➰Fitablé: Pilot study of the metabolic signature of 13C-enriched wheat bran linked to intestinal fermentation in humans: identification of new biomarkers
ERA-HDHL co-funded call ‘Biomarkers for Nutrition and Health’_ 2018-2020
Objective: To assess and differentiate fermentation profiles between subjects by simultaneously analysing the production kinetics of 13C-labelled (stable carbon isotope) intestinal metabolites from 13C-labelled wheat bran in three biological matrices (exhaled gas, plasma and faeces).
Procedure: Six women in their thirties, with normal weight status and above-average daily fibre intake but below national dietary recommendations, consumed eight ¹³C-enriched wheat bran biscuits. Plasma and stool samples were collected up to 72 h post-ingestion to measure Short Chain Fatty Acid (SCFA) and 13C-SCFA concentrations by gas chromatography coupled to an isotope mass spectrometer. The excretion profiles of H2 and CH4 gases expired during fermentation were also measured.
Results: We distinguished between two types of CH4 gas excretion profile: high CH4 gas producers, who exhaled more CH4 gas over a longer period of time, and low CH4 gas producers. The proportion of 13C-butyrate in plasma and faeces tended to be higher in low versus high CH4 producers, and vice versa for 13C-acetate. The kinetics of appearance of branched SCFAs in plasma differed from those of linear SCFAs.
Conclusion: This pilot study enabled us to envisage new procedures for the development of biomarkers revealing the interactions between dietary fibres and the intestinal microbiota. Isotopic labelling enables specific in vivo characterisation of the impact of dietary fibre consumption on metabolite production by the microbiota.
Valorisation :
- Scientific article : Meiller, L., Sauvinet, V., Breyton, AE. et al. Metabolic signature of 13C-labeled wheat bran consumption related to gut fermentation in humans: a pilot study. Eur J Nutr 62, 2633-2648 (2023). doi : 10.1007/s00394-023-03161-5
- Congress: presentation at the Journées Francophones de la Nutrition in 2019 (oral communication) and 2020 (poster communication)
➰ DEEP1B study: Unravelling the enigma of postprandial hyperinsulinemic hypoglycaemia after bariatric surgery
Swiss funding, 2020-2021
Objective: Hypoglycaemia is a known and common complication following bariatric surgery, particularly after Roux-en-Y gastric bypass. The aim of the project was to observe and compare postprandial kinetics of counter-regulatory hormones and glucose flux in patients with this post-surgical complication (Roux-en-Y gastric bypass vs. sleeve gastrectomy), without this complication and who had not undergone bariatric surgery.
Procedure: An insulin-induced postprandial hypoglycaemia test, also called clamp, was performed in 32 adults, 8 in each of 4 groups (patients with and without complication after Roux-en-T gastric bypass, sleeve gastrectomy and without bariatric surgery). Glucose flow was assessed throughout the postprandial period using tracers. The primary endpoint was air under the incremental glucagon curve. Catecholamines, cortisol, growth hormones, pancreatic polypeptides and endogenous glucose production were also measured during the hypoglycaemic period.
Results: The rate of onset of glucose after oral administration, as well as the rates of onset and disappearance of total glucose, were higher in both Roux-en-Y gastric bypass groups compared with the non-surgical control group during the early postprandial period. During hypoglycaemia, glucagon exposure was significantly lower in all surgical groups compared with the non-surgical control group. Pancreatic polypeptide levels were significantly lower in patients with post-bariatric hypoglycaemia than in the non-surgical control group. Other hormonal responses to hypoglycaemia and endogenous glucose production did not differ significantly between groups.
Conclusion: The glucagon response to standardised insulin-induced postprandial hypoglycaemia is attenuated after bariatric surgery compared with the control group (without surgery). These results confirm the existence of adaptive responses to bariatric surgery that may predispose to postprandial hypoglycaemia. However, other counter-regulatory responses did not differ significantly between patients with hypoglycaemia and surgical control individuals. Therefore, we conclude that attenuation of counter-regulation is not a fundamental cause of hypoglycaemia but may contribute to its aetiology.
Publications:
Scientific article: Tripyla, A., Herzig, D., Reverter-Branchat, G. et al. Counter-regulatory responses to postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia vs surgical and non-surgical control individuals. Diabetologia 66, 741-753 (2023). https://doi.org/10.1007/s00125-022-05861-9
➰Breath study: Study of the impact of eating bread enriched with a mix of fibres on the intestinal microbiota and metabolic profile in subjects at metabolic risk
Promotion: Brior
Objective: To determine the impact on microbiota diversity and metabolic profile of two months' intake of bread enriched with a pre-selected fibre mix compared with standard bread in people at metabolic risk and consuming little fibre.
