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Colon target delivery of active ingredients is frequently applied in pharmaceutical products. However, in functional food and beverage applications, dietary supplements, and medical nutrition, formats targeting colonic delivery to improve human health are rare. Nevertheless, there is emerging evidence for beneficial effects of colonic delivered nutrients on gut microbiota and host health which increases the demand for sustainable food grade materials that are regulatory approved for application. In this paper, we describe a double layer coated multi-unit particle system (MUPS) with a diameter of approximately 730 microns consisting of food grade materials: shellac as outer layer, alginate as inner layer, cellulose as a core and riboflavin as active ingredient. The suitability of the MUPS for colonic delivery was tested in three well-established in vitro digestion and fermentation models: the USP Apparatus 3 and the TNO Intestinal Models 1 and 2 (TIM-1 and TIM-2). All systems confirmed the integrity of the MUPS under simulated upper gastrointestinal tract conditions with approximately 90% of the active ingredient being released under simulated ileal-colonic conditions. The TIM-2 model also showed the effects of riboflavin loaded MUPS on the microbiome composition with an increase in the production of short-chain fatty acids, acetate and butyrate. The results of these experiments provide a reliable basis for validation of this vitamin-loaded food grade MUPS in future human clinical trials. In addition, following the recent announcement of the European Commission to restrict intentionally added microplastics to products, the materials used in the described formulation offer an environmentally friendly alternative to often applied methyl acrylate based coatings.

Aims: To estimate whether a mix of pre- and probiotics would strengthen the gut barrier and protect the kidneys in individuals with type 1 diabetes and albuminuria., Methods: Randomized, placebo-controlled, crossover study. Forty-one participants received synbiotic (pre- and probiotics) mix or placebo for 12 weeks with 6 weeks washout. Primary endpoint was change from baseline to end-of-period in UACR. Secondary endpoints were changes in endothelial glycocalyx thickness, inflammatory and intestinal barrier dysfunction markers, glomerular filtration rate (GFR) and ambulatory systolic blood pressure., Results: Thirty-five participants completed the study. Mean age was 58 (SD 10) years, 73 % (n = 30) were male, median UACR was 134 (IQR 63-293) mg/g, estimated GFR was 75 (30) ml/min/1.73m 2 . There was no significant difference in UACR with a mean relative change (CI 95 %) from baseline to end-of-treatment of -3.0 (-18.4; 15.5) % in the synbiotic group and -12.0 (-29.6; 9.6) % in the placebo group with no significant difference between treatment periods (9.37 (-25.2; 44.0) percentage points; p = 0.60). No significant beneficial difference in the secondary end points was demonstrated., Conclusion: Twelve weeks treatment with synbiotic mix had no effect on UACR or on any of the secondary endpoints in subjects with type 1 diabetes and albuminuria., Competing Interests: Declaration of competing interest EBS, NHT, SS, HS and ML have no conflicts of interest. RES and SV are employees of dsm-firmenich, Kaiseraugst, Switzerland. PHG has received lecture fees from Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Elo Water, Genzyme, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, PeerVoice, Sanofi, and Sciarc. He is an advisory board member for AbbVie, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, and Sanofi. None of these entities participated in the design or interpretation of the study. FP has served as a consultant, on advisory boards or as educator for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Sanofi, Mundipharma, MSD, Novartis, Amgen and has received research grants to institution from Novo Nordisk, Boehringer Ingelheim, Amgen and AstraZeneca. PR has received consultancy and/or speaking fees (to SDCC) from AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Eli Lilly, MSD, Novo Nordisk and Sanofi Aventis, and research grants from Novo Nordisk Bayer and AstraZeneca. JS and TWH have shares in Novo Nordisk A/S., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alterations of the microbiome-gut-brain (MGB) axis have been associated with autism spectrum disorder (ASD) and disorders of gut-brain interaction (DGBI). DGBI are highly prevalent in autistic children and are associated with worsening behaviour and anxiety. Treatments such as probiotics, prebiotics and gut-directed hypnotherapy (GDH) have shown efficacy in improving gut symptoms in children. The primary objective of the study was to compare changes in gastrointestinal (GI) scores following a 12-week intervention of synbiotics (prebiotic + probiotic) +/- GDH with a follow-up at 24 weeks. Secondary objectives included changes in behavioural and anxiety symptoms, while changes in gut microbiome composition were assessed as an exploratory objective. Children diagnosed with ASD aged 5.00-10.99 years (n = 40) were recruited and randomised (1:1) to a 12-week intervention of either synbiotics (SYN group) or synbiotics + GDH (COM group). Both the SYN and COM group experienced significant reductions in total GI scores post-intervention and at follow-up (p < 0.001), with no superiority of the COM treatment over the SYN treatment. The COM group showed beneficial reductions in anxiety scores (p = 0.002) and irritability behaviours (p < 0.001) which were not present in the SYN group. At follow-up, only those in the COM group maintained significant reductions in GI pain scores (p < 0.001). There were significant changes in gut microbiota such as increases in Bifidobacterium animalis and Dialister in both groups over time. In conclusion, synbiotics with or without GDH may help support standard care for autistic children who suffer comorbid DGBI. The trial was prospectively registered at clinicialtrials.gov on 16 November 2020 (NCTO4639141)., (© 2024. The Author(s).)

The prevalence of pediatric inflammatory bowel disease (pIBD) has been increasing over the last two decades. Yet, treatment strategies are still limited, in part due to the multifactorial nature of the disease and the complex interplay between genetic, environmental, dietary, immune, and gut microbial factors in its etiology. With their direct and indirect anti-inflammatory properties, human milk oligosaccharides (HMOs) are a promising treatment and management strategy for IBD. However, to date there are no insights into how HMOs may affect pIBD microbiota. Here, we compared the effects of 2'fucosyllactose (2'FL), difucosyllactose (DFL), 3'sialyllactose (3'SL), and blends thereof with fructooligosaccharide (FOS) on microbiota functionality (short- and branched-chain fatty acids, pH, and gas production) and composition (quantitative shallow shotgun sequencing) using fecal material from eight different pediatric Crohn's disease patients inoculated in the SIFR ® technology. In general, all HMO treatments significantly increased total short-chain fatty acid production when compared with FOS, despite equal gas production. We found that 2'FL, either alone or in combination with DFL and 3'SL, exhibited a strong acetogenic and propiogenic effect, and 3'SL an acetogenic effect that surpassed the effects observed with FOS. No differences in overall community diversity between HMO- and FOS-treated pIBD microbiota were observed. There was, however, a stronger bifidogenic effect of 2'FL, 3'SL, 2'FL/DFL, and 2'FL/DFL + 3'SL when compared with FOS. In general, 3'SL and HMO blends enriched a broader species profile, including taxa with potentially anti-inflammatory properties, such as Faecalibacterium prausnitzii and Blautia species. This study suggests HMOs as a promising strategy to beneficially alter the gut microbial profile in pIBD.

Background and Objective: Large intestinal fermentation of dietary fiber may control meal-related glycemia and appetite via the production of short-chain fatty acids (SCFA) and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We investigated whether this mechanism contributes to the efficacy of the Roux-en-Y gastric bypass (RYGB) by assessing the effect of oligofructose-enriched inulin (inulin) vs. maltodextrin (MDX) on breath hydrogen (a marker of intestinal fermentation), plasma SCFAs, gut hormones, insulin and blood glucose concentrations as well as appetite in RYGB patients., Method: Eight RYGB patients were studied on two occasions before and ~8 months after surgery using a cross-over design. Each patient received 300 ml orange juice containing 25 g inulin or an equicaloric load of 15.5 g MDX after an overnight fast followed by a fixed portion snack served 3 h postprandially. Blood samples were collected over 5 h and breath hydrogen measured as well as appetite assessed using visual analog scales., Results: Surgery increased postprandial secretion of GLP-1 and PYY (P ≤ 0.05); lowered blood glucose and plasma insulin increments (P ≤ 0.05) and reduced appetite ratings in response to both inulin and MDX. The effect of inulin on breath hydrogen was accelerated after surgery with an increase that was earlier in onset (2.5 h vs. 3 h, P ≤ 0.05), but less pronounced in magnitude. There was, however, no effect of inulin on plasma SCFAs or plasma GLP-1 and PYY after the snack at 3 h, neither before nor after surgery. Interestingly, inulin appeared to further potentiate the early-phase glucose-lowering and second-meal (3-5 h) appetite-suppressive effect of surgery with the latter showing a strong correlation with early-phase breath hydrogen concentrations., Conclusion: RYGB surgery accelerates large intestinal fermentation of inulin, however, without measurable effects on plasma SCFAs or plasma GLP-1 and PYY. The glucose-lowering and appetite-suppressive effects of surgery appear to be potentiated with inulin., (© 2024. The Author(s).)

