Effect of prebiotic oligosaccharides on bowel habit and the gut microbiota in children with functional constipation (Inside study): study protocol for a randomised, placebo-controlled, multi-centre trial.

BACKGROUND: Functional constipation (FC) in children is a common gastrointestinal disorder with a worldwide-pooled prevalence of 9.5%. Complaints include infrequent bowel movements, painful defecation due to hard and/or large stools, faecal incontinence, and abdominal pain. Prebiotic oligosaccharides have been shown to relieve constipation symptoms in young adults and elderly. However, sufficient evidence is lacking linking additional prebiotic intake to improve symptoms in children with FC. We hypothesise that prebiotic oligosaccharides are able to relieve symptoms of constipation in young children as well. METHODS: In the present randomised, double-blind, placebo-controlled, multi-centre study, we will study the effects of two prebiotic oligosaccharides in comparison to placebo on constipation symptoms in children of 1-5 years (12 to 72 months) of age diagnosed with FC according to the Rome IV criteria for functional gastrointestinal disorders. The primary outcome measure will be change in stool consistency. Secondary outcomes include stool frequency and stool consistency in a number of cases (%). Tertiary outcomes include among others painful defecation, use of rescue medication, and quality of life. In addition, the impact on gut microbiome outcomes such as faecal microbiota composition and metabolites will be investigated. Participants start with a run-in period, after which they will receive supplements delivered in tins with scoops for 8 weeks, containing one of the two prebiotic oligosaccharides or placebo, followed by a 4-week wash-out period. DISCUSSION: This randomised double-blind, placebo-controlled multi-centre study will investigate the effectiveness of prebiotic oligosaccharides in children aged 1-5 years with FC. TRIAL REGISTRATION: ClinicalTrials.gov NCT04282551. Registered on 24 February 2020.

Tolerance and Safety of an Anti-Regurgitation Formula Containing Locust Bean Gum, Pre-, and Postbiotics: A Multi-Country Multi-Center Prospective Randomized Controlled Study in Infants with Regurgitation.

This multi-center prospective randomized controlled trial was a tolerance and safety study investigating the thickener locust bean gum (LBG) in infants with regurgitation, to support the re-evaluation of the safety of LBG in infant formula. The primary objective was to demonstrate that after an 8-week intervention, stool consistency was not inferior (i.e., was not looser or more watery) in infants fed an anti-regurgitation (AR) formula containing LBG vs. the stool consistency of infants fed with an unthickened control formula. A total of 103 full-term infants with regurgitation were randomized to the test or control formula. The test formula contained LBG (0.4 g/100 mL), short-chain galacto-oligosaccharides, and long-chain fructo-oligosaccharides (scGOS/lcFOS; 9:1; 0.4 g/100 mL) and postbiotics and the control formula contained scGOS/lcFOS (0.8 g/100 mL), the same amount of postbiotics, and did not contain LBG. The average stool consistency score at the 8th intervention week was the primary outcome parameter. Secondary outcome parameters were stool consistency at other timepoints, stool frequency, Infant Gastrointestinal Symptom Questionnaire (IGSQ) score, growth, (serious) adverse events ([S]AEs), regurgitation severity, and infant well-being. Overall, the infants were 36.9 ± 12.9 [mean ± SD] days old, 62.7% girls in the test, and 50.0% girls in the control group. The primary analysis showed that the test group did not have looser or more watery stools than the control group. IGSQ sum scores decreased comparably in both groups. The frequency of regurgitation was significantly lower in the test group compared to the control group (mixed model repeated measurement, p ≤ 0.028) and parent-reported well-being scores were favorable. Adequate growth was observed in both groups. Both products were well-tolerated and safe and the AR formula with LBG was efficacious in reducing regurgitation frequency. This study provides further evidence for the dietary management of regurgitation by LBG-containing formulae in infants who are not exclusively breastfed, and the reassurance it can bring to parents.

Agaro-oligosaccharides mitigate deoxynivalenol-induced intestinal inflammation by regulating gut microbiota and enhancing intestinal barrier function in mice.

