Effects of carbohydrate sugars and artificial sweeteners on appetite and the secretion of gastrointestinal satiety peptides

In vitro, both carbohydrate sugars and artificial sweeteners (AS) stimulate the secretion of glucagon-like peptide-1 (GLP-1). It has been suggested that the gut tastes sugars and AS through the same mechanisms as the tongue, with potential effects on gut hormone release. We investigated whether the human gut responds in the same way to AS and carbohydrate sugars, which are perceived by lingual taste as equisweet. We focused on the secretion of gastrointestinal (GI) satiety peptides in relation to appetite perception. We performed a placebo-controlled, double-blind, six-way, cross-over trial including twelve healthy subjects. On separate days, each subject received an intragastric infusion of glucose, fructose or an AS (aspartame, acesulfame K and sucralose) dissolved in 250ml of water or water only (control). In a second part, four subjects received an intragastric infusion of the non-sweet, non-metabolisable sugar analogue 2-deoxy-d-glucose. Glucose stimulated GLP-1 (P=0·002) and peptide tyrosine tyrosine (PYY; P=0·046) secretion and reduced fasting plasma ghrelin (P=0·046), whereas fructose was less effective. Both carbohydrate sugars increased satiety and fullness (albeit not significantly) compared with water. In contrast, equisweet loads of AS did not affect gastrointestinal peptide secretion with minimal effects on appetite. 2-Deoxy-d-glucose increased hunger ratings, however, with no effects on GLP-1, PYY or ghrelin. Our data demonstrate that the secretion of GLP-1, PYY and ghrelin depends on more than the detection of (1) sweetness or (2) the structural analogy to glucos

Microbial vitamin production mediates dietary effects on diabetic risk

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

Understanding the prebiotic potential of different dietary fibers using an <em>in vitro</em> continuous adult fermentation model (PolyFermS)

Abstract 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

Microstructural Changes in Human Ingestive Behavior After Roux-en-Y Gastric Bypass During Liquid Meals

BACKGROUND. Roux-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. METHODS. The 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. RESULTS. At 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). CONCLUSION. RYGB 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 REGISTRATION. NCT03747445; https://clinicaltrials.gov/ct2/show/NCT03747445. FUNDING. This work was supported by the University of Zurich, the Swiss National Fund (32003B_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)

Antioxidant vitamins and prebiotic FOS and XOS differentially shift microbiota composition and function and improve intestinal epithelial barrier in vitro

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

Effect of varying molecular weight of oat β-glucan taken just before eating on postprandial glycemic response in healthy humans

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 &lt; 0.001) and shorter TTP (p &lt; 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.</p

Riboflavin Supplementation Promotes Butyrate Production in the Absence of Gross Compositional Changes in the Gut Microbiota

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.</p

Detection of atomic spin labels in a lipid bi-layer using a single-spin nanodiamond probe

Magnetic field fluctuations arising from fundamental spins are ubiquitous in nanoscale biology, and are a rich source of information about the processes that generate them. However, the ability to detect the few spins involved without averaging over large ensembles has remained elusive. Here we demonstrate the detection of gadolinium spin labels in an artificial cell membrane under ambient conditions using a single-spin nanodiamond sensor. Changes in the spin relaxation time of the sensor located in the lipid bilayer were optically detected and found to be sensitive to near-individual proximal gadolinium atomic labels. The detection of such small numbers of spins in a model biological setting, with projected detection times of one second, opens a new pathway for in-situ nanoscale detection of dynamical processes in biology.Comment: 16 pages, 4 figure

In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells

Background: Bone grafts are required to repair large bone defects after tumour resection or large tr