Low FODMAP Research Articles

Top studies of 2022 relevant to primary care: From the PEER team.

To summarize 10 high-quality medical articles published in 2022 that are relevant to primary care physicians. Routine surveillance of tables of contents in relevant medical journals and EvidenceAlerts was conducted by the PEER (Patients, Experience, Evidence, Research) team, a group of primary care health care professionals with an interest in evidence-based medicine. Articles were selected and ranked based on relevance to practice. Published articles from 2022 most likely to influence primary care practice examined the following subjects: reducing dietary sodium for heart failure; timing of blood pressure medications to reduce cardiovascular outcomes; adding as-needed corticosteroids to rescue puffers for asthma exacerbations; influenza vaccination after myocardial infarction; comparing various medications for diabetes management; tirzepatide for weight loss; low FODMAP diet for irritable bowel syndrome; prune juice for constipation; impact of regular acetaminophen use on patients with hypertension; and time required to care for patients in primary care. Two "honourable mention" studies are also summarized. Research published in 2022 yielded several high-quality articles on various conditions relevant to primary care, including hypertension, heart failure, asthma, and diabetes.

Clinical outcome of disorders of gut-brain interaction in secondary care: A longitudinal study.

Real-world data on the outcome of routine treatment for disorders of gut-brain interaction (DGBI) in secondary care are lacking. A longitudinal study of consecutive adult patients with various DGBI attending this institution's gastroenterology clinic was conducted. Following 2 years of treatment, the proportion of patients with symptom improvement, details of clinical therapy, factors associated with and the impact of 'no symptom improvement' were determined. A total of 289 patients (median age 68 years; 64.7% females; 28.4% irritable bowel syndrome (IBS), 20.1% functional dyspepsia (FD), 8.7% functional constipation (FC), 42.9% overlap syndrome) were recruited. After 2 years, 66.1% patients reported symptom improvement. Patients with overlap syndrome were less likely to have symptomatic improvement compared to those with a single DGBI (Overlap 55.6% vs IBS 74.4% vs FD 72.4% vs FC 76.0%, p = 0.014). Reassurance was associated with symptom improvement (p < 0.001). On multivariate analysis, overlap syndrome remained significantly associated with a poorer outcome (OR 2.27, 95% CI 1.22-4.25, p = 0.010), while providing reassurance was associated with a positive outcome (OR 0.30, 95% CI 0.16-0.56, p < 0.001). Only 25.6% and 14.9% of patients were referred for a low FODMAP diet and psychiatric intervention respectively. DGBI patients who had 'no improvement' were more likely to seek further GI consultations and had more work absenteeism. Two-thirds of DGBI patients in secondary care showed symptom improvement. Patients who were reassured had better symptom improvement, while those with an overlap syndrome were associated with a poorer outcome, resulting in greater healthcare consultation and work absenteeism.

HPAEC-PAD Analytical Evaluation of Carbohydrates Pattern for the Study of Technological Parameters Effects in Low-FODMAP Food Production.

"FODMAPs" (fermentable-oligo-, di-, monosaccharides, and polyols) are a group of fermentable carbohydrates and polyols largely diffused in food products. Despite their beneficial effects as prebiotics, people affected by irritable bowel syndrome manifest symptoms when eating these carbohydrates. A low-FODMAP diet seems to be the only possible therapy proposed for symptom management. Bakery products are a common source of FODMAPs, whose pattern and total amount can be affected by their processing. This work aims at studying some of the technological parameters that can influence the FODMAPs pattern in bakery products during the production process. high-performance anion exchange chromatography coupled to a pulsed amperometric detector (HPAEC-PAD) was used as a highly selective system for carbohydrates evaluation analyses on flours, doughs, and crackers. These analyses were performed using two different columns, the CarboPac PA200 and CarboPac PA1, which are selective for oligosaccharide and simple sugar separation, respectively. emmer and hemp flours were selected to prepare doughs as they contained low oligosaccharide content. Two different mixes of ferments were used at different times of fermentation to evaluate the best conditions to achieve low-FODMAP crackers. the proposed approach allows carbohydrate evaluation during crackers processing and permits the selection of opportune conditions to obtain low-FODMAP products.

Randomized controlled pilot study assessing fructose tolerance during fructose reintroduction in non-constipated irritable bowel syndrome patients successfully treated with a low FODMAP diet.

