scholarly journals The microbiome and metabolome of pre-term infant stool is personalized, and not driven by health outcomes including necrotizing enterocolitis and late-onset sepsis

2017 ◽  
Author(s):  
Stephen Wandro ◽  
Stephanie Osborne ◽  
Claudia Enriquez ◽  
Christine Bixby ◽  
Antonio Arrieta ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Preterm Infant ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Gut Microbiome ◽  
Infant Health ◽  
Late Onset ◽  
Bacterial Composition ◽  
Fecal Samples ◽  
Late Onset Sepsis

AbstractThe assembly and development of the gut microbiome in infants has important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birthweight preterm infants over the first six weeks of life. Infant health outcomes included healthy, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized the bacterial composition by 16S rRNA gene sequencing and metabolome by untargeted gas chromatography mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium and were dominated by Enterobacteriaceae, Enterococcus, and Staphylococcus due to the near uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to which baby the sample came from (Permanova R2=0.48, p<0.001), while clinical status (healthy, NEC, or late-onset sepsis), and overlapping time in the NICU did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (Permanova R2=0.43, p<0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 ± 0.05 (p = 0.03 ± 0.03). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis or a healthy outcome. Overall, preterm infants gut microbial communities were personalized and reflected antibiotic usage.ImportancePreterm infants face health problems likely related to microbial exposures including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from thirty-two preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found the preterm infant microbiome and metabolome were both personalized, and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangling the health consequences of the preterm infant microbiome.

scholarly journals The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis

mSphere ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Stephen Wandro ◽  
Stephanie Osborne ◽  
Claudia Enriquez ◽  
Christine Bixby ◽  
Antonio Arrieta ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Preterm Infant ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Gut Microbiome ◽  
Infant Health ◽  
Late Onset ◽  
Bacterial Composition ◽  
Fecal Samples ◽  
Late Onset Sepsis

ABSTRACTThe assembly and development of the gut microbiome in infants have important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birth weight preterm infants over the first 6 weeks of life. Infant health outcomes included health, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized bacterial compositions by 16S rRNA gene sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. Preterm infant fecal samples lacked beneficialBifidobacteriumspp. and were dominated byEnterobacteriaceae,Enterococcus, andStaphylococcusorganisms due to nearly uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to the baby from which the sample derived (permutational multivariate analysis of variance [PERMANOVA]R2= 0.48,P< 0.001), while clinical status (health, NEC, or late-onset sepsis) and overlapping times in the neonatal intensive care unit (NICU) did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (PERMANOVAR2= 0.43,P< 0.001) and weakly associated with bacterial composition (Mantel statisticr= 0.23 ± 0.05,P< 0.05). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis, or a healthy outcome. Overall, preterm infant gut microbial communities were personalized and reflected antibiotic usage.IMPORTANCEPreterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found that both the preterm infant microbiome and the metabolome were personalized and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangle the health consequences of the preterm infant microbiome.

Dynamics of the Preterm Gut Microbiome in Health and Disease

2021 ◽  
Author(s):  
Alain C Cuna ◽  
Michael J Morowitz ◽  
Ishfaq Ahmed ◽  
Shahid Umar ◽  
Venkatesh Sampath
Keyword(s):  
Preterm Infants ◽  
Gut Microbiome ◽  
Recent Literature ◽  
Late Onset ◽  
Perinatal Period ◽  
Future Directions ◽  
Late Onset Sepsis ◽  
Microbiome Research ◽  
Life Threatening ◽  
Health And Disease

Advances in metagenomics have allowed a detailed study of the gut microbiome, and its role in human health and disease. Infants born prematurely possess a fragile gut microbial ecosystem that is vulnerable to perturbation. Alterations in the developing gut microbiome in preterm infants are linked to life-threatening diseases such as necrotizing enterocolitis (NEC) and late onset sepsis; and may impact future risk of asthma, atopy, obesity, and psychosocial disease. In this mini review, we summarize recent literature on the origins and patterns of development of the preterm gut microbiome in the perinatal period. The host-microbiome-environmental factors that portend development of dysbiotic intestinal microbial patterns associated with NEC and sepsis are reviewed. Strategies to manipulate the microbiome and mitigate dysbiosis, including the use of probiotics and prebiotics will also be discussed. Finally, we explore the challenges and future directions of gut microbiome research in preterm infants.

