Early Benefits of a Starter Formula Enriched in Prebiotics and Probiotics on the Gut Microbiota of Healthy Infants Born to HIV+ Mothers: A Randomized Double-Blind Controlled Trial

The gut microbiota of infants is shaped by both the mode of delivery and the type of feeding. The gut of vaginally and cesarean-delivered infants is colonized at different rates and with different bacterial species, leading to differences in the gut microbial composition, which may persist up to 6 months. In a multicenter, randomized, controlled, double-blind trial conducted in South Africa, we tested the effect of a formula supplemented with a prebiotic (a mixture of bovine milk-derived oligosaccharides [BMOS] generated from whey permeate and containing galactooligosaccharides and milk oligosaccharides such as 3′- and 6′-sialyllactose) and the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) strain CNCM I-3446 on the bifidobacteria levels in the gut of infants born vaginally or via cesarean section in early life. Additionally, the safety of the new formulation was evaluated. A total of 430 healthy, full-term infants born to HIV-positive mothers who had elected to feed their child beginning from birth (≤3 days old) exclusively with formula were randomized into this multicenter trial of four parallel groups. A total of 421 infants who had any study formula intake were included in the full analysis set (FAS). The first two groups consisted of cesarean-delivered infants assigned to the Test formula (n = 92) (a starter infant formula [IF] containing BMOS at a total oligosaccharide concentration of 5.8 ± 1.0 g/100 g of powder formula [8 g/L in the reconstituted formula] + B. lactis [1 × 10 7 colony-forming units {cfu}/g]) or a Control IF (n = 101); the second two groups consisted of vaginally delivered infants randomized to the same Test (n = 115) or Control (n = 113) formulas from the time of enrollment to 6 months. The primary efficacy outcome was fecal bifidobacteria count at 10 days, and the primary safety outcome was daily weight gain (g/d) between 10 days and 4 months. At 10 days, fecal bifidobacteria counts were significantly higher in the Test formula than in the Control formula group among infants with cesarean birth (median [range] log: 9.41 [6.30–10.94] cfu/g versus 6.30 [6.30–10.51] cfu/g; P = 0.002) but not among those with vaginal birth (median [range] log: 10.06 [5.93–10.77] cfu/g versus 9.85 [6.15–10.79] cfu/g; P = 0.126). The lower bound of the two-sided 95% confidence interval of the difference in the mean daily weight gain between the Test and Control formula groups was more than –3 g/d in both the vaginally and cesarean-delivered infants, indicating that growth in the Test formula-fed infants was not inferior to that of Control formula-fed infants. At 10 days and 4 weeks, the fecal pH of infants fed the Test formula was significantly lower than in those fed the Control formula, irrespective of mode of delivery: for vaginal delivery: 4.93 versus 5.59; P < 0.001 (10 days) and 5.01 versus 5.71; P < 0.001 (4 weeks); for cesarean delivery: 5.14 versus 5.65, P = 0.009 (10 days) and 5.06 versus 5.75, P < 0.001 (4 weeks). At 3 months, this acidification effect only persisted among cesarean-born infants. IF supplemented with the prebiotic BMOS and probiotic B. lactis induced a strong bifidogenic effect in both delivering modes, but more explicitly correcting the low bifidobacteria level found in cesarean-born infants from birth. The supplemented IF lowered the fecal pH and improved the fecal microbiota in both normal and cesarean-delivered infants. The use of bifidobacteria as a probiotic even in infants who are immunologically at risk is safe and well tolerated.

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Randomized Clinical Trial: Efficacy of a New Synbiotic in Adults with Metabolic Syndrome

Central Asian Journal of Global Health ◽

10.5195/cajgh.2013.111 ◽

2014 ◽

Vol 2 ◽

Author(s):

Almagul Kushugulova ◽

Valerii Benberin ◽

Raushan Karabayeva ◽

Saule Saduakhasova ◽

Samat Kozhakhmetov ◽

...

