Gut-lung axis and asthma: A historical review on mechanism and future perspective.

BACKGROUND: Gut microbiota are closely related to the development and regulation of the host immune system by regulating the maturation of immune cells and the resistance to pathogens, which affects the host immunity. Early use of antibiotics disrupts the homeostasis of gut microbiota and increases the risk of asthma. Gut microbiota actively interact with the host immune system via the gut-lung axis, a bidirectional communication pathway between the gut and lung. The manipulation of gut microbiota through probiotics, helminth therapy, and fecal microbiota transplantation (FMT) to combat asthma has become a hot research topic. BODY: This review mainly describes the current immune pathogenesis of asthma, gut microbiota and the role of the gut-lung axis in asthma. Moreover, the potential of manipulating the gut microbiota and its metabolites as a treatment strategy for asthma has been discussed. CONCLUSION: The gut-lung axis has a bidirectional effect on asthma. Gut microecology imbalance contributes to asthma through bacterial structural components and metabolites. Asthma, in turn, can also cause intestinal damage through inflammation throughout the body. The manipulation of gut microbiota through probiotics, helminth therapy, and FMT can inform the treatment strategies for asthma by regulating the maturation of immune cells and the resistance to pathogens.

Multi-omics analyses of gut microbiota via 16S rRNA gene sequencing, LC-MS/MS and diffusion tension imaging reveal aberrant microbiota-gut-brain axis in very low or extremely low birth weight infants with white matter injury.

OBJECTIVE: The goal of this study was to comprehensively investigate the characteristics of gut microbiota dysbiosis and metabolites levels in very low or extremely low birth weight (VLBW/ELBW) infants with white matter injury (WMI). METHODS: In this prospective cohort study, preterm infants with gestational age < 32 weeks and weight < 1.5 kg were investigated. Additionally, fecal samples were collected on days zero, 14d and 28d after admission to the intensive care unit. All subjects underwent brain scan via MRI and DTI at a corrected gestational age of 37 ~ 40 weeks. Based on the results of MRI examination, the VLBW/ELBW infants were divided into two groups: WMI and non-WMI. Finally, based on a multi-omics approach, we performed 16S rRNA gene sequencing, LC-MS/MS, and diffusion tension imaging to identify quantifiable and informative biomarkers for WMI. RESULT: We enrolled 23 patients with and 48 patients without WMI. The results of 16S RNA sequencing revealed an increase in the number of Staphylococcus and Acinetobacter species in the fecal samples of infants with WMI, as well as increasing levels of S. caprae and A._johnsonii. LEfSe analysis (LDA ≥ 4) showed that the WMI group carried an abundance of Staphylococcus species including S. caprae, members of the phyla Bacteroidota and Actinobacteriota, and Acinetobacter species. A total of 139 metabolic markers were significantly and differentially expressed between WMI and nWMI. KEGG pathway enrichment analysis revealed that the WMI group showed significant downregulation of 17 metabolic pathways including biosynthesis of arginine and primary bile acids. The WMI group showed delayed brain myelination, especially in the paraventricular white matter and splenium of corpus callosum. Staphylococcus species may affect WMI by downregulating metabolites such as cholic acid, allocholic acid, and 1,3-butadiene. Gut microbiota such as Acinetobacter and Bacteroidetes may alter white matter structurally by upregulating metabolites such as cinobufagin. CONCLUSION: Based on 16S RNA sequencing results, severe gut microbiota dysbiosis was observed in the WMI group. The results might reveal damage to potential signaling pathways of microbiota-gut-brain axis in gut microbiota. The mechanism was mediated via downregulation of the bile acid biosynthetic pathway.

Antenatal steroid as an independent risk factor for vitamin K2 deficiency in newborns: A Chinese single-center, retrospective study.

OBJECTIVES: To identified vitamin K2 deficiency rate and risk factors among newborns in China and assess the importance of high-risk maternal intakes of vitamin K2. METHODS: This retrospective study was performed at the Neonatology Department, the Affiliated Hospital of Guangdong Medical University, China. Routinely collected mother-neonate hospitalization data from July 2020 to January 2021 were analyzed. In total, data from 200 neonates who had completed vitamin K2 tests were utilized to assess the prevalence of vitamin K2 deficiency and identify the potential risk factors. According to the vitamin K2 level, the neonates were divided into 2 groups: cases (vitamin K2 deficiency) and controls (no vitamin K2 deficiency). The potential risk factors for vitamin K2 deficiency were evaluated by univariate and multivariate logistic regression. RESULTS: The vitamin K2 level in 24 of the 200 neonates was undetectable (<0.05 ng/mL). The prevalence of low serum vitamin K2 (<0.1 ng/ml) was 33%. Study subjects with antenatal corticosteroids use had an approximately 5-fold greater risk of developing vitamin K2 deficiency. In the univariate analyses, small-for-gestational-age (SGA), caesarean section, maternal gestational diabetes and premature rupture of the membranes were risk factors for vitamin K2 deficiency. In the multivariate logistic regression analysis, high antenatal corticosteroids use, cesarean section, and SGA were independently associated with vitamin K2 deficiency. CONCLUSION: The present study demonstrated that antenatal corticosteroids use is independently associated with vitamin K2 deficiency. This finding highlights the importance of routine vitamin K2 supplementation in late-stage pregnant women and neonates in China.

