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1.
Dietary Fibre Intake Is Associated with Serum Levels of Uraemic Toxins in Children with Chronic Kidney Disease.
El Amouri, A, Snauwaert, E, Foulon, A, Vande Moortel, C, Van Dyck, M, Van Hoeck, K, Godefroid, N, Glorieux, G, Van Biesen, W, Vande Walle, J, et al
Toxins. 2021;(3)
Abstract
Imbalanced colonic microbial metabolism plays a pivotal role in generating protein-bound uraemic toxins (PBUTs), which accumulate with deteriorating kidney function and contribute to the uraemic burden of children with chronic kidney disease (CKD). Dietary choices impact the gut microbiome and metabolism. The aim of this study was to investigate the relation between dietary fibre and gut-derived PBUTs in paediatric CKD. Sixty-one (44 male) CKD children (9 ± 5 years) were prospectively followed for two years. Dietary fibre intake was evaluated by either 24-h recalls (73%) or 3-day food records (27%) at the same time of blood sampling for assessment of total and free serum levels of different PBUTs using liquid chromatography. We used linear mixed models to assess associations between fibre intake and PBUT levels. We found an inverse association between increase in fibre consumption (g/day) and serum concentrations of free indoxyl sulfate (-3.1% (-5.9%; -0.3%) (p = 0.035)), free p-cresyl sulfate (-2.5% (-4.7%; -0.3%) (p = 0.034)), total indole acetic acid (IAA) (-1.6% (-3.0%; -0.3%) (p = 0.020)), free IAA (-6.6% (-9.3%; -3.7%) (p < 0.001)), total serum p-cresyl glucuronide (pCG) (-3.0% (-5.6%; -0.5%) (p = 0.021)) and free pCG levels (-3.3% (-5.8%; -0.8%) (p = 0.010)). The observed associations between dietary fibre intake and the investigated PBUTs highlight potential benefits of fibre intake for the paediatric CKD population. The present observational findings should inform and guide adaptations of dietary prescriptions in children with CKD.
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Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects.
Pai, N, Popov, J, Hill, L, Hartung, E, Grzywacz, K, Moayyedi, P, ,
Gastroenterology. 2021;(2):388-393.e3
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Evaluation of the gut microbiota after metformin intervention in children with obesity: A metagenomic study of a randomized controlled trial.
Pastor-Villaescusa, B, Plaza-Díaz, J, Egea-Zorrilla, A, Leis, R, Bueno, G, Hoyos, R, Vázquez-Cobela, R, Latorre, M, Cañete, MD, Caballero-Villarraso, J, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;:111117
Abstract
BACKGROUND Metformin, a first-line oral antidiabetic agent that has shown promising results in terms of treating childhood and adolescent obesity, might influence the composition of the gut microbiota. We aimed to evaluate whether the gut microbiota of non-diabetic children with obesity changes after a metformin intervention. METHODS The study was a multicenter and double-blind randomized controlled trial in 160 children with obesity. Children were randomly assigned to receive either metformin (1 g/day) or placebo for 6 months in combination with healthy lifestyle recommendations in both groups. Then, we conducted a metagenomic analysis in a subsample obtained from 33 children (15 metformin, 18 placebo). A linear mixed-effects model (LMM) was used to determine the abundance changes from baseline to six months according to treatment. To analyze the data by clusters, a principal component analysis was performed to understand whether lifestyle habits have a different influence on the microbiota depending on the treatment group. RESULTS Actinobacteria abundance was higher after placebo treatment compared with metformin. However, the interaction time x treatment just showed a trend to be significant (4.6% to 8.1% after placebo vs. 3.8 % to 2.6 % after metformin treatment, p = 0.055). At genus level, only the abundance of Bacillus was significantly higher after the placebo intervention compared with metformin (2.5% to 5.7% after placebo vs. 1.5 % to 0.8 % after metformin treatment, p = 0.044). Furthermore, different ensembles formed by Firmicutes, Bacteroidetes, and Verrucomicrobia were found according to the interventions under a similar food consumption. CONCLUSION Further studies with a large sample size controlled by lifestyle patterns are required in obese children and adolescents to clarify whether metformin might trigger gut microbiota alterations. TRIAL REGISTRATION Registered on the European Clinical Trials Database (EudraCT, ID: 2010-023061-21) on 14 November 2011.