Limited data exist to guide FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) reintroduction to assess tolerance following a low FODMAP diet (LFD). Fructose reintroduction is often stepwise up to 7.5 g fructose (e.g., three tsp of honey). We aimed to determine the fructose tolerance threshold in non-constipated, LFD-responsive patients with irritable bowel syndrome (IBS) and assess whether stool microbiome predicted LFD response or fructose tolerance. Thirty-nine non-constipated IBS patients (51% women, mean age 33.7 years) completed a 4-week LFD. LFD responders were defined as those who reported adequate relief of IBS symptoms following the LFD. Responders were randomized to one of the three solution groups (100% fructose, 56% fructose/44% glucose, or 100% glucose) and received four doses (2.5, 5, 10, 15 g) for 3 days each. Patients reached their tolerance dose if their mean daily IBS symptom severity (visual analog scale [VAS], 0-100 mm) was >20 mm higher than post-LFD VAS. Stool samples before and after LFD were analyzed using shotgun metagenomics. Seventy-nine percent of patients were LFD responders. Most responders tolerated the 15 g sugar dose. There was no significant difference in mean dose tolerated between solution groups (p = 0.56). Compared to baseline, microbiome composition (beta diversity) significantly shifted and six bacterial genes in fructose and mannose metabolism pathways decreased after LFD, irrespective of LFD response or the solution group. Non-constipated, LFD-responsive IBS patients should be reintroduced to fructose in higher doses than 15 g to assess tolerance. LFD is associated with significant changes in microbial composition and bacterial genes involved in FODMAP metabolism.

The effect of the FODMAP and rebamipid diet on the activity of disaccharidases in patients with enteropathy with impaired membrane digestion

To compare the effect of a diet low in fermentable oligo-, di-, monosaccharides and polyols (fermentable oligosaccharides, disaccharides, monosaccharides and polyols - FODMAP) and rebamipide on carbohydrate tolerance and disaccharidases activity in patients with maldigestive enteropathy (ENMP). The study included 61 patients with ENMP with reduced small intestine carbohydrases. Their glucoamylase activity was 100 ng glucose/mg tissue × min (quartile 53, 72), maltase - 504 (quartile 258, 708), sucrase - 43 (quartile 25, 58), lactase - 8 (quartile 4, 20). Group 1 included 19 people on a low FODMAP diet. The 2nd group included 42 patients who were on a normal diet and received rebamipide 300 mg/day. Patients were monitored weekly for 8 weeks. In 16 patients of the 1st group, abdominal pain and stool disorders decreased, in 15 patients, swelling and rumbling in the abdomen stopped. Glucoamylase activity increased to 196 (quartile 133, 446, р<0.024) ng glucose/mg tissue × min, maltase activity increased to 889 (quartile 554, 1555, p<0.145), sucrase activity increased to 67 (quartile 43, 175, p<0.039), lactase activity increased to 13 (quartile 9, 21, p<0.02). After the diet was discontinued, intestinal symptoms in patients of group 1 resumed. In 27 patients of the 2nd group after 4 weeks dyspeptic manifestations decreased, in 34 patients the tolerability of products containing FODMAP improved. Continuation of treatment up to 8 weeks contributed to a further improvement in well-being. Glucoamylase activity increased after 4 and 8 weeks to 189 (quartile 107, 357, p<0.013) and 203 (quartile 160, 536, p<0.005), respectively; maltase - up to 812 (quartile 487, 915, p<0.005) and 966 (quartile 621, 2195, р<0.0012); sucrases - up to 60 (quartile 34, 105, p<0.013) and 75 (quartile 52, 245, р=0.003); lactase - up to 12 (quartile 8, 12, p<0.132) and 15 ng glucose/mg tissue ×min (quartile 10, 20, р<0.092). The clinical symptoms of fermentable carbohydrate intolerance and increased membrane enzyme activity are reduced by a low FODMAP diet in patients with ENMT, but clinical symptoms of food intolerance reappear when switching to a normal diet. Treatment with rebamipide improves food tolerance and consistently increases the activity of TSOTS enzymes after 4 and 8 weeks.

Screening and Application of Novel Homofermentative Lactic Acid Bacteria Results in Low-FODMAP Whole-Wheat Bread

FODMAPs are fermentable oligo-, di-, monosaccharides, and polyols. The application of homofermentative lactic acid bacteria (LAB) has been investigated as a promising approach for producing low-FODMAP whole-wheat bread. The low-FODMAP diet is recommended to treat irritable bowel syndrome (IBS). Wheat flour is staple to many diets and is a significant source of fructans, which are considered FODMAPs. The reduction of fructans via sourdough fermentation, generally associated with heterofermentative lactic acid bacteria (LAB), often leads to the accumulation of other FODMAPs. A collection of 244 wild-type LAB strains was isolated from different environments and their specific FODMAP utilisation profiles established. Three homofermentative strains were selected for production of whole-wheat sourdough bread. These were Lactiplantibacillus plantarum FST1.7 (FST1.7), Lacticaseibacillus paracasei R3 (R3), and Pediococcus pentosaceus RYE106 (RYE106). Carbohydrate levels in flour, sourdoughs (before and after 48 h fermentation), and resulting breads were analysed via HPAEC-PAD and compared with whole-wheat bread leavened with baker’s yeast. While strain R3 was the most efficient in FODMAP reduction, breads produced with all three test strains had FODMAP content below cut-off levels that would trigger IBS symptoms. Results of this study highlighted the potential of homofermentative LAB in producing low-FODMAP whole-wheat bread.

