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Prebiotic Galacto-Oligosaccharides Impact Stool Frequency and Fecal Microbiota in Self-Reported Constipated Adults: A Randomized Clinical Trial.
Schoemaker, MH, Hageman, JHJ, Ten Haaf, D, Hartog, A, Scholtens, PAMJ, Boekhorst, J, Nauta, A, Bos, R
Nutrients. 2022;(2)
Abstract
Constipation is a major issue for 10-20% of the global population. In a double-blind randomized placebo-controlled clinical trial, we aimed to determine a dose-response effect of galacto-oligosaccharides (GOS) on stool characteristics and fecal microbiota in 132 adults with self-reported constipation according to Rome IV criteria (including less than three bowel movements per week). Subjects (94% females, aged: 18-59 years) received either 11 g or 5.5 g of BiotisTM GOS, or a control product, once daily for three weeks. Validated questionnaires were conducted weekly to study primarily stool frequency and secondary stool consistency. At base- and endline, stool samples were taken to study fecal microbiota. A trend towards an increased stool frequency was observed after the intervention with 11 g of GOS compared to control. While during screening everybody was considered constipated, not all subjects (n = 78) had less than three bowel movements per week at baseline. In total, 11 g of GOS increased stool frequency compared to control in subjects with a low stool frequency at baseline (≤3 bowel movements per week) and in self-reported constipated adults 35 years of age or older. A clear dose-response of GOS was seen on fecal Bifidobacterium, and 11 g of GOS significantly increased Anaerostipes hadrus. In conclusion, GOS seems to be a solution to benefit adults with a low stool frequency and middle-aged adults with self-reported constipation.
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Effects of prebiotics on postprandial GLP-1, GLP-2 and glucose regulation in patients with type 2 diabetes: A randomised, double-blind, placebo-controlled crossover trial.
Birkeland, E, Gharagozlian, S, Gulseth, HL, Birkeland, KI, Hartmann, B, Holst, JJ, Holst, R, Aas, AM
Diabetic medicine : a journal of the British Diabetic Association. 2021;(10):e14657
Abstract
AIMS: We aimed to investigate the effect of prebiotic inulin-type fructans (ITF) versus a control supplement on postprandial levels of glucagon-like peptide-1 and -2 (GLP-1 and -2), glucose and insulin in people with type 2 diabetes. METHODS Adult men and women with type 2 diabetes were randomised in a double-blind, placebo-controlled crossover study. The study participants received 16 g/d ITF and 16 g/d control supplement (maltodextrin) for 6 weeks each in two phases separated by a 4-week washout. A standardised mixed-meal test was performed before and after each intake period. The primary end point was changes in the GLP-1 response, and secondary end points were GLP-2, glucose and insulin responses. Data were analysed using mixed-model analysis. RESULTS A total of 29 participants were included in the study. Differences between and within the two treatments in estimated area under the curves were not significant. Yet, the predicted means for meal-induced GLP-1 response in plasma showed a 4.8% decline after the prebiotic treatment and an 8.6% increase after the control treatment (difference in changes between the treatments, p < 0.001). Fasting or postprandial glucose, insulin or GLP-2 levels were not changed. CONCLUSIONS Our findings do not support that ITF improve incretin responses or glucose regulations in this population. Clinicaltrials.gov (NCT02569684).
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A double-blind, 377-subject randomized study identifies Ruminococcus, Coprococcus, Christensenella, and Collinsella as long-term potential key players in the modulation of the gut microbiome of lactose intolerant individuals by galacto-oligosaccharides.
Azcarate-Peril, MA, Roach, J, Marsh, A, Chey, WD, Sandborn, WJ, Ritter, AJ, Savaiano, DA, Klaenhammer, TR
Gut microbes. 2021;(1):1957536
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Abstract
Background. Our recent publication (Chey et al., Nutrients 2020) showed that a 30-day administration of pure galacto-oligosaccharides (GOS) significantly reduced symptoms and altered the fecal microbiome in patients with lactose intolerance (LI). Results. In this addendum, we performed an in-depth analysis of the fecal microbiome of the 377 LI patients randomized to one of two GOS doses (Low, 10-15 grams/day or High, 15-20 grams/day), or placebo in a multi-center, double-blinded, placebo-controlled trial. Sequencing of 16S rRNA amplicons was done on GOS or placebo groups at weeks zero (baseline), four (end of treatment), nine, 16 and 22. Taxa impacted by treatment and subsequent dairy consumption included lactose-fermenting species of Bifidobacterium, Lactobacillus, Lactococcus, and Streptococcus. Increased secondary fermentation microorganisms included Coprococcus and Ruminococcus species, Blautia producta, and Methanobrevibacterium. Finally, tertiary fermenters that use acetate to generate butyrate were also increased, including Faecalibacterium prausnitzii, Roseburia faecis, and C. eutactus. Conclusions. Results confirmed and expanded data on GOS microbiome modulation in LI individuals. Microbiome analysis at 16 and 22 weeks after treatment further suggested relatively long-term benefits when individuals continued consumption of dairy products.
