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Alterations of gut microbiota are associated with blood pressure: a cross-sectional clinical trial in Northwestern China.
Lv, J, Wang, J, Yu, Y, Zhao, M, Yang, W, Liu, J, Zhao, Y, Yang, Y, Wang, G, Guo, L, et al
Journal of translational medicine. 2023;21(1):429
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Hypertension (HTN) is a complex and modifiable risk factor for cardiovascular diseases (CVDs) and stroke, while a diverse range of endogenous and environmental factors contribute to both HTN onset and progression. The adult gut microbiota (GM) consists of trillions of microorganisms and maintains the gut immunity and whole-body homeostasis. The aim of this study was to investigate the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. This study was a cross-sectional study. Participants were randomly selected for the HTN and control groups. A total of 36 HTN subjects (24 females and 12 males) and 18 controls (9 females and 9 males) were randomly selected for metagenomic analysis. Results showed a positive association between GM characteristics and alterations and HTN in both females and males. Thus, GM dysbiosis underlies HTN pathogenesis. Authors conclude that further studies are needed to elucidate the underlying mechanisms and potential therapeutic interventions targeting GM for HTN prevention and management
Abstract
BACKGROUND The human gut microbiota (GM) is involved in the pathogenesis of hypertension (HTN), and could be affected by various factors, including sex and geography. However, available data directly linking GM to HTN based on sex differences are limited. METHODS This study investigated the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. A total of 87 HTN subjects and 45 controls were recruited with demographic and clinical characteristics documented. Fecal samples were collected for 16S rRNA gene sequencing and metagenomic sequencing. RESULTS GM diversity was observed higher in females compared to males, and principal coordinate analysis showed an obvious segregation of females and males. Four predominant phyla of fecal GM included Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria. LEfSe analysis indicated that phylum unidentified_Bacteria was enriched in HTN females, while Leuconostocaceae, Weissella and Weissella_cibaria were enriched in control females (P < 0.05). Functionally, ROC analysis revealed that Cellular Processes (0.796, 95% CI 0.620 ~ 0.916), Human Diseases (0.773, 95% CI 0.595 ~ 0.900), Signal transduction (0.806, 95% CI 0.631 ~ 0.922) and Two-component system (0.806, 95% CI 0.631 ~ 0.922) could differentiate HTN females as effective functional classifiers, which were also positively correlated with systolic blood pressure levels. CONCLUSIONS This work provides evidence of fecal GM characteristics in HTN females and males in a northwestern Chinese population, further supporting the notion that GM dysbiosis may participate in the pathogenesis of HTN, and the role of sex differences should be considered. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019191. Registered 30 October 2018 - Retrospectively registered, http://www.chictr.org.cn/ .
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Influence of timing of maternal antibiotic administration during caesarean section on infant microbial colonisation: a randomised controlled trial.
Dierikx, T, Berkhout, D, Eck, A, Tims, S, van Limbergen, J, Visser, D, de Boer, M, de Boer, N, Touw, D, Benninga, M, et al
Gut. 2022;71(9):1803-1811
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Early-life microbiome acquisition and development can be compromised by external perturbations such as delivery via caesarean section (CS), formula feeding and antibiotics. Currently, based on revised international guidelines, all infants born by CS are exposed to broad-spectrum antibiotics via the umbilical cord. Even though there was not an increase in the incidence of neonatal sepsis, the effects on the gut microbiota colonisation and long-term health consequences remain largely unknown. The hypothesis for this study was that exposure to antibiotics in children delivered by CS, related to the revised international guidelines, influences the microbial colonisation process and may impact health outcome. This study is a randomised controlled trial on the microbiome and health state of infants up to 3 years of age. The study enrolled women delivering via CS who received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20) and women who had a vaginal delivery (n=23). Results show that CS delivery in general leads to a profound impact on the initial microbial colonisation. Furthermore, maternal antibiotic administration prior to CS does not lead to a ‘second hit’ on the already compromised microbiome in CS born infants. Authors conclude that early-life microbiome development is strongly affected by mode of delivery.
