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Effect of ancient Khorasan wheat on gut microbiota, inflammation, and short-chain fatty acid production in patients with fibromyalgia.
Baldi, S, Pagliai, G, Dinu, M, Di Gloria, L, Nannini, G, Curini, L, Pallecchi, M, Russo, E, Niccolai, E, Danza, G, et al
World journal of gastroenterology. 2022;28(18):1965-1980
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Fibromyalgia (FM) is a systemic syndrome of unclear aetiology, characterized by widespread pain and tenderness, sleeping disorders, fatigue, and cognitive dysfunction. In many cases, gastrointestinal distress is also reported, suggesting a potential involvement of the gut microbiota (GM), as demonstrated by the frequent dysbiosis found in FM subjects. The aim of this study was to examine whether a replacement diet with ancient Khorasan wheat could influence the GM composition, the faecal molecular immune profile, and short-chain fatty acids (SCFAs) production in patients suffering fibromyalgia syndrome. This study was a randomised, double-blind crossover trial which enrolled patients with documented FM who consumed control wheat products or Khorasan wheat products for 8 weeks and then crossed over. Participants (n=20) were randomly assigned to one of the two groups. Results showed that: - both 8-week interventions did not significantly modify either the microbial composition and diversity or the SCFAs levels; - in terms of changes in microbial abundances produced by each dietary intervention, Khorasan wheat products (KD) did not result in modifications at any taxonomic level, whereas the controlled diet (CD) was associated with a significant increase of Turicibacter spp. [bacteria belonging to the phylum Firmicutes]; - faecal molecular inflammatory profile showed that CD resulted in an increased level of a particular anti-inflammatory marker, while no significant differences were reported after KD. Authors conclude that an ancient Khorasan wheat diet results in some beneficial GM compositional and functional modifications that positively correlate with an improvement of fibromyalgia symptomatology.
Abstract
BACKGROUND Fibromyalgia (FM) syndrome is mainly characterized by widespread pain, sleeping disorders, fatigue, and cognitive dysfunction. In many cases, gastrointestinal distress is also reported, suggesting the potential pathogenic role of the gut microbiota (GM). The GM is deeply influenced by several environmental factors, especially the diet, and recent findings highlighted significant symptom improvement in FM patients following various nutritional interventions such as vegetarian diet, low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols based diets, gluten-free diet, and especially an ancient grain supplementation. In particular, a recent study reported that a replacement diet with ancient Khorasan wheat led to an overall improvement in symptom severity of FM patients. AIM: To examine the effects of ancient Khorasan wheat on the GM, inflammation, and short-chain fatty acid production in FM patients. METHODS After a 2-wk run-in period, 20 FM patients were enrolled in this randomized, double-blind crossover trial. In detail, they were assigned to consume either Khorasan or control wheat products for 8 wk and then, following an 8-wk washout period, crossed. Before and after treatments, GM characterization was performed by 16S rRNA sequencing while the fecal molecular inflammatory response and the short-chain fatty acids (SCFAs) were respectively determined with the Luminex MAGPIX detection system and a mass chromatography-mass spectrometry method. RESULTS The Khorasan wheat replacement diet, in comparison with the control wheat diet, had more positive effects on intestinal microbiota composition and on both the fecal immune and SCFAs profiles such as the significant increase of butyric acid levels (P = 0.054), candidatus Saccharibacteria (P = 9.95e-06) and Actinobacteria, and the reduction of Enterococcaceae (P = 4.97e-04). Moreover, the improvement of various FM symptoms along with the variation of some gut bacteria after the Khorasan wheat diet have been documented; in fact we reported positive correlations between Actinobacteria and both Tiredness Symptoms Scale (P < 0.001) and Functional Outcome of Sleep Questionnaire (P < 0.05) scores, between Verrucomicrobiae and both Widespread Pain Index (WPI) + Symptom Severity scale (SS) (P < 0.05) and WPI (P < 0.05) scores, between candidatus Saccharibacteria and SS score (P < 0.05), and between Bacteroidales and Sleep-Related and Safety Behaviour Questionnaire score (P < 0.05). CONCLUSION The replacement diet based on ancient Khorasan wheat results in beneficial GM compositional and functional modifications that positively correlate with an improvement of FM symptomatology.