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A specific dietary fibre supplementation improves cognitive performance-an exploratory randomised, placebo-controlled, crossover study.
Berding, K, Long-Smith, CM, Carbia, C, Bastiaanssen, TFS, van de Wouw, M, Wiley, N, Strain, CR, Fouhy, F, Stanton, C, Cryan, JF, et al
Psychopharmacology. 2021;(1):149-163
Abstract
RATIONALE The impact of the microbiota on the gut-brain axis is increasingly appreciated. A growing body of literature demonstrates that use of dietary fibre and prebiotics can manipulate the microbiota and affect host health. However, the influence on cognition and acute stress response is less well understood. OBJECTIVES The objective of this study was to investigate the efficacy of a dietary fibre, polydextrose (PDX), in improving cognitive performance and acute stress responses through manipulation of the gut microbiota in a healthy population. METHODS In this double-blind, randomised, placebo-controlled, crossover design study, 18 healthy female participants received 12.5 g Litesse®Ultra (> 90% PDX polymer) or maltodextrin for 4 weeks. Cognitive performance, mood, acute stress responses, microbiota composition, and inflammatory markers were assessed pre- and post-intervention. RESULTS PDX improved cognitive flexibility as evidenced by the decrease in the number of errors made in the Intra-Extra Dimensional Set Shift (IED) task. A better performance in sustained attention was observed through higher number of correct responses and rejections in the Rapid Visual Information Processing (RVP) task. Although there was no change in microbial diversity, abundance of Ruminiclostridium 5 significantly increased after PDX supplementation compared with placebo. PDX supplementation attenuated the increase of adhesion receptor CD62L on classical monocytes observed in the placebo group. CONCLUSIONS Supplementation with the PDX resulted in a modest improvement in cognitive performance. The results indicate that PDX could benefit gut-to-brain communication and modulate behavioural responses.
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The Prebiotic Effects of Oats on Blood Lipids, Gut Microbiota, and Short-Chain Fatty Acids in Mildly Hypercholesterolemic Subjects Compared With Rice: A Randomized, Controlled Trial.
Xu, D, Feng, M, Chu, Y, Wang, S, Shete, V, Tuohy, KM, Liu, F, Zhou, X, Kamil, A, Pan, D, et al
Frontiers in immunology. 2021;:787797
Abstract
Phytochemicals derived from oats are reported to possess a beneficial effect on modulating dyslipidemia, specifically on lowering total and LDL cholesterol. However, deeper insights into its mechanism remain unclear. In this randomized controlled study, we assigned 210 mildly hypercholesterolemic subjects from three study centers across China (Beijing, Nanjing, and Shanghai) to consume 80 g of oats or rice daily for 45 days. Plasma lipid profiles, short chain fatty acids (SCFAs), and fecal microbiota were measured. The results showed that total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C) decreased significantly with both oats and rice intake after 30 and 45 days. The reduction in TC and non-HDL-C was greater in the participants consuming oats compared with rice at day 45 (p = 0.011 and 0.049, respectively). Oat consumption significantly increased the abundance of Akkermansia muciniphila and Roseburia, and the relative abundance of Dialister, Butyrivibrio, and Paraprevotella, and decreased unclassified f-Sutterellaceae. In the oat group, Bifidobacterium abundance was negatively correlated with LDL-C (p = 0.01, r = -0.31) and, TC and LDL-C were negatively correlated to Faecalibacterium prausnitzii (p = 0.02, r = -0.29; p = 0.03, r = -0.27, respectively). Enterobacteriaceae, Roseburia, and Faecalibacterium prausnitzii were positively correlated with plasma butyric acid and valeric acid concentrations and negatively correlated to isobutyric acid. HDL-C was negatively correlated with valeric acid (p = 0.02, r = -0.25) and total triglyceride (TG) was positively correlated to isovaleric acid (p = 0.03, r = 0.23). Taken together, oats consumption significantly reduced TC and LDL-C, and also mediated a prebiotic effect on gut microbiome. Akkermansia muciniphila, Roseburia, Bifidobacterium, and Faecalibacterium prausnitzii, and plasma SCFA correlated with oat-induced changes in plasma lipids, suggesting prebiotic activity of oats to modulate gut microbiome could contribute towards its cholesterol-lowering effect.
