Identification and evaluation of probiotic potential of Bifidobacterium breve AHC3 isolated from chicken intestines and its effect on necrotizing enterocolitis (NEC) in newborn SD rats
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SUBMITTER: Lin X
PROVIDER: S-EPMC10621988 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo develop an animal model which replicates neonatal NEC and characterizes the importance of bacterial fermentation of formula and short chain fatty acids (SCFAs) in its pathogenesis.BackgroundNEC is a severe form of intestinal inflammation in preterm neonates and current models do not reproduce the human condition.MethodsThree groups of newborn piglets: Formula alone (FO), Bacteria alone (E.coli: BO) and E.coli-fermented formula (FF) were anesthetized, instrumented and underwent post-pyloric injection of formula, bacteria or fermented-formula. SCFA levels were measured by gas chromatography-mass spectrometry. At 6 h bowel appearance was assessed, histologic and molecular analysis of intestine were performed. Gut inflammation (p65 NF-κB, TLR4, TNF-α, IL-1β), apoptosis (cleaved caspase-3, BAX, apoptosis) and tight junction proteins (claudin-2, occludin) were measured.ResultsSCFAs were increased in FF. Small bowel from FF piglet's demonstrated inflammation, coagulative necrosis and pneumatosis resembling human NEC. Histologic gut injury (injury score, mast cell activation) were increased by Bacteria, but more severe in FF piglets. Intestinal expression of p65 NF-κB, NF-κB activation, TNF-α and IL-1β were increased in BO and markedly increased in the FF group (P<0.05 vs. FO). Intestine from Bacteria piglets demonstrated increased apoptotic index, pro-apoptotic protein expression and decreased tight junction proteins. These changes were more severe in FF piglets.ConclusionsOur piglet model demonstrates the findings of NEC in human neonates: systemic acidosis, intestinal inflammation, pneumatosis and portal venous gas. Bacteria alone can initiate intestinal inflammation, injury and apoptosis, but bacterial fermentation of formula generates SCFAs which contribute to the pathogenesis of NEC.
| S-EPMC6056052 | biostudies-literature
Project description:ObjectiveBetter measures are needed to identify infants at risk for developing necrotizing enterocolitis (NEC) and facilitate communication about risk across transitions. Although NEC is multi-factorial, quantification of composite risk for NEC in an individual infant is not clearly defined. The objective of this study was to describe the derivation, validation and calibration testing of a novel clinical NEC risk index, GutCheck(NEC). Individual risk factors were weighted to assess composite odds of developing NEC. GutCheck(NEC) is designed to improve communication about NEC risk and coordination of care among clinicians across an infant's clinical course.Study designOn the basis of a synthesis of research evidence about NEC risk and an e-Delphi study including 35 neonatal experts, we identified NEC risk factors believed by the experts to be most relevant for a NEC risk index, then applied a logistic model building process to derive and validate GutCheck(NEC). De-identified data from the Pediatrix BabySteps Clinical Data Warehouse (discharge date 2007 to 2011) were split into three samples for derivation, validation and calibration. By comparing infants with medical NEC, surgical NEC and those who died to infants without NEC, we derived the logistic model using the un-matched derivation set. Discrimination was then tested in a case-control matched validation set and an un-matched calibration set using receiver operating characteristic curves.ResultSampled from a cohort of 58 820 infants, the randomly selected derivation set (n=35 013) revealed nine independent risk factors (gestational age, history of packed red blood cell transfusion, unit NEC rate, late-onset sepsis, multiple infections, hypotension treated with inotropic medications, Black or Hispanic race, outborn status and metabolic acidosis) and two risk reducers (human milk feeding on both days 7 and 14 of life, and probiotics). Unit NEC rate carried the most weight in the summed score. Validation using a 2:1 matched case-control sample (n=360) demonstrated fair to good discrimination. In the calibration set (n=23 447), GutCheck(NEC) scores (range 0 to 58) discriminated those infants who developed surgical NEC (area under the curve (AUC)=0.84, 95% confidence interval (CI) 0.82 to 0.84) and NEC leading to death (AUC=0.83, 95% CI 0.81 to 0.85), more accurately than medical NEC (AUC= 0.72, 95% CI 0.70 to 0.74).ConclusionGutCheck(NEC) represents weighted composite risk for NEC and discriminated infants who developed NEC from those who did not with very good accuracy. We speculate that targeting modifiable NEC risk factors could reduce national NEC prevalence.