Characteristics and properties of a polysaccharide isolated from Wolfiporia cocos as potential dietary supplement for IBS.

As low FODMAP (Fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet therapy is recommended for most of Irritable Bowel Syndrome (IBS) patients, the consequent insufficient of dietary fibers (DFs) intake exert an adverse impact on intestinal health. It is necessary to find suitable DFs for IBS patients. This study extracted a water-insoluble polysaccharide from Wolfiporia cocos (WIP) by alkali-extraction and acid-precipitation method. Its molecular weight was detected by high performance gel permeation chromatography (HPGPC) analysis. The structure of WIP was analyzed by Fourier transform infrared (FT-IR) spectrum, Nuclear Magnetic Resonance (NMR) spectra and X-ray diffraction (XRD). The properties related to stability, digestion, viscosity, osmotic activity, adsorption and fermentation were investigated, aimed to explore the feasibility of WIP as a new DF supplement for patients with IBS. In addition, 16S rRNA sequencing analysis was conducted to explore its effects on IBS-related gut microbiota. The results showed that WIP had a single homogeneous composition and the molecular weight was 8.1 × 103 Da. WIP was indicated as a kind of pyranose form with β anomeric configuration and the main chain of WIP was 1,3-β-glucan with amorphous structure. In addition to good thermal stability, WIP also has low bioavailability and can reach the colon mostly without being digested. Moreover, the low viscosity and osmotic activity, the high water- swelling and water/oil-holding capacity, fructose adsorption capacity and poor fermentation performance of WIP demonstrated that it is suitable for IBS patients. It is worth noting that WIP regulates IBS associated gut microbiota effectively, such as the abundance of Lachnospiraceae and Prevotella. These findings provide a theoretical basis for the development of WIP as a dietary supplement for IBS patients with low FODMAP diet therapy. GRAPHICAL ABSTRACT.

The impact of diet and ethnicity on gut microbiota variation in irritable bowel syndrome: A multi-center study.

The gut microbiota in irritable bowel syndrome (IBS) is known to vary with diet. We aim to (i) analyze the gut microbiota composition of IBS patients from a multi-ethnic population and (ii) explore the impact of a low FODMAP diet on gastrointestinal symptoms and gut microbiota composition among IBS patients. A multi-center study of multi-ethnic Asian patients with IBS was conducted in two phases: (i) an initial cross-sectional gut microbiota composition study of IBS patients and healthy controls, followed by (ii) a single-arm 6-week dietary interventional study of the IBS patients alone, exploring clinical and gut microbiota changes. A total of 34 adult IBS patients (IBS sub-types of IBS-D 44.1%, IBS-C 32.4%, and IBS-M 23.5%) and 15 healthy controls were recruited. A greater abundance of Parabacteroides species with lower levels of bacterial fermenters and short-chain fatty acids producers were found among IBS patients compared with healthy controls. Age and ethnicity were found to be associated with gut microbiota composition. Following a low FODMAP dietary intervention, symptom and quality of life improvement were observed in 24 (70.6%) IBS patients. Symptom improvement was associated with adherence to the low FODMAP diet (46.7% poor adherence vs 92.9% good adherence, P=0.014), and gut microbiota patterns, particularly with a greater abundance of Bifidobacterium longum, Anaerotignum propionicum, and Blautia species post-intervention. Gut microbiota variation in multi-ethnic IBS patients may be related to dietary intake and may be helpful to identify patients who are likely to respond to a low FODMAP diet.

