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 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.

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.

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.

Prolonged empiric antibiotics and time to full enteral feed in preterm infants less than 29 weeks of gestational age

2021 ◽  
pp. 1-5
Author(s):  
M.R. Alturk ◽  
H. Salama ◽  
H. Al Rifai ◽  
M. Al Qubaisi ◽  
S. Alobaidly
Keyword(s):  
Parenteral Nutrition ◽  
Preterm Infants ◽  
Antibiotic Treatment ◽  
Gestational Age ◽  
Late Onset ◽  
Blood Cultures ◽  
Hospital Death ◽  
Late Onset Sepsis ◽  
Empiric Antibiotic ◽  
Antibiotic Courses

BACKGROUND: Early empiric antibiotic exposure appears to negatively influence feeding tolerance in preterm infants. However, the effect of prolonged antibiotic treatment is unknown. The objective of this study was to investigate whether prolonged antibiotics impact the time to full enteral feed in infants less than 29 weeks of gestational age with negative blood cultures. METHODS: Retrospective data for infants less than 29 weeks gestation age were retrieved from the PEARL-Peristat perinatal registry in Qatar. Exclusion criteria were major congenital anomalies, conditions requiring surgery in the first 10 days of life, positive blood cultures in the first 48 hours of life, and death within the first week of life. Antibiotic courses were categorized as prolonged if continued more than 48 hours. The primary outcome was the duration of total parenteral nutrition. RESULTS: Of 199 study infants, 185 (92.9%) underwent antibiotic treatment for >  48 hours despite negative blood cultures. The median duration of parenteral nutrition was not significantly different between the prolonged and short antibiotic groups (25 and 22 days, respectively; p = 0.139). Infants with prolonged antibiotic courses experienced non-significantly higher levels of necrotizing enterocolitis (7.1% and 18.4%, respectively), bronchopulmonary dysplasia (28.6% and 45.4%, respectively), and retinopathy of prematurity (14.3% and 38.4%, respectively). There were no differences in the late-onset sepsis rate (78.6% and 82.1%, respectively) and the in-hospital death rate (7.1% and 7.6%, respectively). CONCLUSIONS: Prolonged antibiotic treatment in infants less than 29 weeks gestation with negative blood cultures has no significant impact on the time to full enteral feed.

ELFIN, the United Kingdom preterm lactoferrin trial: interpretation and future questions

2020 ◽  
Author(s):  
Janet Elizabeth Berrington ◽  
William McGuire ◽  
NIcholas David Embleton
Keyword(s):  
United Kingdom ◽  
Preterm Infants ◽  
Late Onset ◽  
Disease Onset ◽  
Intervention Group ◽  
Control Group ◽  
Bovine Lactoferrin ◽  
The United Kingdom ◽  
Late Onset Sepsis ◽  
The Uk

Previous studies suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32 weeks gestation) may reduce late onset sepsis (LOS) and necrotising enterocolitis (NEC), but have been underpowered. The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the United Kingdom (UK), aimed to further address this issue with a well powered double blinded placebo controlled trial of >2200 preterm infants. ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. 316 (29%) of 1093 infants in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group with an adjusted risk ratio of 0·95 (95% CI 0·86–1·04; p=0· 233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungals in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in different trials. Further exploration is being undertaken in the UK NIHR funded Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials (MAGPIE) study, for which results should be available soon.

Ohio Statewide Quality-Improvement Collaborative to Reduce Late-Onset Sepsis in Preterm Infants

PEDIATRICS ◽  
2011 ◽  
Vol 127 (3) ◽  
pp. 427-435 ◽  
Author(s):  
H. C. Kaplan ◽  
C. Lannon ◽  
M. C. Walsh ◽  
E. F. Donovan ◽  
Keyword(s):  
Quality Improvement ◽  
Preterm Infants ◽  
Late Onset ◽  
Quality Improvement Collaborative ◽  
Late Onset Sepsis

scholarly journals Cause of preterm birth and late-onset sepsis in very preterm infants: the EPIPAGE-2 cohort study

2021 ◽  
Author(s):  
Mathilde Letouzey ◽  
◽  
Laurence Foix-L’Hélias ◽  
Héloïse Torchin ◽  
Ayoub Mitha ◽  
...  
Keyword(s):  
Cohort Study ◽  
Preterm Birth ◽  
Preterm Infants ◽  
Late Onset ◽  
Very Preterm Infants ◽  
Very Preterm ◽  
Late Onset Sepsis

Impaired Cytokine Responses to Live Staphylococcus epidermidis in Preterm Infants Precede Gram-positive, Late-onset Sepsis

2020 ◽  
Author(s):  
Tobias Strunk ◽  
Julie Hibbert ◽  
Dorota Doherty ◽  
Elizabeth Nathan ◽  
Karen Simmer ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Staphylococcus Epidermidis ◽  
Late Onset ◽  
Gram Positive ◽  
Cytokine Responses ◽  
Inflammatory Protein ◽  
Late Onset Sepsis ◽  
Immunological Mechanisms ◽  
Factor Α

Abstract Background Late-onset sepsis (LOS) with Staphylococcus epidermidis is common in preterm infants, but the immunological mechanisms underlying heightened susceptibility are poorly understood. Our aim is to characterize the ontogeny of cytokine responses to live S. epidermidis in preterm infants with and without subsequent Gram-positive LOS. Methods We conducted a prospective, observational cohort study of preterm infants (&lt;30 weeks gestational age [GA]) with blood sampling on Days 1, 7, 14, 21, and 28 of life. Cytokine responses in peripheral whole blood stimulated with live S. epidermidis were analyzed by 11-plex immunoassay. Results Of 129 infants (mean GA, 26.2 weeks; mean birth weight, 887g), 23 (17.8%) had confirmed LOS with Gram-positive organisms and 15 (11.6%) had clinical sepsis, with median onsets at 13 and 15 days, respectively. Blood cytokine responses to an in vitro S. epidermidis challenge were similar between infected and uninfected infants on Day 1, but diverged thereafter. Infants with subsequent LOS displayed broadly reduced S. epidermidis–induced responses from Day 7 onwards, compared to those who did not develop LOS. This pattern was observed with chemokines (interleukin [IL]-8, monocyte chemotactic protein–1, and macrophage inflammatory protein–1α), pro-inflammatory cytokines (IL-1, IL-6, and tumor necrosis factor–α) and the regulatory cytokine IL-10. Conclusions Cytokine responses to a live S. epidermidis challenge are impaired in infants with LOS and precede the onset of clinical illness. Quantifying pathogen-specific cytokine responses at Day 7 may identify those high-risk preterm infants at the greatest risk of LOS, and prospective replication is warranted.

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