Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-analysis of Randomized Trials

Morgan, Rebecca L.; Preidis, Geoffrey A.; Kashyap, Purna C.; Weizman, Adam V.; Sadeghirad, Behnam; Chang, Yaping; Flórez, Iván D.; Foroutan, Farid; Shahid, Shaneela; Zeraatkar, Dena

doi:10.1053/j.gastro.2020.05.096

Cited by 158 publications

(147 citation statements)

References 84 publications

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“…and one or more Bifidobacterium spp , both probiotic formulation fulfill the criteria of a probiotic regimen with moderate to high-quality evidence of reduced all-cause mortality as recently shown in a large metaanalysis. 7 The viability of the probiotic strains within the two products and the absence of contaminating bacteria were confirmed by culture; the identity of the respective bacterial strains was confirmed by sequencing. Sequencing also confirmed the different subspecies of the two Bifidobacterium longum strains (subsp.…”

Section: Methodsmentioning

confidence: 97%

“…Oral administration of probiotic bacteria to preterm neonates was reported to decrease the all-cause mortality and in particular the incidence of NEC in a number of studies. 6 , 7 Despite these promising results and the subsequent routine probiotic administration to preterm neonates in some institutions, 8 , 9 the precise influence of the administered probiotic bacteria on the existing microbial ecosystem during and following the intervention has remained incompletely understood. In particular, this relates to the selection and comparative analysis of probiotic strains and formulations, the persistence of the administered probiotic bacteria as well as their influence on the preexisting colonizing bacteria.…”

Section: Introductionmentioning

confidence: 99%

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Influence of probiotic supplementation on the developing microbiota in human preterm neonates

et al. 2020

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Background Oral administration of probiotic bacteria to preterm neonates has been recommended to prevent the development of necrotizing enterocolitis (NEC). The influence of probiotics on the endogenous microbiome, however, has remained incompletely understood. Study design & methods Here, we performed an observational study including 80 preterm neonates born at a gestational age <32-weeks to characterize the persistence of probiotic bacteria after no treatment or oral administration of two different probiotic formula and their influence on the microbial ecosystem during and after the intervention and their association with the development of NEC. Weekly fecal samples were profiled by 16S rRNA sequencing and monitored for the presence of the probiotic bacteria by quantitative PCR. Results Microbiota profiles differed significantly between the control group and both probiotic groups. Probiotic supplementation was associated with lower temporal variation as well as higher relative abundance of Bifidobacterium and Enterobacter combined with reduced abundance of Escherichia, Enterococcus , and Klebsiella . Colonization by probiotic bifidobacteria was observed in approximately 50% of infants although it remained transient in the majority of cases. A significantly reduced monthly incidence of NEC was observed in neonates supplemented with probiotics. Conclusion Our results demonstrate successful transient colonization by probiotic bacteria and a significant influence on the endogenous microbiota with a reduced abundance of bacterial taxa associated with the development of NEC. These results emphasize that probiotic supplementation may allow targeted manipulation of the enteric microbiota and confer a clinical benefit. (Clinical Trial Registry accession number: DRKS/GCTR 00021034)

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Section: Methodsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Influence of probiotic supplementation on the developing microbiota in human preterm neonates

et al. 2020

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“…Olsen and colleagues provided a systematic review and meta-analysis of 12 studies comprising 10,800 preterm or low birth weight infants receiving prophylaxis with primarily combination strains containing Lactobacillus and Bifidobacterium who experienced a significantly decreased risk of NEC (RR = 0.55, 95% CI, 0.39–0.78; p = 0.0006) and overall mortality (RR = 0.72, 95% CI, 0.61–0.85; p < 0.0001) when compared to healthy controls [ 61 ], supporting the growing evidence for probiotics as a preventative strategy in NEC. A recent large network meta-analysis of 63 RCTs and 15,712 preterm, low birth weight infants compared the effectiveness of single versus multiple strain probiotics [ 62 ]. This meta-analysis concluded that a combination of one or greater strains of Lactobacillus species and one or greater strains of Bifidobacterium species are the most efficacious in the prevention of all-cause mortality and NEC Bell stage 2 [ 62 ].…”

Section: Probiotics and The Preterm Infant Microbiomementioning

confidence: 99%

“…A recent large network meta-analysis of 63 RCTs and 15,712 preterm, low birth weight infants compared the effectiveness of single versus multiple strain probiotics [ 62 ]. This meta-analysis concluded that a combination of one or greater strains of Lactobacillus species and one or greater strains of Bifidobacterium species are the most efficacious in the prevention of all-cause mortality and NEC Bell stage 2 [ 62 ]. Additional evidence suggested that Bacillus species, Enterococcus species, Bifidobacterium species, and S. thermophilus are also effective in preventing stage 2 NEC [ 62 ].…”