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Butyrate-Rich Diets Improve Redox Status and Fibrin Lysis in Behçet's Syndrome.
Emmi, G, Bettiol, A, Niccolai, E, Ramazzotti, M, Amedei, A, Pagliai, G, Taddei, N, Sofi, F, Fiorillo, C, Prisco, D, et al
Circulation research. 2021;(2):278-280
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Effects of vegetarian versus Mediterranean diet on kidney function: Findings from the CARDIVEG study.
Dinu, M, Colombini, B, Pagliai, G, Giangrandi, I, Cesari, F, Gori, A, Giusti, B, Marcucci, R, Sofi, F
European journal of clinical investigation. 2021;(9):e13576
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Abstract
BACKGROUND The aim of the present study was to assess the effects of a lacto-ovo-vegetarian diet (VD), compared to a Mediterranean diet (MD), on kidney function in a group of subjects with medium-to-low cardiovascular risk profile. METHODS We analysed 107 subjects (82 women, 25 men; median age 52) who followed a VD (n = 54) and a MD (n = 53) for 3 months in the CARDIVEG study, a randomized, open, crossover trial that compared the effects of these 2 diets on cardiovascular disease risk. RESULTS The effect of the two diets on kidney function markers was evaluated by conducting a general linear model for repeated measurements adjusted for possible confounding factors such as age, sex, physical activity, alcohol, smoking, hypertension, LDL cholesterol, glucose and body weight change. A significant reduction in creatinine (-5.3%; P < .001), urea nitrogen levels (-9%; P = .001), blood urea nitrogen (BUN) (-8.7%; P = .001) and BUN/creatinine ratio (-5.8%; P < .001), and an increase in estimated glomerular filtration rate (eGFR) (+3.5%; P = .001) was observed during the VD period. On the contrary, no significant changes were noted in the MD group. Variations obtained in the two dietary interventions were significantly different (P < .0001) for creatinine levels, BUN/creatinine and eGFR, for which opposite trends were observed in the VD and MD groups. CONCLUSIONS In a selected group of subjects with medium-to-low cardiovascular risk profile, a 3 month VD period determined significant improvements in kidney function markers. Further trials are needed to confirm these results.
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Effects of a dietary intervention with Mediterranean and vegetarian diets on hormones that influence energy balance: results from the CARDIVEG study.
Dinu, M, Colombini, B, Pagliai, G, Cesari, F, Gori, A, Giusti, B, Marcucci, R, Sofi, F
International journal of food sciences and nutrition. 2020;(3):362-369
Abstract
A randomised, open, crossover trial with two intervention periods was used to compare the effects of a 3-month dietary intervention with Mediterranean diet (MD) and vegetarian diet (VD) on hormones that influence energy balance, and to investigate the relationship with changes in body composition. After 3 months, no significant differences between the two diets were observed. Both MD and VD resulted in a significant (p < .05) reduction in leptin-to-adiponectin ratio and anthropometric parameters, MD resulted in a significant decrease in leptin levels (-7.4%), while VD determined a significant increase in adiponectin (+6.8%) and a significant decrease in visfatin (-12.7%) levels. In both groups, changes in leptin, insulin and HOMA-IR were significantly and positively correlated with changes in anthropometric parameters. In conclusion, both MD and VD have led to a slight but significant improvement in hormones that influence energy balance. The effect was more evident in participants who lost weight and fat mass.
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Influence of a 3-month low-calorie Mediterranean diet compared to the vegetarian diet on human gut microbiota and SCFA: the CARDIVEG Study.
