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Randomized controlled trial demonstrates response to a probiotic intervention for metabolic syndrome that may correspond to diet.
Wastyk, HC, Perelman, D, Topf, M, Fragiadakis, GK, Robinson, JL, Sonnenburg, JL, Gardner, CD, Sonnenburg, ED
Gut microbes. 2023;15(1):2178794
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Rates of metabolic syndrome are high throughout developed countries. Metabolic syndrome is a cluster of conditions that occur together and increase your risk for heart disease, stroke, and type 2 diabetes. Studies in animals and humans have shown that the composition of the gut microbiome may be linked to metabolic syndrome and that it is affected by diet. This randomised control trial of 39 individuals showed that the supplementation of a probiotic containing three different probiotic strains did not have a population wide effect but did influence a subset of individuals. These individuals had a different microbiome by the end of the trial and a decrease in blood pressure and blood lipids. Interestingly these individuals also had a higher dietary intake of sugar, yet a lower blood sugar level. It was concluded that the response to probiotic supplements may be dependent upon an individual’s diet. This study could be used by healthcare professionals to understand that diet may influence the success of probiotics, however more research is warranted before firm conclusions are made on the optimal diet during supplementation.
Abstract
An individual's immune and metabolic status is coupled to their microbiome. Probiotics offer a promising, safe route to influence host health, possibly via the microbiome. Here, we report an 18-week, randomized prospective study that explores the effects of a probiotic vs. placebo supplement on 39 adults with elevated parameters of metabolic syndrome. We performed longitudinal sampling of stool and blood to profile the human microbiome and immune system. While we did not see changes in metabolic syndrome markers in response to the probiotic across the entire cohort, there were significant improvements in triglycerides and diastolic blood pressure in a subset of probiotic arm participants. Conversely, the non-responders had increased blood glucose and insulin levels over time. The responders had a distinct microbiome profile at the end of the intervention relative to the non-responders and placebo arm. Importantly, diet was a key differentiating factor between responders and non-responders. Our results show participant-specific effects of a probiotic supplement on improving parameters of metabolic syndrome and suggest that dietary factors may enhance stability and efficacy of the supplement.
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Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis.
Gómez-Pérez, AM, Ruiz-Limón, P, Salas-Salvadó, J, Vioque, J, Corella, D, Fitó, M, Vidal, J, Atzeni, A, Torres-Collado, L, Álvarez-Sala, A, et al
Gut microbes. 2023;15(1):2223339
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Nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease. The aim of this study was to evaluate the changes in the microbiota associated with changes in biochemical markers of NAFLD/NASH after an intervention. This substudy was conducted in the frame of the PREDIMED-Plus study, a 6-year, multicentre, randomised clinical trial for primary prevention of cardiovascular disease (CVD) conducted in men aged 55–75 years and women aged 60–75 years with overweight or obesity and metabolic syndrome. Results showed a relationship between liver disease biochemical indexes changes and gut microbiota changes within a context of a Mediterranean lifestyle. In fact, two noninvasive scores for liver steatosis and liver fibrosis, usually used in clinical practice, could differentiate gut microbiota populations. Authors conclude that their findings highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.
Abstract
To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations. What You Need to KnowWhat is the context:Obesity and metabolic syndrome have been associated with nonalcoholic fatty liver disease (NAFLD). Gut microbiota and its interaction with the environment may play a key role in NAFLD.What is new:Mediterranean diet and physical activity can modify the scores for liver steatosis (HSI) and liver fibrosis (FIB−4) in only one year. A relation between the changes in these scores and gut microbiota changes was found.What is the impact:The discovery of microbiota-based biomarkers for NAFLD and the development of strategies to modulate gut microbiota in the treatment of NAFLD.
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Effects of inulin supplementation on body composition and metabolic outcomes in children with obesity.
