Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial.

Chitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice. Its effects in healthy subjects has recently been studied, revealing its interaction with the gut microbiota. In this double-blind, randomized, cross-over, twice 3-week exploratory study, we investigated the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control. Before and after interventions, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H2] and methane [CH4]) were evaluated. Gut microbiota composition (16S rRNA gene sequencing analysis), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H2, assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. In conclusion, we showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H2 production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention.

Increasing the diversity of dietary fibers in a daily-consumed bread modifies gut microbiota and metabolic profile in subjects at cardiometabolic risk.

Some cardiometabolic risk factors such as dyslipidemia and insulin resistance are known to be associated with low gut microbiota richness. A link between gut microbiota richness and the diversity of consumed dietary fibers (DF) has also been reported. We introduced a larger diversity of consumed DF by using a daily consumed bread in subjects at cardiometabolic risk and assessed the impacts on the composition and functions of gut microbiota as well as on cardiometabolic profile. Thirty-nine subjects at cardiometabolic risk were included in a double-blind, randomized, cross-over, twice 8-week study, and consumed daily 150 g of standard bread or enriched with a 7-dietary fiber mixture (5.55 g and 16.05 g of fibers, respectively). Before and after intervention, stool samples were collected for gut microbiota analysis from species determination down to gene-level abundance using shotgun metagenomics, and cardiometabolic profile was assessed. Multi-fiber bread consumption significantly decreased Bacteroides vulgatus, whereas it increased Parabacteroides distasonis, Fusicatenibacter saccharivorans, an unclassified Acutalibacteraceae and an unclassified Eisenbergiella (q < 0.1). The fraction of gut microbiota carrying the gene coding for five families/subfamilies of glycoside hydrolases (CAZymes) were also increased and negatively correlated with peaks and total/incremental area under curve (tAUC/iAUC) of postprandial glycemia and insulinemia. Compared to control bread, multi-fiber bread decreased total cholesterol (-0.42 mM; q < 0.01), LDL cholesterol (-0.36 mM; q < 0.01), insulin (-2.77 mIU/l; q < 0.05), and HOMA (-0.78; q < 0.05). In conclusion, increasing the diversity of DF in a daily consumed product modifies gut microbiota composition and function and could be a relevant nutritional tool to improve cardiometabolic profile.

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study.

BACKGROUND AND AIMS: In type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients' diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet. METHODS AND RESULTS: For this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System. Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140-180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet. CONCLUSION: One week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control. REGISTRATION NUMBER: in clinicaltrials.gov: NCT03289494.

Development of a Repertoire and a Food Frequency Questionnaire for Estimating Dietary Fiber Intake Considering Prebiotics: Input from the FiberTAG Project.

Most official food composition tables and food questionnaires do not provide enough data to assess fermentable dietary fibers (DF) that can exert a health effect through their interaction with the gut microbiota. The aim of this study was to develop a database and a food frequency questionnaire (FFQ) allowing detailed DF intake estimation including prebiotic (oligo)saccharides. A repertoire of DF detailing total, soluble DF, insoluble DF and prebiotic (oligo)saccharides (inulin-type fructans, fructo-oligosaccharides and galacto-oligosaccharides) in food products consumed in Europe has been established. A 12 month FFQ was developed and submitted to 15 healthy volunteers from the FiberTAG study. Our data report a total DF intake of 38 g/day in the tested population. Fructan and fructo-oligosaccharides intake, linked notably to condiments (garlic and onions) ingestion, reached 5 and 2 g/day, respectively, galacto-oligosaccharides intake level being lower (1 g/day). We conclude that the FiberTAG repertoire and FFQ are major tools for the evaluation of the total amount of DF including prebiotics. Their use can be helpful in intervention or observational studies devoted to analyze microbiota-nutrient interactions in different pathological contexts, as well as to revisit DF intake recommendations as part of healthy lifestyles considering specific DF.

Design and Validation of a Diet Rich in Slowly Digestible Starch for Type 2 Diabetic Patients for Significant Improvement in Glycemic Profile.

