inform the development of new treatments for AN. Therefore, the aim of this systematic review was to identify which treatments are effective in improving GI symptoms in patients with AN. METHOD: A systematic search for studies of AN treatments measuring GI symptoms pre- and post-treatment was conducted in May 2020 (PROSPERO ID: CRD42020181328). After removal of duplicates, title and abstracts of 3,370 studies were screened. Methodological quality was assessed using National Institute of Health Quality Assessment Tool. RESULTS: Following full-text screening, 13 studies (12 observational studies and 1 randomized double-blind placebo-controlled trial) with 401 participants met eligibility criteria and were included. All observational studies included a component of nutritional rehabilitation, with half (n = 6) involving concurrent psychological treatment. The randomized controlled trial reported a drug therapy. Eleven studies reported an improvement in all (n = 6) or at least one (n = 5) patient-reported GI symptom following treatment. Two studies reported no change. Methodological quality was fair or poor across all studies. DISCUSSION: This is the first systematic review to synthesize available evidence on the trajectory of patient-reported GI symptoms from commencement to end of treatment for AN. The results suggest that most studies showed improvement in one or more GI symptom in response to current treatments. Future therapeutic approaches should consider GI symptoms within their design for optimal treatment adherence and outcomes.

OBJETIVO: Las alteraciones gastrointestinales (GI) son una experiencia frecuente y gravosa para los pacientes que padecen anorexia nerviosa (AN). La forma en que los síntomas gastrointestinales responden a las intervenciones actuales no está bien caracterizada, sin embargo es fundamental para facilitar el éxito del tratamiento, e informar el desarrollo de nuevos tratamientos para la AN. Por lo tanto, el objetivo de esta revisión sistemática fue identificar qué tratamientos son eficaces para mejorar los síntomas gastrointestinales en pacientes que padecen AN. MÉTODO: En mayo de 2020 se llevó a cabo una búsqueda sistemática de estudios de tratamientos para AN que midieron los síntomas gastrointestinales antes y después del tratamiento (PROSPERO ID: CRD42020181328). Después de la eliminación de duplicados, se examinaron el título y los resúmenes de 3370 estudios. La calidad metodológica fue evaluada utilizando la Herramienta de Evaluación de la Calidad del Instituto Nacional de Salud. RESULTADOS: Después de la detección completa de texto, 13 estudios (12 estudios observacionales y un ensayo aleatorizado doble ciego controlado con placebo) con 401 participantes cumplieron con los criterios de elegibilidad y fueron incluidos. Todos los estudios observacionales incluyeron un componente de rehabilitación nutricional, con la mitad (n=6) involucrando un tratamiento psicológico simultáneo. El ensayo controlado aleatorizado reportó tratamiento farmacológico. Once studies informaron de una mejora en todos (n=6) o al menos un (n=5) paciente reportó síntomas gastrointestinales después del tratamiento. Dos estudios no reportaron ningún cambio. La calidad metodológica fue justa o pobre en todos los estudios. DISCUSIÓN: Esta es la primera revisión sistemática que sintetiza la evidencia disponible sobre la trayectoria de los síntomas GI notificados por el paciente desde el inicio hasta el final del tratamiento para la AN. Los resultados sugieren que la mayoría de los estudios mostraron mejoría en uno o más síntomas gastrointestinales en respuesta a los tratamientos actuales. Los futuros abordajes terapéuticos deben considerar los síntomas gastrointestinales dentro de su diseño para una adherencia y resultados óptimos en el tratamiento.

Assessing the feasibility of an m-Health intervention for changing diet quality and mood in individuals with depression: the My Food & Mood program.