Visuthranukul, C, Chamni, S, Kwanbunbumpen, T, Saengpanit, P, Chongpison, Y, Tepaamorndech, S, Panichsillaphakit, E, Uaariyapanichkul, J, Nonpat, N, Chomtho, S
Scientific reports. 2022;12(1):13014
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The prevalence of overweight and obesity among children and adolescents has risen dramatically. Overweight and obese children are at risk of developing co-morbidities such as type 2 diabetes mellitus, hypertension, dyslipidaemia, metabolic syndrome, non-alcohol fatty liver disease and premature cardiovascular diseases. Furthermore, obese children are highly prone to become obese adults. The aim of this study was to determine the effects of prebiotic (as inulin) supplementation on body weight, adiposity, and metabolic profiles in obese Thai children. This study is a randomised double-blinded placebo-controlled trial. Participants (n=165) were randomly allocated to 3 groups: inulin, placebo, and dietary fibre advice group. Results show that the intensive behavioural modification and frequent follow-up are effective strategies to reduce body mass index and adiposity in obese children. Furthermore, even though inulin supplementation did not demonstrate considerable effect on adiposity and metabolic outcomes, it can increase fat-free mass in these children. Authors conclude that further research regarding the change of gut microbiota composition and their metabolites are needed to determine inulin’s impact on host microbe interaction in obese paediatric population.
Abstract
Inulin might improve body composition in obese children. We aimed to determine the effects of inulin supplementation on body composition and metabolic outcomes in obese children. A randomized, double-blinded placebo-controlled study was conducted in obese Thai children aged 7-15 years. Participants were assigned to 3 treatment groups for 6 months: 13 g of extracted inulin powder from Thai Jerusalem artichoke, isocaloric maltodextrin, and dietary fiber advice groups. Body composition was assessed by bioelectrical impedance analysis. One-hundred and fifty-five children completed the study (mean age 10.4 ± 2.2 years, BMI z-score 3.2 ± 1.0, 59% male). The drop-out rate was 6%. The inulin extract yielded more than 90% compliance without significant gastrointestinal side effects. All three groups demonstrated a significant decrease in BMI z-score, fat mass index (FMI), and trunk FMI, but the differences between groups were not observed. Fat-free mass index significantly increased only in the inulin group (16.18 ± 1.90 vs. 16.38 ± 1.98 kg/m2, P = 0.009). There were no significant differences in the metabolic profiles between groups. Despite showing no substantial effect on adiposity, inulin may increase fat-free mass in obese children. Further research in the change of gut microbiota composition is needed to determine inulin's impact on host-microbe interaction in pediatric obesity.
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Yogurt, cultured fermented milk, and health: a systematic review.
Savaiano, DA, Hutkins, RW
Nutrition reviews. 2021;79(5):599-614
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Many fermented foods are associated with health benefits, including fermented dairy products. Whereby diary itself is part of many nutritional guidelines, the guidances rarely distinguish between dairy and fermented dairy. This qualitative, systematic review sought to capture how consumption of fermented milk products influences health. The review included 108 studies, with over 70% reporting beneficial health outcomes. A small number of studies reported insignificant or neutral results and four unfavourable ones. The aspects of health that were considered included lactose digestion and tolerance, gut health and disease, diarrhoea and constipation, irritable bowel syndrome, cardiovascular health and disease, hypertension, blood lipids, cancer risk, colorectal/breast/prostate cancer, weight and body composition, diabetes risk and metabolic syndrome and bone health. The authors concluded that eating fermented dairy products aided lactose digestion and showed a consistent link with reduced risk of breast and colorectal cancer, type 2 diabetes, and improved weight maintenance, cardiovascular, bone, and gastrointestinal health. As dairy appears to increase the risk for prostate cancer, fermented dairy seems to be no different here to unfermented dairy at increasing the risk. Some potential mechanisms are proposed in the discussion section, how fermented dairy may elicit its health benefits. Given the predominant health benefits of fermented dairy, the authors encouraged to include fermented dairy into national nutrition guidelines and stress distinction between dairy and fermented dairy products. This review captures current evidence of the widespread health benefits of fermented dairy consumption worthwhile considering in clinical practice. In the absence of more clear findings in relation to prostate cancer and prevention, a cautious approach to dairy and fermented dairy consumption may be warranted.