Omega-3 polyunsaturated fatty acids (PUFAs) and vitamins exert multiple beneficial effects on host health, some of which may be mediated through the gut microbiome. We investigated the prebiotic potential of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and lipid-soluble phylloquinone (vitamin K 1 ), each at 0.2x, 1x and 5x using the simulator of the human intestinal microbial ecosystem (SHIME®) to exclude in vivo systemic effects and host-microbe interactions.Microbial community composition and, diversity [shotgun metagenomic sequencing] and microbial activity [pH, gas pressure, and production of short-chain fatty acids (SCFAs)] were measured over a period of 48 h. Fermentations supernatants were used to investigate the effect on gut barrier integrity using a Caco-2/goblet cell co-culture model.We found that EPA, DHA and vitamin K 1 increased alpha-diversity at 24 h when compared with control. Moreover, there was an effect on beta-diversity with changes in gut microbial composition, such as an increase in the Firmicutes/Bacteroidetes (F/B) ratio and a consistent increase in Veillonella and Dialister abundances with all treatments. DHA, EPA, and vitamin K 1 also modulated metabolic activity of the gut microbiome by increasing total SCFAs which was related mainly to an increase in propionate (highest with EPA and vitamin K 1 at 0.2x). Finally, we found that EPA and DHA increased gut barrier integrity with DHA at 1x and EPA at 5x ( p  < 0.05, respectively). In conclusion, our in vitro data further establish a role of PUFAs and vitamin K to modulate the gut microbiome with effects on the production of SCFAs and barrier integrity.

Accurate dietary assessment is crucial for nutrition and health research. Traditional methods, such as food records, food frequency questionnaires, and 24-hour dietary recalls (24HR), have limitations, such as the need for trained interviewers, time-consuming procedures, and inaccuracies in estimations. Novel technologies, such as image-based dietary assessment apps, have been developed to overcome these limitations. SNAQ is a novel image-based food-recognition app which, based on computer vision, assesses food type and volume, and provides nutritional information about dietary intake. This cross-sectional observational study aimed to investigate the validity of SNAQ as a dietary assessment tool for measuring energy and macronutrient intake in adult women with normal body weight ( n  = 30), compared to doubly labeled water (DLW), a reference method for total daily energy expenditure (TDEE). Energy intake was also estimated using a one-day 24HR for direct comparison. Bland-Altman plots, paired difference tests, and Pearson's correlation coefficient were used to assess agreement and relationships between the methods. SNAQ showed a slightly higher agreement (bias = -329.6 kcal/day) with DLW for total daily energy intake (TDEI) compared to 24HR (bias = -543.0 kcal/day). While both SNAQ and 24HR tended to underestimate TDEI, only 24HR significantly differed from DLW in this regard ( p  < 0.001). There was no significant relationship between estimated TDEI and TDEE using SNAQ ( R 2  = 27%, p  = 0.50) or 24HR ( R 2  = 34%, p  = 0.20) and there were no significant differences in energy and macronutrient intake estimates between SNAQ and 24HR (Δ = 213.4 kcal/day). In conclusion, these results indicate that SNAQ provides a closer representation of energy intake in adult women with normal body weight than 24HR when compared to DLW, but no relationship was found between the energy estimates of DLW and of the two dietary assessment tools. Further research is needed to determine the clinical relevance and support the implementation of SNAQ in research and clinical settings. Clinical trial registration : This study is registered on ClinicalTrials.gov with the unique identifier NCT04600596 (https://clinicaltrials.gov/ct2/show/NCT04600596)., Competing Interests: SNAQ AG developed the customized version of the app, SNAQ Study, in exchange for financial compensation. RS is employed by DSM Nutritional Products. AS is a member of the scientific advisory board of Gila Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Serra, Alceste, Hauser, Hulshof, Meijer, Thalheimer, Steinert, Gerber, Spector, Gero and Bueter.)

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) cause intestinal discomfort in patients with irritable bowel syndrome (IBS). An enzyme mix (2500 SU invertase, 2400 GalU α-galactosidase, 10,000 ALU β-galactosidase) optimized for FODMAP digestion, and/or human milk oligosaccharides (HMO) (2'-FL, DFL, and LNnT), were evaluated for effects on microbial community activity and composition in short-term colonic incubations using the fecal microbiota of four patients with IBS-D symptoms under the following test conditions: (i) FODMAP, (ii) pre-digested (with enzyme mix) FODMAP, (iii) FODMAP + HMO, and (iv) pre-digested FODMAP + HMO. Pre-digested FODMAP reduced short-chain fatty acid (SCFA) production versus FODMAP; HMO restored this. A 10-day experiment with the simulator of the human intestinal microbial ecosystem (SHIME ® ), using fecal samples from two patients with IBS-D, further evaluated these findings. FODMAP resulted in decreased microbial diversity versus blank. Pre-digestion with the enzyme mix restored microbial diversity, improved FODMAP digestibility, and reduced gas pressure versus undigested FODMAP; however, SCFA production decreased. HMO restored SCFA production along with an increase in gas pressure and increased abundance of Lachnospiraceae . When used in combination, the FODMAP enzyme mix and HMO may resolve FODMAP-related IBS symptoms while maintaining a healthy gut microbiome via prebiotic activity.

Aims: We performed a randomized, placebo-controlled trial, RIBOGUT, to study the effect of 2 weeks supplementation with either 50 or 100 mg/d of riboflavin on (i) Faecalibacterium prausnitzii abundance, (ii) gut microbiota composition, (iii) short-chain fatty acid (SCFA) profiles, and (iv) the satiety and gut hormones. Results: Neither dose of riboflavin, analyzed separately, impacted the abundance of F. prausnitzii , and only minor differences in SCFA concentrations were observed. However, combining the results of the 50 and 100 mg/d groups showed a significant increase in butyrate production. While the gut bacterial diversity was not affected by riboflavin supplementation, the complexity and stability of the bacterial network were enhanced. Oral glucose tolerance tests showed a trend of increased plasma insulin concentration and GLP-1 after 100 mg/d supplementation. Innovation : Dietary supplements, such as vitamins, promote health by either directly targeting host physiology or indirectly via gut microbiota modulation. Here, we show for the first time that riboflavin intervention changes the activity of the microbiota. The butyrate production increased after intervention and although the composition did not change significantly, the network of microbial interactions was enforced. Conclusion : This RIBOGUT study suggests that oral riboflavin supplementation promotes butyrate production in the absence of major shifts in gut microbiota composition. ClinicalTrials.gov Identifier: NCT02929459.