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Evaluation of a Nutraceutical Product with Probiotics, Vitamin D, Plus Banaba Leaf Extracts (Lagerstroemia speciosa) in Glycemic Control.
Signorini, L, Ballini, A, Arrigoni, R, De Leonardis, F, Saini, R, Cantore, S, De Vito, D, Coscia, MF, Dipalma, G, Santacroce, L, et al
Endocrine, metabolic & immune disorders drug targets. 2021;(7):1356-1365
Abstract
BACKGROUND Dysbiosis is related to changes in the composition and behaviour of intestinal microbiota, which may contribute to an age-related decline in metabolic and immune system functioning (immune-senescence). OBJECTIVE The microbiota-targeted dietary and probiotic interventions have been shown to favorably affect the host health by an enhancement of antioxidant activity, improving immune homeostasis, suppression of chronic inflammation, regulation of metabolism and prevention of insulin resistance. RESULTS In our study, the use of specific probiotics strains improved the serum concentration of glycemic markers, thereby promoting better overall health. CONCLUSION Probiotics may help correct defects in the gut microbial environment improving metabolic parameters, such as blood sugar levels, glycosylated hemoglobin and a decrease in body weight.
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Quantifying technical confounders in microbiome studies.
Bartolomaeus, TUP, Birkner, T, Bartolomaeus, H, Löber, U, Avery, EG, Mähler, A, Weber, D, Kochlik, B, Balogh, A, Wilck, N, et al
Cardiovascular research. 2021;(3):863-875
Abstract
AIMS: Recent technical developments have allowed the study of the human microbiome to accelerate at an unprecedented pace. Methodological differences may have considerable impact on the results obtained. Thus, we investigated how different storage, isolation, and DNA extraction methods can influence the characterization of the intestinal microbiome, compared to the impact of true biological signals such as intraindividual variability, nutrition, health, and demographics. METHODS AND RESULTS An observative cohort study in 27 healthy subjects was performed. Participants were instructed to collect stool samples twice spaced by a week, using six different methods (naive and Zymo DNA/RNA Shield on dry ice, OMNIgene GUT, RNALater, 95% ethanol, Zymo DNA/RNA Shield at room temperature). DNA extraction from all samples was performed comparatively using QIAamp Power Fecal and ZymoBIOMICS DNA Kits. 16S rRNA sequencing of the gut microbiota as well as qPCRs were performed on the isolated DNA. Metrics included alpha diversity as well as multivariate and univariate comparisons of samples, controlling for covariate patterns computationally. Interindividual differences explained 7.4% of overall microbiome variability, whereas the choice of DNA extraction method explained a further 5.7%. At phylum level, the tested kits differed in their recovery of Gram-positive bacteria, which is reflected in a significantly skewed enterotype distribution. CONCLUSION DNA extraction methods had the highest impact on observed microbiome variability, and were comparable to interindividual differences, thus may spuriously mimic the microbiome signatures of various health and nutrition factors. Conversely, collection methods had a relatively small influence on microbiome composition. The present study provides necessary insight into the technical variables which can lead to divergent results from seemingly similar study designs. We anticipate that these results will contribute to future efforts towards standardization of microbiome quantification procedures in clinical research.
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Which patients discontinue? Issues on Levodopa/carbidopa intestinal gel treatment: Italian multicentre survey of 905 patients with long-term follow-up.
