scholarly journals A synbiotic intervention modulates meta-omics signatures of gut redox potential and acidity in elective caesarean born infants

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Christophe Lay ◽  
Collins Wenhan Chu ◽  
Rikky Wenang Purbojati ◽  
Enzo Acerbi ◽  
Daniela I. Drautz-Moses ◽  
...  

Abstract Background The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. Trial registration The study was registered in the Dutch Trial Register (Number: 2838) on 4th April 2011.

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 427
Author(s):  
Stefania Cicolari ◽  
Chiara Pavanello ◽  
Elena Olmastroni ◽  
Marina Del Puppo ◽  
Marco Bertolotti ◽  
...  

Background: Oxysterol relationship with cardiovascular (CV) risk factors is poorly explored, especially in moderately hypercholesterolaemic subjects. Moreover, the impact of nutraceuticals controlling hypercholesterolaemia on plasma levels of 24-, 25- and 27-hydroxycholesterol (24-OHC, 25-OHC, 27-OHC) is unknown. Methods: Subjects (n = 33; 18–70 years) with moderate hypercholesterolaemia (low-density lipoprotein cholesterol (LDL-C:): 130–200 mg/dL), in primary CV prevention as well as low CV risk were studied cross-sectionally. Moreover, they were evaluated after treatment with a nutraceutical combination (Bifidobacterium longum BB536, red yeast rice extract (10 mg/dose monacolin K)), following a double-blind, randomized, placebo-controlled design. We evaluated 24-OHC, 25-OHC and 27-OHC levels by gas chromatography/mass spectrometry analysis. Results: 24-OHC and 25-OHC were significantly correlated, 24-OHC was correlated with apoB. 27-OHC and 27-OHC/total cholesterol (TC) were higher in men (median 209 ng/mL and 77 ng/mg, respectively) vs. women (median 168 ng/mL and 56 ng/mg, respectively); 27-OHC/TC was significantly correlated with abdominal circumference, visceral fat and, negatively, with high-density lipoprotein cholesterol (HDL-C). Triglycerides were significantly correlated with 24-OHC, 25-OHC and 27-OHC and with 24-OHC/TC and 25-OHC/TC. After intervention, 27-OHC levels were significantly reduced by 10.4% in the nutraceutical group Levels of 24-OHC, 24-OHC/TC, 25-OHC, 25-OHC/TC and 27-OHC/TC were unchanged. Conclusions: In this study, conducted in moderate hypercholesterolemic subjects, we observed novel relationships between 24-OHC, 25-OHC and 27-OHC and CV risk biomarkers. In addition, no adverse changes of OHC levels upon nutraceutical treatment were found.


Gut ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 645-653 ◽  
Author(s):  
Daniela Paganini ◽  
Mary A Uyoga ◽  
Guus A M Kortman ◽  
Colin I Cercamondi ◽  
Hans C Winkler ◽  
...  

ObjectiveMany African infants receiving iron fortificants also receive antibiotics. Antibiotic efficacy against enteropathogens may be modified by high colonic iron concentrations. In this study, we evaluated the effect of antibiotics on the infant gut microbiome and diarrhoea when given with or without iron-containing micronutrient powders (MNPs).DesignIn a controlled intervention trial, four groups of community-dwelling infants (n=28; aged 8–10 months) received either: (A) antibiotics for 5 days and iron-MNPs for 40 days (Fe+Ab+); (B) antibiotics and no-iron-MNPs (Fe−Ab+); (C) no antibiotics and iron-MNPs (Fe+Ab−); or (D) no antibiotics and no-iron-MNPs (Fe−Ab−). We collected a faecal sample before the first antibiotic dose (D0) and after 5, 10, 20 and 40 days (D5–D40) to assess the gut microbiome composition by 16S profiling, enteropathogens by quantitative PCR, faecal calprotectin and pH and assessed morbidity over the 40-day study period.ResultsIn Fe+Ab+, there was a decrease in Bifidobacterium abundances (p<0.05), but no decrease in Fe−Ab+. In Fe−Ab+, there was a decrease in abundances of pathogenic Escherichia coli (p<0.05), but no decrease in Fe+Ab+. In Fe−Ab+, there was a decrease in pH (p<0.05), but no decrease in Fe+Ab+. Longitudinal prevalence of diarrhoea was higher in Fe+Ab+ (19.6%) compared with Fe−Ab+ (12.4%) (p=0.04) and compared with Fe+Ab− (5.2%) (p=0.00).ConclusionOur findings need confirmation in a larger study but suggest that, in African infants, iron fortification modifies the response to broad-spectrum antibiotics: iron may reduce their efficacy against potential enteropathogens, particularly pathogenic E. coli, and may increase risk for diarrhoea.Trial registration numberNCT02118402; Pre-results.


