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Effects of Synbiotic Supplement on Human Gut Microbiota, Body Composition and Weight Loss in Obesity.
Sergeev, IN, Aljutaily, T, Walton, G, Huarte, E
Nutrients. 2020;12(1)
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The gut microbiota plays a role in the development of obesity and associated diseases. Whilst energy-restricted, low-carbohydrate, high-protein diets can facilitate substantial weight-loss, they also have been linked to ill-effects and unfavourable changes in the gut microbiota from excess protein fermentation. Pro-and prebiotics (synbiotics) have become a promising intervention in the management of obesity. This small placebo-controlled clinical trial involved 20 obese adults following an energy-restricted (approx.950 kcal/day) low-carbohydrate, high-protein diet. The study examined whether a supplementary synbiotic contributed to additional changes in body composition and metabolic biomarkers. The synbiotic contained Lactobacilli spp. and Bifidobacteria spp. and a prebiotic mixture of galactooligosaccharides. Overall, at the end of the 3-month trial, there was no remarkable difference between the groups. Both experienced a significant and decreasing trend in body mass, waist circumference, body mass index, fat mass, fat percentage, and glucose level, affirming the known benefits of the described weight-loss diet. However, the synbiotic supplementation group had a greater decrease in HbA1C and significant alterations in gut microbiota, showing an increased abundance of gut bacteria associated with positive health effects. Due to the complexity of microbial species and host interactions, the authors advocate for more research to identify their significance and shed light on contradictory findings. This study identified that synbiotics may not contribute to additional changes in body composition when combined with an energy-restricted, low-carbohydrate, high-protein diet but they can offer additional health benefits by inducing favourable changes to the gut microbiota.
Abstract
Targeting gut microbiota with synbiotics (probiotic supplements containing prebiotic components) is emerging as a promising intervention in the comprehensive nutritional approach to reducing obesity. Weight loss resulting from low-carbohydrate high-protein diets can be significant but has also been linked to potentially negative health effects due to increased bacterial fermentation of undigested protein within the colon and subsequent changes in gut microbiota composition. Correcting obesity-induced disruption of gut microbiota with synbiotics can be more effective than supplementation with probiotics alone because prebiotic components of synbiotics support the growth and survival of positive bacteria therein. The purpose of this placebo-controlled intervention clinical trial was to evaluate the effects of a synbiotic supplement on the composition, richness and diversity of gut microbiota and associations of microbial species with body composition parameters and biomarkers of obesity in human subjects participating in a weight loss program. The probiotic component of the synbiotic used in the study contained Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium longum, and Bifidobacterium bifidum and the prebiotic component was a galactooligosaccharide mixture. The results showed no statistically significant differences in body composition (body mass, BMI, body fat mass, body fat percentage, body lean mass, and bone mineral content) between the placebo and synbiotic groups at the end of the clinical trial (3-month intervention, 20 human subjects participating in weight loss intervention based on a low-carbohydrate, high-protein, reduced energy diet). Synbiotic supplementation increased the abundance of gut bacteria associated with positive health effects, especially Bifidobacterium and Lactobacillus, and it also appeared to increase the gut microbiota richness. A decreasing trend in the gut microbiota diversity in the placebo and synbiotic groups was observed at the end of trial, which may imply the effect of the high-protein low-carbohydrate diet used in the weight loss program. Regression analysis performed to correlate abundance of species following supplementation with body composition parameters and biomarkers of obesity found an association between a decrease over time in blood glucose and an increase in Lactobacillus abundance, particularly in the synbiotic group. However, the decrease over time in body mass, BMI, waist circumstance, and body fat mass was associated with a decrease in Bifidobacterium abundance. The results obtained support the conclusion that synbiotic supplement used in this clinical trial modulates human gut microbiota by increasing abundance of potentially beneficial microbial species.
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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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Total and Subtypes of Dietary Fat Intake and Its Association with Components of the Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Risk.