Sensi, M, Cossu, G, Mancini, F, Pilleri, M, Zibetti, M, Modugno, N, Quatrale, R, Tamma, F, Antonini, A, ,
Parkinsonism & related disorders. 2017;:90-92
Abstract
OBJECTIVES To report the results of a national survey aimed at quantifying the current level of diffusion of Levodopa/carbidopa intestinal gel (LCIG) in Italy. METHODS Sixty Parkinson's Disease (PD) specialists in Italy were invited to complete a survey covering issues on clinical and practical aspects of LCIG therapy. RESULTS Clinical features of 905 patients were collected retrospectively. The majority of centres reported the use of a multidisciplinary team, biochemistry testing, neurophysiological and neuropsychological tests before and after treatment, in addition to caregivers' training and patient's follow as outpatients. Most centres (60%) used internal guidelines for patient selection. The overall rate of adverse events was 55.1%. Weight loss, chronic polyneuropathy and stoma infection were the most frequently reported. 40% of centres used replacement therapy with Vitamin B12 and Folic acid from the start of LCIG and continued this for the duration of treatment. The rate of discontinuation was of 25.7% overall, with 9.5% of cases occurring in the first year. The main causes of withdrawal were device-related complications, disease progression (comorbidity, severe dementia) and caregiver and/or patient dissatisfaction. CONCLUSIONS In Italy LCIG infusion is managed in a uniform manner at a clinical, practical and organizational level even though the selection criteria are not standardized through the country. The high percentage of patients remaining on treatment in the short- and long-term follow-up confirms effectiveness of treatment, careful follow-up, and appropriate patient and caregivers training.
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A Diet Low in FODMAPs Reduces Symptoms in Patients With Irritable Bowel Syndrome and A Probiotic Restores Bifidobacterium Species: A Randomized Controlled Trial.
Staudacher, HM, Lomer, MCE, Farquharson, FM, Louis, P, Fava, F, Franciosi, E, Scholz, M, Tuohy, KM, Lindsay, JO, Irving, PM, et al
Gastroenterology. 2017;(4):936-947
Abstract
BACKGROUND & AIMS Dietary restriction of fermentable carbohydrates (a low FODMAP diet) has been reported to reduce symptoms in some patients with irritable bowel syndrome (IBS). We performed a randomized, placebo-controlled study to determine its effects on symptoms and the fecal microbiota in patients with IBS. METHODS We performed a 2×2 factorial trial of 104 patients with IBS (18-65 years old), based on the Rome III criteria, at 2 hospitals in the United Kingdom. Patients were randomly assigned (blinded) to groups given counselling to follow a sham diet or diet low in FODMAPs for 4 weeks, along with a placebo or multistrain probiotic formulation, resulting in 4 groups (27 receiving sham diet/placebo, 26 receiving sham diet/probiotic, 24 receiving low FODMAP diet /placebo, and 27 receiving low FODMAP diet/probiotic). The sham diet restricted a similar number of staple and non-staple foods as the low FODMAP diet; the diets had similar degrees of difficulty to follow. Dietary counselling was given to patients in all groups and data on foods eaten and compliance were collected. The incidence and severity of 15 gastrointestinal symptoms and overall symptoms were measured daily for 7 days before the study period; along with stool frequency and consistency. At baseline, global and individual symptoms were measured, along with generic and disease-specific health-related quality of life, using standard scoring systems. All data were collected again at 4 weeks, and patients answered questions about adequate symptom relief. Fecal samples were collected at baseline and after 4 weeks and analyzed by quantitative PCR and 16S rRNA sequencing. The co-primary endpoints were adequate relief of symptoms and stool Bifidobacterium species abundance at 4 weeks. RESULTS There was no significant interaction between the interventions in adequate relief of symptoms (P = .52) or Bifidobacterium species (P = .68). In the intention-to-treat analysis, a higher proportion of patients in the low FODMAP diet had adequate symptom relief (57%) than in the sham diet group (38%), although the difference was not statistically significant (P = .051). In the per-protocol analysis, a significantly higher proportion of patients on the low FODMAP diet had adequate symptom relief (61%) than in the sham diet group (39%) (P = .042). Total mean IBS-Severity Scoring System score was significantly lower for patients on the low FODMAP diet (173 ± 95) than the sham diet (224 ± 89) (P = .001), but not different between those given probiotic (207 ± 98) or placebo (192 ± 93) (P = .721) Abundance of Bifidobacterium species was lower in fecal samples from patients on the low FODMAP diet (8.8 rRNA genes/g) than patients on the sham diet (9.2 rRNA genes/g) (P = .008), but higher in patients given probiotic (9.1 rRNA genes/g) than patients given placebo (8.8 rRNA genes/g) (P = .019). There was no effect of the low FODMAP diet on microbiota diversity in fecal samples. CONCLUSIONS In a placebo-controlled study of patients with IBS, a low FODMAP diet associates with adequate symptom relief and significantly reduced symptom scores compared with placebo. It is not clear whether changes resulted from collective FODMAP restriction or removal of a single component, such as lactose. Co-administration of the multistrain probiotic increased numbers of Bifidobacterium species, compared with placebo, and might be given to restore these bacteria to patients on a low FODMAP diet. Trial registration no: ISRCTN02275221.