| S-EPMC4420242 | biostudies-literature
Project description:BackgroundNecrotizing enterocolitis (NEC) is a disastrous gastrointestinal disease of newborns, and the mortality rate of infants with NEC is approximately 20%-30%. The exploration of pathogenic targets of NEC will be conducive to timely diagnosis of NEC.MethodsThe whole transcriptome RNA sequencing was performed on NEC samples to reveal the expression of lncRNAs, circRNAs, miRNAs and mRNAs. Using differential expression analysis, cross analysis, target prediction, enrichment analysis, the pathogenic ceRNA network and target was found.ResultsPreliminarily, 281 DEmRNAs, 21 DEmiRNAs, 253 DElncRNAs and 207 DEcircRNAs were identified in NEC samples compared with controls. After target prediction and cross analyses, a key ceRNA regulatory network was built including 2 lncRNAs, 4 circRNAs, 2 miRNAs and 20 mRNAs. These 20 mRNAs were significantly enriched in many carbohydrate metabolism related pathways. After cross analysis of hypoxia-, carbohydrate metabolism-related genes, and 20 core genes, one gene HK2 was finally obtained. Dendritic cells activated were significantly differentially infiltrated and negatively correlated with HK2 expression in NEC samples.ConclusionsThe promising pathogenic hypoxia-related gene HK2 has been firstly identified in NEC, which might also involve in the carbohydrate metabolism in NEC.
| S-EPMC9597967 | biostudies-literature
Project description:BackgroundBifidobacterium breve is an obligate anaerobic gram-positive bacillus mainly found in the gastrointestinal tract of human infants. Few cases of necrotizing fasciitis caused by B. breve have been reported.Case presentationA 42-year-old Japanese man with type 2 diabetes mellitus, obesity, cellulitis of the back, and subcutaneous abscess of the right inguinal region presented with rapidly developing erythema, swelling and severe pain in the right inguinal region. Computed tomography showed widespread gas in the right leg region. Cultures of blood and a swab of the wound abscess grew gram-positive bacilli. Mass spectrography and 16 S rDNA analysis confirmed the gram-positive bacilli as B. breve. The patient recovered following extensive debridement and antibacterial therapy.ConclusionUnidentified necrotizing fasciitis can be caused by B. breve, especially in compromised hosts.
| S-EPMC9830150 | biostudies-literature
Project description:Necrotizing Enterocolitis (NEC) is an inflammation causing injury to the bowel in newborns. This project uses a rodent model that mimics the intestinal pathological changes seen in NEC to study the effect of formula feeding and hypoxia on NEC development Keywords: time series, diet, hypoxia
2003-07-16 | GSE491 | GEO
Project description:The effect of MDANP effects on ER stress signalling not well known or elucidated. Endoplasmic reticulum (ER) stress plays a critical role in necrotizing enterocolitis (NEC) pathogenesis through the PERK-eIF2ɑ-QRICH1 axis. The present study aimed to explore the protective effects of MDANP in NEC development. Firstly, a function screening was designed to identify the candidate peptides in human milk, and then the identified peptides were validated in NEC patients. In vivo, NEC was induced in mice pups and divided into four groups: (1) control group, (2) NEC group, (3) MDANP + NEC group, and (4) NS + NEC group. In vitro, lentivirus-mediated QRICH1 silencing, was used to transfect NCM460 cell lines, then stimulated with LPS. After LPS stimulation, cells were treated with chemically synthesized MDANP, and the essential proteins in the QRICH1 signalling pathway in cells were tested and compared. After the small-scale screening, a peptide (SKSKKFRRPDIQYPDATDED) named MDANP was determined as the principal peptide. Its protective effect against NEC through inhibiting the expression of ERS key proteins and impeding the intestinal cells' apoptosis was observed in the animal models. Furthermore, the inhibitive effect of MDANP on apoptosis of intestinal epithelial cells through modulating the PERK-eIF2ɑ-QRICH1 ERS pathway was also confirmed in vitro. Taken together, our data suggest that MDANP effectively ameliorates apoptosis in NEC through attenuating PERK-eIF2ɑ-QRICH1.