Agarose-derived agaro-oligosaccharides (AgaroS) have been extensively studied in terms of structures and bioactivities; they reportedly possess antioxidant and anti-inflammatory activities that maintain intestinal homeostasis and host health. However, the protective effects of AgaroS on deoxynivalenol (DON)-induced intestinal dysfunction remain unclear. We investigated the effects of AgaroS on DON-induced intestinal dysfunction in mice and explored the underlying protective mechanisms. In total, 32 mice were randomly allocated to four treatments (n = 8 each) for 28 days. From day 1 to day 21, the control (CON) and DON groups received oral phosphate-buffered saline (200 µL per day); the AgaroS and AgaroS + DON groups received 200 mg AgaroS per kg body weight once daily by orogastric gavage. Experimental intestinal injury was induced by adding DON (4.8 mg per kg body weight) via gavage from day 21 to day 28. Phosphate-buffered saline was administered once daily by gavage in the CON and AgaroS groups. Herein, AgaroS supplementation led to a higher final body weight and smaller body weight loss and a lower concentration of plasma inflammatory cytokines, compared with the DON group. The DON group showed a significantly reduced ileal villus height and villus height/crypt depth, compared with the CON and AgaroS + DON groups. However, AgaroS supplementation improved DON-induced intestinal injury in mice. Compared with the DON group, ileal and colonic protein expression levels of claudin, occludin, Ki67, and mucin2 were significantly higher in the AgaroS supplementation group. Colonic levels of the anti-inflammatory cytokine IL-1ß tended to be higher in the DON group than in the AgaroS + DON group. AgaroS altered the gut microbiota composition, accompanied by increased production of short-chain fatty acids in mice. In conclusion, our findings highlight a promising anti-mycotoxin approach whereby AgaroS alleviate DON-induced intestinal inflammation by modulating intestinal barrier functional integrity and gut microbiota in mice.

Human milk oligosaccharides 3'-sialyllactose and 6'-sialyllactose attenuate LPS-induced lung injury by inhibiting STAT1 and NF-κB signaling pathways.

Acute lung injury (ALI) is the leading cause of respiratory diseases induced by uncontrolled inflammation and cell death. Lipopolysaccharide (LPS) is a major trigger of ALI in the progression through macrophage differentiation and the accelerated release of pro-inflammatory cytokines. The present study aimed to investigate the protective effects of human milk oligosaccharides, specifically 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL), on LPS-induced ALI and elucidate their underlying signaling pathways. The inhibitory effects of 3'-SL and 6'-SL on inflammation were evaluated using LPS-treated RAW 264.7 macrophages. To establish the ALI model, mice were treated with 10 mg/kg LPS for 24 h. Histological changes in the lung tissues were assessed using hematoxylin and eosin staining and immunofluorescence. LPS causes thickening of the alveolar wall infiltration of immune cells in lung tissues and increased serum levels of TNF-α, IL-1ß, and GM-CSF. However, these effects were significantly alleviated by 100 mg/kg of 3'-SL and 6'-SL. Consistent with the inhibitory effects of 3'-SL and 6'-SL on LPS-induced pro-inflammatory cytokine secretion in serum, 3'-SL and 6'-SL suppressed mRNA expression of TNF-α, IL-1ß, MCP-1, iNOS, and COX2 in LPS-induced RAW 264.7 cells. Mechanistically, 3'-SL and 6'-SL abolished LPS-mediated phosphorylation of NF-κB and STAT1. Interestingly, fludarabine treatment, a STAT1 inhibitor, did not affect LPS-mediated NF-κB phosphorylation. In summary, 3'-SL and 6'-SL protect LPS-induced macrophage activation and ALI through the STAT1 and NF-κB signaling pathways.