Keyword(s):

Metabolic Syndrome ◽

Gut Microbiota ◽

Controlled Trial ◽

Adult Population ◽

Glycosylated Hemoglobin ◽

Density Lipoprotein ◽

Laboratory Evaluation ◽

Composition Analysis ◽

Microbial Composition ◽

Double Blind

Introduction: Metabolic syndrome is a lifestyle disease and is a frequent problem among the adult population. Human gut microbiota plays a key role in the development of metabolic syndrome. Recently, the gut microbiota has emerged as an important contributor to the development of obesity and metabolic disorders through its interactions with environmental (e.g. diet) and genetic factors. The aim of this study was to research the effects of synbiotic on the gut microbiota and host metabolism. Methods: We conducted a double-blind, randomized, placebo-controlled trial. Our sample included 180 adults (ages 30-89) with symptoms of metabolic syndrome, who were allocated to either placebo or synbiotic group. The main inclusion criteria were: blood pressure of around 130/90 mmHg; raised fasting plasma glucose (FPG) >100 mg/dL (5.6 mmol/L), previous diagnosis of type 2 diabetes, dyslipidemia triglycerides (TG) of 1.70 mmol/L, a high-density lipoprotein cholesterol (HDL-C) of 0.90 mmol/L in males and 1.0 mmol/L in females, and central obesity with a waist/hip ratio > 0.90 in males or > 0.85 in females or a body mass index > 30 kg/m2. Results: We enrolled 90 adults in the placebo group and 90 in the synbiotic group. The two groups had similar demographic and clinical characteristics. Consent was signed by all patients. All patients underwent clinical and laboratory evaluation, including complete blood tests, glucose test, glycosylated hemoglobin, total cholesterol and triglycerides, cholesterol, LDL, HDL plasma, immunogram, and coprogram. All patients were interviewed with a questionnaire that included 200 questions related to diet, lifestyle, and health. Synbiotic were used by patients in a dose of 200 grams twice a day. The duration of applying of the synbiotic was 90 days. To study the composition of the intestinal microbiota, stool samples were collected before and after applying the synbiotic. The microbial composition will be determined by analyzing the locus of 16S rDNA.Conclusion: This ongoing study is currently undergoing microbial composition analysis in order to establish the efficacy of the new synbiotic in adults with metabolic syndrome.

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The Effects of Genetic Relatedness on the Preterm Infant Gut Microbiota

Microorganisms ◽

10.3390/microorganisms9020278 ◽

2021 ◽

Vol 9 (2) ◽

pp. 278

Author(s):

Shen Jean Lim ◽

Miriam Aguilar-Lopez ◽

Christine Wetzel ◽

Samia V. O. Dutra ◽

Vanessa Bray ◽

...

Keyword(s):

Gut Microbiota ◽

Preterm Infant ◽

Neonatal Intensive Care ◽

Genetic Relatedness ◽

Bovine Milk ◽

Alpha Diversity ◽

Neonatal Intensive Care Units ◽

Rrna Gene ◽

Microbial Composition ◽

Operational Taxonomic Units

The preterm infant gut microbiota is influenced by environmental, endogenous, maternal, and genetic factors. Although siblings share similar gut microbial composition, it is not known how genetic relatedness affects alpha diversity and specific taxa abundances in preterm infants. We analyzed the 16S rRNA gene content of stool samples, ≤ and >3 weeks postnatal age, and clinical data from preterm multiplets and singletons at two Neonatal Intensive Care Units (NICUs), Tampa General Hospital (TGH; FL, USA) and Carle Hospital (IL, USA). Weeks on bovine milk-based fortifier (BMF) and weight gain velocity were significant predictors of alpha diversity. Alpha diversity between siblings were significantly correlated, particularly at ≤3 weeks postnatal age and in the TGH NICU, after controlling for clinical factors. Siblings shared higher gut microbial composition similarity compared to unrelated individuals. After residualizing against clinical covariates, 30 common operational taxonomic units were correlated between siblings across time points. These belonged to the bacterial classes Actinobacteria, Bacilli, Bacteroidia, Clostridia, Erysipelotrichia, and Negativicutes. Besides the influence of BMF and weight variables on the gut microbial diversity, our study identified gut microbial similarities between siblings that suggest genetic or shared maternal and environmental effects on the preterm infant gut microbiota.