Background: Natural products rich in polyphenols have been shown to lower plasma trimethylamine-n-oxide (TMAO) known for its proatherogenic effects by modulating the intestinal microbiota., Objectives: We aimed to determine the impact of Fruitflow, a water-soluble tomato extract, on TMAO, fecal microbiota, and plasma and fecal metabolites., Methods: Overweight and obese adults (n = 22, BMI 28-35 kg/m 2 ) were included in a double-blind, placebo-controlled, cross-over study receiving 2×150 mg Fruitflow per day or placebo (maltodextrin) for 4 wk with a 6-week wash-out between interventions. Stool, blood, and urine samples were collected to assess changes in plasma TMAO (primary outcome) as well as fecal microbiota, fecal and plasma metabolites, and urine TMAO (secondary outcomes). In a subgroup (n = 9), postprandial TMAO was evaluated following a choline-rich breakfast (∼450 mg). Statistical methods included paired t-tests or Wilcoxon signed rank tests and permutational multivariate analysis of variance., Results: Fruitflow, but not placebo, reduced fasting levels of plasma (-1.5 μM, P ≤ 0.05) and urine (-19.1 μM, P ≤ 0.01) TMAO as well as plasma lipopolysaccharides (-5.3 ng/mL, P ≤ 0.05) from baseline to the end of intervention. However, these changes were significant only for urine TMAO levels when comparing between the groups (P ≤ 0.05). Changes in microbial beta, but not alpha, diversity paralleled this with a significant difference in Jaccard distance-based Principal Component (P ≤ 0.05) as well as decreases in Bacteroides, Ruminococccus, and Hungatella and increases in Alistipes when comparing between and within groups (P ≤ 0.05, respectively). There were no between-group differences in SCFAs and bile acids (BAs) in both faces and plasma but several changes within groups such as an increase in fecal cholic acid or plasma pyruvate with Fruitflow (P ≤ 0.05, respectively). An untargeted metabolomic analysis revealed TMAO as the most discriminant plasma metabolite between groups (P ≤ 0.05)., Conclusions: Our results support earlier findings that polyphenol-rich extracts can lower plasma TMAO in overweight and obese adults related to gut microbiota modulation. This trial was registered at clinicaltrials.gov as NCT04160481 (https://clinicaltrials.gov/ct2/show/NCT04160481?term= Fruitflow&draw= 2&rank= 2)., (Copyright © 2022 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Irritable bowel syndrome (IBS) is a functional gastrointestinal disease in the pathogenesis of which gut dysbiosis may play an important role. Thus, probiotics, prebiotics, or microbiota metabolites, such as butyric acid, are considered to be effective therapy for IBS. However, there are still no trials presenting the efficacy of these three biotic components administered simultaneously. This study aims to evaluate the effects of the product comprising sodium butyrate, probiotics, and short-chain fructooligosaccharides (scFOS) on the severity of clinical IBS symptoms and the quality of life (IBS-QOL). This is a randomized double-blind placebo-controlled trial conducted in 120 adults with IBS diagnosed according to Rome IV criteria. The intervention group (n = 60) will receive a mixture of the following components: 300 mg of colon-targeted microencapsulated sodium butyrate combined with probiotic Lactobacillus strains ( L. rhamnosus and L. acidophilus ) and Bifidobacterium strains ( B. longum , B. bifidum , B. lactis ), and 64 mg of prebiotic scFOS. The control group (n = 60) will receive a placebo (maltodextrin). The primary outcomes will be changes in IBS symptoms with the use of the IBS-Severity Scoring System (IBS-SSS), IBS-Global Improvement Scale (IBS-GIS), IBS-Adequate Relief (IBS-AR), and IBS-QOL after 12 weeks of intervention. The secondary outcomes will be the type of stools, patient-recorded symptoms, adverse events, anthropometric and nutritional parameters, and inflammatory cytokine levels. The findings will provide the first evidence of the use of a combination of three biotic compounds in IBS. The study was registered in the clinicaltrials.gov registry under the number NCT05013060.

The drinkometer is a promising device for the study of ingestive behavior of liquid meals in humans. It can be used to investigate behavior in different target populations. However, ingestive behavior has a great variability across study participants. Therefore, a new analytical approach is required for the extraction and analysis of drinkometer-derived data that could account for this variability. We developed an optimized protocol to predict an optimal burst-pause criterion (PC) for the extraction of PC-dependent microstructural parameters of ingestive behavior. These describe the microstructure of bursts, while PC-independent parameters describe the microstructure of sucks. Therefore, a PC is required to analyze separately two physiologically different parts of behavior. To accomplish this burst-pause criterion derivation (BPCD), a Gaussian Mixture Model (GMM) was built for estimation of two probability density functions (PDFs). These model the distribution of inter-suck intervals (ISIs) and inter-burst intervals (IBIs), respectively. The PC is defined at the intersection point of the two density functions. A Kaplan-Meier (KM) survival analysis was performed for post-hoc verification of the fit of the predicted optimal PC to the ISI distribution. In this protocol paper, we present a walkthrough of the data analysis of drinkometer-derived data for the measurement of microstructure of ingestive behavior based on previous results published by our group [1].•Standardization of the burst-pause criterion derivation for drinkometer measurements of ingestive behavior.•All codes are publicly available in a repository.•The method can be easily adapted to studies with larger sample size or more than one study stimulus., (© 2022 Published by Elsevier B.V.)

Roux-en-Y gastric bypass (RYGB) is one of the most effective procedures in the treatment of obesity. However, the predictive value of the microstructure of ingestion has not been widely investigated in this context. Here, we applied a recently developed drinkometer device to analyze the microstructure of ingestive behavior during a liquid meal in women and investigate whether it correlated with measures of weight loss after RYGB. Macro- and microstructural parameters of ingestive behavior of female patients (n = 24) one year after RYGB were measured in two different test sessions within a period of two weeks using the drinkometer. A Pearson correlation analysis was performed to compare the macro- and microstructural parameters of ingestive behavior with the percentage of total weight loss (%TWL), percentage excess BMI loss (%EBMIL), and body mass index (BMI) one year after RYGB, as well as age. A Bonferroni adjusted p < 0.003 was considered significant for the correlation analysis. For all other statistical tests, a p < 0.05 was considered significant. One year after surgery, a significant body weight loss was achieved in our study population (111.2 ± 15.6 kg vs 73.4 ± 11.7 kg; ***p < 0.001), with a mean%TWL of 33.8% (range: 20.4-48.6%). At the first test session,%TWL correlated with suck duration (r = 0.41, 0.05 > p > 0.003);%EBMIL correlated with both suck duration (r = 0.64, *p < 0.003) and inter-suck intervals (ISIs, r = -0.47, *p < 0.003), and, finally, BMI correlated with suck duration (r = 0.62, *p < 0.003) and ISIs (r = 0.48, *p < 0.003). However, at the second test session, no correlation was found between the body weight loss and the recorded ingestive parameters. Furthermore, no statistically significant difference was found in microstructural parameters of ingestive behavior between the two test sessions even though meal size decreased by 20% on the second visit (342.6.6 ± 167 kcal vs. 271.8 ± 142.8 kcal). A greater body weight loss of patients one year after surgery seems to be associated with longer suck duration and shorter ISIs, but only when the stimulus is tested for the first time by the study participants. This study contributes to the current knowledge about the ingestive behavior of bariatric patients one year after RYGB in terms of its association with the achieved weight loss. The use of the drinkometer device for the measurement of microstructure of ingestive behavior should be further expanded to different research questions and patient subgroups other than good responders. Its possible applications in clinical and behavioral research need to be included in the agenda of bariatric research., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Adequate levels of essential vitamins are important for the prevention of diabetes. While the main efforts to address this are currently focused on the intake of vitamin supplements, improving and maintaining intrinsic vitamin production capacity, which is determined by gut microbes, has received insufficient attention. In this study, we systematically investigated the relationship between gut microbial vitamin production and factors related to diabetes and cardiometabolic health in a deeply phenotyped cohort, Lifelines-DEEP (N = 1,135). We found that blood glucose-related factors, lipids, circulating inflammation, and fecal short-chain fatty acids are associated with gut microbial vitamin production. Use of laxatives and metformin are associated with increased levels of vitamin B1/B6 biosynthesis pathways. We further reveal a mediatory role for microbial vitamin B1/B2 production on the influence of fruit intake on diabetes risk. This study provides preliminary evidence for microbiome-targeted vitamin metabolism interventions to promote health.

The gut microbiome plays important roles in the maintenance of host health and the pathogenesis of many diseases. Diet is a key modulator of the gut microbiome. There is increasing evidence that nutrients other than fermentable fiber affect the gut microbial composition. In this review, we discuss the effects of vitamins on the gut microbiome, and related gastrointestinal health, based on in vitro, animal and human studies. Some vitamins, when provided in large doses or when delivered to the large intestine, have been shown to beneficially modulate the gut microbiome by increasing the abundance of presumed commensals (vitamins A, B 2 , D, E, and beta-carotene), increasing or maintaining microbial diversity (vitamins A, B 2 , B 3 , C, K) and richness (vitamin D), increasing short chain fatty acid production (vitamin C), or increasing the abundance of short chain fatty acid producers (vitamins B 2 , E). Others, such as vitamins A and D, modulate the gut immune response or barrier function, thus, indirectly influencing gastrointestinal health or the microbiome. Future research is needed to explore these potential effects and to elucidate the underlying mechanisms and host health benefits., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