New insights into the binding of PF4 to long heparin oligosaccharides in ultralarge complexes using mass spectrometry.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a serious complication caused by heparin drugs. The ultralarge complexes formed by platelet factor 4 (PF4) with heparin or low molecular weight heparins (LMWHs) are important participants in inducing the immune response and HIT. OBJECTIVES: We aim at characterizing the interaction between PF4 and long-chain heparin oligosaccharides and providing robust analytical methods for the analysis of PF4-heparin complexes. METHODS: In this work, the characteristics of PF4-enoxaparin complexes after incubation in different molar ratios and concentrations were analyzed by multiple analytical methods, especially liquid chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry with multiple reaction monitoring were developed to qualitatively and quantitatively monitor heparin oligosaccharides and PF4 in HIT-inducing complexes. RESULTS: The results showed that the largest proportion of ultralarge complexes formed by PF4 and enoxaparin was at a specific molar ratio, ie, a PF4/enoxaparin ratio of 2:1, while the ultralarge complexes contained PF4 tetramer and enoxaparin at a molar ratio of approximately 2:1. CONCLUSION: A binding model of PF4 and enoxaparin in ultralarge complexes is proposed with one heparin oligosaccharide chain (∼ dp18) bound to 2 PF4 tetramers in different morphologies to form ultralarge complexes, while PF4 tetramer is surrounded by multiple heparin chains in smaller complexes. Our study provides new insights into the structural mechanism of PF4-LMWH interaction, which help to further understand the mechanism of LMWH immunogenicity and develop safer heparin products.

IBS randomized study: FODMAPs alter bile acids, phenolic- and tryptophan metabolites, while gluten modifies lipids.

Diet is considered a culprit for symptoms in irritable bowel syndrome (IBS), although the mechanistic understanding of underlying causes is lacking. Metabolomics, i.e., the analysis of metabolites in biological samples may offer a diet-responsive fingerprint for IBS. Our aim was to explore alterations in the plasma metabolome after interventions with fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) or gluten versus control in IBS, and to relate such alterations to symptoms. People with IBS (n = 110) were included in a double-blind, randomized, crossover study with 1-wk provocations of FODMAPs, gluten, or placebo. Symptoms were evaluated with the IBS severity scoring system (IBS-SSS). Untargeted metabolomics was performed on plasma samples using LC-qTOF-MS. Discovery of metabolite alterations by treatment was performed using random forest followed by linear mixed modeling. Associations were studied using Spearman correlation. The metabolome was affected by FODMAP [classification rate (CR) 0.88, P < 0.0001], but less by gluten intake CR 0.72, P = 0.01). FODMAP lowered bile acids, whereas phenolic-derived metabolites and 3-indolepropionic acid (IPA) were higher compared with placebo. IPA and some unidentified metabolites correlated weakly to abdominal pain and quality of life. Gluten affected lipid metabolism weakly, but with no interpretable relationship to IBS. FODMAP affected gut microbial-derived metabolites relating to positive health outcomes. IPA and unknown metabolites correlated weakly to IBS severity. Minor symptom worsening by FODMAP intake must be weighed against general positive health aspects of FODMAP. The gluten intervention affected lipid metabolism weakly with no interpretable association to IBS severity. Registration: www.clinicaltrials.gov as NCT03653689.NEW & NOTEWORTHY In irritable bowel syndrome (IBS), fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) affected microbial-derived metabolites relating to positive health outcomes such as reduced risk of colon cancer, inflammation, and type 2 diabetes, as shown in previous studies. The minor IBS symptom induction by FODMAP intake must be weighed against the positive health aspects of FODMAP consumption. Gluten affected lipids weakly with no association to IBS severity.

Therapeutic Effects of an Anti-Sialyl Lewis x Antibody in a Murine Model of Acute Lung Injury.

Acute respiratory distress syndrome is a life-threatening acute lung injury (ALI) characterized by the destruction of alveoli leading to pulmonary edema. The infiltration and activation of inflammatory cells and production of inflammatory cytokines are both involved in the pathogenesis of ALI. Here, we show that the infiltration of neutrophils, major inflammatory cells causing ALI, into the lung is mediated by sialyl Lewis x (sLex) glycans, which can be efficiently suppressed by a monoclonal antibody (mAb) against these glycans. In fucosyltransferase-IV and -VII double-deficient mice lacking sLex expression, neutrophil infiltration into the lung was significantly suppressed compared with that observed in wild-type mice in a lipopolysaccharide (LPS)-induced ALI model. Administration of a highly specific anti-sLex mAb F2 3 hours after LPS administration significantly suppressed pulmonary neutrophil infiltration, accompanied by the reduced induction of inflammatory cytokines. It was consistently indicated from ex vivo cell rolling assay that mAb F2 blocked the rolling of mouse neutrophils on P-selectin-expressing cells. Overall, these results indicate that the sLex glycan could serve as a therapeutic target against ALI, and also that mAb F2 would be useful for specific targeting of this glycan.