Pagliai, G, Russo, E, Niccolai, E, Dinu, M, Di Pilato, V, Magrini, A, Bartolucci, G, Baldi, S, Menicatti, M, Giusti, B, et al
European journal of nutrition. 2020;(5):2011-2024
Abstract
PURPOSE We evaluated the effect of low-calorie mediterranean (MD) and vegetarian (VD) diets on gut microbiome (GM) composition and short-chain-fatty acids (SCFA) production. METHODS We performed next generation sequencing (NGS) of 16S rRNA and SCFA analysis on fecal samples of 23 overweight omnivores (16 F; 7 M) with low-to-moderate cardiovascular risk. They were randomly assigned to a VD or MD, each lasting 3 months, with a crossover study design. RESULTS Dietary interventions did not produce significant diversity in the GM composition at higher ranks (family and above), neither between nor within MD and VD, but they did it at genus level. MD significantly changed the abundance of Enterorhabdus, Lachnoclostridium and Parabacteroides, while VD significantly affected the abundance of Anaerostipes, Streptococcus, Clostridium sensu stricto, and Odoribacter. Comparison of the mean variation of each SCFA between MD and VD showed an opposite and statistically significant trend for propionic acid (+ 10% vs - 28%, respectively, p = 0.034). In addition, variations of SCFA were negatively correlated with changes of some inflammatory cytokines such as VEGF, MCP-1, IL-17, IP-10 and IL-12, only after MD. Finally, correlation analyses showed a potential relationship-modulated by the two diets-between changes of genera and changes of clinical and biochemical parameters. CONCLUSIONS A short-term dietary intervention with MD or VD does not induce major change in the GM, suggesting that a diet should last longer than 3 months for scratching the microbial resilience. Changes in SCFA production support their role in modulating the inflammatory response, thus mediating the anti-inflammatory and protective properties of MD.
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Mediterranean, but not lacto-ovo-vegetarian, diet positively influence circulating progenitor cells for cardiovascular prevention: The CARDIVEG study.
Cesari, F, Dinu, M, Pagliai, G, Rogolino, A, Giusti, B, Gori, AM, Casini, A, Marcucci, R, Sofi, F
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2019;(6):604-610
Abstract
AIM: To evaluate the possible association between dietary habits and progenitor cells using data obtained from a randomized crossover trial using two different diets, lacto-ovo-vegetarian (VD) and Mediterranean (MD), the CARDIVEG study. METHODS AND RESULTS Eighty clinically healthy subjects with a low-to-moderate cardiovascular risk profile (61 F; 19 M; mean age: 50.7 ± 11.6 years) were randomly assigned to isocaloric VD and MD diets lasting three months each, and then crossed. The two diets showed no effects on endothelial progenitor cells and circulating endothelial cells but opposite effects on circulating progenitor cells. In fact, VD determined significant (p < 0.05) and negative changes on circulating progenitor cells, with an average geometric variation of -130 cells/106 events for CD34+/CD45-/dim, -80 cells/106 events for CD133+/CD45-/dim, and -84 cells/106 events for CD34+/CD133+/CD45-/dim while MD determined significant (p < 0.05) and positive changes for CD34+/CD45-/dim levels, with a geometric mean increase of +54 cells/106 events. No significant correlations were observed between changes in progenitor cells and changes in inflammatory parameters during the VD phase. On the other hand, during the MD phase negative correlations between changes of CD34+/CD45-/dim and interleukin-6 (R = -0.324; p = 0.004) as well as interleukin-8 (R = -0.228; p = 0.04) and monocyte chemotactic protein-1 (R = -0.277; p = 0.01), were observed. These correlations remained significant also after adjustment for confounding factors only for CD34+/CD45-/dim and interleukin-6 (β = -0.282; p = 0.018) and monocyte chemotactic protein-1 (β = -0.254; p = 0.031). CONCLUSIONS MD, but not VD, reported a significant and positive effect on circulating progenitor cells in a group of subjects at low-to-moderate cardiovascular risk, probably acting through the modulation of inflammatory parameters.