Abstract
Consumption of yogurt and other fermented products is associated with improved health outcomes. Although dairy consumption is included in most dietary guidelines, there have been few specific recommendations for yogurt and cultured dairy products. A qualitative systematic review was conducted to determine the effect of consumption of fermented milk products on gastrointestinal and cardiovascular health, cancer risk, weight management, diabetes and metabolic health, and bone density using PRISMA guidelines. English language papers in PubMed were searched, with no date restrictions. In total, 1057 abstracts were screened, of which 602 were excluded owing to lack of appropriate controls, potential biases, and experimental design issues. The remaining 455 papers were independently reviewed by both authors and 108 studies were included in the final review. The authors met regularly to concur, through consensus, on relevance, methods, findings, quality, and conclusions. The included studies were published between 1979 and 2017. From the 108 included studies, 76 reported a favorable outcome of fermented milks on health and 67 of these were considered to be positive or neutral quality according to the Academy of Nutrition and Dietetics' Quality Criteria Checklist. Of the 32 remaining studies, the study outcomes were either not significant (28) or unfavorable (4), and most studies (18) were of neutral quality. A causal relationship exists between lactose digestion and tolerance and yogurt consumption, and consistent associations exist between fermented milk consumption and reduced risk of breast and colorectal cancer and type 2 diabetes, improved weight maintenance, and improved cardiovascular, bone, and gastrointestinal health. Further, an association exists between prostate cancer occurrence and dairy product consumption in general, with no difference between fermented and unfermented products. This article argues that yogurt and other fermented milk products provide favorable health outcomes beyond the milk from which these products are made and that consumption of these products should be encouraged as part of national dietary guidelines. Systematic review registration: PROSPERO registration no. CRD42017068953.
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Exercise Training Modulates Gut Microbiota Profile and Improves Endotoxemia.
Motiani, KK, Collado, MC, Eskelinen, JJ, Virtanen, KA, Löyttyniemi, E, Salminen, S, Nuutila, P, Kalliokoski, KK, Hannukainen, JC
Medicine and science in sports and exercise. 2020;52(1):94-104
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The gut microbiome differs between healthy people and those with metabolic diseases, including metabolic syndrome and type 2 diabetes (T2D) and it is suggested that this association is mediated by endotoxemia, the release of toxins, in particular lipopolysaccharides (LPS), from the gut bacteria. The aim of this study was to investigate the effects of exercise on gut microbiota composition and metabolic endotoxemia in people with prediabetes and T2D. 26 sedentary participants with either prediabetes or T2D took part in either a sprint interval training (SIT) or moderate-intensity continuous training (MICT) three times per week for two weeks. Both training types induced fat loss and improved the gut microbiota, HbA1C (a marker for whole body insulin sensitivity) as well as some markers of systemic and intestinal inflammation, although there were differences in the way the two types of exercise altered the gut bacterial composition. Only SIT improved aerobic capacity. The authors concluded that exercise training improves the gut microbiota and reduces endotoxemia.
Abstract
INTRODUCTION Intestinal metabolism and microbiota profiles are impaired in obesity and insulin resistance. Moreover, dysbiotic gut microbiota has been suggested to promote systemic low-grade inflammation and insulin resistance through the release of endotoxins particularly lipopolysaccharides. We have previously shown that exercise training improves intestinal metabolism in healthy men. To understand whether changes in intestinal metabolism interact with gut microbiota and its release of inflammatory markers, we studied the effects of sprint interval (SIT) and moderate-intensity continuous training (MICT) on intestinal metabolism and microbiota in subjects with insulin resistance. METHODS Twenty-six, sedentary subjects (prediabetic, n = 9; type 2 diabetes, n = 17; age, 49 [SD, 4] yr; body mass index, 30.5 [SD, 3]) were randomized into SIT or MICT. Intestinal insulin-stimulated glucose uptake (GU) and fatty acid uptake (FAU) from circulation were measured using positron emission tomography. Gut microbiota composition was analyzed by 16S rRNA gene sequencing and serum inflammatory markers with multiplex assays and enzyme-linked immunoassay kit. RESULTS V˙O2peak improved only after SIT (P = 0.01). Both training modes reduced systematic and intestinal inflammatory markers (tumor necrosis factor-α, lipopolysaccharide binding protein) (time P < 0.05). Training modified microbiota profile by increasing Bacteroidetes phylum (time P = 0.03) and decreasing Firmicutes/Bacteroidetes ratio (time P = 0.04). Moreover, there was a decrease in Clostridium genus (time P = 0.04) and Blautia (time P = 0.051). Only MICT decreased jejunal FAU (P = 0.02). Training had no significant effect on intestinal GU. Colonic GU associated positively with Bacteroidetes and inversely with Firmicutes phylum, ratio Firmicutes/Bacteroidetes and Blautia genus. CONCLUSIONS Intestinal substrate uptake associates with gut microbiota composition and whole-body insulin sensitivity. Exercise training improves gut microbiota profiles and reduces endotoxemia.