2'-Fucosyllactose and 3-Fucosyllactose Alleviates Interleukin-6-Induced Barrier Dysfunction and Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Modulating the Intestinal Microbiome.

Ulcerative colitis is an inflammatory bowel disease (IBD) with relapsing and remitting patterns, and it is caused by varied factors, such as the intestinal inflammation extent and duration. We examined the preventative effects of human milk oligosaccharides (HMOs) on epithelial barrier integrity and intestinal inflammation in an interleukin (IL)-6-induced cell model and dextran sodium sulfate (DSS)-induced acute mouse colitis model. HMOs including 2'-fucosyllactose (FL) and 3-FL and positive controls including fructooligosaccharide (FOS) and 5-acetylsalicylic acid (5-ASA) were orally administrated once per day to C57BL/6J mice with colitis induced by 5% DSS in the administered drinking water. 2'-FL and 3-FL did not affect the cell viability in Caco-2 cells. Meanwhile, these agents reversed IL-6-reduced intestinal barrier function in Caco-2 cells. Furthermore, 2'-FL and 3-FL reversed the body weight loss and the remarkably short colon lengths in DSS-induced acute colitis mice. Moreover, 2'-FL and 3-FL obviously protected the decreasing expression of zonula occluden-1 and occludin in colon tissue relative to the findings in the DSS-treated control group. 2'-FL and 3-FL significantly reduced IL-6 and tumor necrosis factor-α levels in serum relative to the control findings. The summary of these results shows that HMOs prevent colitis mainly by enhancing intestinal barrier function and advancing anti-inflammatory responses. Therefore, HMOs might suppress inflammatory responses and represent candidate treatments for IBD that protect intestinal integrity.

Safety and Tolerability of Whole Soybean Products: A Dose-Escalating Clinical Trial in Older Adults with Obesity.

Soybean products have nutrients, dietary fiber, and phytoalexins beneficial for cardiovascular and overall health. Despite their high consumption in Asian populations, their safety in Western diets is debated. We conducted a dose-escalating clinical trial of the safety and tolerability of soybean products in eight older adults (70-85 years) with obesity. Whole green soybean pods grown under controlled conditions were processed to flour (WGS) at the United States Department of Agriculture using common cooking techniques such as slicing and heat treatment. WGS incorporated into food products was consumed at 10 g, 20 g, and 30 g/day for one week at each dose. The gastrointestinal outcomes, clinical biomarkers, and adverse events were evaluated. We explored the stimulation of phytoalexin (glyceollin) production in live viable soybean seeds (LSS-G). We compared the compositions of WGS and LSS-G with commercial soybean flour and its fermented and enzymatically hydrolyzed forms. We found that although 30 g WSG was well-tolerated, and it made participants feel full. Our processing produced glyceollins (267 µg/g) in LSS-G. Processing soybean flour decreased the iron content, but reduced the oligosaccharides, which could attenuate flatulence. Providing soybean flour at <30 g/day may be prudent for overall health and to prevent the exclusion of other food groups and nutrients in older adults with obesity.

Update on treatment of abdominal pain in irritable bowel syndrome: A narrative review.

The objectives of this narrative review are to update readers on the current state-of-the-art regarding diverse approaches for the treatment of pain, global symptoms, or adequate relief in irritable bowel syndrome (IBS). The article appraises medications, dietary interventions including low fermentable oligosaccharides, disaccharides, and monosaccharides and polyols (FODMAP) diet, fecal microbial transplantation (FMT), electrical approaches, and behavioral therapies including cognitive behavioral therapy (CBT), gut-directed hypnotherapy (GDH), mindfulness, and open-label placebo. Current evidence demonstrates only modest benefit in global IBS symptoms and pain relief. A future approach that identifies pathophysiological mechanisms of IBS through validated biomarkers has the potential to individualize treatment of patients rather than sequential therapeutic trial and error approaches.