BACKGROUNDRoux-en-Y gastric bypass (RYGB) decreases energy intake and is, therefore, an effective treatment of obesity. The behavioral bases of the decreased calorie intake remain to be elucidated. We applied the methodology of microstructural analysis of meal intake to establish the behavioral features of ingestion in an effort to discern the various controls of feeding as a function of RYGB.METHODSThe ingestive microstructure of a standardized liquid meal in a cohort of 11 RYGB patients, in 10 patients with obesity, and in 10 healthy-weight adults was prospectively assessed from baseline to 1 year with a custom-designed drinkometer. Statistics were performed on log-transformed ratios of change from baseline so that each participant served as their own control, and proportional increases and decreases were numerically symmetrical. Data-driven (3 seconds) and additional burst pause criteria (1 and 5 seconds) were used.RESULTSAt baseline, the mean meal size (909.2 versus 557.6 kCal), burst size (28.8 versus 17.6 mL), and meal duration (433 versus 381 seconds) differed between RYGB patients and healthy-weight controls, whereas suck volume (5.2 versus 4.6 mL) and number of bursts (19.7 versus 20.1) were comparable. At 1 year, the ingestive differences between the RYGB and healthy-weight groups disappeared due to significantly decreased burst size (P = 0.008) and meal duration (P = 0.034) after RYGB. The first-minute intake also decreased after RYGB (P = 0.022).CONCLUSIONRYGB induced dynamic changes in ingestive behavior over the first postoperative year. While the eating pattern of controls remained stable, RYGB patients reduced their meal size by decreasing burst size and meal duration, suggesting that increased postingestive sensibility may mediate postbariatric ingestive behavior.TRIAL REGISTRATIONNCT03747445; https://clinicaltrials.gov/ct2/show/NCT03747445.FUNDINGThis work was supported by the University of Zurich, the Swiss National Fund (32003B&#95;182309), and the Olga Mayenfisch Foundation. Bálint File was supported by the Hungarian Brain Research Program Grant (grant no. 2017-1.2.1-NKP-2017-00002).

Recent and ongoing developments in microbiome science are enabling new frontiers of research for probiotics and prebiotics. Novel types, mechanisms, and applications currently under study have the potential to change scientific understanding as well as nutritional and healthcare applications of these interventions. The expansion of related fields of microbiome-targeted interventions, and an evolving landscape for implementation across regulatory, policy, prescriber, and consumer spheres, portends an era of significant change. In this review we examine recent, emerging, and anticipated trends in probiotic and prebiotic science, and create a vision for broad areas of developing influence in the field., Competing Interests: Declaration of Interests M.C., V.B., R.G., D.G., S.M., D.O., M.I.P., and R.E.S. are involved in research and development projects as employees of companies that produce, sell, and distribute food and/or healthcare products, including probiotics and prebiotics (M.C., Metagenics; V.B., General Mills; R.G., GSK Consumer Healthcare; D.G., Symrise Nutrition; S.M., Reckitt Benckiser; D.O., Danone Nutricia Research; M.I.P., Winclove Probiotics; R.E.S., DSM Nutritional Products). H.D.H has received grant funding from the Hass Avocado Board, the Almond Board of California, and the National Honey Board; presentation honoraria from Kellogg’s Company, PepsiCo, Nutricia North America, Tate & Lyle; and serves on the Grains Food Foundation scientific advisory board. M.A.A., A.B., K.H., K.S.S., D.S., J.V., and G.G. have no conflicts of interest to declare., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae . Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.

An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro , but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.

Circulating tryptophan/large neutral amino acids (tryptophan/LNAA) ratio, an indicator of brain serotonin levels, may be important in appetite regulation, together with gastrointestinal (gastric emptying, plasma cholecystokinin) mechanisms. We have compared effects of intragastric tryptophan ('Trp') on the plasma tryptophan/LNAA ratio in lean and obese men, and the associations of the tryptophan/LNAA ratio, gastric emptying and CCK concentrations with energy intake. Lean and obese male participants (n = 16 each) received 3 g Trp or volume-matched control intragastrically, 15 min before a mixed-nutrient drink (300 mL, 400 kcal) (t = 0 min) in randomised, double-blind fashion. Plasma amino acid (for calculation of the plasma tryptophan/LNAA ratio) and CCK concentrations were measured from t = -20-60 min. Gastric emptying was assessed from t = 0-60 min, and ad-libitum energy intake from a standardised buffet-style meal from t = 60-90 min. The increase in the plasma tryptophan/LNAA ratio was less in obese, than lean, participants (P < 0.05), and greater in lean participants who reduced their energy intake (by >0 kcal) after Trp compared with those who did not (by ≤0 kcal) (P < 0.05). Moreover, in participants who reduced their energy intake, the ratio was lower in obese, than in lean (P < 0.05). There was a trend for an inverse correlation between energy intake with the plasma tryptophan/LNAA ratio in lean (r = -0.4, P = 0.08), but not in obese, participants. There was no significant difference in gastric emptying or CCK between participants who reduced their energy intake and those who did not. In conclusion, the plasma tryptophan/LNAA ratio appears to be a determinant of the suppression of energy intake in response to tryptophan in normal-weight people, but not in those with obesity. The role of the plasma tryptophan/LNAA ratio to regulate energy intake, and potential changes in obesity, warrant evaluation in prospective studies.

The Roux-en-Y gastric bypass (RYGB) remains the most effective treatment for morbidly obese patients to lower body weight and improve glycemic control. There is recent evidence that the mycobiome (fungal microbiome) can aggravate disease severity in a number of diseases including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and hepatitis; moreover, a dysbiotic fungal microbiota has been reported in the obese. We characterized fungal and bacterial microbial composition in fecal samples of 16 morbidly obese patients before and three months after RYGB surgery and compared with nine healthy controls. We found that RYGB surgery induced a clear alteration in structure and composition of the gut fungal and bacterial microbiota. Beta diversity analysis revealed significant differences in bacterial microbiota between obese patients before surgery and healthy controls (P < 0.005) and a significant, unidirectional shift in RYGB patients after surgery (P < 0.001 vs. before surgery). In contrast, there was no significant difference in fungal microbiota between groups but individually specific changes after RYGB surgery. Interestingly, RYGB surgery induced a significant reduction in fungal alpha diversity namely Chao1, Sobs, and Shannon diversity index (P<0.05, respectively) which contrasts the trend for uniform changes in bacteria towards increased richness and diversity post-surgery. We did not observe any inter-kingdom relations in RYGB patients but in the healthy control cohort and there were several correlations between fungi and bacteria and clinical parameters (P<0.05, respectively) that warrant further research. Our study identifies changes in intestinal fungal communities in RYGB patients that are distinct to changes in the bacterial microbiota., Competing Interests: The authors have declared that no competing interests exist.

To see if the molecular weight (MW) and viscosity of oat β-glucan (OBG) when taken before eating determine its effect on postprandial glycemic responses (PPRG), healthy overnight-fasted subjects ( n = 16) were studied on eight separate occasions. Subjects consumed 200 mL water alone (Control) or with 4 g OBG varying in MW and viscosity followed, 2-3 min later, by 113 g white-bread. Blood was taken fasting and at 15, 30, 45, 60, 90, and 120 min after starting to eat. None of the OBG treatments differed significantly from the Control for the a-priori primary endpoint of glucose peak-rise or secondary endpoint of incremental area-under-the-curve (iAUC) over 0-120 min. However, significant differences from the Control were seen for glucose iAUC over 0-45 min and time to peak (TTP) glucose. Lower log(MW) and log(viscosity) were associated with higher iAUC 0-45 ( p < 0.001) and shorter TTP ( p < 0.001). We conclude that when 4 g OBG is taken as a preload, reducing MW does not affect glucose peak rise or iAUC0-120, but rather accelerates the rise in blood glucose and reduces the time it takes glucose to reach the peak. However, this is based on post-hoc calculation of iAUC0-45 and TTP and needs to be confirmed in a subsequent study.

Background and Aims: Crohn's disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD., Methods: In this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention., Results: In total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome., Conclusions: Three weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD., (© European Crohn’s and Colitis Organisation (ECCO) 2019.)

In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite perceptions and subsequent energy intake, and the glycaemic response to, and gastric emptying of, a mixed-nutrient drink. The study consisted of two parts, each including 16 healthy, lean males (age: 23 ± 1 years). In each part, participants received on three separate occasions, in randomised, double-blind fashion, 5 g (Phe-5 g) or 10g ('Phe-10 g) L-phenylalanine, or control, intragastrically, 30 min before a standardised buffet-meal (part A), or a standardised mixed-nutrient drink (part B). In part A, plasma CCK and peptide-YY (PYY), and appetite perceptions, were measured at baseline, after phenylalanine alone, and following the buffet-meal, from which energy intake was assessed. In part B, plasma glucose, glucagon-like peptide-1 (GLP-1), insulin and glucagon were measured at baseline, after phenylalanine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured by 13 C-acetate breath-test. Phe-10 g, but not Phe-5 g, stimulated plasma CCK ( p = 0.01) and suppressed energy intake ( p = 0.012); energy intake was correlated with stimulation of CCK (r = -0.4, p = 0.027), and tended to be associated with stimulation of PYY (r = -0.31, p = 0.082). Both Phe-10 g and Phe-5 g stimulated insulin and glucagon (all p < 0.05), but not GLP-1. Phe-10 g, but not Phe-5 g, reduced overall plasma glucose ( p = 0.043) and peak plasma glucose ( p = 0.017) in response to the mixed-nutrient drink. Phenylalanine had no effect on gastric emptying of the drink. In conclusion, our observations indicate that the energy intake-suppressant effect of phenylalanine is related to the stimulation of CCK and PYY, while the glucoregulatory effect may be independent of stimulation of plasma GLP-1 or slowing of gastric emptying.

