Integrated analysis of microbiota with bile acids for the phototherapy treatment of neonatal jaundice.

Introduction: Infant jaundice is a common condition which results from a high concentration of serum bilirubin. Phototherapy is a widely used treatment for bilirubin clearance. We analyzed the effect of phototherapy on intestinal flora and metabolism of newborns. The aim was to assess the benefit of treatment for hyperbilirubinemia with phototherapy. Material and methods: Fifty-three jaundiced infants hospitalized at our neonatal intensive care unit were treated with phototherapy. Of them, 29 were prescribed antibiotics during the hospitalization. Fecal samples were collected before and 24 h and 48 h after phototherapy. The bacterial species and relative abundance were identified with Macrogene sequencing. The bile acids in feces were identified using liquid chromatography-mass spectroscopy (LC-MS). Results: Differential microbial species/genera and secondary bile acids were found after phototherapy. There are significant differences in the changes of the microbial species/genera between infants who did not receive antibiotic treatment and those who were given antibiotic treatment. Secondary bile acids were also significantly altered. At the same time, the differential microbial species/genera and the differential secondary bile acids interacted with each other. Conclusions: This study identified several differential intestinal microbial species and secondary bile acids in fecal samples from infants with jaundice before and after phototherapy. Phototherapy can change the flora and its metabolism and its long-term impact needs further observation.

Analysis of the effect of phototherapy on intestinal probiotics and metabolism in newborns with jaundice.

Background: In clinical practice, oral probiotics are often given to children with hyperbilirubinaemia who receive phototherapy, but the exact mechanism of the action of the probiotics on hyperbilirubinaemia remains unclear. It is unclear how the effects of phototherapy on the probiotic flora in the neonatal gut, in particular. Materials and methods: Fifty newborns who needed phototherapy from June 2018 to June 2020 were selected as the study subjects, and five healthy newborns in the same period were used as controls to analyse the changes in probiotic bacteria in their faeces. Results: 1. In the intestinal tracts of newborns, Bifidobacterium is the main probiotic strain, with a small amount of Lactobacillus. There were probiotic species changes in the neonatal intestinal microbiota after phototherapy for 24 and 48 h. The amount of Bifidobacterium and Lactobacillus decreased significantly (P < 0.05). 2. A correlation analysis of probiotic species and bile acid metabolism indexes showed that Bifidobacterium was positively correlated with many metabolites (P < 0.05), such as chenodeoxycholic acid, hyodeoxycholic acid, cholic acid, allocholic acid, and ß-cholic acid. It was also negatively correlated with many metabolites (P < 0.05), such as glycocholic acid, sodium, sodium tudca, and chenodeoxycholic acid. Lactobacillus was negatively correlated with metabolites (P < 0.05) such as α-sodium cholate and ß-cholic acid. 3. A correlation analysis between the changes in probiotics and intestinal short-chain fatty acid metabolites after phototherapy showed that acetic acid, butyric acid, caproic acid, and propionic acid decreased and were significantly correlated with Bifidobacterium (P < 0.05). 4. After phototherapy, 17 metabolites changed significantly (P < 0.05). This correlated with many probiotics (P < 0.05). The significantly changed probiotics in this study showed a significant correlation with some intestinal metabolites (P < 0.05). Conclusion: It was found that phototherapy can significantly affect the intestinal probiotic flora and the metabolic indicators of newborns, which may be an important reason for the side effects of phototherapy, and also provides the theoretical basis for the provision of probiotics to newborns with jaundice.

Blockade of NLRP3/Caspase-1/IL-1ß Regulated Th17/Treg Immune Imbalance and Attenuated the Neutrophilic Airway Inflammation in an Ovalbumin-Induced Murine Model of Asthma.