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A structured weight loss program increases gut microbiota phylogenetic diversity and reduces levels of Collinsella in obese type 2 diabetics: A pilot study.
Frost, F, Storck, LJ, Kacprowski, T, Gärtner, S, Rühlemann, M, Bang, C, Franke, A, Völker, U, Aghdassi, AA, Steveling, A, et al
PloS one. 2019;14(7):e0219489
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The global obesity epidemic is a major cause of the increase in type 2 diabetes mellitus (T2DM) and ensuing cardiovascular disease. The causes of obesity are complex ,and it has been shown that changes in the microbiome are associated with obesity. The microbiome can be altered through dietary intervention and weight loss. The aim of this open label pilot study was to investigate the microbiome of obese patients with T2DM during a weight loss programme. During the first six weeks the diet consisted of formula drink providing 800kcal per day, followed by nine weeks during which a regular diet of 1,200-1,500kcal per day was reintroduced, depending on the individuals’ needs. All participants lost weight continuously over the 15 weeks, from an average BMI of 39.6 at the start to 33.1 at the end of the programme. This was accompanied with an improvement in glucose metabolism, total and LDL cholesterol and uric acid levels, but not HDL cholesterol or triglycerides. All participants experienced changes in their microbiome towards greater diversity after the first six weeks of the low-calorie formula diet but these changes were partially reversed at the end of the study period at 15 weeks. A particular type of bacteria, Collinsella, which has been associated with poor metabolic health, was the only type found to remain reduced at the end of the 15 weeks, an 8.4-fold decrease. The authors hypothesise that this reduction in Collinsella may be associated with the improvement of metabolic factor in these patients at the end of the study.
Abstract
The global obesity epidemic constitutes a major cause of morbidity and mortality challenging public health care systems worldwide. Thus, a better understanding of its pathophysiology and the development of novel therapeutic options are urgently needed. Recently, alterations of the intestinal microbiome in the obese have been discussed as a promoting factor in the pathophysiology of obesity and as a contributing factor to related diseases such as type 2 diabetes and metabolic syndrome. The present pilot study investigated the effect of a structured weight loss program on fecal microbiota in obese type 2 diabetics. Twelve study subjects received a low-calorie formula diet for six weeks, followed by a nine week food reintroduction and stabilization period. Fecal microbiota were determined by 16S rRNA gene sequencing of stool samples at baseline, after six weeks and at the end of the study after fifteen weeks. All study subjects lost weight continuously throughout the program. Changes in fecal microbiota were most pronounced after six weeks of low-calorie formula diet, but reverted partially until the end of the study. However, the gut microbiota phylogenetic diversity increased persistently. The abundance of Collinsella, which has previously been associated with atherosclerosis, decreased significantly during the weight loss program. This study underlines the impact of dietary changes on the intestinal microbiome and further demonstrates the beneficial effects of weight loss on gut microbiota. Trial registration: ClinicalTrials.gov NCT02970838.
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial.
Roager, HM, Vogt, JK, Kristensen, M, Hansen, LBS, Ibrügger, S, Mærkedahl, RB, Bahl, MI, Lind, MV, Nielsen, RL, Frøkiær, H, et al
Gut. 2019;68(1):83-93
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Whole grain consumption has been linked with decreased risk of lifestyle-related diseases. While animal studies have shown the gut microbiome to be a mediator of metabolic health, human studies examining the effect of whole grain intake of the gut remain inconclusive. The aim of this study was to investigate the effects of a whole grain diet on the gut microbiome, gut functionality and biomarkers of metabolic health. In this randomised, controlled, crossover study, 50 participants completed two 8-week dietary intervention periods comprising of a whole grain diet and a refined grain diet with a 6-week washout period. Examinations were done at the beginning and end of each intervention period to assess anthropometry and various plasma and gut markers. This study found that a whole grain diet as compared with a refined grain diet reduced energy intake and body weight as well as circulating markers of inflammation. Contrary to the hypothesis, these benefits were all observed independent of changes in the gut microbiome. Based on these results, the authors conclude higher intake of whole grains should be recommended to those at risk of inflammation-related disease.