2011 ◽  
Vol 26 (S2) ◽  
pp. 803-803
Author(s):  
K. Blum ◽  
E. Stice ◽  
Y. Liu ◽  
J. Giordano ◽  
S. Morse ◽  
...  

IntroductionThere is a need to classify patients at genetic risk for drug seeking behavior prior to or upon entry to chemical dependency programs.MethodsThe prevalence of seven risk alleles (DRD2 = A1; SLC6A3 (DAT) = 10R; DRD4 = 3R or 7R; 5HTTLPR = L or LA; MAO = 3R; COMT = G) and corresponding severity risk score (Low (LS) = 1–36%, moderate (MS) = 37–50%, and high (HS) = 51–100%) were calculated. Group 1 consisted of 16 Caucasian male psycho-stimulant addicts, and Group 2 consisted of 10 Chinese male heroin addicts (9 were genotyped). qEEG and fMRI visualized the impact of Neuroadaptagen Amino-Acid Therapy complex on mesolimbic system activation.Results[Findings by Group]74% of the combined groups had a moderate to high genetic addiction risk score (GARS). One acute dose of KB220-IV variant in heroin addicts having brain abnormalities was found to normalize qEEG. Additionally, a randomized double-blind placebo controlled study involving oral KB220-Z variant established qEEG normalization of reward circuitry in abstinent psycho-stimulant abusers (P < 0.03).ConclusionsWe cautiously suggest that long-term activation of dopaminergic receptors will lead to D2 receptor proliferation and enhanced “dopamine sensitivity,” thus reducing aberrant craving behavior especially in carriers of the DRD2 A1 allele. Although supported by 20 clinical trials, KB220-Z awaits PET scanning to determine its chronic effects on D2 receptor numbers.


2020 ◽  
Vol 110 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Delphine M. Hoang ◽  
Elvira I. Levy ◽  
Yvan Vandenplas

2020 ◽  
Vol 10 (11) ◽  
pp. 875 ◽  
Author(s):  
Pierre Besson ◽  
Makii Muthalib ◽  
Christophe De Vassoigne ◽  
Jonh Rothwell ◽  
Stephane Perrey

A single session of priming cathodal transcranial direct current stimulation (tDCS) prior to anodal tDCS (c-a-tDCS) allows cumulative effects on motor learning and retention. However, the impact of multiple sessions of c-a-tDCS priming on learning and retention remains unclear. Here, we tested whether multiple sessions of c-a-tDCS (over 3 consecutive days) applied over the left sensorimotor cortex can further enhance motor learning and retention of an already learned visuo-motor task as compared to anodal tDCS (a-tDCS) or sham. In a between group and randomized double-blind sham-controlled study design, 25 participants separated in 3 independent groups underwent 2 days of baseline training without tDCS followed by 3-days of training with both online and offline tDCS, and two retention tests (1 and 14 days later). Each training block consisted of five trials of a 60 s circular-tracing task intersected by 60 s rest, and performance was assessed in terms of speed–accuracy trade-off represented notably by an index of performance (IP). The main findings of this exploratory study were that multiple sessions of c-a-tDCS significantly further enhanced IP above baseline training levels over the 3 training days that were maintained over the 2 retention days, but these learning and retention performance changes were not significantly different from the sham group. Subtle differences in the changes in speed–accuracy trade-off (components of IP) between c-a-tDCS (maintenance of accuracy over increasing speed) and a-tDCS (increasing speed over maintenance of accuracy) provide preliminary insights to a mechanistic modulation of motor performance with priming and polarity of tDCS.