The fatty acid, lauric acid (C12), and the amino acid, leucine (Leu) stimulate gut hormones, including CCK, associated with suppression of energy intake. In our recent study, intraduodenal infusion of a combination of C12 and l-tryptophan, at loads that individually did not affect energy intake, reduced energy intake substantially, associated with much greater stimulation of CCK. We have now investigated whether combined administration of C12 and Leu would enhance the intake-suppressant effects of each nutrient, when given at loads that each suppress energy intake individually. Sixteen healthy, lean males (age: 23 ± 2 yr) received, in randomized, double-blind fashion, 90-min intraduodenal infusions of control (saline), C12 (0.4 kcal/min), Leu (0.45 kcal/min), or C12+Leu (0.85 kcal/min). Antropyloroduodenal pressures were measured continuously and plasma CCK at 15-min intervals, and energy intake from a standardized buffet-meal, consumed immediately postinfusion, was quantified. All nutrient infusions stimulated plasma CCK compared with control ( P < 0.05). Moreover, C12 and C12+Leu stimulated CCK compared with Leu ( P < 0.05) (mean concentration, pmol/L; control: 2.3 ± 0.3, C12: 3.8 ± 0.3, Leu: 2.7 ± 0.3, and C12+Leu: 4.0 ± 0.4). C12+Leu, but not C12 or Leu, stimulated pyloric pressures ( P < 0.05). C12+Leu and C12 reduced energy intake ( P < 0.05), and there was a trend for Leu to reduce ( P = 0.06) energy intake compared with control, with no differences between the three nutrient treatments (kcal; control: 1398 ± 84, C12: 1226 ± 80, Leu: 1260 ± 92, and C12+Leu: 1208 ± 83). In conclusion, combination of C12 and Leu, at the loads given, did not reduce energy intake beyond their individual effects, possibly because maximal effects had been evoked.

A main target in microbiome research is the understanding and ability to safely and effectively modulate the microbiome to improve health. Hereto, we discuss the role of vitamins in relation to the gut microbiome and present a rationale for the modulation of gut microbial communities via selected systemic and colon-targeted vitamin administration., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The viscosity of oat β-glucan (OBG) determines its effect on serum cholesterol and glycemic responses, but whether OBG viscosity affects gastric emptying, appetite, and ad libitum food intake is unknown., Objectives: We aimed to determine the effect of altering the amount or molecular weight (MW) and, hence, viscosity of OBG in a breakfast meal on the primary endpoint of food intake at a subsequent meal., Methods: Overnight-fasted males (n = 16) and nonpregnant females (n = 12) without diabetes, aged 18-60 y, with BMI 20.0-30.0 kg/m² who were unrestrained eaters participated in a double-blind, randomized, crossover study at a contract research organization. Participants consumed, in random order, breakfast meals equivalent in weight, energy, and macronutrients consisting of white-bread, butter, jam, and 2% milk plus hot cereal [Cream of Rice (CR), or instant-oatmeal plus either 3 g oat-bran (2gOBG), 10 g oat-bran (4gOBG), or 10 g oat-bran plus β-glucanase (4gloMW) to reduce OBG MW and viscosity compared with 4gOBG]. Gastric emptying, subjective appetite, and glucose, insulin, ghrelin, and peptide tyrosine tyrosine (PYY) responses were assessed for 3 h and then subjects were offered an ad libitum lunch (water and pizza)., Results: Pizza intakes (n = 28) after CR, 2gOBG, 4gOBG, and 4gloMW (mean ± SEM: 887 ± 64, 831 ± 61, 834 ± 78, and 847 ± 68 kcal, respectively) were similar (nonsignificant). Compared with CR, 4gOBG significantly reduced glucose (78 ± 10 compared with 135 ± 15 mmol × min/L) and insulin (14.0 ± 1.6 compared with 26.8 ± 3.5 nmol × min/L) incremental area-under-the-curve and delayed gastric-emptying half-time (geometric mean: 285; 95% CI: 184, 442, compared with geometric mean: 105; 95% CI: 95, 117 min), effects not seen after 4gloMW. Subjective appetite, PYY, and ghrelin responses after 2gOBG, 4gOBG, and 4gloMW were similar to those after CR., Conclusions: The results demonstrate that OBG viscosity determines its effect on postprandial glucose, insulin, and gastric emptying. However, we were unable to demonstrate a significant effect of OBG on appetite or food intake, regardless of its viscosity.This trial was registered at clinicaltrials.gov as NCT03490851., (Copyright © The Author(s) 2019.)

Background: The fatty acid, lauric acid ('C12'), and the amino acid, L-tryptophan ('Trp'), modulate gastrointestinal functions including gut hormones and pyloric pressures, which are important for the regulation of energy intake, and both potently suppress energy intake., Objective: We hypothesized that the intraduodenal administration of C12 and Trp, at loads that do not affect energy intake individually, when combined will reduce energy intake, which is associated with greater modulation of gut hormones and pyloric pressures., Design: Sixteen healthy, lean males (age: 24 ± 1.5 y) received 90-min intraduodenal infusions of saline (control), C12 (0.3 kcal/min), Trp (0.1 kcal/min), or C12 + Trp (0.4 kcal/min), in a randomized, double-blind, cross-over study. Antropyloroduodenal pressures were measured continuously, and plasma cholecystokinin (CCK), ghrelin, and glucagon-like peptide-1 (GLP-1) concentrations, appetite perceptions, and gastrointestinal symptoms at 15-min intervals. Immediately after the infusions, energy intake from a standardized buffet meal was quantified., Results: C12 + Trp markedly reduced energy intake (kcal; control: 1,232 ± 72, C12: 1,180 ± 82, Trp: 1,269 ± 73, C12 + Trp: 1,056 ± 106), stimulated plasma CCK (AUC(area under the curve)0-90 min, pmol/L*min; control: 21 ± 8; C12: 129 ± 15; Trp: 97 ± 16; C12 + Trp: 229 ± 22) and GLP-1 (AUC0-90 min, pmol/L*min; control: 102 ± 41; C12: 522 ± 102; Trp: 198 ± 63; C12 + Trp: 545 ± 138), and suppressed ghrelin (AUC0-90 min, pg/mL*min; control: -3,433 ± 2,647; C12: -11,825 ± 3,521; Trp: -8,417 ± 3,734; C12 + Trp: -18,188 ± 4,165) concentrations, but did not stimulate tonic, or phasic, pyloric pressures, compared with the control (all P < 0.05), or have adverse effects. C12 and Trp each stimulated CCK (P < 0.05), but to a lesser degree than C12 + Trp, and did not suppress energy intake or ghrelin. C12, but not Trp, stimulated GLP-1 (P < 0.05) and phasic pyloric pressures (P < 0.05), compared with the control., Conclusion: The combined intraduodenal administration of C12 and Trp, at loads that individually do not affect energy intake, substantially reduces energy intake, which is associated with a marked stimulation of CCK and suppression of ghrelin. The study was registered as a clinical trial at the Australian and New Zealand Clinical Trial Registry (www.anzctr.org.au,) as 12613000899741., (Copyright © American Society for Nutrition 2019.)