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A Randomised, Controlled Trial: Effect of a Multi-Strain Fermented Milk on the Gut Microbiota Recovery after Helicobacter pylori Therapy

Nutrients ◽

10.3390/nu13093171 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3171

Author(s):

Eric Guillemard ◽

Marion Poirel ◽

Florent Schäfer ◽

Laurent Quinquis ◽

Caroline Rossoni ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gut Microbiota ◽

Beta Diversity ◽

Pathogenic Bacteria ◽

Controlled Trial ◽

Eradication Therapy ◽

Fermented Milk ◽

Control Group ◽

Double Blind ◽

Gi Symptoms

Helicobacter pylori (Hp) eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in Hp patients of a Test fermented milk containing yogurt and Lacticaseibacillus (L. paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day Hp treatment, receiving the Test or Control product for 28 days. AAD and GI-symptoms were reported and feces analysed for relative and quantitative gut microbiome composition, short chain fatty acids (SCFA), and calprotectin concentrations, and viability of ingested strains. No effect of Test product was observed on AAD or GI-symptoms. Hp treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and calprotectin, and a decrease of SCFA concentrations. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower (padj = 0.02), some Enterobacteriaceae, including Escherichia-Shigella (padj = 0.0082) and Klebsiella (padj = 0.013), were less abundant, and concentrations of major SCFA (p = 0.035) and valerate (p = 0.045) were higher. Viable Lacticaseibacillus strains were detected during product consumption in feces. Results suggest that, in patients under Hp treatment, the consumption of a multi-strain fermented milk can induce a modest but significant faster recovery of the microbiota composition (beta-diversity) and of SCFA production and limit the increase of potentially pathogenic bacteria.

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Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study

Gut ◽

10.1136/gutjnl-2018-316434 ◽

2018 ◽

Vol 67 (12) ◽

pp. 2107-2115 ◽

Cited By ~ 96

Author(s):

Sofie Ingdam Halkjær ◽

Alice Højer Christensen ◽

Bobby Zhao Sheng Lo ◽

Patrick Denis Browne ◽

Stig Günther ◽

...

Keyword(s):

Gut Microbiota ◽

Controlled Trial ◽

Symptom Relief ◽

Controlled Study ◽

Faecal Microbiota ◽

Double Blind ◽

Double Blind Placebo ◽

Faecal Microbiota Transplantation ◽

Faecal Samples ◽

Significant Difference

ObjectiveIBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS.DesignWe performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected.ResultsA significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not.ConclusionIn this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS.Trial registration numberNCT02788071.

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Effects of aronia berry (poly)phenols on vascular function and gut microbiota: a double-blind randomized controlled trial in adult men

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz075 ◽

2019 ◽

Vol 110 (2) ◽

pp. 316-329 ◽

Cited By ~ 15

Author(s):

Geoffrey Istas ◽

Eleanor Wood ◽

Melanie Le Sayec ◽

Claudia Rawlings ◽

Jeeyoung Yoon ◽

...

Keyword(s):