Julibert, A, Bibiloni, MDM, Bouzas, C, Martínez-González, MÁ, Salas-Salvadó, J, Corella, D, Zomeño, MD, Romaguera, D, Vioque, J, Alonso-Gómez, ÁM, et al
Nutrients. 2019;11(7)
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Obesity, Metabolic Syndrome (MetS) and Cardiovascular Disease (CVD) are becoming a global epidemic and the role of dietary fats is still unclear. The PREDIMED trial is a large study of 6560 Mediterranean men and women, aged 55–75 years old, with overweight/obesity and MetS in which they have tracked all types of dietary fat consumed over a 6-year period to assess the risk factors for CVD. Quality of fat is thought to play an important role in MetS. This study used food questionnaires to measure intake of the following fats: total fat, monounsaturated fatty acids: MUFA, polyunsaturated fatty acids: PUFA, saturated fatty acids: SFA, trans-fatty acids: trans-FA, linoleic acid, a-linolenic acid, and w-3 FA). They were able to divide the participants into groups ranging from highest to lowest fat intake and assess the types of foods and fats being consumed. They found that the group with the highest fat intakes ate less carbohydrates, protein and fibre and had a higher risk of hyperglycaemia (high blood glucose levels). The total fats consumed in this group also included high levels of harmful trans-fatty acids so the researchers concluded that the risk is influenced by the combination of nutrients of the food consumed. They also found that participants who consumed high levels of linoleic acid had significantly higher healthy HDL cholesterol levels and those who consumed high levels of saturated fatty acids and omega 3 had significantly less risk of high triglycerides (another cholesterol marker). Overall they recommend further studies into types of dietary fat to help reduce MetS in the population.
Abstract
Background: The effect of dietary fat intake on the metabolic syndrome (MetS) and in turn on cardiovascular disease (CVD) remains unclear in individuals at high CVD risk. Objective: To assess the association between fat intake and MetS components in an adult Mediterranean population at high CVD risk. Design: Baseline assessment of nutritional adequacy in participants (n = 6560, men and women, 55-75 years old, with overweight/obesity and MetS) in the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial. Methods: Assessment of fat intake (total fat, monounsatured fatty acids: MUFA, polyunsaturated fatty acids: PUFA, saturated fatty acids: SFA, trans-fatty acids: trans-FA, linoleic acid, α-linolenic acid, and ω-3 FA) using a validated food frequency questionnaire, and diet quality using 17-item Mediterranean dietary questionnaire and fat quality index (FQI). Results: Participants in the highest quintile of total dietary fat intake showed lower intake of energy, carbohydrates, protein and fiber, but higher intake of PUFA, MUFA, SFA, TFA, LA, ALA and ω-3 FA. Differences in MetS components were found according to fat intake. Odds (5th vs. 1st quintile): hyperglycemia: 1.3-1.6 times higher for total fat, MUFA, SFA and ω-3 FA intake; low high-density lipoprotein cholesterol (HDL-c): 1.2 higher for LA; hypertriglyceridemia: 0.7 lower for SFA and ω-3 FA intake. Conclusions: Dietary fats played different role on MetS components of high CVD risk patients. Dietary fat intake was associated with higher risk of hyperglycemia.
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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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The Effect of Probiotic Yogurt on Glycemic Control in Type 2 Diabetes or Obesity: A Meta-Analysis of Nine Randomized Controlled Trials.
Barengolts, E, Smith, ED, Reutrakul, S, Tonucci, L, Anothaisintawee, T
Nutrients. 2019;11(3)
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The metabolic disorders type 2 diabetes and obesity are highly prevalent worldwide. There are multiple merging treatments for type 2 diabetes and obesity, but the management of both conditions remains challenging. The aim of the study was to review the effects of probiotics on glycaemic outcomes in type 2 diabetes or obesity. The study is a meta-analysis of RCTs that utilized probiotic yoghurt as a main intervention in participants with type 2 diabetes or obesity. Nine studies were included in the meta-analysis, seven of which were conducted in subjects with type 2 diabetes and the rest were conducted in subjects with obesity. Results indicate that probiotic yoghurt provides no significant improvement compared with the control in glycaemic markers. Authors conclude that their study did not demonstrate the benefits of consuming probiotic yoghurt compared with conventional yoghurt for improving glucose control in patients with type 2 diabetes or obesity.