Microstructural analysis of ingestion provides valuable insight into the roles of chemosensory signals, nutritional content, postingestive events, and physiological state. Our aim was to develop a novel drinkometer for humans to measure detailed aspects of ingestion of an entire liquid meal or drinking session. The drinkometer records, in high definition (1 kHz), the weight of a fluid reservoir from which participants drink via a tube. An ultrasonic sensor measures the height of the fluid to derive density. Drinking speed over time can be displayed as a waveform. The smallest units of ingestion are sucks, which are organized in bursts. By applying probability density functions (PDF) on log e -transformed inter-suck intervals (ISI), an optimal burst-pause criterion (PC) can be identified. Information on ingestive volumes, rates, and durations can be then computed for the entire session, as well as for sucks and bursts. We performed a validation study on 12 healthy adults in overnight-fasted and in non-fasted states in 16 drinking sessions with 8 concentrations of sucrose (0-280 mM) presented in a blinded and random fashion. PDF determined PC = 2.9 s as optimal. Two-way RM-ANOVA revealed that total caloric intake during a drinking session depended on sucrose concentration (P < .001) and fasted state (P = .006); total drinking time (P < .001), total consumed volume (P = .003), number of sucks in total (P < .001), number of sucks per burst (P = .03), and burst duration (P = .02) were significantly influenced by fasting. In contrast, volume per suck (P = .002), suck speed (P < .001), and maximal speed per suck (P < .001) depended on sucrose concentration. We conclude that the novel drinkometer is able to detect differences in microstructural parameters of drinking behavior dependent on different motivational states, thus, adds to the technological toolbox used to explore human ingestive behavior., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Recently, the concept of prebiotics has been revisited to expand beyond non-digestible oligosaccharides, and the requirements for selective stimulation were extended to include microbial groups other than, and additional to, bifidobacteria and lactobacilli. Here, the gut microbiota-modulating effects of well-known and novel prebiotics were studied. An in vitro fermentation screening platform (i-screen) was inoculated with adult fecal microbiota, exposed to different dietary fibers that had a range of concentrations (inulin, alpha-linked galacto-oligosaccharides (alpha-GOS), beta-linked GOS, xylo-oligosaccharides (XOS) from corn cobs and high-fiber sugar cane, and beta-glucan from oats), and compared to a positive fructo-oligosaccharide (FOS) control and a negative control (no fiber addition). All dietary fibers displayed prebiotic activity, with beta-glucan showing more distinct effects on the microbial composition and metabolism compared to the other fibers. Beta-glucan induced the growth of Prevotella and Roseburia with a concomitant increase in propionate production. Inulin and both forms of GOS and XOS had a strong bifidogenic effect on the microbial composition. A dose-response effect was observed for butyrate when exposed to beta-glucan and inulin. The findings of this study support the potential for alpha-GOS, XOS, and oat beta-glucan to serve as novel prebiotics, due to their association with the positive shifts in microbiome composition and short-chain fatty acid production that point to potential health benefits.

There is evidence that oat β-glucan lowers appetite and ad libitum eating; however, not all studies are consistent, and the underpinning mechanisms are not entirely understood. We investigated the effects of 4 g high molecular weight (MW) oat β-glucan on ad libitum eating, subjective appetite, glycemia, insulinemia and plasma GLP-1 responses in 33 normal-weight subjects (22 female/11 male, mean age (y): 26.9 ± 1.0, BMI (kg/m 2 ): 23.5 ± 0.4). The study followed a randomised double-blind, cross-over design with subjects fed two test breakfasts with and without oat β-glucan followed by an ad libitum test meal on two different days. Blood samples and ratings for subjective appetite were collected postprandially at regular time intervals. Oat β-glucan increased feelings of fullness (p = 0.048) and satiety (p = 0.034), but did not affect energy and amount eaten at the ad libitum test meal. There was a treatment by time interaction for plasma GLP-1, plasma insulin and blood glucose. GLP-1 was significantly reduced at 90 min (p = 0.021), blood glucose at 30 min (p = 0.008) and plasma insulin at 30 and 60 min (p = 0.002 and 0.017, respectively) following the oat β-glucan breakfast when compared with the control breakfast. Four grams of high MW oat β-glucan lowers appetite but not ad libitum eating and beneficially modulates postprandial glycaemia, it does however, not increase plasma GLP-1 secretion., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Dietary fiber (DF) comprises a wide range of naturally occurring and modified materials with substantial variations in physical and chemical properties and potential physiologic effects. Although nutrition studies testing the effects of DF usually provide extensive detail on the physiologic responses, many still fail to adequately report the type and properties of the DF itself. This weakens the ability to directly replicate and compare studies and to establish structure-function relations. We outline the factors that affect DF functionality and provide 4 overarching recommendations for the characterization and reporting of DF preparations and DF-containing foods in nutrition research. These relate to 1) undertaking characterization methods that reflect the study hypothesis; 2) adequate reporting of DF source, quantity, and composition; 3) measurement of DF rheological properties; and 4) estimation of the DF fermentation rate and extent. Importantly, the food matrix of the test products should also be considered, because this can influence DF functionality and hence the apparent DF efficacy for health-relevant outcomes. Finally, we point out differences in DF functionality to be considered in acute and longer-term trials, the need to design the control treatment according to the research question, and the importance of reporting the amount and type of DF in the background diet.

[This corrects the article DOI: 10.7717/peerj.5288.].

The beneficial effects of prebiotic fibres on human health have been related to their capacities to alter the gut microbiota and modify the growth of beneficial microorganisms. It is long appreciated that bacterial metabolites affect the host's physiology. The inner lining of the intestinal tract is the first level of interaction between the host and bacteria and their metabolites. Therefore, we set out to test the effects of five common dietary fibres (oat β-glucan 28%; oat β-glucan 94%; dried chicory root containing inulin 75%; xylo-oligosaccharide; inulin 90%) and maltodextrin, after fermentation by human gut microbiota in vitro, on measures of gut barrier integrity using a Caco-2/HT29-MTX co-culture as well as mucus production and immune parameters using HT29-MTX and HT29 cell models, respectively. Our data show that all fibres, fermentation products increased the tightness of the gut barrier with oat β-glucan 28% having the largest effect. Fermentation supernatants were tested also in models of the compromised gut barrier (leaky gut). After the addition of ethanol as basolateral stressor, only fermentation supernatant of oat β-glucan 28%, oat β-glucan 94% and maltodextrin improved the gut barrier integrity, while oat β-glucan 28% and dried chicory root containing inulin 75% significantly improved the gut barrier integrity after addition of rhamnolipids as apical stressor. Using the Luminex Technology, we demonstrated an important role of oat β-glucan fermentation products in modulating cytokine and chemokine productions. Furthermore, treating the goblet cells with effluent from xylo-oligosaccharide fermentation significantly increased mucus production. In summary, our data emphasize the potential positive effects of fermentation supernatant of dietary fibres on gut-related physiological outcomes and show that prebiotic fibres may have promising potential to induce specific gut health benefits., Competing Interests: All authors are employees of DSM Nutritional Products Ltd, Kaiseraugst, Switzerland.

It has become increasingly evident in recent years that the gut microbiome and the brain communicate in a bidirectional manner, with each possibly affecting the other's functions. Substantial research has aimed to understand the mechanisms of this interaction and to outline strategies for preventing or treating nervous system-related disturbances. This review explores the evidence demonstrating how the gut microbiome may affect brain function in adults, thereby having an impact on stress, anxiety, depression, and cognition. In vitro, in vivo, and human studies reporting an association between a change in the gut microbiome and functional changes in the brain are highlighted, as are studies outlining the mechanisms by which the brain affects the microbiome and the gastrointestinal tract. Possible modes of action to explain how the gut microbiome and the brain functionally affect each other are proposed. Supplemental probiotics to combat brain-related dysfunction offer a promising approach, provided future research elucidates their mode of action and possible side effects. Further studies are warranted to establish how pre- and probiotic interventions may help to balance brain function in healthy and diseased individuals.

Objective: To examine the effect of different feeding routes on appetite and metabolic responses after Roux-en-Y gastric bypass (RYGB)., Research Design and Methods: A standard liquid meal was administered either orally, into the gastric remnant, or intraduodenally 6 months after RYGB. Changes in plasma glucose, insulin, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY), and appetite were measured pre- and postprandially., Results: Postprandial GLP-1 and PYY responses were similar, whereas glucose, insulin, and GIP levels differed markedly after oral versus intraduodenal feeding. Intraduodenal feeding prompted an intermediate appetite response (i.e., between oral and intragastric). For postprandial glucose, insulin, and GIP levels, the intraduodenal route was more similar to the intragastric than the oral route. Intragastric administration did not evoke changes in appetite, glucose, or insulin; however, it slightly increased GLP-1 and PYY and moderately increased GIP., Conclusions: Appetite and metabolic responses after RYGB depend on the route by which nutrients enter the gastrointestinal tract., (© 2018 by the American Diabetes Association.)