Irritable bowel syndrome – modern ways of treatment

Introduction&#x0D; Irritable bowel syndrome (IBS) is the most frequent functional disorder of the gastrointestinal tract. Main symptoms are recurring stomach ache connected with defecation, changes of frequency of defecation and/or stool’s consistency. Cause of IBS is still unknown unlike its pathomechanism. Continuous research allows doctors to understand and treat it better.&#x0D; Discussion&#x0D; Diagnosing IBS might be difficult even for the most experienced doctors due to its uncharacteristic symptoms. Therefore diagnosis should be made by using Rome IV Criteria. IBS is divided into 4 subtypes basing on clinical picture: IBS with predominant constipation, IBS with predominant diarrhea, IBS with mixed bowel habits and IBS unclassified. Classification is being performed with the use of Bristol Stool Chart. Choice of remedy should be made depending on the subtype of IBS. Pharmacological treatment is symptomatic and focuses on relieving pain, diarrhea, constipation and bloating. Drugs that can be used are: loperamide, rifaximin, antispasmodic (e.g. hyoscine), antidepressants or laxatives. Treatment should also contain nonpharmacological methods. Nonpharmacological techniques which are proved to help patients contain regular physical activity, body mass reduction, low-FODMAP diet, using probiotics, psychotherapy and supplementing soluble fibre.&#x0D; Conclusions&#x0D; IBS is a big issue for public health as it is lowering quality of life and is generating big indirect costs. Difficulties in diagnosing are increasing those costs. That’s why it is of high importance to find more effective therapy. Raising awareness among doctors is crucial as plenty of methods are available to treat the disease which allows to reduce symptoms and costs.

A272 EVIDENCE OF SEX DIFFERENCES IMPACTING PAIN SIGNALING BY LUMINAL MEDIATORS IN IRRITABLE BOWEL SYNDROME

Abstract Background Irritable bowel syndrome (IBS) is more than twice as common in women and female patients report more severe abdominal pain. This suggests that sex-specific mechanisms may contribute to the pathophysiology of IBS. Many IBS patients have altered gut microbiota and luminal meditators, implicating the gut microbiota in abdominal pain. These luminal mediators can alter excitability of visceral nociceptors, thus potentially contributing to abdominal pain in IBS. Furthermore, in a subset of IBS patients a low FODMAP diet (LFD) reduces the effect of luminal mediators on pain sensing neurons. The LFD may improve abdominal pain at greater rates in women, and numerous putative mechanisms contributing to abdominal pain in IBS are susceptible to sex-specific mediators. However, it is unknown whether luminal mediators have similar effects on visceral pain signaling in both males and females. We hypothesize that luminal mediators will cause greater differences in neuronal excitability and pain signaling in female mice due to sex-specific factors. Purpose To determine whether FS from IBS patients (IBS FS) affects nociceptors from female mice more than nociceptors from male mice. Method Neurons from dorsal root ganglia from male and female mice were incubated overnight in media containing fecal supernatant (FS) from IBS patients (N=2 females) before and after the LFD, or healthy controls (HC, N=1 female and 1 male). Ratiometric Ca2+ imaging with FURA-2-AM was employed to quantify TRPV1 channel sensitization following application of capsaicin (100nM for 1 minute) as a measure of neuronal excitability. Data was analyzed using chi-squared test as well as two-way and mixed-effects model ANOVA as appropriate, followed by Sidak’s multiple comparisons test. Result(s) IBS FS caused a 177% larger Ca2+ influx in response to capsaicin compared to HC FS in female mice (p=0.0148, N=6-7 mice, neurons=43-49). In male mice, IBS FS increased Ca2+ influx by only 13% compared to HC FS (p=0.79, N=5 mice, neurons=28-35). In female mice, 117% more neurons responded to capsaicin after incubation with IBS FS versus HC FS (p=0.0004), while in male mice, only 17% more neurons responded following incubation with IBS FS (p=0.46). Finally, FS from the same IBS patients following a LFD reduced neuronal Ca2+ influx by 39% compared to IBS FS in female mice (p=0.0434, N=4-6 mice, neurons=18-49). In male mice, LFD FS reduced Ca2+ influx by 11% versus IBS FS (p=0.98, N=5 mice, neurons=28-35). Conclusion(s) Nociceptive neurons from female mice are more sensitive to the pro-nociceptive effects of FS from IBS patients, as well as a reduction of these excitatory effects following the LFD. This suggests a potential role of sex hormones in pain signaling in IBS. Disclosure of Interest None Declared

A218 ASSOCIATIONS BETWEEN ADHERENCE TO LITERATURE-DERIVED DIETARY INDICES AND PRE-DISEASE BIOMARKERS: IMPLICATIONS FOR CROHN’S DISEASE PREVENTION