Asthma is a heterogeneous inflammatory disorder of the airways, and multiple studies have addressed the vital role of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/caspase-1/interleukin-1ß (IL-1ß) pathway in asthma, but its impact on ovalbumin- (OVA-) induced neutrophilic asthma remains unclear. Here, we explored this pathway's effect on airway inflammation in neutrophilic asthma to clarify whether blocking this signaling could alleviate asthmatic airway inflammation. Using an established OVA-induced neutrophilic asthma mouse model, we provided asthmatic mice with a highly selective NLRP3 inhibitor, MCC950, and a specific caspase-1 inhibitor, Ac-YVAD-cmk. Our results indicated that asthmatic mice exhibited increased airway hyperresponsiveness, neutrophil infiltration, and airway mucus hypersecretion, upregulated retinoid-related orphan receptor-γt (RORγt) mRNA expression, and downregulated fork head box p3 (Foxp3) mRNA expression, which was concurrent with NLRP3 inflammasome activation and upregulation of caspase-1, IL-1ß, and IL-18 expression in lung. Treatment of NLRP3 inflammasome inhibitors significantly attenuated airway hyperresponsiveness, airway inflammation, and reversed T helper 17 (Th17)/regulatory T (Treg) cell imbalance in asthmatic mice. We propose that the NLRP3/caspase-1/IL-1ß pathway plays an important role in the pathological process of neutrophilic asthma and provides evidence that blocking this pathway could potentially be a treatment strategy to ameliorate airway inflammation in asthma after validation with future experimental and clinical studies.

Characteristics of the intestinal microbiota and metabolism in infants with extrauterine growth restriction.

BACKGROUND: Infants with extrauterine growth restriction (EUGR) experience significant postnatal growth restriction in the first week after birth, which indicates a failure of energy absorption. This study aimed to determine the different intestinal microbial species and metabolites between infants with EUGR and those without EUGR. METHODS: A total of 73 infants hospitalized in a neonatal intensive care unit were enrolled and divided into the EUGR group (n=50) and the non-EUGR group (n=23). Fecal samples were collected during hospitalization. Bacterial species and their relative abundance were identified with metagenome sequencing. The metabolites in the feces and blood were identified with a liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolome. RESULTS: The intestinal microbiota of the EUGR group contained less Bacteroides vulgatus, Dorea unclassified, Lachnospiraceae bacterium 1_1_57FAA, and Roseburia unclassified compared to that of the non-EUGR group. More importantly, the intestinal microbiota of the EUGR group contained Streptococcus mitis_oralis_pneumoniae, while that of the non-EUGR group did not. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) prediction and a correlation analysis identified that the majority of different microbial species higher in the non-EUGR group were related to metabolism. The results of the non-targeted metabolome revealed that several metabolites in the feces and blood were much higher in either group, and some of which were related to the different microbial species. CONCLUSIONS: This study identified several different intestinal microbial species and metabolites in the patients' feces and blood, which may provide evidence to identify the biomarkers of infants with EUGR.

Saccharomyces boulardii modulates necrotizing enterocolitis in neonatal mice by regulating the sirtuin 1/NF­κB pathway and the intestinal microbiota.

Exaggerated inflammatory response and gut microbial dysbiosis play a crucial role in necrotizing enterocolitis (NEC). The probiotic Saccharomyces boulardii (SB) is a yeast that has a beneficial effect on NEC; however, the association between its protective effects and the regulation of the inflammation­related sirtuin 1 (SIRT1)/nuclear factor­κB (NF­κB) signaling pathway and gut microbiota in NEC is unknown. In the present study, the NEC model was established by artificial feeding and lipopolysaccharide (LPS), hypoxia and hypothermia stimulation. Mice were divided into normal, control (artificial feeding), NEC and NEC + SB groups. Hematoxylin and eosin staining demonstrated that SB improved the pathological damage of the intestine caused by NEC in neonatal mice. Furthermore, downregulation of SIRT1 and upregulation of NF­κB expression were confirmed by immunofluorescence staining, western blotting and reverse transcription­quantitative PCR (RT­qPCR) in NEC mice. SB treatment concurrently inhibited the NEC roles on the SIRT1 and NF­κB pathway at both the protein and mRNA levels. Deletion of SIRT1 [SIRT1 knockout (KO)] in the intestine abolished all the effects of SB in NEC mice, including protection of pathological damage and inhibition of the SIRT1/NF­κB pathway activation. The abundance of gut microbial composition, as determined by RT­qPCR, was significantly decreased in the control group compared with the normal group. A further decrease in microbiota abundance was observed in the NEC group, and SB administration significantly improved the enrichment of gut microbiota in neonatal mice with NEC. As anticipated, the increased abundance of gut microbiota modulated by SB was markedly reduced in SIRT1KO NEC mice. The present study revealed that the protective role of SB on NEC was associated with the SIRT1/NF­κB pathway and gut microbiota regulation.