scholarly journals Lactobacillus reuteri in Its Biofilm State Improves Protection from Experimental Necrotizing Enterocolitis

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 918
Author(s):  
Ameer Al-Hadidi ◽  
Jason Navarro ◽  
Steven D. Goodman ◽  
Michael T. Bailey ◽  
Gail E. Besner
Keyword(s):  
Patient Outcomes ◽  
Necrotizing Enterocolitis ◽  
Premature Infants ◽  
Broad Spectrum ◽  
Lactobacillus Reuteri ◽  
Experimental Models ◽  
Significant Morbidity ◽  
Delivery Methods ◽  
Bowel Rest ◽  
Gastrointestinal Dysbiosis

Necrotizing enterocolitis (NEC) is a devastating disease predominately found in premature infants that is associated with significant morbidity and mortality. Despite decades of research, medical management with broad spectrum antibiotics and bowel rest has remained relatively unchanged, with no significant improvement in patient outcomes. The etiology of NEC is multi-factorial; however, gastrointestinal dysbiosis plays a prominent role in a neonate’s vulnerability to and development of NEC. Probiotics have recently emerged as a new avenue for NEC therapy. However, current delivery methods are associated with potential limitations, including the need for at least daily administration in order to obtain any improvement in outcomes. We present a novel formulation of enterally delivered probiotics that addresses the current limitations. A single enteral dose of Lactobacillus reuteri delivered in a biofilm formulation increases probiotic survival in acidic gastric conditions, increases probiotic adherence to gastrointestinal epithelial cells, and reduces the incidence, severity, and neurocognitive sequelae of NEC in experimental models.

scholarly journals Apical sodium-dependent bile acid transporter upregulation is associated with necrotizing enterocolitis

2010 ◽  
Vol 299 (3) ◽  
pp. G623-G631 ◽  
Author(s):  
Melissa D. Halpern ◽  
Jörn-Hendrik Weitkamp ◽  
Sarah K. Mount Patrick ◽  
Holly J. Dobrenen ◽  
Ludmila Khailova ◽  
...  
Keyword(s):  
Necrotizing Enterocolitis ◽  
Premature Infants ◽  
Experimental Models ◽  
Farnesoid X Receptor ◽  
Therapeutic Modality ◽  
Receptor Protein ◽  
Disease Development ◽  
Mrna Levels ◽  
Sodium Dependent ◽  
Gastrointestinal Emergency

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants. Previously, we showed that luminal bile acids (BAs) are increased and correlated with disease development and that the apical sodium-dependent BA transporter (ASBT), which transports BAs from the ileal lumen into enterocytes, is upregulated in rats with NEC. We hypothesized that intraenterocyte, rather than luminal, BAs are associated with NEC and that upregulation of ASBT may be a mechanism by which this occurs. Neonatal rats with or without the ASBT inhibitor SC-435, mice in which ASBT was knocked out, and mice that overproduce BAs were subjected to the NEC protocol. Disease development, ASBT, and the farnesoid X receptor protein, along with luminal and intraenterocyte BA levels, were assessed. In addition, ileal sections from premature infants with and without NEC were examined for ASBT via immunohistology and real-time PCR. When BAs were not transported into enterocytes (rats given SC-435 and ASBT knockout mice), severity and incidence of NEC were reduced. In contrast, in mice that overproduce BAs, ASBT was elevated, intraenterocyte BAs were increased, and disease development was increased. ASBT staining was more intense on the apical membrane of ileal enterocytes from premature infants with NEC than premature infants with non-NEC diagnoses. In addition, ASBT mRNA levels were significantly higher in infants with NEC. These data show that accumulation of intraenterocyte BAs contributes to disease development, elevated ASBT increases disease severity in experimental models of NEC, and ASBT is elevated in human NEC. These data confirm that BAs and upregulation of ASBT play a crucial role in NEC pathogenesis and suggest that inhibition of ASBT could be utilized as a therapeutic modality against this disease.

scholarly journals Trends in Antibiotic Prescribing in Out-of-Hours Primary Care in England from January 2016 to June 2020 to Understand Behaviours during the First Wave of COVID-19