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Low-Calorie Vegetarian Versus Mediterranean Diets for Reducing Body Weight and Improving Cardiovascular Risk Profile: CARDIVEG Study (Cardiovascular Prevention With Vegetarian Diet).
Sofi, F, Dinu, M, Pagliai, G, Cesari, F, Gori, AM, Sereni, A, Becatti, M, Fiorillo, C, Marcucci, R, Casini, A
Circulation. 2018;(11):1103-1113
Abstract
BACKGROUND Only a few randomized dietary intervention studies that investigated the effects of lacto-ovo vegetarian diet (Vd) in clinically healthy omnivorous subjects are available. METHODS We randomly assigned to overweight omnivores with a low-to-moderate cardiovascular risk profile a low-calorie Vd compared with a low-calorie Mediterranean diet (MD), each lasting 3 months, with a crossover design. The primary outcome was the difference in body weight, body mass index, and fat mass changes between the 2 groups. Secondary outcomes were differences in circulating cardiovascular disease risk parameters changes between the 2 groups. RESULTS One hundred eighteen subjects (mean age: 51.1 years, females: 78%) were enrolled. The total participation rate at the end of the study was 84.7%. No differences between the 2 diets in body weight were observed, as reported by similar and significant reductions obtained by both Vd (-1.88 kg) and MD (-1.77 kg). Similar results were observed for body mass index and fat mass. In contrast, significant differences between the 2 interventions were obtained for low-density lipoprotein cholesterol, triglycerides, and vitamin B12 levels. The difference between the Vd and MD groups, in terms of end-of-diet values, was recorded at 9.10 mg/dL for low-density lipoprotein cholesterol (P=0.01), 12.70 mg/dL for triglycerides (P<0.01), and 32.32 pg/mL for vitamin B12 (P<0.01). Finally, no significant difference was found between Vd and MD interventions in oxidative stress markers and inflammatory cytokines, except for interleukin-17, which improved only in the MD group. Forty-six participants during the Vd period and 35 during the MD period reached the target values for ≥1 cardiovascular risk factor. CONCLUSIONS Both Vd and MD were effective in reducing body weight, body mass index, and fat mass, with no significant differences between them. However, Vd was more effective in reducing low-density lipoprotein cholesterol levels, whereas MD led to a greater reduction in triglyceride levels. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT02641834.
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A Khorasan Wheat-Based Replacement Diet Improves Risk Profile of Patients With Nonalcoholic Fatty Liver Disease (NAFLD): A Randomized Clinical Trial.
Dinu, M, Whittaker, A, Pagliai, G, Giangrandi, I, Colombini, B, Gori, AM, Fiorillo, C, Becatti, M, Casini, A, Benedettelli, S, et al
Journal of the American College of Nutrition. 2018;37(6):508-514
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Non-alcoholic fatty liver disease (NAFLD) is prevalent, however early intervention with lifestyle modifications such as weight loss, dietary therapy and physical activity may reverse it. Previous studies have shown that the Mediterranean diet, which includes a large proportion of grains, may reduce NAFLD. However no prior studies have assessed grains in isolation on these individuals. This randomised double blind parallel arm study aimed to assess the effects of a replacement diet with ancient khorasan wheat products on patients with NAFLD. 40 people with mild- moderate NAFLD were assigned to either khorasan wheat diet or a modern wheat grain diet for three months. This comparatively small study found that a khorasan wheat based diet improved liver function and inflammation. However regardless of the diet, measures of oxidative stress, which assesses the imbalance of free radicals and antioxidants in the body, was significantly reduced and some individuals were shown to regress from moderate to mild NAFLD. Nutrition practitioners who have clients with mild-moderate NAFLD may recommend a khorasan wheat based diet in the short term to improve biochemical and inflammatory markers and to potentially reverse disease development.