What Should I Eat? Dietary Recommendations for Patients with Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic disorder thought to be caused by enteric inflammation in a genetically susceptible host. Although the pathogenesis of IBD is largely unknown, it is widely accepted that dietary components play an important role. Human and animal-based studies have explored the role of various dietary components such as meat, artificial sweeteners and food additives in causing enteric inflammation. Several diets have also been studied in patients with IBD, specifically their role in the induction or maintenance of remission. The most well-studied of these include exclusive enteral nutrition and specific carbohydrate diet. A diet low in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols), typically prescribed for patients with irritable bowel syndrome, has also been studied in a specific subgroup of patients with IBD. In this review, we describe the current evidence on how various dietary components can induce enteric and colonic inflammation, and the clinical-epidemiological evidence exploring their role in predisposing to or protecting against the development of IBD. We also discuss several special diets and how they affect clinical outcomes in IBD patients. Based on the available evidence, we provide guidance for patients and clinicians managing IBD regarding the best practice in dietary modifications.

Existing differences between available lists of FODMAP-containing foods.

BACKGROUND AND AIM: reduced intake of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) is useful to treat functional gastrointestinal disorders. However, there is no consensus on which foods should be included in the FODMAP list as FODMAP profile characterization is lacking for many different foods. This study aimed to emphasize the need for a unified FODMAP list to prevent patient confusion. We hypothesized that FODMAP lists do not include all products that may contain high levels of FODMAPs. METHODS: PubMed, ScienceDirect, Scielo, and Cochrane were searched to identify food composition tables, reviews, food analysis publications, laboratory analyses, and clinical trials containing FODMAP lists. RESULTS: of 1,308 articles identified, 10 were selected; 22.6 % of the 204 foods listed were classified differently among studies. This included almonds, avocados, banana, broccoli, soft cheese, eggplant, and walnuts. Nutritional guidance may be taken from existing FODMAP-related literature, but the information given is not always consistent. CONCLUSION: Unvarying lists of low FODMAP foods should be compiled to provide patients with accurate information on FODMAP dieting.

Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet is associated with increased risk of uninvestigated chronic dyspepsia and its symptoms in adults.

BACKGROUND: Assessing the potential effects of a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) diet on functional gastrointestinal symptoms, particularly upper gastrointestinal symptoms, is not clearly understood. The current study aimed to explore the association of a diet low in FODMAPs with uninvestigated chronic dyspepsia (UCD) and functional dyspeptic symptoms in a large population of Iranian adults. METHODS: This cross-sectional study was conducted on 2987 adults. Dietary FODMAPs intake estimated using a validated food-frequency questionnaire. UCD, early satiation, postprandial fullness and gastric pain were determined using a modified and validated version of the Rome III Questionnaire. RESULTS: After controlling for various confounders, consumption of a diet low in FODMAPs was associated with increased risk of UCD in the whole population (OR=1.85; 95% CI: 1.23-2.78; P=0.009) and women (OR=2.41; 95% CI: 1.46-3.95; P=0.004), but not in men. Higher consumption of a low-FODMAPs diet was related to increased risk of postprandial fullness (OR=1.38; 95% CI: 1.08-1.78; P=0.046). The inverse association between FODMAPs and epigastric pain tended to be significant after controlling for eating behaviors (OR=1.31; 95% CI: 0.98-1.76; P=0.084). No significant association was observed for early satiation. CONCLUSIONS: Our data suggest that consumption of a low-FODMAPs diet may increase the risk of UCD and postprandial fullness; however, well-planned randomized controlled trials and prospective cohorts are required to ascertain the effect of FODMAPs on upper gastrointestinal symptoms.

Codonopsis pilosula oligosaccharides modulate the gut microbiota and change serum metabolomic profiles in high-fat diet-induced obese mice.