Tryptophan stimulates plasma cholecystokinin and pyloric pressures, both of which slow gastric emptying. Gastric emptying regulates postprandial blood glucose. Tryptophan has been reported to decrease energy intake. We investigated the effects of intragastric tryptophan on the glycaemic response to, and gastric emptying of, a mixed-nutrient drink, and subsequent energy intake. Lean and obese participants ( n = 16 each) received intragastric infusions of 1.5 g ("Trp-1.5g") or 3.0 g ("Trp-3.0g") tryptophan, or control, and 15 min later consumed a mixed-nutrient drink (56 g carbohydrates). Gastric emptying ( 13 C-acetate breath-test), blood glucose, plasma C-peptide, glucagon, cholecystokinin and tryptophan concentrations were measured ( t = 0-60 min). Energy intake was assessed between t = 60-90 min. In lean individuals, Trp-3.0g, but not Trp-1.5g, slowed gastric emptying, reduced C-peptide AUC and increased glucagon AUC (all P < 0.05), but did not significantly decrease the blood glucose response to the drink, stimulate cholecystokinin or reduce mean energy intake, compared with control. In obese individuals, Trp-3.0g, but not Trp-1.5g, tended to slow gastric emptying ( P = 0.091), did not affect C-peptide AUC , increased glucagon AUC ( P < 0.001) and lowered blood glucose at t = 30 min ( P < 0.05), and did not affect cholecystokinin or mean energy intake. In obese individuals, intragastrically administered tryptophan may reduce postprandial blood glucose by slowing gastric emptying; the lack of effect on mean energy intake requires further investigation., Competing Interests: The authors declare no conflicts of interest. The sponsors had no role in the design of the study, the collection, analyses, or interpretation of data, writing of the manuscript, and in the decision to publish the results.

Consumption of fermentable dietary fibers (DFs), which can induce growth and/or activity of specific beneficial populations, is suggested a promising strategy to modulate the gut microbiota and restore health in microbiota-linked diseases. Until today, inulin and fructo-oligosaccharides (FOS) are the best studied DFs, while little is known about the gut microbiota-modulating effects of β-glucan, α-galactooligosaccharide (α-GOS) and xylo-oligosaccharide (XOS). Here, we used three continuous in vitro fermentation PolyFermS model to study the modulating effect of these DFs on two distinct human adult proximal colon microbiota, independently from the host. Supplementation of DFs, equivalent to a 9 g daily intake, induced a consistent metabolic response depending on the donor microbiota. Irrespective to the DF supplemented, the Bacteroidaceae-Ruminococcaceae dominated microbiota produced more butyrate (up to 96%), while the Prevotellaceae-Ruminococcaceae dominated microbiota produced more propionate (up to 40%). Changes in abundance of specific bacterial taxa upon DF supplementation explained the observed changes in short-chain fatty acid profiles. Our data suggest that the metabolic profile of SCFA profile may be the most suitable and robust read-out to characterize microbiota-modulating effects of a DF and highlights importance to understand the inter-individual response to a prebiotic treatment for mechanistic understanding and human application.

Reducing the glycaemic response to carbohydrate-containing foods may have desirable physiological effects for many people. Here, we aimed to determine the minimum amount of oat β-glucan from oat-bran which, when added to instant-oatmeal, would reduce the glycaemic response by 20% compared to a β-glucan-free cereal. Therefore, the glycaemic responses elicited by one serving (27 g) instant-oatmeal plus 247 g 2% milk (IO, 28 g available-carbohydrate, 1.2 g β-glucan) or IO plus 0.2, 0.4, 0.8 or 1.6 g oat β-glucan (OBG) from oat-bran, or an available-carbohydrate matched portion of cream of rice (CR) plus milk were measured over 2 h in n = 40 subjects using a randomized, cross-over design. The primary endpoint was incremental area under the curve (iAUC). The secondary endpoint was glucose peak-rise. The results showed that grams OBG consumed were significantly correlated with mean iAUC (p = 0.009) and with mean glucose peak-rise (p = 0.002). Each gram of OBG reduced iAUC by 7% and peak-rise by 15%. Thus, to achieve a ≥20% reduction in iAUC relative to CR, 1.6 g OBG had to be added to IO (74 ± 7 vs. 93 ± 6 mmol min L -1 , p < 0.05), but, to achieve a 20% reduction in peak-rise, only 0.4 g OBG was required (2.00 ± 0.1 vs. 2.40 ± 0.1 mmol, p < 0.05). We conclude that adding OBG to IO flattened postprandial glycaemic responses in a dose-dependent fashion; 1.6 g OBG was required to reduce iAUC by ≥20% versus CR, but a 20% reduction in peak-rise required only 0.4 g. The greater effect of OGB on peak-rise than iAUC presumably reflects the way viscous dietary fibres modulate glucose absorption kinetics.

A dietary prebiotic is defined as 'a substrate that is selectively utilized by host microorganisms conferring a health benefit'. Although this definition evolved concomitantly with the knowledge and technological developments that accrued in the last twenty years, what qualifies as prebiotic continues to be a matter of debate. In this statement, we report the outcome of a workshop where academic experts working in the field of prebiotic research met with scientists from industry. The workshop covered three main topics: (i) evolution of the prebiotic concept/definition; (ii) the gut modeling in vitro technology PolyFermS to study prebiotic effects; and (iii) the potential novel microbiome-modulating effects associated with vitamins. The future of prebiotic research is very promising. Indeed, the technological developments observed in recent years provide scientists with powerful tools to investigate the complex ecosystem of gut microbiota. Combining multiple in vitro approaches with in vivo studies is key to understanding the mechanisms of action of prebiotics consumption and their potential beneficial effects on the host., Competing Interests: G.L.F., M.H.M., P.W. and R.E.S. are employees of DSM Nutritional Products. H.J.M.H. received a research grant from DSM Nutritional Products. All remaining authors declare no conflict of interest.

Encouraging scientific research into the health effects of dietary bioactive resveratrol has been confounded by its rapid first-pass metabolism, which leads to low in vivo bioavailability. Preliminary studies have shown that resveratrol can modulate gut microbiota composition, undergo biotransformation to active metabolites via the intestinal microbiota, or affect gut barrier function. In rodents, resveratrol can modify the relative Bacteroidetes:Firmicutes ratio and reverse the gut microbial dysbiosis caused by a high-fat diet. By upregulating the expression of genes involved in maintaining tight junctions between intestinal cells, resveratrol contributes to gut barrier integrity. The composition of the gut microbiome and rapid metabolism of resveratrol determines the production of resveratrol metabolites, which are found at greater concentrations in humans after ingestion than their parent molecule and can have similar biological effects. Resveratrol may affect cardiovascular risk factors such as elevated blood cholesterol or trimethylamine N -oxide concentrations. Modulating the composition of the gut microbiota by resveratrol may affect central energy metabolism and modify concentrations of satiety hormones to produce antiobesity effects. Encouraging research from animal models could be tested in humans., Competing Interests: Author disclosures: JKB, DR, PW, and RES are employees of DSM Nutritional Products, a supplier of nutritional ingredients, including resveratrol, for use in food, dietary supplements, pharmaceutic applications, and animal feed., (© 2017 American Society for Nutrition.)

In contrast to the many studies of the effects of individual amino acids (AAs) on eating, no studies have compared the effects of different AAs on eating and underlying preabsorptive gastrointestinal mechanisms. To compare the effects of intraduodenal infusions of l-tryptophan (TRP), l-leucine (LEU), l-phenylalanine (PHE) and l-glutamine (GLN) on appetite, gastrointestinal hormone responses (including ghrelin, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 [GLP-1]), glycemia (glucagon, insulin and glucose) and test meal size in healthy males, we retrospectively analyzed data from four published independent, randomized, double-blind, placebo-controlled studies of 90-min intraduodenal infusions of the individual AAs. The designs of the studies were identical, except the dose of TRP (0.15 kcal/min) was lower than that of the other AAs (0.45 kcal/min) because higher doses of this AA were not well tolerated. TRP and LEU decreased intake more than PHE (reductions relative to control, ~219 ± 68, ~170 ± 48 and ~12 ± 57 kcal, respectively), and TRP decreased intake more than GLN (~31 ± 82 kcal). These effects of TRP and LEU versus GLN, but not versus PHE, were paralleled by greater decreases in plasma ghrelin, and increases in CCK, concentrations. TRP increased PYY more than GLN or LEU, but not PHE. LEU increased PYY less than PHE. No significant differences were detected for GLP-1. PHE increased glucagon more than TRP or LEU, and increased insulin more than TRP. Under our experimental conditions, intraduodenal TRP and LEU were more satiating than PHE and GLN. The greater satiating efficacy of LEU versus PHE was significantly dissociated from the effects of these AAs on PYY, while the greater satiating potency of TRP versus PHE was significantly dissociated from the effects of these AAs on insulin and glucagon. In contrast, ghrelin and CCK, and potentially other mechanisms, including central sensing of individual AAs, appear to be stronger candidate mechanisms for the relative satiating effects obtained., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Purpose of Review: Insights into physiological mechanisms responsible for weight loss after bariatric surgery (BS) have challenged the traditional view that mechanical restriction and caloric malabsorption are major drivers of weight loss and health benefits after BS. Altered diet selection with an increased postoperative preference for low-sugar and low-fat food has also been implicated as a potential mechanism beyond mere reduction of calorie intake. However, the empirical support for this phenomenon is not uniform and evidence is largely based on indirect measurements, such as self-reported food intake data, which are prone to inaccuracy due to their subjective character., Recent Findings: Most studies indicate that patients not only reduce their caloric intake after BS, but also show a reduced preference of food with high sugar and high fat content. So far, standard behavioral tests to directly measure changes in food intake behavior after BS have been mainly used in animal models. It remains unclear whether there are fundamental shifts in the palatability of high-fat and sugary foods after BS or simply a decrease in the appetitive drive to ingest them. Studies of appetitive behavior in humans after BS have produced equivocal results. Learning processes may play a role as changes in diet selection seem to progress with time after surgery. So far, direct measures of altered food selection in humans after BS are rare and the durability of altered food selection as well as the role of learning remains elusive.

