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Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine.

ABSTRACT: Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (<1500 g, n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids (German Registry of Clinical Trials, No.: DRKS00009290). Regimens including probiotic Bifidobacterium longum subsp. infantis NCDO 2203 supplementation affect microbiome development globally, pointing toward the genomic potential to convert HMOs. Engraftment of NCDO 2203 is associated with a substantial reduction of microbiome-associated antibiotic resistance as compared to regimens using probiotic Lactobacillus rhamnosus LCR 35 or no supplementation. Crucially, the beneficial effects of Bifidobacterium longum subsp. infantis NCDO 2203 supplementation depends on simultaneous feeding with HMOs. We demonstrate that preventive regimens have the highest impact on development and maturation of the gastrointestinal microbiome, enabling the establishment of a resilient microbial ecosystem that reduces pathogenic threats in at-risk preterm infants.

SUBMITTER: Neumann CJ

PROVIDER: S-EPMC10008552 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine.

Neumann Charlotte J CJ Mahnert Alexander A Kumpitsch Christina C Kiu Raymond R Dalby Matthew J MJ Kujawska Magdalena M Madl Tobias T Kurath-Koller Stefan S Urlesberger Berndt B Resch Bernhard B Hall Lindsay J LJ Moissl-Eichinger Christine C

Nature communications 20230311 1

Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (<1500 g, n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profile ...[more]

PMID: 36906612

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Project description:ObjectiveTo determine risk factors and outcomes of necrotizing enterocolitis (NEC)-associated sepsis in infants with NEC.MethodsA retrospective review comparing demographic and clinical information in infants with and without NEC-associated sepsis (defined as positive blood culture at the time of NEC onset).ResultsA total of 209 infants with medical (n = 98) and surgical NEC (n = 111) had a median gestational age of 27 weeks (IQR 25; 30.5) and a median birth weight of 910 g [IQR 655; 1138]. Fifty of 209 (23.9%) infants had NEC-associated sepsis. Infants with NEC-associated sepsis had lower median GA (26.4 vs. 27.4 weeks; p = 0.01), lower birth weight (745 vs. 930 g; p = 0.009), were more likely mechanically ventilated [p < 0.001], received dopamine [p < 0.001], had more evidence of acute kidney injury [60% vs. 38.4%, p = 0.01], longer postoperative ileus (16 [13.0; 22.0] vs. 12 [8; 16] days; p = 0.006), higher levels of C-reactive protein, lower platelet counts, longer hospitalization compared to infants without NEC-associated sepsis. On multivariate regression, cholestasis was an independent risk factor for NEC-associated sepsis (OR 2.94; 95% CI 1.1-8.8, p = 0.038).ConclusionNEC-associated sepsis was associated with greater hemodynamic support, acute kidney injury, longer postoperative ileus, and hospitalization on bivariate analysis, and cholestasis was associated with higher odds of sepsis on multi regression analysis.ImpactNEC-associated sepsis was present in 24% of infants with NEC. Gram-positive bacteria, Gram-negative bacteria, and Candida were found in 15.3%, 10.5%, and 2.8% of cases, respectively. Infants with NEC-associated sepsis had a greater inflammatory response (CRP levels), received more blood transfusion before NEC onset, frequently needed assisted ventilation ionotropic support, and had acute kidney injury after NEC onset. NEC infants with Gram-negative sepsis had higher portal venous gas, received more platelet transfusions before NEC onset, and had higher CRP levels and lower median lymphocyte counts at 24 h after NEC onset than those with Gram-positive sepsis.

Project description:IntroductionOur objective was to compare the vaginal microbiome in low-risk and high-risk pregnant women and to explore a potential association between vaginal microbiome and preterm birth.Material and methodsA pilot, consecutive, longitudinal, multicenter study was conducted in pregnant women at 18-22 weeks of gestation. Participants were assigned to one of three groups: control (normal cervix), pessary (cervical length ≤25 mm) and cerclage (cervical length ≤25 mm or history of preterm birth). Analysis and comparison of vaginal microbiota as a primary outcome was performed at inclusion and at 30 weeks of gestation, along with a follow-up of pregnancy and perinatal outcomes. We assessed the vaginal microbiome of pregnant women presenting a short cervix with that of pregnant women having a normal cervix, and compared the vaginal microbiome of women with a short cervix before and after placement of a cervical pessary or a cervical cerclage.ResultsThe microbiome of our control cohort was dominated by Lactobacillus crispatus and inners. Five community state types were identified and microbiome diversity did not change significantly over 10 weeks in controls. On the other hand, a short cervix was associated with a lower microbial load and higher microbial richness, and was not correlated with Lactobacillus relative abundance. After intervention, the cerclage group (n = 19) had a significant increase in microbial richness and a shift towards community state types driven by various bacterial species, including Lactobacillus mulieris, unidentified Bifidobacterium or Enterococcus. These changes were not significantly observed in the pessary (n = 26) and control (n = 35) groups. The cerclage group had more threatened preterm labor episodes and poorer outcomes than the control and pessary groups.ConclusionsThese findings indicate that a short cervix is associated with an altered vaginal microbiome community structure. The use of a cerclage for preterm birth prevention, as compared with a pessary, was associated with a microbial community harboring a relatively low abundance of Lactobacillus, with more threatened preterm labor episodes, and with poorer clinical outcomes.