Procedure: Randomised, single-blind, cross-over clinical trial on 40 adults (18-70 years), including 2 months' consumption of each type of bread (150g/d) with a wash-out period of approximately one month. Anthropometric and calorimetric measurements as well as basal and postprandial stool, urine and blood samples were collected before and after consumption of each type of bread.
Results: The two months' consumption of fibre-enriched bread did not alter the diversity of the microbiota but did significantly modify its composition. Following the intervention with enriched bread, we also observed a reduction in total cholesterol and LDL-cholesterol, and an improvement in insulin sensitivity as measured by the HOMA index. The effects of the intervention were greater in people with the highest waist circumferences.
Conclusion: Consumption of bread enriched with selected fibres modified the composition and abundance of the intestinal microbiota and improved certain metabolic parameters. We can therefore hypothesise that increasing the quantity and diversity of fibre could be an interesting way of preventing cardiometabolic risks.
Publications :
Scientific article: Ranaivo H, Thirion F, Béra-Maillet C, Guilly S, Simon C, Sothier M, Van Den Berghe L, Feugier-Favier N, Lambert-Porcheron S, Dussous I, Roger L, Roume H, Galleron N, Pons N, Le Chatelier E, Ehrlich SD, Laville M, Doré J, Nazare JA. Increasing dietary fibre diversity in a bread consumed daily modifies gut microbiota and metabolic profile in subjects at cardiometabolic risk. Gut Microbes. 2022 Jan-Dec;14(1):2044722. doi : 10.1080/19490976.2022.2044722.
➰ Polynut study: Study of the effects of polyphenol supplementation on postprandial metabolism following overnutrition rich in lipids and sucrose
Promoted by: HCL
Objectives: It has been shown in rodents that different types of dietary polyphenols, bioactive compounds derived from plants, have protective metabolic effects. They could also help to improve the lipid profile and thus reduce the cardiometabolic risk in humans. The aim of the project was therefore to determine whether supplementing the diet with polyphenols extracted from grapes could limit the deleterious metabolic effects of over-nutrition rich in lipids and sucrose in healthy humans, on hepatic metabolism and lipoproteins.
Procedure: We conducted a randomised, double-blind, parallel-group controlled intervention study on 42 male subjects with a BMI between 23 and 27 kg/m2, using polyphenols (2g/d) versus placebo over 39 consecutive days during overnutrition (+50% of daily energy intake for 31 days) with snack-type foods. At the beginning and end of the protocol, we collected anthropometric parameters, cardio-metabolic profile, inflammatory parameters, composition of the intestinal microbiota, body and liver composition (MRI), insulin sensitivity (clamps) and postprandial lipid metabolism using a test meal containing 13C-labelled triglycerides to monitor the fate of ingested lipids postprandially.
Results: Following the period of overnutrition, all the participants increased their total mass, fat mass and lipids in the liver. Insulin sensitivity did not change, but homeostasis indicators (HOMA-IR and HIR) increased in both groups.
Conclusion: This first clinical trial evaluating the effects of grape polyphenol extract supplementation did not demonstrate any impact of these compounds in reducing the metabolic alterations induced by overnutrition in the participants over a one-month period.
Publications :
Scientific article: Segrestin B, Delage P, Nemeth A, Seyssel K, Disse E, Nazare J-A, Lambert-Porcheron S, Meiller L, Sauvinet V, Chanon S, Simon C, Ratiney H, Beuf O, Pralong F, Naba-al-Huda Y, Boizot A, Gachet M Burton-Pimentel K-J, Vidal H, Meugnier E, Vionnet N et Laville M. Polyphenol Supplementation did not affect insulin sensitivity and fat deposition during one-month overfeeding in randomized placebo-controlled trials in men and in women Front. Nutr. Volume 9 - 2022 | https://doi.org/10.3389/fnut.2022.854255
➰Etude FiberTag : Characterisation of changes in intestinal microbiota composition and activity following chitin-glucan fibre supplementation versus placebo in 15 subjects at metabolic risk
Promoted by: HCL
Objective: It has been shown in obese mice that the consumption of insoluble fibres, such as chitin-glucan, improves certain cardio-metabolic parameters associated with obesity. Indeed, when consumed, these fibres can serve as a substrate for the microbiota to produce metabolites derived from the intestine, such as short-chain fatty acids, which in turn can play a role in improving glycaemic and lipid parameters. The aim of this study was therefore to investigate the impact of chitin-glucan supplementation on the composition of the microbiota and the cardiometabolic profile.
