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Blueberries Improve Abdominal Symptoms, Well-Being and Functioning in Patients with Functional Gastrointestinal Disorders.
Wilder-Smith, CH, Materna, A, Olesen, SS
Nutrients. 2023;15(10)
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Functional gastrointestinal disorders (FGID) are the most common cause of recurring, chronic digestive upsets. Irritable bowel syndrome (IBS) and functional dyspepsia (FD), or persistent indigestion, are the most prevalent types of those disorders. Typical symptoms include pain or discomfort in the abdomen, changes in stool patterns or bloating and may also manifest in symptoms not directly relating to the digestive tract. It remains uncertain what the exact mechanisms of those disorders are. However, scientists identified various factors involved, including immune system activation, sensitisation of the nervous system, dysregulated permeability of the gut walls, and changes in the microbiota, their composition and metabolic activity. Polyphenols are natural compounds found abundantly in plants and are most known for their antioxidant qualities. One frequently studied and rich-source of phenols is Blueberries (Vaccinium spp). Blueberries have antioxidant, anti-inflammatory, and neuroprotective properties, and are known to reverse the permeability of the gut membrane. Hence their use in the management of FGID appeared promising. This double-blind, randomized, cross-over study assessed the benefit of blueberries in 43 people with IBS or FD, between 18–60 years of age. The candidates were given 30g freeze-dried blueberries, the equivalent of 180g of fresh blueberries, or a sugar-based placebo of similar calorific value for 6-weeks each. When receiving the blueberries, greater symptom relief was observed when compared to the placebo group. Blueberry intake also positively reflected in experienced improvement in quality of life. No notable differences were observed between groups in stool patterns and fructose digestion. Blueberries and their beneficial compounds such as polyphenols and fiber appear to have a wide range of benefits that can help manage some of the FGID-associated symptoms. Further studies are needed to understand why, despite some notable benefits, some of the other GI markers remained unaffected. As blueberries are generally well tolerated, they can be a simple and helpful food intervention to complement other FGID management strategies.
Abstract
Blueberries beneficially modulate physiologic mechanisms relevant to the pathogenesis of functional gastrointestinal disorders (FGID). Forty-three patients with FGID received freeze-dried blueberries (equivalent to 180 g fresh blueberries) or sugar and energy-matched placebo in a double-blind, randomized, cross-over study. After 6 weeks of treatment, the differences in Gastrointestinal Clinical Rating Scale (GSRS) scores and abdominal symptom relief were compared as primary outcome measures. The quality of life and life functioning ratings (OQ45.2 questionnaire), Bristol stool scales, and fructose breath test results constituted secondary outcome measures. Blueberry treatment resulted in more patients with relevant abdominal symptom relief compared to placebo (53% vs. 30%, p = 0.03). Total and pain GSRS scores improved insignificantly (mean treatment differences [95% CI]: -3.4 [-7.4 to 0.6] (p = 0.09) and -1.0 [-2.2 to 0.1] (p = 0.08), respectively). OQ45.2 scores improved during blueberry treatment compared to placebo (treatment difference -3.2 [95% CI: -5.6 to -0], p = 0.01). Treatment effect differences for the further measures did not reach statistical significance. Blueberries relieved abdominal symptoms and improved general markers of well-being, quality of life, and life functioning more than placebo in patients with FGID. Consequently, the polyphenol and fiber components of blueberries exert broad beneficial effects separate from the sugars present in both treatments.
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Effects of FODMAPs and Gluten on Gut Microbiota and Their Association with the Metabolome in Irritable Bowel Syndrome: A Double-Blind, Randomized, Cross-Over Intervention Study.