Project description:Preterm birth (PTB) is a major cause of infant morbidity and mortality. The aim of this study was to investigate the effect of vaginal microbiota and metabolites on the outcome of pregnant women. In this study, a total of 127 pregnant women provided written informed consent prior to enrollment in accordance with the approved institutional guidelines, but only 45 pregnancies met the experimental requirements, and then blood and cervical vaginal fluid (CVF) samples were collected before delivery (at the second week after cervical cerclage). Pregnant women with PTB exhibited high white blood cell and neutrophil contents, high neutrophil-to-lymphocyte ratio (NLR), and high systemic inflammation response index (SIRI) in the blood. Vaginal microbiome revealed that the proportion of beneficial bacteria (including Lactobacillus, [Ruminococcus] gnavus group, and Megamonas) significantly decreased in the PTB group, and the proportion of harmful bacteria (including Desulfovibrionaceae, Helicobacter, and Gardnerella) significantly increased, which is strongly related to the biochemical parameters of blood (white blood cells, neutrophils, NLR, and SIRI). In addition, vaginal metabolomics-based liquid chromatography-Orbitrap-tandem mass spectrometry (LC-Orbitrap-MS/MS) found that the alteration in vaginal metabolites in pregnant women with PTB is involved in starch and sucrose metabolism; arginine and praline metabolism; galactose metabolism; purine metabolism; arginine metabolism; tryptophan metabolism and N-glycan biosynthesis; cysteine and methionine metabolism; taurine and hypotaurine metabolism; amino acid metabolism; propanoate metabolism; valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and steroid hormone biosynthesis. These results elaborated that distinct vaginal microbiome and metabolome profiles in women with preterm delivery following cervical cerclage provide valuable information for establishing the prediction models for PTB.

Project description:ObjectivesThe gut microbiota among preterm infants is shaped by sex and feeding types. However, sex-specific weekly patterns of gut microbiome profiles among preterm infants during their neonatal intensive care unit (NICU) hospitalization remain unclear. This study aimed to investigate the effect of sex on the weekly development of preterm neonatal gut microbiota in the first 4 weeks of NICU hospitalization.MethodsThis secondary data analysis included 28 preterm neonates with 261 stool samples collected from January 2014 to February 2015 in the Northeastern United States. The 16S rRNA V4 gene regions of the stool samples were sequenced and aligned against the SILVA 132 database by using Mothur 1.42.3. The sex-specific weekly diversity indexes and relative abundance of bacterial taxonomic composition were generated by Mothur and analyzed by R packages. Sex-specific weekly compositional patterns of the gut microbiome and predicted metabolic functions of gut microbiome profiles were compared, respectively.ResultsIn each week of the NICU hospitalization, preterm females and males had significantly distinguished β-diversity indices and compositions of gut microbiota. Both females and males had significantly enriched Bifidobacterium, a protection feature, in stool samples collected in the third week compared with those in the second week. The predicted metabolic pathways were significantly different between females and males in the second, third, and fourth week of the NICU hospitalization. Both females and males had significantly abundant pathways. Males consistently had more abundance of "lipopolysaccharide biosynthesis" than females in the second, third, and fourth week. Males also had a significant abundance of "membrane and intracellular structural molecules" and "glycan biosynthesis and metabolism" in the second and third week.ConclusionsSex shaped the weekly patterns of preterm neonatal gut microbiome profiles during the first 4 weeks of the NICU hospitalization. Further clinical interventions should consider the distinct gut microbiota compositions and predicted functional profiles between female and male preterm neonates.

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Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine.

Publications

Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine.

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