RESUMO
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.
Assuntos
Colecistocinina/metabolismo , Derivação Gástrica , Grelina/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptídeo YY/metabolismo , Glicemia/metabolismo , Ingestão de Alimentos/fisiologia , Humanos , Obesidade/metabolismoRESUMO
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/m2) 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 (â¼450 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).
Assuntos
Microbioma Gastrointestinal , Solanum lycopersicum , Adulto , Humanos , Sobrepeso , Estudos Cross-Over , Obesidade , Metilaminas/metabolismo , ÓxidosRESUMO
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.
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Colecistocinina/sangue , Ingestão de Energia , Motilidade Gastrointestinal/efeitos dos fármacos , Ácidos Láuricos/farmacologia , Leucina/farmacologia , Adolescente , Adulto , Apetite/efeitos dos fármacos , Método Duplo-Cego , Ingestão de Alimentos/efeitos dos fármacos , Humanos , Ácidos Láuricos/administração & dosagem , Leucina/administração & dosagem , Masculino , Adulto JovemRESUMO
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 (1â¯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 loge-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 (0-280â¯mM) presented in a blinded and random fashion. PDF determined PCâ¯=â¯2.9â¯s as optimal. Two-way RM-ANOVA revealed that total caloric intake during a drinking session depended on sucrose concentration (Pâ¯<â¯.001) and fasted state (Pâ¯=â¯.006); total drinking time (Pâ¯<â¯.001), total consumed volume (Pâ¯=â¯.003), number of sucks in total (Pâ¯<â¯.001), number of sucks per burst (Pâ¯=â¯.03), and burst duration (Pâ¯=â¯.02) were significantly influenced by fasting. In contrast, volume per suck (Pâ¯=â¯.002), suck speed (Pâ¯<â¯.001), and maximal speed per suck (Pâ¯<â¯.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.
Assuntos
Ingestão de Líquidos , Ingestão de Energia , Adulto , Algoritmos , Estudos Cross-Over , Sacarose Alimentar/administração & dosagem , Ingestão de Alimentos , Jejum , Feminino , Humanos , Masculino , Projetos Piloto , Estudo de Prova de Conceito , Comportamento de SucçãoRESUMO
There is evidence that oat ß-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 4â¯g high molecular weight (MW) oat ß-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⯱â¯1.0, BMI (kg/m2): 23.5⯱â¯0.4). The study followed a randomised double-blind, cross-over design with subjects fed two test breakfasts with and without oat ß-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 ß-glucan increased feelings of fullness (pâ¯=â¯0.048) and satiety (pâ¯=â¯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 90â¯min (pâ¯=â¯0.021), blood glucose at 30â¯min (pâ¯=â¯0.008) and plasma insulin at 30 and 60â¯min (pâ¯=â¯0.002 and 0.017, respectively) following the oat ß-glucan breakfast when compared with the control breakfast. Four grams of high MW oat ß-glucan lowers appetite but not ad libitum eating and beneficially modulates postprandial glycaemia, it does however, not increase plasma GLP-1 secretion.
Assuntos
Apetite/efeitos dos fármacos , Avena , Desjejum/fisiologia , Ingestão de Alimentos/efeitos dos fármacos , beta-Glucanas/administração & dosagem , Adulto , Glicemia/metabolismo , Estudos Cross-Over , Método Duplo-Cego , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Voluntários Saudáveis , Humanos , Insulina/sangue , Masculino , Período Pós-Prandial , Saciação/efeitos dos fármacosRESUMO
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.
Assuntos
Biodiversidade , Microbioma Gastrointestinal , Prebióticos , Fibras na Dieta , Ácidos Graxos Voláteis/metabolismo , Fezes/microbiologia , Fermentação , Humanos , Metagenoma , Metagenômica/métodos , RNA Ribossômico 16S/genéticaRESUMO
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 13C-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 (AUC0-60min) 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 AUC0-60min 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 AUC0-60min (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.
Assuntos
Bebidas/análise , Glicemia/metabolismo , Carboidratos da Dieta/farmacologia , Esvaziamento Gástrico/efeitos dos fármacos , Insulina/sangue , Lisina/farmacologia , Adulto , Testes Respiratórios , Dióxido de Carbono , Carboidratos da Dieta/análise , Relação Dose-Resposta a Droga , Método Duplo-Cego , Ingestão de Alimentos , Feminino , Humanos , Lisina/administração & dosagem , Masculino , Adulto JovemRESUMO
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.