Obesity has become a major health problem worldwide, linked to gut microbiota imbalance and chronic inflammation. This study aims to evaluate whether Codonopsis pilosula oligosaccharides (CPOs) can alleviate obesity and related metabolic complications in high-fat diet (HFD) induced obese mice. Male C57BL/6J mice were fed with a HFD for 16 weeks and treated daily with CPOs (500 mg kg-1). CPO supplementation decreased body weight and fat accumulation and improved glucose tolerance in HFD-fed mice. CPOs also reversed the effects of the HFD on inflammatory markers and improved macrophage infiltration. The results of gut microbiota analysis showed that CPOs could also regulate gut microbiota composition, significantly increasing the abundance of the beneficial bacteria Muribaculaceae spp., Alistipes and Clostridium and decreasing the abundance of the harmful bacteria Rikenella, Enterobacteriaceae spp., Collinsella and Megasphaera in HFD mice. Based on serum non-targeted metabolomics analysis, 20 key metabolites responding to CPO treatment were identified, and their biological functions were mainly related to tryptophan and bile acid metabolism. The results demonstrate that CPO supplementation can ameliorate HFD-induced obesity and obesity-related metabolic disorders. It can be used as a novel gut microbiota modulator to prevent HFD-induced gut dysbiosis.

Gastrointestinal effects of diets low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols.

PURPOSE OF REVIEW: Food ingestion is an exacerbator of gastrointestinal symptoms, regardless of origin. Sufferers mistakenly assume that they have suffered an allergic reaction to a given food. Although classical IgE-mediated allergic reactions are rarely culpable, evidence for a role for intolerance to certain carbohydrates in irritable bowel syndrome (IBS) and related conditions increases. This review assesses the status of a commonly implicated group of poorly absorbed carbohydrates (fermentable oligosaccharides, disaccharides, monosaccharides and polyols - FODMAPs) in gastrointestinal pathophysiology. RECENT FINDINGS: Although evidence of efficacy for low FODMAP diets in IBS accumulates, the magnitude of this effect has declined in recent studies. Comparisons to other dietary approaches have revealed conflicting results; some suggest superiority, others find parity. Concerns had been raised regarding long-term nutritional, psychological and microbiological impacts of FODMAP restriction; providing that the diet is administered in the recommended manner, these do not appear to be clinically important. The mechanisms whereby FODMAPs cause gastrointestinal symptoms continue to be explored. SUMMARY: FODMAPS induce gastrointestinal symptoms in susceptible individuals and their restriction provides clinical benefits. The magnitude of these benefits, the superiority of FODMAP restriction over other dietary approaches and the mechanisms of its effects continue to be defined.

Carbohydrate Maldigestion and Intolerance.

This review summarizes dietary carbohydrate intolerance conditions and recent advances on the possible role of carbohydrate maldigestion and dietary outcomes in patients with functional bowel disease. When malabsorbed carbohydrates reach the colon, they are fermented by colonic bacteria, with the production of short-chain fatty acids and gas lowering colonic pH. The appearance of diarrhoea or symptoms of flatulence depends in part on the balance between the production and elimination of these fermentation products. Different studies have shown that there are no differences in the frequency of sugar malabsorption between patients with irritable bowel disease (IBS) and healthy controls; however, the severity of symptoms after a sugar challenge is higher in patients than in controls. A diet low in 'Fermentable, Oligo-Di- and Monosaccharides and Polyols' (FODMAPs) is an effective treatment for global symptoms and abdominal pain in IBS, but its implementation should be supervised by a trained dietitian. A 'bottom-up' approach to the low-FODMAP diet has been suggested to avoid an alteration of gut microbiota and nutritional status. Two approaches have been suggested in this regard: starting with only certain subgroups of the low-FODMAP diet based on dietary history or with a gluten-free diet.

Gastrointestinal Tolerance of Short-Chain Fructo-Oligosaccharides from Sugar Beet: An Observational, Connected, Dose-Ranging Study in Healthy Volunteers.

Dietary fibres are important in the human diet with multiple health benefits. This study aimed to determine the gastrointestinal tolerance of short-chain fructo-oligosaccharides (scFOS), well-known prebiotic fibres, at doses up to 40 g/d. An observational, connected, dose-ranging trial was conducted in 116 healthy volunteers. During the first week, the participants were instructed to consume their usual diet. During the second week, half of the subjects consumed 15 g scFOS per day, and the other half consumed 20 g scFOS per day. For the third week, the scFOS dose was doubled for all subjects. Gastrointestinal symptom severity was reported daily, as well as stool consistency and frequency. The results show that scFOS are well tolerated up to 40 g/d; all reported symptoms remained very mild from a clinical perspective. Stool consistency stayed normal, between 3 and 5 on the Bristol stool scale, confirming that no diarrhoea appeared after scFOS intake. Stool frequency also remained within the normal range. In conclusion, scFOS intake is well tolerated up to 40 g/d in healthy subjects. Thanks to their short chains and unique composition, scFOS prebiotic fibres are much better tolerated than other types of inulin-type fructans with longer chains. The digestive tolerance of fibres should be considered when added to foods and beverages.