Abstract
OBJECTIVE KAMUT khorasan is an ancient grain with widely acclaimed health benefits. The aim of this study was to investigate the effects of a replacement diet with ancient khorasan wheat products in patients with NAFLD, in comparison to a similar replacement diet with control products made from organic semi-whole-grain modern wheat. METHODS Forty NAFLD patients (12 M/28 F; age 55.2 ± 10.4 years) with mild to moderate liver steatosis were included. The experimental design was a randomized, double-blind, parallel-arm study with 20 participants assigned to consume either KAMUT khorasan or control wheat products (pasta, bread, crackers, biscuits) over a 3-month period. Anthropometric measurements, blood analyses, and ultrasonography examination were performed at both the beginning and end of each dietary intervention. RESULTS After the implementation of a general linear model for repeated measurements adjusted for baseline demographic details, risk factors, and medication, alanine aminotransferase (ALT) was significantly reduced by 12%, aspartate aminotransferase (AST) by 14%, alkaline phosphatase (ALP) by 8%, and cholesterol by 6% only in the khorasan group (p < 0.05 for all). Similarly, significant reductions in circulating proinflammatory tumor necrosis factor-alpha by 50%, interleukin l-receptor antagonist-alpha by 37%, interleukin-8 by 24%, and interferon gamma by 24% were evident only in participants who consumed the khorasan products (p < 0.05 for all). Finally, significant improvements in the liver steatosis grading, Doppler perfusion index values, and reactive oxygen species (ROS) production were evident after consumption of both the khorasan and control products. CONCLUSIONS This study suggests that a short-term replacement diet with ancient KAMUT khorasan products is most effective in reducing metabolic risk factors and ameliorating the liver profile in patients with NAFLD.
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Mediterranean versus vegetarian diet for cardiovascular disease prevention (the CARDIVEG study): study protocol for a randomized controlled trial.
Sofi, F, Dinu, M, Pagliai, G, Cesari, F, Marcucci, R, Casini, A
Trials. 2016;(1):233
Abstract
BACKGROUND Nutrition is able to alter the cardiovascular health of the general population. However, the optimal dietary strategy for cardiovascular disease prevention is still far from being defined. Mediterranean and vegetarian diets are those reporting the greatest grade of evidence in the literature, but no experimental studies comparing these two dietary patterns are available. METHODS/DESIGN This is an open randomized crossover clinical trial including healthy subjects with a low-to-medium cardiovascular risk profile, characterized by being overweight and by the presence of at least an additional metabolic risk factor (abdominal obesity, high total cholesterol, high LDL cholesterol, high triglycerides, impaired glucose fasting levels) but free from medications. A total of 100 subjects will be included and randomly assigned to two groups: Mediterranean calorie-restricted diet (n = 50) and vegetarian calorie-restricted diet (n = 50). The intervention phases will last 3 months each, and at the end of intervention phase I the groups will be crossed over. The two diets will be isocaloric and of three different sizes (1400 - 1600 - 1800 kcal/day), according to specific energy requirements. Adherence to the dietary intervention will be established through questionnaires and 24-h dietary recall. Anthropometric measurements, body composition, blood samples and stool samples will be obtained from each participant at the beginning and at the end of each intervention phase. The primary outcome measure will be change in weight from baseline. The secondary outcome measures will be variations of anthropometric and bioelectrical impedance variables as well as traditional and innovative cardiovascular biomarkers. DISCUSSION Despite all the data supporting the efficacy of Mediterranean and vegetarian diets on the prevention of cardiovascular diseases, no studies have directly compared these two dietary profiles. The trial will test whether there are statistically significant differences between these dietary profiles in reducing the cardiovascular risk burden for the general population. TRIAL REGISTRATION ClinicalTrials.gov NCT02641834.