scholarly journals Oropharyngeal Administration of Colostrum for Preventing Necrotizing Enterocolitis and Late-onset Sepsis in Preterm Infants with Gestational Age ≤ 32 Weeks: A Single-center Randomized Controlled Trial

2021 ◽  
Author(s):  
xia ouyang ◽  
changyi yang ◽  
wenlong xiu ◽  
yanhua hu ◽  
susu mei ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Enteral Feeding ◽  
Gestational Age ◽  
Late Onset ◽  
Controlled Trial ◽  
Control Group ◽  
Clinical Trial Registry ◽  
Late Onset Sepsis ◽  
Full Enteral Feeding

Abstract BackgroundOropharyngeal administration of colostrum (OAC) may provide immunoprotective and anti-inflammatory effects that potentially reduce the incidence of necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) and improve short-term outcomes.ObjectiveTo evaluate the role of OAC in the early prevention of NEC and LOS in preterm infants with gestational age (GA) ≤ 32 weeks.MethodsA randomized, placebo-controlled trial was conducted in a 40-bed tertiary neonatal intensive care unit (NICU) in China. Preterm infants with GA ≤ 32 weeks were divided randomly into an OAC group, which received 0.4 ml maternal colostrum smearing via the oropharyngeal route every 3 hours for 10 days beginning within the first 48 hours after birth, and a control group, which received normal saline instead. Data from the two groups were collected and compared.ResultsA total of 127 patients in the OAC group and 125 patients in the control group were finally enrolled. The incidence of NEC (Bell stage 2 or 3) and LOS was lower in the OAC group [2.4% vs. 10.4%, χ2 = 6.845, ༰=0.009; 4.7% vs. 13.6%, χ2 = 5.983, ༰=0.014]. In addition, the incidence of intraventricular hemorrhage (IVH) (stage 3 or 4) was lower [1.6% vs. 7.2%,χ2 = 4.775, ༰=0.029], and the time of achieving full enteral feeding was shorter [ 22.0 days vs. 25.0 days༌Z = 6༌424.500༌P = 0.009)] in the OAC group. No cases of adverse reactions were observed in either group.ConclusionsOAC is a safe and simple NICU procedure that yields a potential advantage in decreasing the incidence of NEC, LOS, and severe IVH and shortening the time to achieve full enteral feeding in preterm infants with GA ≤ 32 weeks.Trial registrationChinese Clinical Trial Registry, ChiCTR1900023697, Registered 8 June 2019, Retrospectively registered, http://www.chictr.org.cn/edit.aspx? pid = 39398

scholarly journals A significant decrease in hemoglobin concentrations may predict occurrence of necrotizing enterocolitis in preterm infants with late-onset sepsis

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095227
Author(s):  
Na Cai ◽  
Wenting Fan ◽  
Min Tao ◽  
Wei Liao
Keyword(s):  
Risk Factor ◽  
Blood Cell ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Independent Risk Factor ◽  
Late Onset ◽  
Demographic Data ◽  
Red Blood Cell Transfusion ◽  
Clinical Value ◽  
Late Onset Sepsis

Objective This study aimed to examine the clinical value of a decrease in hemoglobin concentration (HC) after the onset of sepsis for predicting occurrence of necrotizing enterocolitis (NEC) in preterm infants with late-onset sepsis. Methods We performed a retrospective cohort study between January 2015 and January 2020. Premature neonates (gestational age <37 weeks) with late-onset sepsis (age >3 days) were enrolled. According to the degree of reduction in HC, neonates were divided into the non-decrease group, mild decrease group, and severe decrease group. Demographic data, perinatal conditions, blood cell count analysis, blood culture, and treatment measures were compared. Results Eighty premature infants with sepsis were studied. The mortality rate and incidence of NEC were significantly higher in the severe decrease group than in the non-decrease and mild decrease groups. Significant differences were observed in the decrease in HC, red blood cell transfusion, and ventilator application between the NEC and non-NEC groups. A significant decrease in HC was an independent risk factor for NEC in preterm infants with sepsis. Conclusion A significant decrease in HC is an independent risk factor for NEC and may predict the occurrence of NEC in preterm infants with sepsis.