Evidence-Based and Emerging Dietary Approaches to Upper Disorders of Gut-Brain Interaction.

Food ingestion is a major symptom trigger in functional esophageal and gastroduodenal disorders and gastroparesis. This review summarizes current knowledge and identifies areas of research on the role of food factors and the opportunities for dietary intervention in these disorders. While many patients experiencing functional esophageal and gastroduodenal disorders identify specific food items as symptom triggers, available data do not allow the identification of specific nutrient groups that are more likely to induce symptoms. In functional dyspepsia (FD), recent studies have shown the potential efficacy of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, although the underlying mechanism of action is unclear. Reports of favorable responses to gluten elimination in patients with FD are confounded by the concomitant benefit of reduced intake of fructans, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols present in wheat. Emerging data based on a 6-food elimination diet and confocal laser endomicroscopic evaluation of mucosal responses to food proteins suggest a role for duodenal allergic reactions in FD symptom generation. In patients with gastroparesis, a low-residue diet has been shown to improve symptoms. Novel dietary approaches under evaluation are the Mediterranean diet and the heating/cooling diet approach.

Effects of an Extensively Hydrolyzed Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety and Infection Risk in Infants with Cow's Milk Protein Allergy: A Randomized, Multi-Center Trial.

This randomized clinical trial (Registration: NCT03085134) assessed if an extensively hydrolyzed formula (EHF) supplemented with two human milk oligosaccharides (HMO) and reduced protein content (2.20 g/100 kcal) supports normal growth in infants with cow's milk protein allergy (CMPA). Secondary outcomes were gastrointestinal tolerability, safety, and effect on infections. Nonbreastfed infants aged 0−6 months with CMPA were enrolled. Body weight, length, and head circumference were measured monthly for 4 months (primary study endpoint), after 6 months, and at the age of 12 months. Of 200 infants screened, 194 (mean age 3.2 months) were randomized. At the 4-month follow-up, daily weight gain for the test formula was noninferior to the control formula; p < 0.005. There were no significant group differences in anthropometric parameters. Both formulas were safe and well tolerated. Infants in the HMO group had a statistically significant reduction in the frequency of upper respiratory tract infections and a lower incidence of ear infections at 12 months (per protocol analysis). The relative risk of lower respiratory tract and gastrointestinal infections was reduced by 30−40%, but this was not statistically significant due to sample size limitations. In summary, the HMO-supplemented formula supports normal growth in infants with CMPA and suggests a protective effect against respiratory and ear infections in the first year of life.

Irritable bowel syndrome and diet.

PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder (FGID) characterized by chronic abdominal pain and altered bowel habits. The diagnosis of IBS is based on the presence of defined clinical Rome IV criteria in the absence of alarm features. The majority of patients with IBS report of food triggers eliciting typical IBS symptoms and trying to modify their dietary intake. RECENT FINDINGS: FGID including IBS are defined as disorders of the gut-brain interaction. A large proportion of individuals with IBS link their symptoms to dietary factors, and recent clinical studies have shown benefits of a diet low in FODMAPs (Fermentable Oligo-, Di-, and Monosaccharides and Polyols) on IBS symptoms and quality of life. Dietary interventions mediate directly changes of luminal gut contents affecting chemosensing-enteroendocrine cells in the modulation of the gut brain microbiome axis in IBS patients. Long-term assessment of clinical outcomes in patients on a low FODMAP diet is needed. Professional guidelines have incorporated the suggestion to offer IBS patients a diet low in FODMAPs. SUMMARY: The FGIDs, including IBS, are defined as gut-brain disorders. Low FODMAP diet has been shown in clinical trials to reduce IBS symptoms but long-term efficacy and nutritional side-effects remain uncertain.