Assuntos
Cirurgia Bariátrica/métodos , Preferências Alimentares , Obesidade Mórbida , Redução de Peso/fisiologia , Animais , Restrição Calórica/métodos , Restrição Calórica/psicologia , Dieta com Restrição de Gorduras/métodos , Dieta com Restrição de Gorduras/psicologia , Preferências Alimentares/fisiologia , Preferências Alimentares/psicologia , Humanos , Obesidade Mórbida/psicologia , Obesidade Mórbida/cirurgia , Período Pós-OperatórioRESUMO
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 K1), 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 K1 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 K1 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 K1 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.
Assuntos
Ácidos Graxos Ômega-3 , Microbioma Gastrointestinal , Microbiota , Humanos , Vitamina K 1 , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Células CACO-2 , Vitamina K , Ácidos Graxos Insaturados , Ácidos GraxosRESUMO
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 ß-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.
Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Ecossistema , Leite Humano , Oligossacarídeos , Ácidos Graxos Voláteis , DigestãoRESUMO
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.
Assuntos
Butiratos , Microbioma Gastrointestinal , Butiratos/farmacologia , Promoção da Saúde , Ácidos Graxos Voláteis/farmacologia , Suplementos Nutricionais , Riboflavina/farmacologiaRESUMO
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 (R2 = 27%, p = 0.50) or 24HR (R2 = 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).
RESUMO
It is widely accepted that gastric parameters such as gastric distention provide a direct negative feedback signal to inhibit eating; moreover, gastric and intestinal signals have been reported to synergize to promote satiation. However, there are few human data exploring the potential interaction effects of gastric and intestinal signals in the short-term control of appetite and the secretion of satiation peptides. We performed experiments in healthy subjects receiving either a rapid intragastric load or a continuous intraduodenal infusion of glucose or a mixed liquid meal. Intraduodenal infusions (3 kcal/min) were at rates comparable with the duodenal delivery of these nutrients under physiological conditions. Intraduodenal infusions of glucose elicited only weak effects on appetite and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). In contrast, identical amounts of glucose delivered intragastrically markedly suppressed appetite (P < 0.05) paralleled by greatly increased plasma levels of GLP-1 and PYY (≤3-fold, P < 0.05). Administration of the mixed liquid meal showed a comparable phenomenon. In contrast to GLP-1 and PYY, plasma ghrelin was suppressed to a similar degree with both intragastric and intraduodenal nutrients. Our data confirm that the stomach is an important element in the short-term control of appetite and suggest that gastric and intestinal signals interact to mediate early fullness and satiation potentially by increased GLP-1 and PYY secretions.
Assuntos
Apetite/fisiologia , Neuropeptídeos/metabolismo , Saciação/fisiologia , Estômago/fisiologia , Adulto , Glicemia/metabolismo , Método Duplo-Cego , Duodeno/fisiologia , Feminino , Esvaziamento Gástrico/fisiologia , Grelina/sangue , Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Glucose/administração & dosagem , Glucose/farmacologia , Humanos , Insulina/sangue , Intubação Gastrointestinal , Masculino , Peptídeo YY/sangue , Adulto JovemRESUMO
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.
Assuntos
Diabetes Mellitus , Microbioma Gastrointestinal , Humanos , Vitaminas , Promoção da Saúde , TiaminaRESUMO
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.
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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].â¢Standardization of the burst-pause criterion derivation for drinkometer measurements of ingestive behavior.â¢All codes are publicly available in a repository.â¢The method can be easily adapted to studies with larger sample size or more than one study stimulus.
RESUMO
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.
Assuntos
Derivação Gástrica , Obesidade Mórbida , Índice de Massa Corporal , Feminino , Derivação Gástrica/métodos , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
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 250 ml 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 glucose.
Assuntos
Apetite/efeitos dos fármacos , Aspartame/farmacologia , Carboidratos/farmacologia , Trato Gastrointestinal/metabolismo , Resposta de Saciedade/efeitos dos fármacos , Tiazinas/farmacologia , Adulto , Glicemia , Estudos Cross-Over , Método Duplo-Cego , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Glucagon/sangue , Humanos , Insulina/sangue , Masculino , Edulcorantes/farmacologia , Adulto JovemRESUMO
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, B2, D, E, and beta-carotene), increasing or maintaining microbial diversity (vitamins A, B2, B3, 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 B2, 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.
Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Ácidos Graxos Voláteis , Humanos , Vitamina A/farmacologia , Vitaminas/farmacologiaRESUMO
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_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).