This study aimed at designing a-diet high in slowly digestible starch (SDS) by carefully selecting high-SDS starchy products and to validate its implementation, acceptance, and impact on the postprandial glycemic response in patients with type 2 diabetes (T2D). Starchy products were screened and classified as being either high (high-SDS) or low (low-SDS) in SDS (in vitro SDS method). A randomized controlled cross-over pilot study was performed: Eight patients with T2D consumed randomly a high-SDS or a low-SDS diet for one week each, while their glycemic profile was monitored for 6 days. Based on 250 food product SDS analyses and dietary recommendations for patients with T2D, the high-SDS and low-SDS diets were designed. The high-SDS diet significantly increased SDS intake and the SDS/carbohydrates proportion compared to the low-SDS diet (61.6 vs. 11.6 g/day and 30% vs. 6%; p < 0.0001, respectively). Increasing the SDS/carbohydrate proportion to 50% of the meal was significantly correlated with a 12% decrease in tAUC0-120 min and a 14% decrease in the glycemic peak value (p < 0.001 for both). A high-SDS diet can be easily designed by carefully selecting commercial starchy products and providing relevant recommendations for T2D to improve their glycemic profile.

Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: towards a gut sphingomyelin-cholesterol interplay.

OBJECTIVE: To investigate whether milk polar lipids (PL) impact human intestinal lipid absorption, metabolism, microbiota and associated markers of cardiometabolic health. DESIGN: A double-blind, randomised controlled 4-week study involving 58 postmenopausal women was used to assess the chronic effects of milk PL consumption (0, 3 or 5 g-PL/day) on lipid metabolism and gut microbiota. The acute effects of milk PL on intestinal absorption and metabolism of cholesterol were assessed in a randomised controlled crossover study using tracers in ileostomy patients. RESULTS: Over 4 weeks, milk PL significantly reduced fasting and postprandial plasma concentrations of cholesterol and surrogate lipid markers of cardiovascular disease risk, including total/high-density lipoprotein-cholesterol and apolipoprotein (Apo)B/ApoA1 ratios. The highest PL dose preferentially induced a decreased number of intestine-derived chylomicron particles. Also, milk PL increased faecal loss of coprostanol, a gut-derived metabolite of cholesterol, but major bacterial populations and faecal short-chain fatty acids were not affected by milk PL, regardless of the dose. Acute ingestion of milk PL by ileostomy patients shows that milk PL decreased cholesterol absorption and increased cholesterol-ileal efflux, which can be explained by the observed co-excretion with milk sphingomyelin in the gut. CONCLUSION: The present data demonstrate for the first time in humans that milk PL can improve the cardiometabolic health by decreasing several lipid cardiovascular markers, notably through a reduced intestinal cholesterol absorption involving specific interactions in the gut, without disturbing the major bacterial phyla of gut microbiota. TRIAL REGISTRATION NUMBER: NCT02099032 and NCT02146339; Results.

Modulation of Starch Digestibility in Breakfast Cereals Consumed by Subjects with Metabolic Risk: Impact on Markers of Oxidative Stress and Inflammation during Fasting and the Postprandial Period.

SCOPE: Decreasing postprandial glycaemic excursions may have a beneficial effect on inflammatory and oxidative stress profiles. In this study, we investigated the impact of carbohydrate digestibility modulation per se, as a means of reducing the glycaemic response, on metabolic and inflammatory responses in subjects with metabolic risk factors. METHODS AND RESULTS: Twenty healthy subjects with metabolic risk consumed a cereal product either high in Slowly Digestible Starch (HSDS) or low in SDS (LSDS) at breakfast daily for 3 weeks, in a cross-over design. Following each 3-week session, postprandial glycaemia, insulinaemia, the lipid profile, inflammation and oxidative stress markers were assessed and compared to those induced by ingestion of a glucose solution (as a reference). The 2-h glycaemic and insulinaemic responses were significantly lower following the HSDS breakfast compared with the LSDS breakfast or glucose. No significant differences between the products were observed in terms of the lipid profile, C-reactive protein, IL-6 and tumour necrosis factor alpha. We observed a slight increase in fasting lipid peroxidation markers, including an increase in plasma malondialdehyde (MDA) and a decrease in whole blood glutathione (GSH), without significant alteration of urinary F2-isoprostanes or plasma glutathione peroxidase (GPx) activity. CONCLUSION: Consumption of HSDS products for 3 weeks significantly altered both postprandial glycaemia and insulinaemia, but was not sufficient to modify the inflammatory profile. Consumption of both cereal products was associated with a slightly higher fasting oxidative stress profile.

Cereal processing influences postprandial glucose metabolism as well as the GI effect.