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Dexamethasone versus standard treatment for postoperative nausea and vomiting in gastrointestinal surgery: randomised controlled trial (DREAMS Trial).
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BMJ (Clinical research ed.). 2017;:j1455
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Abstract
UNLABELLED Objectives To determine whether preoperative dexamethasone reduces postoperative vomiting in patients undergoing elective bowel surgery and whether it is associated with other measurable benefits during recovery from surgery, including quicker return to oral diet and reduced length of stay.Design Pragmatic two arm parallel group randomised trial with blinded postoperative care and outcome assessment.Setting 45 UK hospitals.Participants 1350 patients aged 18 or over undergoing elective open or laparoscopic bowel surgery for malignant or benign pathology.Interventions Addition of a single dose of 8 mg intravenous dexamethasone at induction of anaesthesia compared with standard care.Main outcome measures Primary outcome: reported vomiting within 24 hours reported by patient or clinician. SECONDARY OUTCOMES vomiting with 72 and 120 hours reported by patient or clinician; use of antiemetics and postoperative nausea and vomiting at 24, 72, and 120 hours rated by patient; fatigue and quality of life at 120 hours or discharge and at 30 days; time to return to fluid and food intake; length of hospital stay; adverse events.Results 1350 participants were recruited and randomly allocated to additional dexamethasone (n=674) or standard care (n=676) at induction of anaesthesia. Vomiting within 24 hours of surgery occurred in 172 (25.5%) participants in the dexamethasone arm and 223 (33.0%) allocated standard care (number needed to treat (NNT) 13, 95% confidence interval 5 to 22; P=0.003). Additional postoperative antiemetics were given (on demand) to 265 (39.3%) participants allocated dexamethasone and 351 (51.9%) allocated standard care (NNT 8, 5 to 11; P<0.001). Reduction in on demand antiemetics remained up to 72 hours. There was no increase in complications.Conclusions Addition of a single dose of 8 mg intravenous dexamethasone at induction of anaesthesia significantly reduces both the incidence of postoperative nausea and vomiting at 24 hours and the need for rescue antiemetics for up to 72 hours in patients undergoing large and small bowel surgery, with no increase in adverse events.Trial registration EudraCT (2010-022894-32) and ISRCTN (ISRCTN21973627).
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Belgian multicenter experience with intestinal transplantation.