| S-EPMC10739873 | biostudies-literature
Project description:Background & aimsSingle immunoglobulin interleukin-1-related receptor (SIGIRR) is a major inhibitor of Toll-like receptor signaling. Our laboratory identified a novel SIGIRR stop mutation (p.Y168X) in an infant who died of severe necrotizing enterocolitis (NEC). Herein, we investigated the mechanisms by which SIGIRR mutations induce Toll-like receptor hyper-responsiveness in the neonatal gut, disrupting postnatal intestinal adaptation.MethodsClustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 was used to generate transgenic mice encoding the SIGIRR p.Y168X mutation. Ileal lysates, mouse intestinal epithelial cell (IEC) lysates, and intestinal sections were used to assess inflammation, signal transducer and activator of transcription 3 (STAT3) phosphorylation, microRNA (miRNA), and interleukin-1-related-associated kinase 1 (IRAK1) expression. Western blot, quantitative reverse-transcription polymerase chain reaction(qRT-PCR), and luciferase assays were performed to investigate SIGIRR-STAT3 signaling in human intestinal epithelial cells (HIEC) expressing wild-type or SIGIRR (p.Y168X) plasmids.ResultsSigirrTg mice showed increased intestinal inflammation and nuclear factor-κB activation concomitant with decreased IEC expression of miR-146a and miR-155. Mechanistic studies in HIECs showed that although SIGIRR induced STAT3-mediated expression of miR-146a and miR-155, the p.Y168X mutation disrupted SIGIRR-mediated STAT3-dependent miRNA expression. Chromatin immunoprecipitation and luciferase assays showed that SIGIRR activation of STAT3-induced miRNA expression is dependent on IRAK1. Both in HIECs and in the mouse intestine, decreased expression of miR-146a observed with the p.Y168X mutation increased expression of IRAK1, a protein whose down-regulation is important for postnatal gut adaptation.ConclusionsOur results uncover a novel pathway (SIGIRR-STAT3-miRNA-IRAK1 repression) by which SIGIRR regulates postnatal intestine adaptation, which is disrupted by a SIGIRR mutation identified in human NEC. These data provide new insights into how human genetic mutations in SIGIRR identified in NEC result in loss of postnatal intestinal immune tolerance.
| S-EPMC8688179 | biostudies-literature
Project description:Necrotizing enterocolitis (NEC) is a complex intestinal disease that primarily affects premature neonates. Given its significant mortality and morbidity, there is an urgent need to develop improved prophylactic measures against the disease. One potential preventative strategy for NEC is the use of probiotics. Although there has been significant interest for decades in probiotics in neonatal care, no clear guidelines exist regarding which probiotic to use or for which patients, and no FDA-approved products exist on the market for NEC. In addition, there is lack of agreement regarding the benefits of probiotics in neonates, as well as some concerns about the safety and efficacy of available products. We discuss currently available probiotics as well as next-generation probiotics and novel delivery strategies which may offer an avenue to capitalize on the benefits of probiotics, while minimizing the risks. Thus, probiotics may still prove to be an effective prevention strategy for NEC, although further product development and research is needed to support use in the preterm population.
| S-EPMC10017871 | biostudies-literature
Project description:This study aimed to investigate the effect of supplementation with the probiotic Bifidobacterium breve M-16V on the maturation of the intestinal and circulating immune system during suckling. In order to achieve this purpose, neonatal Lewis rats were supplemented with the probiotic strain from the 6th to the 18th day of life. The animals were weighed during the study, and faecal samples were obtained and evaluated daily. On day 19, rats were euthanized and intestinal wash samples, mesenteric lymph node (MLN) cells, splenocytes and intraepithelial lymphocytes (IEL) were obtained. The probiotic supplementation in early life did not modify the growth curve and did not enhance the systemic immune maturation. However, it increased the proportion of cells bearing TLR4 in the MLN and IEL, and enhanced the percentage of the integrin αEβ7+ and CD62L+ cells in the MLN and that of the integrin αEβ7+ cells in the IEL, suggesting an enhancement of the homing process of naïve T lymphocytes to the MLN, and the retention of activated lymphocytes in the intraepithelial compartment. Interestingly, B. breve M-16V enhanced the intestinal IgA synthesis. In conclusion, supplementation with the probiotic strain B. breve M-16V during suckling improves the development of mucosal immunity in early life.
| S-EPMC5098803 | biostudies-literature
Project description:Specific intestinal microbiota has been shown to induce Foxp3(+) regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103(+) dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103(+) DCs from Il10(-/-), Tlr2(-/-), and Myd88(-/-) mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103(+) DCs failed to induce IL-10 production from co-cultured Il27ra(-/-) T cells. B. breve treatment of Tlr2(-/-) mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103(+) DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4(+) T cells from wild-type mice, but not Il10(-/-) mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells.
| S-EPMC3364948 | biostudies-literature