Gut Microbiota ◽

Vascular Function ◽

Cardiovascular Health ◽

Controlled Trial ◽

Healthy Population ◽

Microbiota Composition ◽

Double Blind ◽

Phenolic Metabolites ◽

Healthy Men ◽

Gut Microbiota Composition

ABSTRACT Background Aronia melanocarpa is a rich source of (poly)phenols. Previous research has demonstrated that these berries may provide cardiovascular health benefits in high-risk populations. However, very few studies have investigated the effects of daily consumption of dietary achievable amounts of the berries in healthy subjects. Objectives The aim of this study was to investigate the effects of aronia berries on vascular function and gut microbiota composition in a healthy population. Methods A double-blind, placebo-controlled, parallel designed study was conducted in 66 healthy men randomly allocated to consume a (poly)phenol-rich extract (116 mg, 75 g berries), a whole fruit powder (12 mg, 10 g berries), or placebo (maltodextrin) for 12 wk. Flow-mediated dilation (FMD), arterial stiffness, blood pressure, heart rate, and serum biochemistry were assessed. Plasma (poly)phenol metabolites were analyzed by LC-MS. Gut microbiota composition was determined via 16S rRNA sequencing in stool samples. Results Consumption of aronia whole fruit and extract powder for 12 wk led to a significant increase in FMD over control of 0.9% ± 0.4% (95% CI: 0.13%, 1.72%) and 1.2% ± 0.4% (95% CI: 0.36%, 1.97%), respectively. Acute improvements in FMD were also observed 2 h after consumption of aronia extract on day 1 (1.1% ± 0.3%, P = 0.003) and 12 wk later (1.5% ± 0.4%, P = 0.0001). Circulating plasma phenolic metabolites increased upon consumption of the aronia treatments. Although no changes were found in gut microbiota diversity, consumption of aronia extract increased the growth of Anaerostipes (+10.6%, P = 0.01), whereas aronia whole fruit showed significant increases in Bacteroides (+193%, P = 0.01). Correlation analysis identified significant associations between changes in FMD, aronia-derived phenolic metabolites, and specific gut microbial genera. Conclusions In healthy men, consumption of aronia berry (poly)phenols improved endothelial function and modulated gut microbiota composition, indicating that regular aronia consumption has the potential to maintain cardiovascular health in individuals at low risk of cardiovascular disease. This trial was registered at CLINICALTRIALs.gov as NCT03041961.

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Antithrombin Therapy for Severe Preeclampsia

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614071 ◽

2000 ◽

Vol 84 (10) ◽

pp. 583-590 ◽

Cited By ~ 42

Author(s):

Masahiro Maki ◽

Toshihiko Terao ◽

Tsuyomu Ikenoue ◽

Kazuo Satoh ◽

Masao Nakabayashi ◽

...

Keyword(s):

Weight Gain ◽

Perinatal Outcome ◽

Controlled Trial ◽

Severe Preeclampsia ◽

Fetal Weight ◽

Low Birth Weight Infants ◽

Double Blind ◽

Biophysical Profile ◽

The Difference ◽

Estimated Fetal Weight

SummaryA double-blind, randomized, placebo-controlled trial was conducted to evaluate whether treatment with Antithrombin (AT) concentrates improved the clinical and perinatal outcome in patients with severe preeclampsia. Severe preeclamptic patients (24 to 35 weeks of gestation, Gestosis Index (GI) > 6 points) were randomized into two groups: 66 received AT and 67 received placebo. There were no statistical differences in the clinical profiles of the two groups. Study drugs were given intravenously once daily for 7 consecutive days. Maternal symptoms were evaluated from the difference of GI between before and after treatment, and fetal findings were evaluated from the changes of the biophysical profile score and the estimated fetal weight gain. Improvement was significantly greater in the AT group for both the GI (p = 0.020) and the estimated fetal weight gain (p = 0.029). The improvement of coagulation parameters was also evaluated. The D-dimer levels increased significantly in the placebo group (p = 0.026), but did not change in the AT group. Gestation was significantly prolonged (p = 0.007), and the number of low-birth weight infants was significantly smaller (p = 0.011) in the AT group. No adverse events related to AT were observed. It is revealed that AT concentrate therapy for preeclampsia is effective and safe, leading to an improved perinatal outcome.

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PROVIT: Supplementary Probiotic Treatment and Vitamin B7 in Depression—A Randomized Controlled Trial

Nutrients ◽

10.3390/nu12113422 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3422

Author(s):

Eva Z. Reininghaus ◽

Martina Platzer ◽

Alexandra Kohlhammer-Dohr ◽

Carlo Hamm ◽

Sabrina Mörkl ◽

...