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Calorie restriction in combination with prebiotic supplementation in obese women with depression: effects on metabolic and clinical response.
Vaghef-Mehrabany, E, Ranjbar, F, Asghari-Jafarabadi, M, Hosseinpour-Arjmand, S, Ebrahimi-Mameghani, M
Nutritional neuroscience. 2021;(5):339-353
Abstract
BACKGROUND Major depressive disorder (MDD) is a common psychiatric disorder, closely associated with obesity. This study aimed to assess the effects of prebiotics combined with calorie restriction on clinical and metabolic response in obese women with MDD. METHODS In an 8-week double-blind placebo-controlled randomized clinical trial, 62 obese women with MDD were equally allocated into either prebiotic (10 g/day Inulin) or placebo (10 g/day Maltodextrin) group. In addition, all the participants were also prescribed a 25% calorie-restricted diet (registration ID: IRCT20100209003320N15). Depression was assessed by Hamilton depression rating scale (HDRS) and Beck depression inventory (BDI-II) pre- and post-intervention. Anthropometric measures, fasting serum levels of glucose, insulin and lipid profile were assessed, and dietary assessments were performed pre- and post-intervention. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS 45 patients completed the trial. There were no significant between-group differences for MDD symptoms and other study outcomes, post-intervention. Weight, waist and hip circumferences, systolic blood pressure, and HDRS score significantly decreased in both groups, while fat mass and total cholesterol (TC) declined only in the prebiotic arm. Those who had ≥1.9 kg weight loss showed significantly improved HDRS score, compared to women with <1.9 kg weight reduction, irrespective of the supplement they took. CONCLUSION Although prebiotic supplementation had some beneficial metabolic effects, calorie restriction and weight loss seem to play a more important role in improving depressive symptoms among obese women with MDD.
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Effect of wheat bran derived prebiotic supplementation on gastrointestinal transit, gut microbiota, and metabolic health: a randomized controlled trial in healthy adults with a slow gut transit.
Müller, M, Hermes, GDA, Emanuel E, C, Holst, JJ, Zoetendal, EG, Smidt, H, Troost, F, Schaap, FG, Damink, SO, Jocken, JWE, et al
Gut microbes. 2020;(1):1704141
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Abstract
Acute intake of the wheat bran extract Arabinoxylan-Oligosaccharide (AXOS) modulates the gut microbiota, improves stool characteristics and postprandial glycemia in healthy humans. Yet, little is known on how long-term AXOS intake influences gastrointestinal (GI) functioning, gut microbiota, and metabolic health. In this randomized, placebo-controlled, double-blind study, we evaluated the effects of AXOS intake on GI function and metabolic health in adults with slow GI transit without constipation. Forty-eight normoglycemic adults were included with whole-gut transit time (WGTT) of >35 h receiving either 15 g/day AXOS or placebo (maltodextrin) for 12-wks. The primary outcome was WGTT, and secondary outcomes included stool parameters, gut permeability, short-chain fatty acids (SCFA), microbiota composition, energy expenditure, substrate oxidation, glucose, insulin, lipids, gut hormones, and adipose tissue (AT) function. WGTT was unchanged, but stool consistency softened after AXOS. 12-wks of AXOS intake significantly changed the microbiota by increasing Bifidobacterium and decreasing microbial alpha-diversity. With a good classification accuracy, overall microbiota composition classified responders with decreased WGTT after AXOS. The incretin hormone Glucagon-like protein 1 was reduced after AXOS compared to placebo. Energy expenditure, plasma metabolites, AT parameters, SCFA, and gut permeability were unchanged. In conclusion, intake of wheat bran extract increases fecal Bifidobacterium and softens stool consistency without major effects on energy metabolism in healthy humans with a slow GI transit. We show that overall gut microbiota classified responders with decreased WGTT after AXOS highlighting that GI transit and change thereof were associated with gut microbiota independent of Bifidobacterium. NCT02491125.
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Inulin-type fructan intervention restricts the increase in gut microbiome-generated indole in patients with peritoneal dialysis: a randomized crossover study.