Background: Many intervention studies have tested the effect of dietary fibers (DFs) on appetite-related outcomes, with inconsistent results. However, DFs comprise a wide range of compounds with diverse properties, and the specific contribution of these to appetite control is not well characterized. Objective: The influence of specific DF characteristics [i.e., viscosity, gel-forming capacity, fermentability, or molecular weight (MW)] on appetite-related outcomes was assessed in healthy humans. Design: Controlled human intervention trials that tested the effects of well-characterized DFs on appetite ratings or energy intake were identified from a systematic search of literature. Studies were included only if they reported 1 ) DF name and origin and 2 ) data on viscosity, gelling properties, fermentability, or MW of the DF materials or DF-containing matrixes. Results: A high proportion of the potentially relevant literature was excluded because of lack of adequate DF characterization. In total, 49 articles that met these criteria were identified, which reported 90 comparisons of various DFs in foods, beverages, or supplements in acute or sustained-exposure trials. In 51 of the 90 comparisons, the DF-containing material of interest was efficacious for ≥1 appetite-related outcome. Reported differences in material viscosity, MW, or fermentability did not clearly correspond to differences in efficacy, whereas gel-forming DF sources were consistently efficacious (but with very few comparisons). Conclusions: The overall inconsistent relations of DF properties with respect to efficacy may reflect variation in measurement methodology, nature of the DF preparation and matrix, and study designs. Methods of DF characterization, incorporation, and study design are too inconsistent to allow generalized conclusions about the effects of DF properties on appetite and preclude the development of reliable, predictive, structure-function relations. Improved standards for characterization and reporting of DF sources and DF-containing materials are strongly recommended for future studies on the effects of DF on human physiology. This trial was registered at http://www.crd.york.ac.uk/PROSPERO as CRD42015015336., (© 2017 American Society for Nutrition.)

Background: Lysine is reported to lower the glycemic response to oral glucose in humans and, albeit at high loads, to slow gastric emptying of glucose and decrease food intake in rats. Objective: We investigated the effects of intragastrically administered lysine on early (15 min) and later (60 min) blood glucose and insulin responses to and gastric emptying of a mixed-nutrient drink, and effects on subsequent energy intake. Methods: Twelve healthy volunteers (7 men and 5 women; mean ± SEM age: 24 ± 2 y) received intragastric infusions (200 mL) containing 5 or 10 g l-lysine or a control solution within 2 min on 3 different occasions in randomized order. Fifteen minutes later, participants consumed a mixed-nutrient drink (300 mL, 400 kcal, and 56 g carbohydrates) within 1 min. For the next hour ( t = 0-60 min), we collected blood samples every 15 min (to measure blood glucose, plasma insulin, and plasma glucagon) and breath samples every 5 min (to measure gastric emptying via a 13 C-acetate breath test). We then quantified subjects' energy intake from a buffet-style meal ( t = 60-90 min). Results: There were no differences between the 2 lysine treatments; hence, data were pooled for further analysis. Lysine did not affect blood glucose at 15 min or the blood glucose area under the curve from 0 to 60 min (AUC 0-60 min ) but it decreased blood glucose at 60 min compared with the control solution (-9.1% ± 3.1%, P < 0.01). Similarly, the early insulin response and insulin AUC 0-60 min were not affected by lysine, but plasma insulin at 60 min was 20.9% ± 5.6% lower than after the control ( P < 0.05). Plasma glucagon at both 15 min (20.7% ± 4.7%, P < 0.001) and 60 min (14.1% ± 5.4%, P < 0.05) and the glucagon AUC 0-60 min ( P < 0.01) were greater after lysine than after the control. Lysine did not slow gastric emptying, and there was no effect on energy intake. Conclusion: In healthy adults, lysine slightly reduced the glycemic response to an oral mixed-macronutrient drink, an effect that was apparently independent of insulin or slowing of gastric emptying. This trial was registered at www.anzctr.orgau as 12614000837628., Competing Interests: Author disclosures: SSU, PCEF, IN, RES, MH, and CF-B, no conflicts of interest., (© 2017 American Society for Nutrition.)

The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials., (Copyright © 2017 the American Physiological Society.)

Emerging evidence suggests that the gut microbiota has a critical role in both the maintenance of human health and the pathogenesis of many diseases. Modifying the colonic microbiota using functional foods has attracted significant research effort and product development. The pioneering concept of prebiotics, as introduced by Gibson and Roberfroid in the 1990s, emphasized the importance of diet in the modulation of the gut microbiota and its relationships to human health. Increasing knowledge of the intestinal microbiota now suggests a more comprehensive definition. This paper briefly reviews the basics of the prebiotic concept with a discussion of recent attempts to refine the concept to open the door for novel prebiotic food ingredients, such as polyphenols, minerals and vitamins.

Background: The branched-chain amino acids leucine and isoleucine lower blood glucose after oral glucose ingestion, and the intraduodenal infusion of leucine decreases energy intake in healthy, lean men., Objective: We investigated the effects of the intragastric administration of leucine and isoleucine on the gastric emptying of, and blood glucose responses to, a physiologic mixed-macronutrient drink and subsequent energy intake., Design: In 2 separate studies, 12 healthy, lean subjects received on 3 separate occasions an intragastric infusion of 5 g leucine (leucine-5g) or an intragastric infusion of 10 g leucine (leucine-10g), an intragastric infusion of 5 g isoleucine (isoleucine-5g) or an intragastric infusion of 10 g isoleucine (isoleucine-10g), or a control. Fifteen minutes later, subjects consumed a mixed-nutrient drink (400 kcal, 56 g carbohydrates, 15 g protein, and 12 g fat), and gastric emptying ( 13 C-acetate breath test) and blood glucose, plasma insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (leucine study only) were measured for 60 min. Immediately afterward, energy intake from a cold, buffet-style meal was assessed., Results: Compared with the control, leucine-10g decreased the blood glucose area under the curve (AUC) (P < 0.05) and tended to reduce peak blood glucose (P = 0.07), whereas effects of leucine-5g were NS. Leucine-10g, but not leucine-5g, increased plasma insulin and C-peptide AUCs (P < 0.01 for both), but neither dose affected glucagon, GLP-1, GIP, cholecystokinin, gastric emptying, or energy intake. Compared with the control, isoleucine-10g reduced the blood glucose AUC and peak blood glucose (P < 0.01), whereas effects of isoleucine-5g were NS. Neither load affected insulin, C-peptide, glucagon, GLP-1, or GIP. Isoleucine-10g, but not isoleucine-5g, slowed gastric emptying (P < 0.05), but gastric emptying was not correlated with the blood glucose AUC. Isoleucine did not affect energy intake., Conclusions: In healthy subjects, both leucine and isoleucine reduced blood glucose in response to a mixed-nutrient drink but did not affect subsequent energy intake. The mechanisms underlying glucose lowering appear to differ; leucine stimulated insulin, whereas isoleucine acted insulin independently. These trials were registered at www.anzctr.org.au as 12613000899741 and 12614000837628., (© 2016 American Society for Nutrition.)