Procedure: We set up a randomised, double-blind, crossover trial with two 3-week sequences of dietary supplements (4.5g chitin-glucan versus 4.5g placebo) and a 4-week wash-out period in 15 volunteers at metabolic risk. Before and at the end of the two interventions, fasting and postprandial metabolic parameters following a FlexMeal challenge (meal rich in sugar and lipids), exhaled gases (CH4 and H2), the composition of the intestinal microbiota, the concentration of bile acid, short- and long-chain fatty acids, zonulin, calprotectin and LBP were analysed and compared.
Results: Chitin-glucan supplementation in subjects at metabolic risk, compared with placebo, induced changes in the composition of the microbiota, in particular changes in the abundance of certain species. We also showed that with supplementation compared with placebo, there was an increase in H2 exhalation following a high-fibre breakfast, suggesting that chitin-glucan induces more fermentation in response to a high-fibre diet.These changes were accompanied by significant improvements in glucose profiles only in the high H2 producers (as measured by the lactulose test) and in postprandial lipid profiles (reduction in the incremental air curve and triglyceride peak following a FlexMeal).Conclusion: This study demonstrates the health benefits of 3-week chitin-glucan supplementation in subjects at metabolic risk. In addition, this study shows that the lactilose test to define the type of H2 producer could non-invasively predict the efficacy of a nutritional intervention with fibre.
Publications :
Scientific article: Ranaivo H, Zhang Z, Alligier M, Van Den Berghe L, Sothier M, Lambert-Porcheron S, Feugier N, Cuerq C, Machon C, Neyrinck AM, Seethaler B, Rodriguez J, Roumain M, Muccioli GG, Maquet V, Laville M, Bischoff SC, Walter J, Delzenne NM, Nazare JA. Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial. Sci Rep. 2022 May 25;12(1):8830. doi: 10.1038/s41598-022-12920-z.
➰ KBE study: Impact of slowly digestible starch in patients with type 2 diabetes on glycaemic control and cardio-metabolic and inflammatory benefits
Sponsor: Mondelez
Objectives: Glycaemic variability in people with diabetes is the cause of many complications. There are several types of starch, including slowly digestible starches, which prolong the release of glucose into the blood and may therefore be of interest in treating significant glycaemic variability. The aim of this project is to assess the impact of a diet rich in slowly digestible starch on glycaemic variability and profiles, and cardiometabolic profiles compared with a diet low in slowly digestible starch, in people with type 2 diabetes who have been treated. The aim is to provide refined and more precise dietary recommendations for preventing complications associated with type 2 diabetes.
Before proposing a large-scale clinical trial, the team set up a pilot study, the main aim of which was to assess the ability of continuous glucose monitoring systems (CGMS) to discriminate between differences in glycaemic profits over the day depending on whether people were eating a diet rich in slowly digestible starch or one low in it.
Procedure: To carry out the pilot study, a randomised, controlled, single-blind, crossover clinical trial was set up in 8 patients with treated type 2 diabetes. For one week, the patients had to consume a diet rich in slowly digestible starch and for another week a diet low in slowly digestible starch. The order between the two diets was randomly assigned to each volunteer and the two periods were separated by a two-week wash-out period. A CGMS was fitted at the start of each intervention week, recording blood glucose levels over the week and providing a blood glucose profile.
Results: In the clinical trial, we observed favourable and significant changes in the glycaemic profile (reduction in glycaemic variability and postprandial excursions) thanks to CGMS and following a week's diet rich in slowly digestible starch compared with a poor diet. Further investigations will nevertheless be needed to confirm this effect on a larger scale and over the long term, and to better understand the impact of this intervention on the biomarkers and comorbidities of type 2 diabetes.
Conclusion: Following the results of the pilot study, a randomised, controlled, single-blind, two-arm parallel clinical trial was conducted on 51 patients who consumed either a slowly digestible starch-rich diet or a slowly digestible starch-low control diet for 12 weeks, depending on their arm. Continuous glucose monitoring systems (CGMS) were used to measure numerous parameters of glycaemic variability. In addition, metabolic exploration days were used to collect fasting and postprandial metabolic parameters following a Flexmeal (a meal very rich in sugar and fat) before and at the end of the follow-up period. The results of the trial are currently being analysed and should be published shortly.
Publications:
Scientific article: Breyton A-E, Goux A, Lambert-Porcheron S, Meynier A, Sothier M, VanDen Berghe L, Brack O, Disse E, Laville M, Vinoy S, Nazare J-A. Modulation of starch digestibility significantly improves glycaemic variability in type 2 diabetic subjects: A pilot study. J.numecd. 2021 Jan 4;31 (1). doi: 10.1016/j.numecd.2020.08.010
Breyton A-E, Lambert-Porcheron S, Laville M, Vinoy S, Nazare J-A. CGMS and glycemic variability, relevance in Clinical Research to Evaluate Intervention in T2D, a Literature Review. Frontier in Endocrinology. 2021; 12. doi : 10.3389/fendo.2021.666008