scholarly journals Gut Dysbiosis With Bacilli Dominance and Accumulation of Fermentation Products Precedes Late-onset Sepsis in Preterm Infants

2018 ◽  
Vol 69 (2) ◽  
pp. 268-277 ◽  
Author(s):  
S Graspeuntner ◽  
S Waschina ◽  
S Künzel ◽  
N Twisselmann ◽  
T K Rausch ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Gut Microbiome ◽  
Late Onset ◽  
Anaerobic Bacteria ◽  
Gene Profiling ◽  
Rrna Gene ◽  
Coagulase Negative Staphylococci ◽  
Fermentation Products ◽  
Gut Dysbiosis ◽  
Late Onset Sepsis

Abstract Background Gut dysbiosis has been suggested as a major risk factor for the development of late-onset sepsis (LOS), a main cause of mortality and morbidity in preterm infants. We aimed to assess specific signatures of the gut microbiome, including metabolic profiles, in preterm infants <34 weeks of gestation preceding LOS. Methods In a single-center cohort, fecal samples from preterm infants were prospectively collected during the period of highest vulnerability for LOS (days 7, 14, and 21 of life). Following 16S rRNA gene profiling, we assessed microbial community function using microbial metabolic network modeling. Data were adjusted for gestational age and use of probiotics. Results We studied stool samples from 71 preterm infants with LOS and 164 unaffected controls (no LOS/necrotizing enterocolitis). In most cases, the bacteria isolated in diagnostic blood culture corresponded to the genera in the gut microbiome. LOS cases had a decelerated development of microbial diversity. Before onset of disease, LOS cases had specific gut microbiome signatures with higher abundance of Bacilli (specifically coagulase-negative Staphylococci) and a lack of anaerobic bacteria. In silico modeling of bacterial community metabolism suggested accumulation of the fermentation products ethanol and formic acid in LOS cases before the onset of disease. Conclusions Intestinal dysbiosis preceding LOS is characterized by an accumulation of Bacilli and their fermentation products and a paucity of anaerobic bacteria. Early microbiome and metabolic patterns may become a valuable biomarker to guide individualized prevention strategies of LOS in highly vulnerable populations.

Immune cell subsets at birth may help to predict risk of late-onset sepsis and necrotizing enterocolitis in preterm infants

2016 ◽  
Vol 93 ◽  
pp. 9-16 ◽  
Author(s):  
Konrad Bochennek ◽  
Esther Fryns ◽  
Boris Wittekindt ◽  
Horst Buxmann ◽  
Andrea Quaiser ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Immune Cell ◽  
Late Onset ◽  
Late Onset Sepsis ◽  
Immune Cell Subsets

scholarly journals Patterned progression of gut microbiota associated with necrotizing enterocolitis and late onset sepsis in preterm infants: a prospective study in a Chinese neonatal intensive care unit

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7310 ◽  
Author(s):  
Jiayi Liu ◽  
Yuqing Li ◽  
Yi Feng ◽  
Liya Pan ◽  
Zhoulonglong Xie ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Neonatal Intensive Care ◽  
Late Onset ◽  
Control Group ◽  
High Morbidity ◽  
Asian Populations ◽  
Late Onset Sepsis ◽  
Underlying Mechanisms

Necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) are two common premature birth complications with high morbidity and mortality. Recent studies in Europe and America have linked gut microbiota dysbiosis to their etiology. However, similar studies in Asian populations remain scant. In this pilot study, we profiled gut microbiota of 24 Chinese preterm infants from birth till death or discharge from NICU. Four of them developed NEC and three developed LOS. Unexpectedly, we detected highly-diversified microbiota with similar compositions in all patients shortly after birth. However, as patients aged, the microbial diversities in case groups differed significantly from that of the control group. These differences emerged after the third day of life and persisted throughout the course of both NEC and LOS. Using a Zero-Inflated Beta Regression Model with Random Effects (ZIBR), we detected higher Bacillus (p = 0.032) and Solibacillus (p = 0.047) before the onset of NEC and LOS. During NEC progression, Enterococcus, Streptococcus and Peptoclostridium were the dominant genera while during LOS progression; Klebsiella was the only dominant genus that was also detected by the diagnostic hemoculture. These results warrant further studies to identify causative microbial patterns and underlying mechanisms.

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