Section: Probiotics and The Preterm Infant Microbiomementioning

confidence: 99%

The Role of Human Milk Oligosaccharides and Probiotics on the Neonatal Microbiome and Risk of Necrotizing Enterocolitis: A Narrative Review

2020

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Preterm infants are a vulnerable population at risk of intestinal dysbiosis. The newborn microbiome is dominated by Bifidobacterium species, though abnormal microbial colonization can occur by exogenous factors such as mode of delivery, formula feeding, and exposure to antibiotics. Therefore, preterm infants are predisposed to sepsis and necrotizing enterocolitis (NEC), a fatal gastrointestinal disorder, due to an impaired intestinal barrier, immature immunity, and a dysbiotic gut microbiome. Properties of human milk serve as protection in the prevention of NEC. Human milk oligosaccharides (HMOs) and the microbiome of breast milk are immunomodulatory components that provide intestinal homeostasis through regulation of the microbiome and protection of the intestinal barrier. Enteral probiotic supplements have been trialed to evaluate their impact on establishing intestinal homeostasis. Here, we review the protective role of HMOs, probiotics, and synbiotic combinations in protecting a vulnerable population from the pathogenic features associated with necrotizing enterocolitis.

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“…Accordingly, these fluids contain bioactive factors that inhibit TLR4-mediated epithelial injury, reduce inflammatory signaling integral to NEC pathogenesis, and support intestinal maturation (25,26). Similarly, probiotic administration has yielded promising results in establishing a healthy microbiome, supporting epithelial development, and reducing NEC incidence (28,50). These protective pathways have led to new potential prophylactic strategies to reduce the risk of NEC onset.…”

Section: Introductionmentioning

confidence: 99%

Human placental-derived stem cell therapy ameliorates experimental necrotizing enterocolitis and supports restoration of the intestinal stem cell niche

Weis

Deal

Mekkey

et al. 2020

Preprint

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Necrotizing enterocolitis (NEC), a life-threatening intestinal disease, is becoming a larger proportionate cause of morbidity and mortality in premature infants. To date, therapeutic options remain elusive. Based on recent cell therapy studies, we investigated the effect of a human placental-derived stem cell (hPSC) therapy on intestinal damage in an experimental NEC rat pup model. NEC was induced in newborn Sprague-Dawley rat pups for 4 days via formula feeding, hypoxia, and LPS. NEC pups received intraperitoneal (ip) injections of either saline or hPSC (NEC-hPSC) at 32 and 56 hours into NEC induction. At 4 days, intestinal macroscopic and histological damage, epithelial cell composition, and inflammatory marker expression of the ileum was assessed. Breastfed (BF) littermates were used as controls. NEC pups developed significant bowel dilation and fragility in the ileum. Further, NEC induced loss of normal villi-crypt morphology, disruption of epithelial proliferation and apoptosis, and loss of Paneth cells and LGR5+ stem cells in the crypt. hPSC treatment improved macroscopic intestinal health with reduced ileal dilation and fragility. Histologically, hPSC administration had a significant reparative effect on the villi-crypt morphology and epithelium. In addition to a trend of decreased inflammatory marker expression, hPSC-NEC pups had increased epithelial proliferation and decreased apoptosis when compared to NEC littermates. Further, the intestinal stem cell niche of Paneth cells and LGR5+ stem cells was increased with hPSC therapy. Together, these data demonstrate hPSC can promote epithelial healing of NEC intestinal damage in part through support of the intestinal stem cell niche.New and NoteworthyThese studies demonstrate a human placental-derived stem cell (hPSC) therapeutic strategy for necrotizing enterocolitis (NEC). In an experimental model of NEC, hPSC administration improved macroscopic intestinal health, ameliorated epithelial morphology, and supported the intestinal stem cell niche. Our data suggest that hPSC are a potential therapeutic approach to attenuate established intestinal NEC damage. Further, we show hPSC are a novel research tool that can now be utilized to elucidate critical neonatal repair mechanisms to overcome NEC disease.

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Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-analysis of Randomized Trials

Cited by 158 publications

References 84 publications

Influence of probiotic supplementation on the developing microbiota in human preterm neonates

Influence of probiotic supplementation on the developing microbiota in human preterm neonates

The Role of Human Milk Oligosaccharides and Probiotics on the Neonatal Microbiome and Risk of Necrotizing Enterocolitis: A Narrative Review

Human placental-derived stem cell therapy ameliorates experimental necrotizing enterocolitis and supports restoration of the intestinal stem cell niche

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