Ceulemans, LJ, Monbaliu, D, De Roover, A, Detry, O, Troisi, RI, Rogiers, X, Reding, R, Lerut, JP, Ysebaert, D, Chapelle, T, et al
Transplant international : official journal of the European Society for Organ Transplantation. 2015;(12):1362-70
Abstract
Intestinal transplantation (ITx) has evolved from an experimental procedure toward a clinical reality but remains a challenging procedure. The aim of this survey was to analyze the multicenter Belgian ITx experience. From 1999 to 2014, 24 ITx in 23 patients were performed in Belgium, divided over five centers. Median recipient age was 38 years (8 months-57 years); male/female ratio was 13/10; six were children; and 17 adults. Intestinal failure was related to intestinal ischemia (n = 5), volvulus (n = 5), splanchnic thrombosis (n = 4), Crohn (n = 2), pseudo-obstruction (n = 2), microvillus inclusion (n = 2), Churg-Strauss (n = 1), necrotizing enterocolitis (n = 1), intestinal atresia (n = 1), and chronic rejection (n = 1). Graft type was isolated ITx (n = 9), combined liver-ITx (n = 11) and multivisceralTx (n = 4). One was a living donor-related transplantation and five patients received simultaneously a kidney graft. Early acute rejection occurred in 8; late acute rejection in 4; and chronic rejection in 2. Two patients developed a post-transplant lymphoproliferative disease. Nine patients have died. Among 14 survivors at last follow-up, 11 have been transplanted for more than 1 year. None of the latter has developed renal failure, and all were nutritionally independent with a Karnofsky score > 90%. One-/five-year patient and graft survivals were 71.1%, 62.8%, 58.7% and 53.1%, respectively. Based on this experience, ITx has come of age in Belgium as a lifesaving and potentially quality of life restoring therapy.
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Impact of personalized diet and probiotic supplementation on inflammation, nutritional parameters and intestinal microbiota - The "RISTOMED project": Randomized controlled trial in healthy older people.
Valentini, L, Pinto, A, Bourdel-Marchasson, I, Ostan, R, Brigidi, P, Turroni, S, Hrelia, S, Hrelia, P, Bereswill, S, Fischer, A, et al
Clinical nutrition (Edinburgh, Scotland). 2015;(4):593-602
Abstract
OBJECTIVES To assess the impact of a personalized diet, with or without addition of VSL#3 preparation, on biomarkers of inflammation, nutrition, oxidative stress and intestinal microbiota in 62 healthy persons aged 65-85 years. DESIGN Open label, randomized, multicenter study. PRIMARY ENDPOINT High-sensitivity C-reactive protein. SETTING Community. INTERVENTIONS Eight week web-based dietary advice (RISTOMED platform) alone or with supplementation of VSL#3 (2 capsules per day). The RISTOMED diet was optimized to reduce inflammation and oxidative stress. MEASUREMENTS Blood and stool samples were collected on days 1 and 56. RESULTS Diet alone reduced ESR (p = 0.02), plasma levels of cholesterol (p < 0.01) and glucose (p = 0.03). Addition of VSL#3 reduced ESR (p = 0.05) and improved folate (p = 0.007), vitamin B12 (p = 0.001) and homocysteine (p < 0.001) plasma levels. Neither intervention demonstrated any further effects on inflammation. Subgroup analysis showed 40 participants without signs of low-grade inflammation (hsCRP<3 mg/l, subgroup 1) and 21 participants with low-grade inflammation at baseline (hsCRP≥3 mg/l, subgroup 2). In subgroup 2 addition of VSL#3 increased bifidobacteria (p = 0.005) in more participants and improved both folate (p = 0.015) and vitamin B12 (p = 0.035) levels compared with subgroup 1. The increases were positively correlated to the change in the bifidobacteria concentration for folate (p = 0.023) and vitamin B12 (p = 0.001). As expected change in homocysteine correlated negatively to change in folate (r = -0.629, p = 0.002) and vitamin B12 (r = -0.482, p = 0.026). CONCLUSIONS Addition of VSL#3 increased bifidobacteria and supported adequate folate and vitamin B12 concentrations in subjects with low-grade inflammation. Decrease in homocysteine with VSL#3 was clinically relevant. suggesting protective potentials for aging-associated conditions, e.g. cardiovascular or neurological diseases. ClinicalTrials.gov: NCT01069445-NCT01179789.