Abstract
Probiotic yogurt is suggested as a nutritional approach in type 2 diabetes (T2D) and obesity. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the effects of probiotic yogurt on glycemic outcomes in T2D or obesity. The databases used to search for RCTs included Medline and Scopus. The RCTs were eligible if outcomes included selected glycemic markers. In nine eligible trials, 237 and 235 subjects were in treatment (probiotic yogurt) and control (mostly conventional yogurt) groups, respectively. There was no significant difference for pooled unstandardized mean difference (USMD) hemoglobin A1c (HbA1c) by probiotic yogurt compared with the control in T2D (USMD: -0.366; 95% CI: -0.755, 0.024, p = 0.066) and obesity (USMD: 0.116, 95% CI: -0.007, 0.238, p = 0.065). Similarly, there were no effects of probiotic yogurt on fasting blood glucose, fasting insulin, or insulin resistance (estimated by homeostatic model assessment of insulin resistance (HOMA-IR)) in either T2D or obesity. In conclusion, the present meta-analysis has not demonstrated the benefits of consuming probiotic compared with conventional yogurt for improving glucose control in patients with diabetes or obesity. Larger trials are needed to verify the benefits of probiotic and/or conventional yogurt or other probiotic fermented milk (e.g., kefir) on glycemic markers in patients with diabetes and obesity.
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The Effects of Extra Virgin Olive Oil on Alanine Aminotransferase, Aspartate Aminotransferase, and Ultrasonographic Indices of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Patients Undergoing Low Calorie Diet.
Shidfar, F, Bahrololumi, SS, Doaei, S, Mohammadzadeh, A, Gholamalizadeh, M, Mohammadimanesh, A
Canadian journal of gastroenterology & hepatology. 2018;2018:1053710
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Non-alcoholic fatty liver disease (NAFLD) is a risk factor for cardiovascular disease (CVD), which is the most common cause of death. The traditional Mediterranean diet has been shown to reduce the risk of NAFLD and CVD and this protective effect is thought to be in part due to the use of olive oil in this dietary pattern. The aim of this randomised, single-blind study was to evaluate the effect of virgin olive oil as part of a low-calorie diet on markers of NAFLD. 43 overweight or obese patients with NAFLD, characterised by increased liver enzymes (ALT and AST), were randomised to either a low calorie diet with normal fat or a low calorie diet with 20% of total energy intake from olive oil (overall percentage of fat 30% of total energy intake in both groups) for three months. Significant weight loss was observed in both groups, with no significant difference between groups. There was a reduction in liver enzymes in the olive oil group which was significantly greater than in the control group. The severity of liver steatosis (the accumulation of fat in the liver) did not change significantly in either group. The authors concluded that a low calorie diet with virgin olive oil led to slight weight loss and improvements in markers for NAFLD.
Abstract
Background: Coronary artery disease is the most common cause of death in the patients with nonalcoholic fatty liver disease (NAFLD). Studies have shown that there is a strong relation between the increase in the aminotransferase levels and fat accumulation in the liver with cardiovascular complications, independent of all aspects of the metabolic syndrome. This study aimed to examine the effect of virgin olive oil on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the severity of steatosis in the NAFLD patients undergoing a weight-loss diet. Methods: This clinical trial was carried out on 50 patients with nonalcoholic fatty liver (mean age of 45.91 ± 9.61 years, mean BMI of 29.7 ± 0.58 Kg/m2) and the subjects were randomly assigned to the olive oil group (receiving the equivalent of 20% of their total daily energy requirement from olive oil) or the control group (with normal consumption of oil) for 12 weeks. All the patients received a hypocaloric diet during the study. At the beginning and the end of the study, the serum levels of ALT and AST and liver steatosis were measured. Findings: A significant decrease in the level of ALT enzymes was observed in the control group at the end of the study (P = 0.004). In the olive oil group, both enzymes decreased compared to baseline measurements (P < 0.01). There were significant differences in the ALT and AST levels between the two groups (P < 0.02). The severity of liver steatosis did not change significantly during the study. Conclusion: The consumption of a low calorie diet enriched with olive oil, along with slight weight reduction, reinforces the desired effects of weight loss in improving the levels of the hepatic enzymes.
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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.
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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.