Recent randomized controlled trials have shown that improving diet quality reduces symptoms in those with depression. The provision of digital health interventions that can support dietary change in those with depression has important benefits with respect to reach, accessibility convenience and cost. The My Food & Mood study used single arm cohort design to test the feasibility of such an intervention. Participants with current depressive symptoms were recruited and enrolled online to use the My Food & Mood m-Health (smartphone delivered) program for 8 weeks. Participants completed depression (PHQ-8) and dietary questionnaires (MEDAS) at baseline, week 4 and week 8. Metrics of use and intensity of use engagement measures were calculated from system logs and data entries. There was a significant change in both MEDAS score (t = 8.147, df = 44, p < 0.001) and PHQ-8 score (t = -7.199, df = 44, p < 0.001) throughout the study. There was a moderate positive association between change in MEDAS score and activities completed, goals and weeks engaged, and a strong inverse association between change in MEDAS score and change in PHQ-8 score. An m-Health program targeting dietary intervention in those with depression was feasible. Dietary change was associated with higher engagement and reduced depressive symptoms.

Conducting research on diet-microbiome interactions: A review of current challenges, essential methodological principles, and recommendations for best practice in study design.

Diet is one of the strongest modulators of the gut microbiome. However, the complexity of the interactions between diet and the microbial community emphasises the need for a robust study design and continued methodological development. This review aims to summarise considerations for conducting high-quality diet-microbiome research, outline key challenges unique to the field, and provide advice for addressing these in a practical manner useful to dietitians, microbiologists, gastroenterologists and other diet-microbiome researchers. Searches of databases and references from relevant articles were conducted using the primary search terms 'diet', 'diet intervention', 'dietary analysis', 'microbiome' and 'microbiota', alone or in combination. Publications were considered relevant if they addressed methods for diet and/or microbiome research, or were a human study relevant to diet-microbiome interactions. Best-practice design in diet-microbiome research requires appropriate consideration of the study population and careful choice of trial design and data collection methodology. Ongoing challenges include the collection of dietary data that accurately reflects intake at a timescale relevant to microbial community structure and metabolism, measurement of nutrients in foods pertinent to microbes, improving ability to measure and understand microbial metabolic and functional properties, adequately powering studies, and the considered analysis of multivariate compositional datasets. Collaboration across the disciplines of nutrition science and microbiology is crucial for high-quality diet-microbiome research. Improvements in our understanding of the interaction between nutrient intake and microbial metabolism, as well as continued methodological innovation, will facilitate development of effective evidence-based personalised dietary treatments.

Pilot study investigating the effect of enteral and parenteral nutrition on the gastrointestinal microbiome post-allogeneic transplantation.

Nutrition support is frequently required post-allogeneic haematopoietic progenitor cell transplantation (HPCT); however, the impact of mode of feeding on the gastrointestinal microbiome has not been explored. This study aimed to determine if there is a difference in the microbiome between patients receiving enteral nutrition (EN) and parenteral nutrition (PN) post-allogeneic HPCT. Twenty-three patients received either early EN or PN when required. Stool samples were collected at 30 days post-transplant and analysed with shotgun metagenomic sequencing. There was no difference in microbial diversity between patients who received predominantly EN (n = 13) vs. PN (n = 10) however patients who received predominantly EN had greater abundance of Faecalibacterium (P < 0·001) and ruminococcus E bromii (P = 0·026). Patients who had minimal oral intake for a longer duration during provision of nutrition support had a different overall microbial profile (P = 0·044), lower microbial diversity (P = 0·004) and lower abundance of faecalibacterium prausnitzii_C (P = 0·030) and Blautia (P = 0·007) compared to patients with greater oral intake. Lower microbial diversity was found in patients who received additional beta lactam antibiotics (P = 0·042) or had a longer length of hospital stay (P = 0·019). Post-HPCT oral intake should be encouraged to maintain microbiota diversity and, if nutrition support is required, EN may promote a more optimal microbiota profile.