2012 ◽  
Vol 56 (8) ◽  
pp. 4062-4070 ◽  
Author(s):  
Federica Cruciani ◽  
Patrizia Brigidi ◽  
Fiorella Calanni ◽  
Vittoria Lauro ◽  
Raffaella Tacchi ◽  
...  

ABSTRACTBacterial vaginosis (BV) is a common vaginal disorder characterized by an alteration of the vaginal bacterial morphotypes, associated with sexually transmitted infections and adverse pregnancy outcomes. The purpose of the present study was to evaluate the impact of different doses of rifaximin vaginal tablets (100 mg/day for 5 days, 25 mg/day for 5 days, and 100 mg/day for 2 days) on the vaginal microbiota of 102 European patients with BV enrolled in a multicenter, double-blind, randomized, placebo-controlled study. An integrated molecular approach based on quantitative PCR (qPCR) and PCR-denaturing gradient gel electrophoresis (PCR-DGGE) was used to investigate the effects of vaginal tablets containing the antibiotic. An increase in members of the genusLactobacillusand a decrease in the BV-related bacterial groups after the antibiotic treatment were demonstrated by qPCR. PCR-DGGE profiles confirmed the capability of rifaximin to modulate the composition of the vaginal microbial communities and to reduce their complexity. This molecular analysis supported the clinical observation that rifaximin at 25 mg/day for 5 days represents an effective treatment to be used in future pivotal studies for the treatment of BV.


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 268-268 ◽  
Author(s):  
D. A. Yardley ◽  
R. Ismail-Khan ◽  
P. Klein

268 Background: Hormonal therapy, including AIs, is the mainstay of ER+ breast cancer (BC) treatment; however, both acquired and intrinsic resistance limits its clinical benefit. Entinostat is a novel, oral, class I selective histone deacetylase inhibitor that has been shown to inhibit growth factor signaling pathways that mediate AI resistance. This study was designed to evaluate the impact of the addition of entinostat to exemestane therapy on progression-free survival (PFS). Methods: Postmenopausal women with ER+ advanced BC who had progressed on a non-steroidal AI were randomized to exemestane 25 mg daily + entinostat 5 mg or placebo weekly. Results: A total of 130 women were enrolled (66 exemestane+placebo; 64 exemestane+entinostat). All but 1 patient had Stage IV disease, and 82% had measurable disease. All patients had received prior hormonal therapy (1 prior line 42%; >1 prior line 58%), and 62% had received prior chemotherapy (33% in the advanced BC setting). Analysis of the intent-to-treat population showed that PFS was significantly (defined prospectively as p <0.10) longer with exemestane+entinostat than with exemestane+placebo (4.28 versus 2.27 months, respectively; hazard ratio [HR] = 0.73; p=0.06). Entinostat combined with exemestane was well-tolerated with the most frequent adverse events (AEs) consisting of fatigue, gastrointestinal disturbances, and hematologic abnormalities. AEs with a ≥20% higher incidence with exemestane+entinostat than with exemestane+placebo were fatigue (46% versus 26%, respectively) and uncomplicated neutropenia (25% versus 0%, respectively). The serious AE rate was similar for exemestane+entinostat (13%) and exemestane+placebo (12%). Conclusions: Exemestane+entinostat significantly prolonged the median PFS and reduced the risk of disease progression by 27% versus exemestane+placebo (HR = 0.73). In light of these positive data, a phase III evaluation of this combination is planned.


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