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 32
Author(s):  
Nina J. Zhu ◽  
Monsey McLeod ◽  
Cliodna A. M. McNulty ◽  
Donna M. Lecky ◽  
Alison H. Holmes ◽  
...  
Keyword(s):  
Primary Care ◽  
Time Series ◽  
Patient Outcomes ◽  
Broad Spectrum ◽  
Antibiotic Prescribing ◽  
Broad Spectrum Antibiotic ◽  
Out Of Hours ◽  
Broad Spectrum Antibiotics ◽  
National Quality ◽  
General Practices

We describe the trend of antibiotic prescribing in out-of-hours (OOH) general practices (GP) before and during England’s first wave of the COVID-19 pandemic. We analysed practice-level prescribing records between January 2016 to June 2020 to report the trends for the total prescribing volume, prescribing of broad-spectrum antibiotics and key agents included in the national Quality Premium. We performed a time-series analysis to detect measurable changes in the prescribing volume associated with COVID-19. Before COVID-19, the total prescribing volume and the percentage of broad-spectrum antibiotics continued to decrease in-hours (IH). The prescribing of broad-spectrum antibiotics was higher in OOH (OOH: 10.1%, IH: 8.7%), but a consistent decrease in the trimethoprim-to-nitrofurantoin ratio was observed OOH. The OOH antibiotic prescribing volume diverged from the historical trend in March 2020 and started to decrease by 5088 items per month. Broad-spectrum antibiotic prescribing started to increase in OOH and IH. In OOH, co-amoxiclav and doxycycline peaked in March to May in 2020, which was out of sync with seasonality peaks (Winter) in previous years. While this increase might be explained by the implementation of the national guideline to use co-amoxiclav and doxycycline to manage pneumonia in the community during COVID-19, further investigation is required to see whether the observed reduction in OOH antibiotic prescribing persists and how this reduction might influence antimicrobial resistance and patient outcomes.

scholarly journals Lactobacillus reuteri DSM 17938 differentially modulates effector memory T cells and Foxp3+ regulatory T cells in a mouse model of necrotizing enterocolitis

2014 ◽  
Vol 307 (2) ◽  
pp. G177-G186 ◽  
Author(s):  
Yuying Liu ◽  
Dat Q. Tran ◽  
Nicole Y. Fatheree ◽  
J. Marc Rhoads
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Necrotizing Enterocolitis ◽  
Lactobacillus Reuteri ◽  
Intestinal Inflammation ◽  
Treg Cells ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Mesenteric Lymph Nodes ◽  
Mesenteric Lymph

Necrotizing enterocolitis (NEC) is an inflammatory disease with evidence of increased production of proinflammatory cytokines in the intestinal mucosa. Lactobacillus reuteri DSM 17938 (LR17938) has been shown to have anti-inflammatory activities in an experimental model of NEC. Activated effector lymphocyte recruitment to sites of inflammation requires the sequential engagement of adhesion molecules such as CD44. The phenotype of CD44+CD45RBlo separates T effector/memory (Tem) cells from naive (CD44−CD45RBhi) cells. It is unknown whether these Tem cells participate in the inflammation associated with NEC and can be altered by LR17938. NEC was induced in 8- to 10-day-old C57BL/6J mice by gavage feeding with formula and exposure to hypoxia and cold stress for 4 days. Survival curves and histological scores were analyzed. Lymphocytes isolated from mesenteric lymph nodes and ileum were labeled for CD4, CD44, CD45RB, intracellular Foxp3, and Helios and subsequently analyzed by flow cytometry. LR17938 decreased mortality and the incidence and severity of NEC. The percentage of Tem cells in the ileum and mesenteric lymph nodes was increased in NEC but decreased by LR17938. Conversely, the percentage of CD4+Foxp3+ regulatory T (Treg) cells in the intestine decreased during NEC and was restored to normal by LR17938. The majority of the Treg cells preserved by LR17938 were Helios+ subsets, possibly of thymic origin. In conclusion, LR17938 may represent a useful treatment to prevent NEC. The mechanism of protection by LR17938 involves modulation of the balance between Tem and Treg cells. These T cell subsets might be potential biomarkers and therapeutic targets during intestinal inflammation.