Keyword(s):

Gut Microbiota ◽

Clinical Symptoms ◽

Psychiatric Symptoms ◽

Controlled Trial ◽

Intervention Group ◽

Double Blind ◽

16S Rrna Analysis ◽

Brain Functions ◽

Β Diversity ◽

Probiotic Treatment

Gut microbiota are suspected to affect brain functions and behavior as well as lowering inflammation status. Therefore, an effect on depression has already been suggested by recent research. The aim of this randomized double-blind controlled trial was to evaluate the effect of probiotic treatment in depressed individuals. Within inpatient care, 82 currently depressed individuals were randomly assigned to either receive a multistrain probiotic plus biotin treatment or biotin plus placebo for 28 days. Clinical symptoms as well as gut microbiome were analyzed at the begin of the study, after one and after four weeks. After 16S rRNA analysis, microbiome samples were bioinformatically explored using QIIME, SPSS, R and Piphillin. Both groups improved significantly regarding psychiatric symptoms. Ruminococcus gauvreauii and Coprococcus 3 were more abundant and β-diversity was higher in the probiotics group after 28 days. KEGG-analysis showed elevated inflammation-regulatory and metabolic pathways in the intervention group. The elevated abundance of potentially beneficial bacteria after probiotic treatment allows speculations on the functionality of probiotic treatment in depressed individuals. Furthermore, the finding of upregulated vitamin B6 and B7 synthesis underlines the connection between the quality of diet, gut microbiota and mental health through the regulation of metabolic functions, anti-inflammatory and anti-apoptotic properties. Concluding, four-week probiotic plus biotin supplementation, in inpatient individuals with a major depressive disorder diagnosis, showed an overall beneficial effect of clinical treatment. However, probiotic intervention compared to placebo only differed in microbial diversity profile, not in clinical outcome measures.

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Metformin for Prevention of Weight Gain and Insulin Resistance with Olanzapine: A Double-Blind Placebo-Controlled Trial

The Canadian Journal of Psychiatry ◽

10.1177/070674370605100310 ◽

2006 ◽

Vol 51 (3) ◽

pp. 192-196 ◽

Cited By ~ 81

Author(s):

Trino Baptista ◽

Jessan Martínez ◽

Anny Lacruz ◽

Nairy Rangel ◽

Serge Beaulieu ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo

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CoMET: a protocol for a randomised controlled trial of co-commencement of METformin as an adjunctive treatment to attenuate weight gain and metabolic syndrome in patients with schizophrenia newly commenced on clozapine

BMJ Open ◽

10.1136/bmjopen-2017-021000 ◽

2018 ◽

Vol 8 (3) ◽

pp. e021000 ◽

Cited By ~ 5

Author(s):

Dan Siskind ◽

Nadia Friend ◽

Anthony Russell ◽

John J McGrath ◽

Carmen Lim ◽

...

Keyword(s):

Metabolic Syndrome ◽

Body Weight ◽

Weight Gain ◽

Controlled Trial ◽

Adjunctive Treatment ◽

Double Blind ◽

Human Research Ethics ◽

Increased Risk ◽

Point Body ◽

Randomised Controlled

IntroductionClozapine, while effective in treatment refractory schizophrenia, is associated with significant weight gain, heart disease and increased risk of type 2 diabetes mellitus (T2DM). Although there is evidence for weight loss with metformin for people with obesity who are already taking clozapine, there have been no published trials that have investigated the effect of metformin in attenuating weight gain at the time of clozapine initiation.Methods and analysisA 24-week double-blind placebo-controlled trial of concomitant prescription of metformin at clozapine commencement. Eighty-six people being commenced on clozapine will be randomised to placebo or metformin (variable dose, up to 2 g/day). The primary outcome is comparative end point body weight, between the placebo and metformin groups. Secondary outcomes are comparative rates of conversion to T2DM, alteration of metabolic syndrome parameters, proportion gaining >5% body weight and changes in diet and appetite. We will additionally examine biomarkers associated with change in weight among trial participants.Ethics and disseminationEthics approval was granted by the Metro South Human Research Ethics Committee HREC/17/QPAH/538-SSA/17/QPAH/565. We plan to submit a manuscript of the results to a peer-reviewed journal, and present results at conferences, consumer forums and hospital grand rounds.Trial registration numberACTRN12617001547336; Pre-results.

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