OBJECTIVE: Technological processes may influence the release of glucose in starch. The aim of this study was to compare the metabolic response and the kinetics of appearance of exogenous glucose from 2 cereal products consumed at breakfast. METHODS: Twenty-five healthy men were submitted to a randomized, open, crossover study that was divided into 2 parts: 12 of the 25 subjects were included in the "isotope part," and the 13 other subjects were included in the "glycemic part." On test days, subjects received biscuits (low glycemic index [GI], high slowly available glucose [SAG]) or extruded cereals (medium GI, low SAG) as part of a breakfast similar in terms of caloric and macronutrient content. The postprandial phase lasted 270 minutes. RESULTS: The rate of appearance (RaE) of exogenous glucose was significantly lower after consumption of biscuits in the first part of the morning (90-150 minutes) than after consumption of extruded cereals (p ≤ 0.05). Conversely, at 210 minutes, it was significantly higher with biscuits (p ≤ 0.01). For the first 2 hours, plasma glucose and insulin were significantly lower after biscuits during the glycemic part. C-peptide plasma concentrations were significantly lower at 90, 120, and 150 minutes after ingestion of the biscuits (p ≤ 0.05). CONCLUSION: The consumption of biscuits with a high content of slowly digestible starch reduces the appearance rate of glucose in the first part of the morning and prolongs this release in the late phase of the morning (210 minutes). Our results also emphasize that modulation of glucose availability at breakfast is an important factor for metabolic control throughout the morning in healthy subjects due to the lowering of blood glucose and insulin excursions.

A controlled study of consumption of beta-glucan-enriched soups for 2 months by type 2 diabetic free-living subjects.

Type 2 diabetes is associated with a higher cardiovascular risk and there has been a growing interest in using dietary intervention to improve lipid profile and glucose control. The present work aims at analysing the effects of the enrichment of a normal diet with beta-glucan (3.5 g/d) in free-living type 2 diabetic subjects for 2 months, using a palatable soup. This trial was a parallel, placebo-controlled, double-blinded randomised study performed in fifty-three type 2 diabetic subjects. During a 3-week run-in period, subjects daily consumed a ready meal control soup (without beta-glucan). For the following 8 weeks, subjects were randomly assigned to consume daily either a control soup or a beta-glucan soup. Changes in lipid profile (total cholesterol (TC), HDL- and LDL-cholesterol (HDLc and LDLc), apo B and TAG) and in glucose control (HbA1c and fasting glucose) were measured. There was no significant alteration in lipid profile in the two groups (TC, HDLc, LDLc and apo B). TAG decreased significantly in the beta-glucan group compared with the control group ( - 0.12 (SD 0.38) v. 0.12 (SD 0.44) mmol/l, P = 0.03). HbA1c and fasting glucose were not reduced in any group. A single daily ingestion of 3.5 g beta-glucan, as required by official dietary recommendations, for 8 weeks did not change the lipid profile and HbA1c in type 2 diabetic subjects. To improve the metabolic profile of type 2 diabetic subjects in the long term, the quantity, the food vectors and the tolerability of beta-glucan products may be re-evaluated.

Effect of postprandial modulation of glucose availability: short- and long-term analysis.

Low glycaemic index (LGI) foods have been proposed as potential means to decrease postprandial glucose excursions and thus to improve diabetes management. We modulated glucose availability of cereal products and thus their glycaemic index to study the metabolic effect of LGI foods on daylong glucose control acutely and in the long term following a 5-week GI intervention diet in free-living subjects. In this randomised, parallel trial, two groups of nineteen overweight subjects followed an ad libitum 5-week intervention diet in which usual starch was replaced by either LGI or high GI (HGI) starch. During the exploration days (days 1 and 36), subjects ate their assigned 13C-labelled test breakfast (LGI or HGI), and total and exogenous glucose kinetics (using stable isotopes), postprandial concentrations of glucose, insulin, lipid profile and nutrient oxidation were assessed after the test breakfast and a standardised lunch. At day 1, LGI breakfast significantly decreased post-breakfast glycaemic response with a parallel decrease in exogenous and total glucose appearance (P < 0.05). Post-lunch and post-breakfast glycaemic responses were positively correlated (r 0.79, P < 0.0001). Following the 5-week diet, difference between the groups in terms of glucose kinetics and response was maintained (no significant interaction group x time) but tended to decrease over time for the post-breakfast glycaemic response. Post-lunch and post-breakfast glycaemic responses remained positively correlated (r 0.47, P = 0.004). Modulation of postprandial glucose availability at breakfast decreased plasma exogenous glucose appearance and improved glucose control at the subsequent lunch. After 5 weeks, these effects were maintained in healthy subjects but remained to be confirmed in the longer term.

Changes in gene expression in skeletal muscle in response to fat overfeeding in lean men.