Li, L, Xiong, Q, Zhao, J, Lin, X, He, S, Wu, N, Yao, Y, Liang, W, Zuo, X, Ying, C
The American journal of clinical nutrition. 2020;(5):1087-1099
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BACKGROUND Indoxyl sulfate (IS) and p-cresyl sulfate (pCS), 2 important protein-bound uremic toxins, are independent risk factors for cardiovascular disease in patients with end-stage renal disease. Indole and p-cresol are gut microbiome-generated precursors of IS and pCS. OBJECTIVE The aim of the present study was to determine whether inulin-type fructans (ITFs) reduce the production of indole and p-cresol by altering their producing bacteria in patients with peritoneal dialysis. METHODS Patients receiving peritoneal dialysis for >3 mo without diabetes and not using antibiotics were recruited to a randomized, double-blind, placebo-controlled, crossover trial of ITF intervention over 36 wk (12-wk washout). The primary outcomes were gut microbiome, fecal indole and p-cresol, indole-producing bacteria, p-cresol-producing bacteria, and serum IS and pCS. The secondary outcomes were fecal pH, 24-h urine, and dialysis removal of IS and pCS. RESULTS Of 21 individuals randomly assigned, 15 completed the study. The daily nutrient intakes, including protein, tryptophan, and tyrosine, were isostatic during the prebiotic, washout, and placebo intervention. There were no baseline differences in the outcomes of interest between treatments. For fecal indole, its concentrations did not change significantly in either treatment. However, there was a trend toward the treatment-by-time effect (P = 0.052), with a quantitative reduction in the ITF treatment and an increase in the control. The difference in the changes between the 2 treatments was significant (-10.07 ± 7.48 μg/g vs +13.35 ± 7.66 μg/g; P = 0.040). Similar to Bacteroides thetaiotaomicron, there was a difference over time between the 2 treatments, with a significant treatment and time interaction effect (P = 0.047). There were no treatment, time, or interaction effects for fecal p-cresol, serum IS and pCS, 24-h urine, and dialysis removal of IS and pCS. CONCLUSIONS Our results suggested that ITFs restricted the increase in gut microbiome-generated indole in patients with peritoneal dialysis. This trial was registered at http://www.chictr.org.cn/showproj.aspx?proj=21228 as ChiCTR-INR-17013739.
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Prebiotic supplementation does not affect reading and cognitive performance in children: A randomised placebo-controlled study.
Capitão, LP, Baião, R, Baek, HK, Kappelmann, N, Sharman, R, Harvey, CJ, Montgomery, P, Burnet, PW
Journal of psychopharmacology (Oxford, England). 2020;(1):148-152
Abstract
Based on the emerging interest in the effects of gut microbiota on cognition, this proof-of-concept study assessed how children aged 7 to 9 with low reading scores responded to the ingestion of a 3-month prebiotic supplement versus a placebo. As a secondary aim, the effects of the prebiotic on cognition, sleep, behaviour, mood, anxiety, and cortisol were assessed. In this sample, the prebiotic did not affect any of the outcome measures.
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Response of the Human Milk Microbiota to A Maternal Prebiotic Intervention is Individual and Influenced by Maternal Age.
Padilha, M, Brejnrod, A, Danneskiold-Samsøe, NB, Hoffmann, C, de Melo Iaucci, J, Cabral, VP, Xavier-Santos, D, Taddei, CR, Kristiansen, K, Saad, SMI
Nutrients. 2020;(4)
Abstract
Maternal bacteria are shared with infants via breastfeeding. Prebiotics modulate the gut microbiota, promoting health benefits. We investigated whether the maternal diet supplementation with a prebiotic (fructooligosaccharides, FOS) could influence the milk microbiota. Twenty-eight lactating women received 4.5 g of fructooligosaccharides + 2 g of maltodextrin (FOS group) and twenty-five received 2 g of maltodextrin (placebo group) for 20 days. Breast-milk samples were taken before and after the intervention. The DNA from samples was used for 16S rRNA sequencing. No statistical differences between the groups were found for the bacterial genera after the intervention. However, the distances of the trajectories covered by paired samples from the beginning to the end of the supplementation were higher for the FOS group (p = 0.0007) indicating greater changes in milk microbiota compared to the control group. Linear regression models suggested that the maternal age influenced the response for FOS supplementation (p = 0.02). Interestingly, the pattern of changes to genus abundance upon supplementation was not shared between mothers. We demonstrated that manipulating the human milk microbiota through prebiotics is possible, and the maternal age can affect this response. .