Volatile Organic Compounds in Feces Associate With Response to Dietary Intervention in Patients With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Dietary interventions are effective in management of patients with irritable bowel syndrome (IBS), although responses vary. We investigated whether fecal levels of volatile organic compounds (VOCs) associate with response to dietary interventions in patients with IBS. METHODS: Adults who fulfilled the Rome III criteria for IBS were recruited to a 2x2 factorial randomized controlled trial. Patients were randomly assigned to a group counselled to follow a diet low in fructans, galacto-oligosaccharides, lactose, fructose, and polyols (low-FODMAP diet, n = 46) or a group that received placebo dietary advice (sham diet, n = 47) for 4 weeks. Patients from each group were also given either a multi-strain probiotic or placebo supplement. Response was defined as a reduction of 50 points or more on the validated IBS symptom scoring system. Fecal samples were collected from participants at baseline and end of the 4-week study period; VOCs were analyzed by a gas-chromatography sensor device. VOC profiles were determined using a pipeline involving wavelet transformation followed by feature selection based on random forest. A partial least squares classifier was constructed to classify VOC profiles by response and accuracies were determined using 10-fold cross-validation. RESULTS: Data from 93 patients who completed the study (63 female) were used in the final analysis. More patients responded to the low-FODMAP diet (37/46, 80%) than the sham diet (21/47, 45%) (P < .001), but there was no difference in response between patients given the probiotic (31/49, 63%) vs the placebo (27/44, 61%) (P = .850), with no interaction between the diet and supplement interventions. At baseline, VOC profiles contained 15 features that classified response to the low-FODMAP diet with a mean accuracy of 97% (95% CI, 96%-99%) and 10 features that classified response to probiotic with a mean accuracy of 89% (95% CI, 86%-92%). End of treatment models achieved similar predictive powers and accuracies. CONCLUSION: Fecal VOC profiling is a low cost, non-invasive tool that might be used to predict responses of patients with IBS to low-FODMAP diet and probiotics and identify their mechanisms of action. ISRCTN registry no: 02275221.

A Diet Low in FODMAPs Reduces Symptoms in Patients With Irritable Bowel Syndrome and A Probiotic Restores Bifidobacterium Species: A Randomized Controlled Trial.

BACKGROUND & AIMS: Dietary restriction of fermentable carbohydrates (a low FODMAP diet) has been reported to reduce symptoms in some patients with irritable bowel syndrome (IBS). We performed a randomized, placebo-controlled study to determine its effects on symptoms and the fecal microbiota in patients with IBS. METHODS: We performed a 2×2 factorial trial of 104 patients with IBS (18-65 years old), based on the Rome III criteria, at 2 hospitals in the United Kingdom. Patients were randomly assigned (blinded) to groups given counselling to follow a sham diet or diet low in FODMAPs for 4 weeks, along with a placebo or multistrain probiotic formulation, resulting in 4 groups (27 receiving sham diet/placebo, 26 receiving sham diet/probiotic, 24 receiving low FODMAP diet /placebo, and 27 receiving low FODMAP diet/probiotic). The sham diet restricted a similar number of staple and non-staple foods as the low FODMAP diet; the diets had similar degrees of difficulty to follow. Dietary counselling was given to patients in all groups and data on foods eaten and compliance were collected. The incidence and severity of 15 gastrointestinal symptoms and overall symptoms were measured daily for 7 days before the study period; along with stool frequency and consistency. At baseline, global and individual symptoms were measured, along with generic and disease-specific health-related quality of life, using standard scoring systems. All data were collected again at 4 weeks, and patients answered questions about adequate symptom relief. Fecal samples were collected at baseline and after 4 weeks and analyzed by quantitative PCR and 16S rRNA sequencing. The co-primary endpoints were adequate relief of symptoms and stool Bifidobacterium species abundance at 4 weeks. RESULTS: There was no significant interaction between the interventions in adequate relief of symptoms (P = .52) or Bifidobacterium species (P = .68). In the intention-to-treat analysis, a higher proportion of patients in the low FODMAP diet had adequate symptom relief (57%) than in the sham diet group (38%), although the difference was not statistically significant (P = .051). In the per-protocol analysis, a significantly higher proportion of patients on the low FODMAP diet had adequate symptom relief (61%) than in the sham diet group (39%) (P = .042). Total mean IBS-Severity Scoring System score was significantly lower for patients on the low FODMAP diet (173 ± 95) than the sham diet (224 ± 89) (P = .001), but not different between those given probiotic (207 ± 98) or placebo (192 ± 93) (P = .721) Abundance of Bifidobacterium species was lower in fecal samples from patients on the low FODMAP diet (8.8 rRNA genes/g) than patients on the sham diet (9.2 rRNA genes/g) (P = .008), but higher in patients given probiotic (9.1 rRNA genes/g) than patients given placebo (8.8 rRNA genes/g) (P = .019). There was no effect of the low FODMAP diet on microbiota diversity in fecal samples. CONCLUSIONS: In a placebo-controlled study of patients with IBS, a low FODMAP diet associates with adequate symptom relief and significantly reduced symptom scores compared with placebo. It is not clear whether changes resulted from collective FODMAP restriction or removal of a single component, such as lactose. Co-administration of the multistrain probiotic increased numbers of Bifidobacterium species, compared with placebo, and might be given to restore these bacteria to patients on a low FODMAP diet. Trial registration no: ISRCTN02275221.