Abstract Background The incidence of Crohn’s disease (CD) is increasing globally, indicating a significant environmental influence such as diet. A plethora of dietary adherence (DA) patterns exist in the literature: the Mediterranean Diet (MD), Empirical Dietary Inflammatory Pattern (EDIP), Specific Carbohydrate Diet (SCD), and low Fermentable Oligosaccharide, Disaccharide, Monosaccharide, or Polyol diet (FODMAP) are all potential candidates to maintain a reduced level of inflammation, improving gastrointestinal function. Contrary, the Westernized diet (WD) is generally reported as a diet promoting inflammation in humans. Purpose To determine if DA to literature-derived dietary indices in a cohort of first-degree relatives (FDRs) of CD patients can modulate pre-disease biomarkers. Method We used food frequency questionnaire (FFQ) data from 2,696 healthy FDR subjects of the Crohn’s Colitis Canada- Genes, Environment, Microbial (CCC-GEM) project. We rederived each of the following scores using our FFQ data, utilizing originally described methods for the MD, EDIP, SCD, low FODMAP, and WD to obtain DA. Each diet was correlated pairwise via Kendall’s Tau. We fit multivariable regression models to identify the association of DA (top quintile vs remaining) and: i) intestinal permeability using urinary fractional excretion of lactulose to mannitol ratio (LMR), LMR≥0.03 defined abnormal; ii) subclinical inflammation using fecal calprotectin (FCP) measured with BÜHLMANN fCAL® ELISA, FCP≥250µg/g defined inflammation; and iii) fecal microbiome richness and composition using 16S rRNA sequencing. Two-sided p&amp;lt;0.05 for primary and q&amp;lt;0.05 for secondary analysis defined significance. Result(s) There were positive correlations between the MD, SCD, and low FODMAP, these diets negatively correlated with the WD. The EDIP negatively correlated with the SCD and low FODMAP, did not correlate with the MD, and positively correlated with the WD. No diet was associated with abnormal LMR or FCP. Only the SCD was associated with increased microbial richness (q=0.03). All diets were associated with microbial genera: the MD (n=18 taxa, (2.0-7&amp;lt;q-values&amp;lt; 0.04), EDIP (n=9, [2.8-4-0.05]), SCD (n=13, [3.7-11-0.05]), low FODMAP (n=14, [1.3-7-0.05]), and WD (n=1, [0.03]). Conclusion(s) This study shows that literature-derived dietary indices correlate generally with each other, yet none were not associated with abnormal LMR or FCP. However, we found that diet can impact microbiome richness and composition. Thus, it is tempting to speculate that diet is a possible intervention capable of maintain microbiome homeostasis to reduce future risk of CD. Submitted on behalf of the CCC-GEM consortium. Funding Crohn’s and Colitis Canada Genetics Environment Microbial (CCC-GEM) III The Leona M. and Harry B. Helmsley Charitable Trust Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Disease Disclosure of Interest None Declared

A19 INVESTIGATING MECHANISMS THAT DRIVE SYMPTOMS IN IRRITABLE BOWEL SYNDROME PATIENTS WITH PERCEIVED GLUTEN SENSITIVITY

Abstract Background Patients with irritable bowel syndrome (IBS) often report gastrointestinal symptoms after consuming wheat and gluten-containing foods. It is, however, unclear whether gluten is the main driver of symptoms, as other immunogenic peptides, such as amylase trypsin inhibitors (ATI), poorly digestible fiber (inulin, part of FODMAP) or even the nocebo effect may contribute to symptom generation. Purpose To evaluate whether whole wheat containing ATIs and/or purified gluten trigger gastrointestinal symptoms compared to nocebo in patients with IBS adopting a gluten-free diet (GFD). Method We conducted a double-blind, randomized, nocebo-controlled crossover study in adult IBS patients (Rome IV criteria) who previously perceived improvement of symptoms while on a GFD. The study was approved by the Hamilton Research Ethics Board (HiREB #4367). Participants were challenged for 7 days with whole wheat, purified gluten, and nocebo (gluten-free flour) added to low FODMAP cereal bars. Each challenge was followed by a 2-week washout. Patients remained on a GFD throughout the study, diet adherence was assessed by a dietitian and stool gluten immunogenic peptides (GIP; Biomedal). Gastrointestinal symptoms were assessed by IBS Symptom Severity Score (IBS-SSS); increases &amp;gt;50 points were considered a significant worsening. Blood samples were collected to assess immune markers and celiac (HLA DQ2, DQ8 and DQ7) genotype. Statistical comparisons used Friedman rank sum tests and paired Wilcoxon signed rank tests. Result(s) Twenty-nine IBS patients (27 female, mean age=42, SD=14.4 years) were enrolled in the study; 1 dropped. Similar proportions of patients reacted symptomatically to wheat (11/28, 39.3%), gluten (10/28, 35.7%) and nocebo (8/28, 28.6%). However, there was an overall significant increase in IBS symptoms after wheat (+39.5 on IBS-SSS; p=0.030) but not after gluten (+27.5; p=0.051) or nocebo (+5.5; p=0.236) challenges (Figure 1). Ten participants experienced IBS-SSS symptoms &amp;gt;175 during baseline and did not worsen further during the challenges. TNF-α trended from 1.35 pg/mL after nocebo, 1.47 pg/mL after gluten, to 1.57 pg/mL after wheat; however, this was not significant. Baseline adherence to a GFD was rated excellent in 19 (68%), good in 6 (21%), and fair in 3 (11%) participants. Median GIP levels were 0.584 µg/g after wheat, 0.432 µg/g after gluten, and 0.095 µg/g after nocebo; p&amp;lt;0.0001. Celiac predisposition genes were present in 19/24 participants (10/24 had DQ2, 2/24 had DQ8, and 9/24 had DQ7). Image Conclusion(s) IBS patients self-reporting wheat or gluten sensitivity had worse symptoms after whole wheat, but not purified gluten or nocebo challenge. However, similar proportions of IBS patients reacted to each intervention, suggesting that central mechanisms play an important role in symptom genesis. Furthermore, one third of patients had high symptoms during a GFD and did not react to wheat or gluten challenges, suggesting that other mechanisms are driving their IBS symptoms. Please acknowledge all funding agencies by checking the applicable boxes below CIHR, Other Please indicate your source of funding; Society for the Study of Celiac Disease (Nestle); Canadian Digestive Health Foundation Disclosure of Interest None Declared