Abstract
OBJECTIVE Revised guidelines for caesarean section (CS) advise maternal antibiotic administration prior to skin incision instead of after umbilical cord clamping, unintentionally exposing the infant to antibiotics antenatally. We aimed to investigate if timing of intrapartum antibiotics contributes to the impairment of microbiota colonisation in CS born infants. DESIGN In this randomised controlled trial, women delivering via CS received antibiotics prior to skin incision (n=20) or after umbilical cord clamping (n=20). A third control group of vaginally delivering women (n=23) was included. Faecal microbiota was determined from all infants at 1, 7 and 28 days after birth and at 3 years by 16S rRNA gene sequencing and whole-metagenome shotgun sequencing. RESULTS Compared with vaginally born infants, profound differences were found in microbial diversity and composition in both CS groups in the first month of life. A decreased abundance in species belonging to the genera Bacteroides and Bifidobacterium was found with a concurrent increase in members belonging to the phylum Proteobacteria. These differences could not be observed at 3 years of age. No statistically significant differences were observed in taxonomic and functional composition of the microbiome between both CS groups at any of the time points. CONCLUSION We confirmed that microbiome colonisation is strongly affected by CS delivery. Our findings suggest that maternal antibiotic administration prior to CS does not result in a second hit on the compromised microbiome. Future, larger studies should confirm that antenatal antibiotic exposure in CS born infants does not aggravate colonisation impairment and impact long-term health.
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Gut microbiota varies by opioid use, circulating leptin and oxytocin in African American men with diabetes and high burden of chronic disease.
Barengolts, E, Green, SJ, Eisenberg, Y, Akbar, A, Reddivari, B, Layden, BT, Dugas, L, Chlipala, G
PloS one. 2018;13(3):e0194171
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Obesity and type 2 diabetes (T2D) can lead to alterations of the composition of the gut microbiota. The gut microbiota, in turn, has been suggested to play a role in the development of psychological conditions, such as anxiety, depression and drug addiction. This cross-sectional study included 99 mostly overweight/obese African American men, with or without T2D, and with or without opioid addiction and other psychiatric disorders. The aim of the study was to determine, whether the gut microbiota composition was linked to T2D and the use of opioids in these patients. Furthermore, the researchers looked at the associations between leptin and oxytocin levels in the blood and the gut microbiota, and whether these hormone biomarkers could be indicative of obesity and psychosocial behaviour, such as opioid addiction. The authors found that some bacterial species in the gut were affected by T2D, diabetes medication and opioid use in the studied subjects. A relationship was also observed between leptin and oxytocin levels and the abundance of certain bacteria in the gut in subjects without T2D. The authors conclude that targeting the gut microbiota could be used for the management of T2D and associated psychiatric disorders. However, more studies are needed to provide further understanding of the connections between the gut microbiota and the brain.
Abstract
OBJECTIVE The gut microbiota is known to be related to type 2 diabetes (T2D), psychiatric conditions, and opioid use. In this study, we tested the hypothesis that variability in gut microbiota in T2D is associated with psycho-metabolic health. METHODS A cross-sectional study was conducted among African American men (AAM) (n = 99) that were outpatients at a Chicago VA Medical Center. The main outcome measures included fecal microbiota ecology (by 16S rRNA gene sequencing), psychiatric disorders including opioid use, and circulating leptin and oxytocin as representative hormone biomarkers for obesity and psychological pro-social behavior. RESULTS The study subjects had prevalent overweight/obesity (78%), T2D (50%) and co-morbid psychiatric (65%) and opioid use (45%) disorders. In the analysis of microbiota, the data showed interactions of opioids, T2D and metformin with Bifidobacterium and Prevotella genera. The differential analysis of Bifidobacterium stratified by opioids, T2D and metformin, showed significant interactions among these factors indicating that the effect of one factor was changed by the other (FDR-adjusted p [q] < 0.01). In addition, the pair-wise comparison showed that participants with T2D not taking metformin had a significant 6.74 log2 fold increase in Bifidobacterium in opioid users as compared to non-users (q = 2.2 x 10-8). Since metformin was not included in this pair-wise comparison, the significant 'q' suggested association of opioid use with Bifidobacterium abundance. The differences in Bifidobacterium abundance could possibly be explained by opioids acting as organic cation transporter 1 (OCT1) inhibitors. Analysis stratified by lower and higher leptin and oxytocin (divided by the 50th percentile) in the subgroup without T2D showed lower Dialister in High-Leptin vs. Low-Leptin (p = 0.03). Contrary, the opposite was shown for oxytocin, higher Dialister in High-Oxytocin vs. Low-Oxytocin (p = 0.04). CONCLUSIONS The study demonstrated for the first time that Bifidobacterium and Prevotella abundance was affected by interactions of T2D, metformin and opioid use. Also, in subjects without T2D Dialister abundance varied according to circulating leptin and oxytocin.