Carbohydrate Malabsorption in Necrotizing Enterocolitis

PEDIATRICS ◽  
1976 ◽  
Vol 57 (2) ◽  
pp. 201-204
Author(s):  
Linda Sue Book ◽  
John J. Herbst ◽  
August L. Jung
Keyword(s):  
Necrotizing Enterocolitis ◽  
Premature Infants ◽  
Clinical Symptoms ◽  
Advanced Disease ◽  
Full Term ◽  
Term Infants ◽  
Stool Specimens ◽  
Reducing Substances ◽  
Carbohydrate Intolerance ◽  
Prospective Investigation

A prospective investigation was conducted to determine if infants with necrotizing enterocolitis had evidence of carbohydrate intolerance prior to the onset of clinical symptoms of advanced disease. Stool specimens were examined for fecal reducing substances with Clintest tablets from well, full-term infants and sick premature infants. Only two of 45 (4.4%) formula-fed, full-term infants demonstrated higher than 2 + fecal reducing substances. Ten of 14 (71%) formula-fed premature infants who developed necrotizing enterocolitis had higher than 2 + reducing substances detected in their stools. Daily measurement of fecal reducing substances can be a useful adjunct in the management of sick premature infants.

scholarly journals Experimental Modeling of Necrotizing Enterocolitis: Pathogenesis, Predictors, Prevention of the Disease

2020 ◽  
Vol 13 (3) ◽  
pp. 293-300
Author(s):  
Irina Karpova ◽  
Daria Molchanova ◽  
Tatiana Ladygina
Keyword(s):  
Necrotizing Enterocolitis ◽  
Systemic Disease ◽  
Interleukin 1 ◽  
Bacterial Flora ◽  
Experimental Studies ◽  
Experimental Models ◽  
Current Data ◽  
Experimental Modeling ◽  
Antibacterial Drug ◽  
The Impact

Introduction. The incidence rate of necrotizing enterocolitis is 2.4:1000 of newborns. The number of complications reaches 51-68%, and mortality rate varies from 4 to 80%. The aim of the study was to present current data of Russian and foreign experimental studies related to necrotizing enterocolitis in children. Results. Currently, infants with low and very low body weight constitute the most proportion of patients with enterocolitis; the development of the disease in this cohort of patients has its distinctive features. In this regard, the issues of pathogenesis, the impact of risk factors and methods of prevention of the pathological process remain underinvestigated. Experimental models were used to study the features of the toll-interleukin 1 receptor domain containing adapter protein (TIRAP), the etiology of Toll-like receptor 4 expression, and the reasons for the increased levels of inflammatory mediators. The mechanism of intestinal-brain reciprocal communication was confirmed. The role of the bacterial flora and effectiveness of the antibacterial drug effect on this flora was also determined. Biomarkers of enterocolitis, such as an epidermal growth factor, interleukins, claudins 2, 3, 4, were detected using experimental modeling. Various options for disease prevention ranging from ischemic preconditioning to probiotics application and breastfeeding were analyzed, the latter ones having beneficial ability to form natural defenses in newborns. Conclusions. Thus, necrotizing enterocolitis is a severe systemic disease. Experimental modeling allows analyzing the most complex, unsolved problems and introducing novel knowledge into clinical practice.

scholarly journals Influence of Family Integrated Care on the Intestinal Microbiome of Preterm Infants With Necrotizing Enterocolitis and Enterostomy: A Preliminary Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Mengyang Yang ◽  
Juan Du ◽  
Qin Yang ◽  
Wenyan Dou ◽  
Min Jiang ◽  
...  
Keyword(s):  
Integrated Care ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Premature Infants ◽  
Intestinal Flora ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Α Diversity ◽  
Family Integrated Care ◽  
Family Integrated