OBJECTIVE: The adaptive mechanisms in response to excess energy supply are still poorly known in humans. Our aims were to define metabolic responses and changes in gene expression in skeletal muscle of healthy volunteers during fat overfeeding. RESEARCH METHODS AND PROCEDURES: Eight lean young healthy men were given a diet rich in saturated fat with an excess of approximately 550 kcal/d for 4 weeks. Using oligonucleotide microarrays, gene expression changes in skeletal muscle were analyzed at Day 0, Day 14, and Day 28. RESULTS: Fat overfeeding led to an increase in body weight (1.0 +/- 0.3 kg) and waist circumference (2.2 +/- 0.5 cm, p = 0.005) and a significant decrease in fasting non-esterified fatty acid plasma levels (-29 +/- 5%, p = 0.028). Respiratory quotient was significantly increased (0.84 +/- 0.01 to 0.88 +/- 0.02, p = 0.034) and lipid oxidation rate tended to decrease. The expression of 55 genes was modified in skeletal muscle. The main pathways indicated a coordinated stimulation of triacylglycerol synthesis, inhibition of lipolysis, reduction of fatty acid oxidation, and development of adipocytes. Promoter analysis of the regulated genes suggests that sterol regulatory element binding proteins might be important players of the short-term adaptation to fat overfeeding in human skeletal muscle. DISCUSSION: This combined metabolic and genomic investigation shows that fat overfeeding for 28 days promotes the storage of the excess energy in lean men and demonstrates the usefulness of a transcriptomic approach to a better understanding of the metabolic adaptation to changes in nutritional behavior in human.

Beneficial effects of a 5-week low-glycaemic index regimen on weight control and cardiovascular risk factors in overweight non-diabetic subjects.

The glycaemic index (GI) has been developed in order to classify food according to the postprandial glycaemic response. This parameter is of interest, especially for people prone to glucose intolerance; however, the effects of a low-GI (LGI) diet on body weight, carbohydrate and lipid metabolism remain controversial. We studied the effects of either a LGI or high-GI (HGI) diet on weight control and cardiovascular risk factors in overweight, non-diabetic subjects. The study was a randomized 5-week intervention trial. The thirty-eight subjects (BMI 27.3 (sem 0.2) kg/m2) followed an intervention diet in which usual starch was replaced ad libitum with either LGI or HGI starch. Mean body weight decrease was significant in the LGI group ( - 1.1 (sEM 0.3) kg, P = 0.004) and was significantly greater than in the HGI group ( - 0.3 (sEM 0.2) kg, P = 0.04 between groups). Hunger sensation scales showed a trend towards a decrease in hunger sensation before lunch and dinner in the LGI group when compared with the HGI group (P = 0.09). No significant increase in insulin sensitivity was noticed. The LGI diet also decreased total cholesterol by 9.6 % (P < 0.001), LDL-cholesterol by 8.6 % (P = 0.01) and both LDL-:HDL-cholesterol ratio (10.1 %, P = 0.003) and total:HDL-cholesterol ratio (8.5 %, P = 0.001) while no significant changes were observed in the HGI group. Lowering the GI of daily meals with simple dietary recommendations results in increased weight loss and improved lipid profile and is relatively easy to implement with few constraints. These potential benefits of consuming a LGI diet can be useful to develop practical dietetic advice.

Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity.

To determine whether increased lipogenesis contributes to human obesity, we measured (postabsorptive state), in lean and obese subjects, lipid synthesis (deuterated water method) and the mRNA concentration (RT-competitive PCR) in subcutaneous adipose tissue of fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1c. Before energy restriction, obese subjects had an increased contribution of hepatic lipogenesis to the circulating triglyceride pool (14.5 +/- 1.3 vs. 7.5 +/- 1.9%, P < 0.01) without enhancement of cholesterol synthesis. This increased hepatic lipogenesis represented an excess of 2-5 g/day of triglycerides, which would represent 0.7-1.8 kg on a yearly basis. The lipogenic capacity of adipose tissue appeared, on the contrary, decreased with lower FAS mRNA levels (P < 0.01) and a trend for decreased SREBP-1c mRNA (P = 0.06). Energy restriction in obese patients decreased plasma insulin (P < 0.05) and leptin (P < 0.05) and normalized hepatic lipogenesis. FAS mRNA levels were unchanged, whereas SREBP-1c increased. In conclusion, subjects with established obesity have an increased hepatic lipogenesis that could contribute to their excessive fat mass but no evidence for an increased lipogenic capacity of adipose tissue.