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Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin.
Brown, RG, Marchesi, JR, Lee, YS, Smith, A, Lehne, B, Kindinger, LM, Terzidou, V, Holmes, E, Nicholson, JK, Bennett, PR, et al
BMC medicine. 2018;16(1):9
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Preterm premature rupture of the membranes (PPROM) is a pregnancy complication in which the amniotic sac ruptures before week 37 of the pregnancy, leading to an increased risk of infection and premature birth. Women who experience PPROM are usually given antibiotics to help prevent infections which, left untreated, could endanger their babies’ lives. It is thought that disturbances in the mum’s vaginal bacteria may be related to the risk of PPROM. In this study, researchers examined the vaginal bacteria of women with PPROM, before and after antibiotic treatment. A total of 250 pregnant women who had been identified as at risk of a premature birth were included in the study. Disturbance of the normal vaginal bacteria, characterised by low levels of Lactobacillus, was present in a third of women who went on to develop PPROM. This disturbance of the normal vaginal bacteria was made worse by antibiotic treatment particularly in women initially colonised by Lactobacillus spp. Lower levels of Lactobacillus and increased abundance of Sneathia spp. were associated with an increased likelihood of funisitis (inflammation of the umbilical cord) and sepsis in the newborn. The authors concluded that the composition of the vaginal microbiota is a risk factor for PPROM and is associated with unfavourable short-term outcomes for the mother and newborn. This highlights vaginal microbiota as a potentially modifiable risk factor for PPROM and they suggest that the routine use of antibiotics such as erythromycin for PPROM should be re-examined.
Abstract
BACKGROUND Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30% of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM is strongly associated with ascending vaginal infection, prophylactic antibiotics are widely used. The evolution of vaginal microbiota compositions associated with PPROM and the impact of antibiotics on bacterial compositions are unknown. METHODS We prospectively assessed vaginal microbiota prior to and following PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the impact of erythromycin prophylaxis on bacterial load and community structures. RESULTS In contrast to pregnancies delivering at term, vaginal dysbiosis characterised by Lactobacillus spp. depletion was present prior to the rupture of fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women initially colonised by Lactobacillus spp. Lactobacillus depletion and increased relative abundance of Sneathia spp. were associated with subsequent funisitis and early onset neonatal sepsis. CONCLUSIONS Our data show that vaginal microbiota composition is a risk factor for subsequent PPROM and is associated with adverse short-term maternal and neonatal outcomes. This highlights vaginal microbiota as a potentially modifiable antenatal risk factor for PPROM and suggests that routine use of erythromycin for PPROM be re-examined.
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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.
Halkjær, SI, Christensen, AH, Lo, BZS, Browne, PD, Günther, S, Hansen, LH, Petersen, AM
Gut. 2018;67(12):2107-2115
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Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder of unknown cause. It is thought that the bacterial composition of the GI tract (microbiota) plays an important role in IBS. Faecal microbiota transplantation (FMT) has been shown to create lasting changes in the bacterial composition of the recipient’s GI tract in a number of conditions. The aim of this randomised, double-blind placebo-controlled study was to evaluate the effects of FMT on symptoms and gut microbiota in patients with IBS. 52 IBS patients received either orally administered FMT or placebo, following pre-treatment in the form of a bowel cleanse. IBS severity scores and quality of life were assessed and faecal samples obtained at baseline, and 1, 3 and 6 months after treatment. Quality of life and IBS severity scores improved in both groups, but significantly more so in the placebo group. The healthy faecal donors had higher microbial biodiversity (a sign of a healthy microbial composition) than patients with IBS prior to treatment. Patients in the FMT group had an increase in biodiversity to the extent that this group was not statistically different from the healthy donors any more, whilst no significant changes in the microbiota were observed in the placebo group. The authors conclude that more studies are required to examine the potential role of FMT in treating IBS, evaluating different factors such as route of administration, pre-treatment, duration of treatment and dose.
Abstract
OBJECTIVE IBS 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. DESIGN We 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. RESULTS A 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. CONCLUSION In 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 NUMBER NCT02788071.