Nordin, E, Hellström, PM, Dicksved, J, Pelve, E, Landberg, R, Brunius, C
Nutrients. 2023;15(13)
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Irritable bowel syndrome (IBS) is defined as recurring abdominal pain in relation to stool irregularities. The mechanisms behind IBS are poorly understood, but changes in gut microbiota composition, intestinal barrier function, enteroendocrine cell population, low-grade inflammation and gut–brain axis modulations are believed to play a role. The aim of this study was to investigate how fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) and gluten affected gut microbiota and circulating metabolite profiles, as well as to investigate potential links between gut microbiota, metabolites, and IBS symptoms. This study was a double-blind, placebo-controlled three-way crossover study. Both the study personnel and participants were blinded. Results showed that consumption of high FODMAP foods, but not gluten, altered the gut microbiota composition, in particular causing changes to microbiota and metabolites, previously associated with improved metabolic health and reduced inflammation. There were also minor effects of FODMAPs and gluten on short-chain fatty acids. Authors conclude that the intake of FODMAP, but not gluten, over one week altered the gut microbiota composition, with only weak associations with IBS symptoms. Healthcare practitioners working with IBS should consider the impacts on the gut microbiome when advising the use of a low-FODMAP diet.
Abstract
BACKGROUND A mechanistic understanding of the effects of dietary treatment in irritable bowel syndrome (IBS) is lacking. Our aim was therefore to investigate how fermentable oligo- di-, monosaccharides, and polyols (FODMAPs) and gluten affected gut microbiota and circulating metabolite profiles, as well as to investigate potential links between gut microbiota, metabolites, and IBS symptoms. METHODS We used data from a double-blind, randomized, crossover study with week-long provocations of FODMAPs, gluten, and placebo in participants with IBS. To study the effects of the provocations on fecal microbiota, fecal and plasma short-chain fatty acids, the untargeted plasma metabolome, and IBS symptoms, we used Random Forest, linear mixed model and Spearman correlation analysis. RESULTS FODMAPs increased fecal saccharolytic bacteria, plasma phenolic-derived metabolites, 3-indolepropionate, and decreased isobutyrate and bile acids. Gluten decreased fecal isovalerate and altered carnitine derivatives, CoA, and fatty acids in plasma. For FODMAPs, modest correlations were observed between microbiota and phenolic-derived metabolites and 3-indolepropionate, previously associated with improved metabolic health, and reduced inflammation. Correlations between molecular data and IBS symptoms were weak. CONCLUSIONS FODMAPs, but not gluten, altered microbiota composition and correlated with phenolic-derived metabolites and 3-indolepropionate, with only weak associations with IBS symptoms. Thus, the minor effect of FODMAPs on IBS symptoms must be weighed against the effect on microbiota and metabolites related to positive health factors.
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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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Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial.
Leong, KSW, Jayasinghe, TN, Wilson, BC, Derraik, JGB, Albert, BB, Chiavaroli, V, Svirskis, DM, Beck, KL, Conlon, CA, Jiang, Y, et al
JAMA network open. 2020;3(12):e2030415
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Obesity has become a global pandemic even in adolescents. Lifestyle interventions have had limited impact on this cohort and drugs targeting obesity are often unlicensed in children. The gut microbiome has a role in weight regulation and may be a new target in adolescents with obesity. This randomised control trial of 87 adolescents with obesity over 26 weeks, aimed to assess if faecal microbiome transfer (FMT), which is a method whereby faecal matter is transplanted from one person to another, can be used to treat obesity. The results showed that FMT did not have an effect on body mass index (BMI) and the intervention group had a marginally increased BMI after FMT. Other disorders associated with obesity such as blood sugar levels were also unaffected by FMT, however there was a reduction in fat storage around the middle. It was concluded that FMT alone is not adequate to improve obesity in adolescents, but may reduce fat stored around the middle. Healthcare professionals could use this study to understand that simply transplanting one person’s gut microbiome to another, may not be enough. Targeted personalised approaches may be required, however further research is needed.
Abstract
Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation. Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism. Design, Setting, and Participants: This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020. Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo. Main Outcomes and Measures: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition. Results: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial. Conclusions and Relevance: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.
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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.