Nutritional implications of dietary interventions for managing gastrointestinal disorders.

PURPOSE OF REVIEW: The aim of this review is to summarize some of the key dietary interventions recommended for common gastrointestinal disorders and to discuss recent evidence regarding their nutritional implications. RECENT FINDINGS: The gluten-free diet has been shown to negatively influence overall diet quality. The gluten-free diet is essential in celiac disease, although it is increasingly used for other perceived health benefits for which an analysis of perceived benefit should be weighed against any nutritional risks. Evidence from short-term controlled trials of a diet low in fermentable oligosaccharides, disaccharides, monosaccharide and polyols in irritable bowel syndrome suggests compromised intake of nutrients such as fiber, iron, and calcium, although findings vary across studies. Meanwhile long-term uncontrolled trials suggest dietary adequacy improves with reintroduction and personalization. Although high-fiber diets may be beneficial in diverticular disease and constipation, it may lead to reductions in energy intake and nutrient absorption in at-risk populations. SUMMARY: The role of therapeutic diets in the management of gastrointestinal disorders is increasingly recognized, but there are limited studies investigating their nutritional implications. The judicious use of dietetic expertise should minimize potential nutritional deficits, however further prospective trials are needed to identify the individuals and nutrients most at risk.

The low FODMAP diet: recent advances in understanding its mechanisms and efficacy in IBS.

There is an intensifying interest in the interaction between diet and the functional GI symptoms experienced in IBS. Recent studies have used MRI to demonstrate that short-chain fermentable carbohydrates increase small intestinal water volume and colonic gas production that, in those with visceral hypersensitivity, induces functional GI symptoms. Dietary restriction of short-chain fermentable carbohydrates (the low fermentable oligosaccharide, disaccharide, monosaccharide and polyol (FODMAP) diet) is now increasingly used in the clinical setting. Initial research evaluating the efficacy of the low FODMAP diet was limited by retrospective study design and lack of comparator groups, but more recently well-designed clinical trials have been published. There are currently at least 10 randomised controlled trials or randomised comparative trials showing the low FODMAP diet leads to clinical response in 50%-80% of patients with IBS, in particular with improvements in bloating, flatulence, diarrhoea and global symptoms. However, in conjunction with the beneficial clinical impact, recent studies have also demonstrated that the low FODMAP diet leads to profound changes in the microbiota and metabolome, the duration and clinical relevance of which are as yet unknown. This review aims to present recent advances in the understanding of the mechanisms by which the low FODMAP diet impacts on symptoms in IBS, recent evidence for its efficacy, current findings regarding the consequences of the diet on the microbiome and recommendations for areas for future research.