Abstract
OBJECTIVE To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. RESULTS 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. CONCLUSION Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. TRIAL REGISTRATION NUMBER NCT01731366; Results.
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Role of whole grains versus fruits and vegetables in reducing subclinical inflammation and promoting gastrointestinal health in individuals affected by overweight and obesity: a randomized controlled trial.
Kopf, JC, Suhr, MJ, Clarke, J, Eyun, SI, Riethoven, JM, Ramer-Tait, AE, Rose, DJ
Nutrition journal. 2018;17(1):72
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Poor diet is the leading risk factor for premature death and disability in the United States. Poor diets lead to metabolic syndrome and its associated diseases such as heart disease and diabetes. The purpose of this study was to determine the impact of increasing intake of wholegrains or fruit and vegetables against a typical Western diet on inflammatory makers and gut microbiota composition. The study was a randomized, parallel arm feeding trial which enrolled fifty-two participants. The subjects were randomized into three groups (control, wholegrains, and fruit and vegetables). Results indicate that the wholegrain and fruit and vegetable diets had significant positive impacts on inflammatory markers. Interestingly, while both treatment groups decreased inflammatory markers, each decreased a different biomarker. The treatments induced individualised changes in microbiota composition such that treatment group differences were not identified. Authors conclude that wholegrain and fruit and vegetable diets have a positive impact on metabolic health in individuals affected by overweight or obesity.
Abstract
BACKGROUND Whole grains (WG) and fruits and vegetables (FV) have been shown to reduce the risk of metabolic disease, possibly via modulation of the gut microbiota. The purpose of this study was to determine the impact of increasing intake of either WG or FV on inflammatory markers and gut microbiota composition. METHODS A randomized parallel arm feeding trial was completed on forty-nine subjects with overweight or obesity and low intakes of FV and WG. Individuals were randomized into three groups (3 servings/d provided): WG, FV, and a control (refined grains). Stool and blood samples were collected at the beginning of the study and after 6 weeks. Inflammatory markers [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP), and high sensitivity C-reactive protein (hs-CRP)] were measured. Stool sample analysis included short/branched chain fatty acids (S/BCFA) and microbiota composition. RESULTS There was a significant decrease in LBP for participants on the WG (- 0.2 μg/mL, p = 0.02) and FV (- 0.2 μg/mL, p = 0.005) diets, with no change in those on the control diet (0.1 μg/mL, p = 0.08). The FV diet induced a significant change in IL-6 (- 1.5 pg/mL, p = 0.006), but no significant change was observed for the other treatments (control, - 0.009 pg/mL, p = 0.99; WG, - 0.29, p = 0.68). The WG diet resulted in a significant decrease in TNF-α (- 3.7 pg/mL; p < 0.001), whereas no significant effects were found for those on the other diets (control, - 0.6 pg/mL, p = 0.6; FV, - 1.4 pg/mL, p = 0.2). The treatments induced individualized changes in microbiota composition such that treatment group differences were not identified, except for a significant increase in α-diversity in the FV group. The proportions of Clostridiales (Firmicutes phylum) at baseline were correlated with the magnitude of change in LBP during the study. CONCLUSIONS These data demonstrate that WG and FV intake can have positive effects on metabolic health; however, different markers of inflammation were reduced on each diet suggesting that the anti-inflammatory effects were facilitated via different mechanisms. The anti-inflammatory effects were not related to changes in gut microbiota composition during the intervention, but were correlated with microbiota composition at baseline. TRIAL REGISTRATION ClinicalTrials.gov , NCT02602496 , Nov 4, 2017.
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Fructose metabolism and metabolic disease.