Current evidence for dietary therapies in irritable bowel syndrome.

Diet appears to trigger symptoms in the majority of individuals with irritable bowel syndrome (IBS) and is associated with a reduced quality of life. There has been a recent focus on the role of dietary therapies to manage individuals with IBS. The aim of this review is to discuss the utility of traditional dietary advice (TDA), low-FODMAP diet (LFD) and gluten-free diet (GFD) in IBS. Several recent randomized controlled trials (RCTs) have been published demonstrating the efficacy of the LFD and GFD in IBS, with the evidence base for TDA being predominantly based on clinical experience, with emerging RCTs evaluating TDA. Only one RCT has been published to date comparing TDA, LFD and GFD head to head, with no difference noted between diets in terms of efficacy. However, TDA has been noted to be more patient-friendly and is commonly implemented as a first-line dietary therapy. Dietary therapies have been demonstrated to improve symptoms in patients with IBS. In view of insufficient evidence to recommend one diet over another currently, specialist dietetic input in conjunction with patient preference is required to determine implementation of dietary therapies. Novel methods of dietetic delivery are required in view of the lack of dietetic provision to deliver these therapies.

Gastrointestinal tract involvement in systemic sclerosis: The roles of diet and the microbiome

BackgroundAlterations in gastrointestinal (GI) microbial composition have been reported in patients with systemic sclerosis (SSc). However, it is unclear to what degree these alterations and/or dietary changes contribute to the SSc-GI phenotype. ObjectivesOur study aimed to 1) evaluate the relationship between GI microbial composition and SSc-GI symptoms, and 2) compare GI symptoms and GI microbial composition between SSc patients adhering to a low versus non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet. MethodsAdult SSc patients were consecutively recruited to provide stool specimens for bacterial 16S rRNA gene sequencing. Patients completed the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (GIT 2.0) and the Diet History Questionnaire (DHQ) II and were classified as adhering to a low or non-low FODMAP diet. GI microbial differences were assessed using three metrics of alpha diversity (species richness, evenness, and phylogenetic diversity), as well as beta diversity (overall microbial composition). Differential abundance analysis was performed to identify specific genera associated with SSc-GI phenotype and low versus non-low FODMAP diet. ResultsOf the 66 total SSc patients included, the majority were women (n = 56) with a mean disease duration of 9.6 years. Thirty-five participants completed the DHQ II. Increased severity of GI symptoms (total GIT 2.0 score) was associated with decreased species diversity and differences in GI microbial composition. Specifically, pathobiont genera (e.g., Klebsiella and Enterococcus) were significantly more abundant in patients with increased GI symptom severity. When comparing low (N = 19) versus non-low (N = 16) FODMAP groups, there were no significant differences in GI symptom severity or in alpha and beta diversity. Compared with the low FODMAP group, the non-low FODMAP group had greater abundance of the pathobiont Enterococcus. ConclusionSSc patients reporting more severe GI symptoms exhibited GI microbial dysbiosis characterized by less species diversity and alterations in microbial composition. A low FODMAP diet was not associated with significant alterations in GI microbial composition or reduced SSc-GI symptoms; however, randomized controlled trials are needed to evaluate the impact of specific diets on GI symptoms in SSc.

Low FODMAP Diet Relieves Visceral Hypersensitivity and Is Associated with Changes in Colonic Microcirculation in Water Avoidance Mice Model.