The aim of this study was to investigate the influence of family integrated care (FICare) on the intestinal microbiome of preterm infants with necrotizing enterocolitis and enterostomy. This was a prospective pilot study at Beijing Children's Hospital. Premature infants with an enterostomy who met the enrollment criteria were divided into the 2-week FICare and non-FICare groups (non-randomly). We collected their fecal samples and subjected the intestinal microbiomes to 16S rRNA gene sequencing. Operational taxonomic units (OTU) were analyzed to assess the intestinal microbiome richness, and we then carried out α-diversity, β-diversity, and species clustering analyses and a linear discriminant analysis (LDA) effect size (LEfSe) analysis to identify the differences in the microbial communities between the two groups. There were 12 patients enrolled in the study (FICare, n = 7; non-FICare, n = 5). There were no significant between-group differences in demographic characteristics, or in the relative abundances of phyla and genera. The major bacterial phyla were Proteobacteria, Firmicutes, and Actinobacteria, and Serratia, Enterococcus, Cronobacter, and Bifidobacterium dominated at the genus level. The α-diversity analysis indicated that the intestinal flora was more diverse in the non-FICare group than the FICare group (p < 0.05). However, most of the other indicators did not suggest a difference between the two groups. There was a high proportion of shared OTUs between the two groups, and the PCoA and clustering analyses indicated that the two groups were difficult to distinguish, indicating that the intestinal microbiomes were relatively similar between the groups. In summary, short-term FICare had no significant positive effect on the establishment of intestinal flora diversity in premature infants with necrotizing enterocolitis and enterostomy. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-OPN-17011801).

scholarly journals Protective effect of Lactobacillus reuteri DSM 17938 against experimental necrotizing enterocolitis is mediated by Toll-like receptor 2

2018 ◽  
Vol 315 (2) ◽  
pp. G231-G240 ◽  
Author(s):  
Thomas K. Hoang ◽  
Baokun He ◽  
Ting Wang ◽  
Dat Q. Tran ◽  
J. Marc Rhoads ◽  
...  
Keyword(s):  
T Cells ◽  
Necrotizing Enterocolitis ◽  
Immune Modulation ◽  
Lactobacillus Reuteri ◽  
Inflammatory Responses ◽  
Cow Milk ◽  
Toll Like Receptor ◽  
Toll Like Receptor 2 ◽  
Anti Inflammatory

Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to reduce the incidence and severity of necrotizing enterocolitis (NEC). It is unclear if preventing NEC by LR 17938 is mediated by Toll-like receptor 2 (TLR2), which is known to mediate proinflammatory responses to bacterial cell wall components. NEC was induced in newborn TLR2−/− or wild-type (WT) mice by the combination of gavage-feeding cow milk-based formula and exposure to hypoxia and cold stress. Treatment groups were administered formula supplemented with LR 17938 or placebo (deMan-Rogosa-Sharpe media). We observed that LR 17938 significantly reduced the incidence of NEC and reduced the percentage of activated effector CD4+T cells, while increasing Foxp3+ regulatory T cells in the intestinal mucosa of WT mice with NEC, but not in TLR2−/− mice. Dendritic cell (DC) activation by LR 17938 was mediated by TLR2. The percentage of tolerogenic DC in the intestine of WT mice was increased by LR 17938 treatment during NEC, a finding not observed in TLR2−/− mice. Furthermore, gut levels of proinflammatory cytokines IL-1β and IFN-γ were decreased after treatment with LR 17938 in WT mice but not in TLR2−/− mice. In conclusion, the combined in vivo and in vitro findings suggest that TLR2 receptors are involved in DC recognition and DC-priming of T cells to protect against NEC after oral administration of LR 17938. Our studies further clarify a major mechanism of probiotic LR 17938 action in preventing NEC by showing that neonatal immune modulation of LR 17938 is mediated by a mechanism requiring TLR2. NEW & NOTEWORTHY Lactobacillus reuteri DSM 17938 (LR 17938) has been shown to protect against necrotizing enterocolitis (NEC) in neonates and in neonatal animal models. The role of Toll-like receptor 2 (TLR2) as a sensor for gram-positive probiotics, activating downstream anti-inflammatory responses is unclear. Our current studies examined TLR2 −/− mice subjected to experimental NEC and demonstrated that the anti-inflammatory effects of LR 17938 are mediated via a mechanism requiring TLR2.

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