Hannou, SA, Haslam, DE, McKeown, NM, Herman, MA
The Journal of clinical investigation. 2018;128(2):545-555
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Sugar consumption is thought to be a contributing factor in the increase in diabetes and obesity and the associated risk of cardiovascular disease worldwide. Sucrose (table sugar) and high fructose corn syrup contain almost equal amounts of fructose and glucose and are commonly added to processed foods. Whilst long-term studies are lacking, some short-term intervention studies show that fructose can impair lipid metabolism and insulin sensitivity in humans. This article reviews the biochemistry and molecular genetics of fructose metabolism as well as potential mechanisms by which excessive fructose consumption contributes to cardiometabolic disease. Fructose absorption in the human intestine is saturable, and there is a large range in capacity to absorb fructose between individuals, and unabsorbed fructose may contribute to gastrointestinal symptoms including pain and bloating. Fructose concentrations in the blood can increase 10-fold after consumption, but are rapidly cleared, mostly by the liver, where it provides substrate for metabolic processes, but may also be involved in signalling functions. Fructose may enhance glucose uptake by the liver and storage as glycogen and lipids. It may also increase production of uric acid which is implicated with gout. Excessive fructose consumption affects lipid metabolism and may contribute to fat accumulation in the liver and increase circulating triglycerides, a risk factor for heart disease. In animal models it also induces increased insulin levels. Fructose is one of the sweetest sugars which may affect appetite and overeating. It may also induce addiction-like behaviours such as binging and dependence in part by stimulating dopaminergic pathways. It also appears to induce leptin resistance which further increases food intake and obesity.
Abstract
Increased sugar consumption is increasingly considered to be a contributor to the worldwide epidemics of obesity and diabetes and their associated cardiometabolic risks. As a result of its unique metabolic properties, the fructose component of sugar may be particularly harmful. Diets high in fructose can rapidly produce all of the key features of the metabolic syndrome. Here we review the biology of fructose metabolism as well as potential mechanisms by which excessive fructose consumption may contribute to cardiometabolic disease.
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Changes in Gut Microbiota-Related Metabolites and Long-term Successful Weight Loss in Response to Weight-Loss Diets: The POUNDS Lost Trial.
Heianza, Y, Sun, D, Smith, SR, Bray, GA, Sacks, FM, Qi, L
Diabetes care. 2018;41(3):413-419
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Evidence has demonstrated that weight loss contributes to lowering the risk of developing type 2 diabetes among obese patients. The aim of this study was to examine whether diet-induced metabolites were associated with improvements in adiposity and metabolism during a weight-loss diet intervention in 510 overweight and obese individuals. Participants were randomly assigned to one of four diets with varying macronutrient composition to adhere to for six months. Blood samples and anthropometric data were taken at baseline and 6 months to monitor changes. This study found that overweight and obese individuals with reduced choline or L-carnitine levels achieved greater improvements of adiposity and energy metabolism. Based on these results, the authors conclude that metabolites are predictive of patient responsiveness to dietary interventions, and suggest further studies evaluate these effects in the pre-diabetic obese population.
Abstract
OBJECTIVE Adiposity and the gut microbiota are both related to the risk of type 2 diabetes. We aimed to comprehensively examine how changes induced by a weight-loss diet intervention in gut microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors (choline and l-carnitine), were associated with improvements in adiposity and regional fat deposition. RESEARCH DESIGN AND METHODS This study included 510 overweight and obese individuals who were randomly assigned one of four diets varying in macronutrient intake. We examined associations of 6-month changes in blood metabolites (TMAO, choline, and l-carnitine) with improvements in body weight (BW), waist circumference (WC), body fat composition, fat distribution, and resting energy expenditure (REE). RESULTS Individuals with a greater reduction of choline (P < 0.0001) and l-carnitine (P < 0.01) rather than TMAO showed significant losses of BW and WC at 6 months. The reduction of choline was significantly predictive of decreases in body fat composition, fat distribution, and REE. Results of sensitivity analysis showed that the baseline diabetes risk status, such as the presence of hyperglycemia (31% of the total participants) and fasting glucose levels, did not modify the associations. Early changes in choline and l-carnitine were significantly predictive of weight loss over 2 years (P < 0.05 for all). Individuals with increases in choline or l-carnitine were 2.35-times (95% CI 1.38, 4.00) or 1.77-times (1.06, 2.95) more likely to fail to lose weight (-5% or more loss) at 2 years. CONCLUSIONS Overweight and obese individuals who showed decreases in circulating choline or l-carnitine levels achieved greater improvements of adiposity and energy metabolism by eating a low-calorie weight-loss diet, suggesting that such metabolites are predictive of individuals' response to the treatment. Further investigations are necessary to confirm our findings, particularly in a population with prediabetes that is more representative of the U.S. population with obesity.