(1) Background: Irritable bowel syndrome (IBS) is a global public health problem, the pathogenesis of which has not been fully explored. Limiting fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can relieve symptoms in some patients with IBS. Studies have shown that normal microcirculation perfusion is necessary to maintain the primary function of the gastrointestinal system. Here, we hypothesized that IBS pathogenesis might be related to abnormalities in colonic microcirculation. A low-FODMAP diet could alleviate visceral hypersensitivity (VH) by improving colonic microcirculation; (2) Methods: C57BL/6 mice were raised to establish an IBS-like rodent model using water avoidance (WA) stress or SHAM-WA as a control, one hour per day for ten days. The mice in the WA group were administered different levels of the FODMAP diet: 2.1% regular FODMAP (WA-RF), 10% high FODMAP diet (WA-HF), 5% medium FODMAP diet (WA-MF), and 0% low FODMAP diet (WA-LF) for the following 14 days. The body weight and food consumption of the mice were recorded. Visceral sensitivity was measured as colorectal distention (CRD) using the abdominal withdrawal reflex (AWR) score. Colonic microcirculation was assessed using laser speckle contrast imaging (LCSI). Vascular endothelial-derived growth factor (VEGF) was detected using immunofluorescence staining; (3) Results: The threshold values of CRD pressure in the WA-RF, WA-HF, and WA-MF groups were significantly lower than those in the SHAM-WA group. Moreover, we observed that colonic microcirculation perfusion decreased, and the expression of VEGF protein increased in these three groups of mice. Interestingly, a low-FODMAP dietary intervention could reverse this situation. Specifically, a low-FODMAP diet increased colonic microcirculation perfusion, reduced VEGF protein expression in mice, and increased the threshold of VH. There was a significant positive correlation between colonic microcirculation and threshold for VH; (4) Conclusions: These results demonstrate that a low-FODMAP diet can alter VH by affecting colonic microcirculation. Changes in intestinal microcirculation may be related to VEGF expression.

Mechanisms behind the Role of SIBO in Non-Alcoholic Fatty Liver Disease: An Interplay between Liver, Gut Microbiota and Nutrition

Abstract: Nonalcoholic fatty liver disease (NAFLD) is known as the leading cause of chronic liver disease in both children and adults. Increasing evidence suggests that dysbiosis of the intestinal microbiota plays a key role in the regulation of various metabolic and inflammatory pathways, which may result in the development of NAFLD. When normal liver physiology is impaired, gut-derived factors may lead to increased tissue damage and inflammation. Small intestinal bacterial overgrowth (SIBO) is defined as a condition in which a large amount of intestinal bacteria are present in the small intestine. The permeability of the intestinal barrier increases with SIBO, resulting in an increase in bacterial translocation and endotoxemia. SIBO is assumed to play a critical role in the development and progression of NAFLD. Therefore, this review focuses on the mechanisms in which SIBO may play a role in NAFLD and possible nutritional management strategies such as a low FODMAP diet, probiotics and prebiotics targeting SIBO and NAFLD.

Gastrointestinal Manifestations and Low-FODMAP Protocol in a Cohort of Fabry Disease Adult Patients.

Fabry disease (FD) is an X-linked lysosomal disorder caused by α-galactosidase A enzyme deficiency. Gastrointestinal (GI) manifestations are reported in FD with a prevalence of about 50%, usually treated by Enzymatic Replacement Therapy (ERT) or oral treatment. Since FODMAPs (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) can be involved in GI manifestations and dysbiosis in FD patients, a low-FODMAP diet could represent an alternative adjunctive treatment in FD subjects, as well as being useful for reducing symptoms in Irritable Bowel Syndrome (IBS). We retrospectively assessed data from 36 adult FD patients followed at the Inherited Metabolic Rare Diseases Adult Centre of the University Hospital of Padova (mean age 47.6 ± 16.2 years). Patients were screened for GI symptoms by IBS severity score and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires. In symptomatic patients, the low-FODMAP diet was proposed in order to improve GI manifestations; it consists of a phase of elimination of fermentable saccharides, succeeded by a gradual reintegration of the same. Severe or moderate GI symptoms were found in 61.1% of patients, with no correlation to the therapy in use, and significantly more severe in the classical form of FD. The protocol was completed by seven patients affected by severe GI manifestations, significantly higher than the others. The low-FODMAP diet significantly improved indigestion, diarrhoea, and constipation. This dietetic protocol seemed to have a positive impact on intestinal symptoms, by identifying and reducing the intake of the foods most related to the onset of disorders and improving the clinical manifestations. A low-FODMAP diet may be an effective alternative approach to improve intestinal manifestations and quality of life, and nutrition can play an important role in the multidisciplinary care of patients with FD.

Os efeitos da dieta FODMAP em crianças e adolescentes com a síndrome do intestino irritável - revisão sistemática

INTRODUCTION: Food is a triggering factor for irritable bowel syndrome (IBS) symptoms. One therapeutic management option that has had beneficial effects is a low-FODMAP diet (acronym for fermentable oligosaccharides, disaccharides, monosaccharides and polyols). OBJECTIVE: To analyze the efficacy and effects of a low-FODMAP diet in pediatric patients with IBS. METHODS: Systematic review using data from PubMed, SciELO and BVS using the descriptors “(Irritable bowel syndrome) AND (FODMAP)”, age filter from 0 to 18 years, in English, Portuguese and Spanish, with a 10-year temporal filter. Duplicate articles, articles not in agreement with the theme and non-scientific work were excluded. RESULTS AND DISCUSSION: 445 articles were found, but only 3 articles were selected among the eligibility criteria. The studies analyzed make comparisons between the test group and the placebo group, or compare children on a typical American infant diet with a reduced FODMAP diet. It is evident that the low FODMAP diet reduces the symptoms of IBS, but it has factors that make it difficult to be practicable, such as: difficulty in being taught and understood, high cost, impact on the intestinal microbiota, presence of side effects such as constipation, in addition to the impact psychological impact of these restrictions for this age group. CONCLUSION: A low-FODMAP diet is a therapy that alleviates the clinical conditions manifested in IBS, but its applicability is limited. More clinical and experimental studies are needed in order to establish whether the benefits of inserting this restrictive diet outweigh the possible harms.

ЭНТЕРОПАТИИ С НАРУШЕНИЕМ МЕМБРАННОГО ПИЩЕВАРЕНИЯ И СИНДРОМ РАЗДРАЖЕННОГО КИШЕЧНИКА – СОЧЕТАННАЯ ПАТОЛОГИЯ

The article describes the clinical manifestations and their causes in the pathology of the small intestine in patients who complain of excessive bloating, recurrent abdominal pain syndrome, stool disorders with a tendency to relaxation. Such patients repeatedly return to the doctor. The evidence of a decrease in the activity of disaccharidases in this cohort of patients is presented. The emphasis is placed on the need to study the nutritional history, to identify products that provoke a violation of membrane digestion. The classification of carbohydrates with indication of products containing them is given. The essence of repeated and persistent clinical manifestations due to impaired membrane digestion and absorption of carbohydrates in the small intestine is explained, which leads to their appearance in the large intestine in different volumes, which is accompanied by the splitting of carbohydrates with the formation of gases. On the one hand, this is a normal process, but when it gets out of control, the patient gets to the doctor. The essence of a carbohydrate–restricted diet is described - this is the low FODMAP diet and its decoding. The products containing oligosaccharides are indicated, which are capable of being cleaved by the enzyme alpha-galactosidase, which is absent in the human body, but is present in the microflora of the large intestine. Advice is given on limiting the intake of such products, both in terms of the frequency of intake and the volume of portions containing them, in order to avoid excessive amounts of intestinal gases, the development of a clinically painful condition. A thorough study of the nutritional history and the necessary correction of eating behavior is the main idea of this article, dedicated to the same type of clinical picture with varying degrees of manifestations of its symptoms.

InVitro Efficacy of Targeted Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols Enzymatic Digestion in a High-Fidelity Simulated Gastrointestinal Environment.

Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in bowel habits. Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) are poorly absorbed short-chain carbohydrates that may drive commensal microbial gas production, promoting abdominal pain in IBS. Low-FODMAP diet can result in symptomatic improvement in 50%-80% of IBS patients. However, this diet is not meant to be sustained long term, with concern for downstream nutrition and microbial issues. In this study, we evaluate the function of a targeted FODMAP enzymatic digestion food supplement FODMAP enzymatic digestion (FODZYME) containing a fructan-hydrolase enzyme (with significant inulinase activity) in a simulated gastrointestinal environment. Using SHIME (Simulator of the Human Intestinal Microbial Ecosystem), a multi-compartment simulator of the human gut, FODZYME dose finding assay in modeled gastrointestinal conditions assessed enzymatic ability to hydrolyze 3 g of inulin. Full intestinal modeling assessing digestion of inulin, absorption of fructose, gas production, and other measures of commensal microbial behavior was completed using 1.125 g of FODZYME. After 30 minutes, 90% of the inulin was converted to fructose by 1.125 g of FODZYME. Doubling dosage showed no significant improvement in conversion, whereas a half dose decreased performance to 77.2%. Seventy percent of released fructose was absorbed during simulated small intestinal transit, with a corresponding decrease in microbial gas production, and a small decrease in butyrate and short-chain fatty acid production. FODZYME specifically breaks down inulin in representative gastrointestinal conditions, resulting in decreased gas production while substantially preserving short-chain fatty acid and butyrate production in the model colon. Our results suggest dietary supplementation with FODZYME would decrease intestinal FODMAP burden and gas production.