Correlation of ABO blood groups with treatment response and efficacy in infants with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide.

OBJECTIVE: Not all infants with persistent pulmonary hypertension of the newborn (PPHN) respond to inhaled nitric oxide (iNO) therapy, as it is known to improve oxygenation in only 50% to 60% of cases. In this study, we investigated whether ABO blood groups were a relevant factor affecting the improvement of oxygenation by nitric oxide (NO) therapy in infants with PPHN. METHODS: This study was a retrospective, multicenter, and cohort-controlled trial that involved 37 medical units. Infants with PPHN who met the inclusion criteria and were treated with NO (a vasodilator) alone from July 1, 2015, to June 30, 2020, were selected and assigned into three groups: blood type A, blood type B, and blood type O (there were only 7 cases of blood type AB, with a small number of cases, and therefore, blood type AB was excluded for further analysis). The response to iNO therapy was defined as an increase in the ratio of the partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) > 20% from the basal value after treatment. Oxygenation was assessed mainly based on the two values, oxygenation index (OI) and PaO2/FiO2. The correlation of ABO blood groups with responses to iNO therapy and their influence on the efficacy of iNO therapy was analyzed based on the collected data. RESULTS: The highest proportion of infants with PPHN who eventually responded to iNO therapy was infants with blood type O. Infants with blood type O more readily responded to iNO therapy than infants with blood type B. Oxygenation after iNO treatment group was optimal in the blood type O group and was the worst in the blood type A group among the three groups. Infants with blood type O showed better efficacy than those with blood types A and B. CONCLUSION: ABO blood groups are correlated with responses to iNO therapy in infants with PPHN, and different blood groups also affect the efficacy of NO therapy in infants with PPHN. Specifically, infants with blood type O have a better response and experience the best efficacy to iNO therapy.

Early gut microbiota in very low and extremely low birth weight preterm infants with feeding intolerance: a prospective case-control study.

The potential role of the gut microbiota in the pathogenesis of feeding intolerance (FI) remains unclear. Understanding the role of the gut microbiota could provide a new avenue for microbiota-targeted therapeutics. This study aimed to explore the associations between aberrant gut microbiota and FI in very low or extremely low birth weight (VLBW/ELBW) preterm infants. In this observational case-control study, VLBW/ELBW infants were divided into two groups: FI group and feeding tolerance (FT) group. 16S rRNA gene sequencing was performed to analyze the gut microbial diversity and composition of the infants. The differences in the gut microbiota of the two groups were compared. In total, 165 stool samples were obtained from 44 infants, among which, 31 developed FI and 13 served as controls. Alpha diversity was the highest in the meconium samples of the two groups. LEfSe analysis revealed that the abundances of Peptostreptococcaceae, Clostridiales and Clostridia in the FT group were significantly higher than in the FI group. At the phylum level, the FI group was dominated by Proteobacteria, and the FT group was dominated by Firmicutes. The meconium samples of the FI group had higher proportions of γ-proteobacteria and Escherichia-Shigella and a lower proportion of Bacteroides compared with the FT group. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that aberrant gut bacteria in the FI group were strongly associated with dysregulation of C5-Branched-dibasic-acid-metabolism, protein kinases, and sporulation. These findings reveal candidate microbial markers to prevent FI. Increased relative abundances of γ-proteobacteria and Escherichia-Shigella and decreased abundance of Bacteroides in meconium were associated with an increased risk of FI, while Peptostreptococcaceae, Clostridiales and Clostridia reduced the risk of FI in VLBW/ELBW infants.

Short term outcomes of extremely low birth weight infants from a multicenter cohort study in Guangdong of China.

With the increase in extremely low birth weight (ELBW) infants, their outcome attracted worldwide attention. However, in China, the related studies are rare. The hospitalized records of ELBW infants discharged from twenty-six neonatal intensive care units in Guangdong Province of China during 2008-2017 were analyzed. A total of 2575 ELBW infants were enrolled and the overall survival rate was 55.11%. From 2008 to 2017, the number of ELBW infants increased rapidly from 91 to 466, and the survival rate improved steadily from 41.76% to 62.02%. Increased survival is closely related to birth weight (BW), regional economic development, and specialized hospital. The incidence of complications was neonatal respiratory distress syndrome (85.2%), oxygen dependency at 28 days (63.7%), retinopathy of prematurity (39.3%), intraventricular hemorrhage (29.4%), necrotizing enterocolitis (12.0%), and periventricular leukomalacia (8.0%). Among the 1156 nonsurvivors, 90.0% of infants died during the neonatal period (≤ 28 days). A total of 768 ELBW infants died after treatment withdrawal, for reasons of economic and/or poor outcome. The number of ELBW infants is increasing in Guangdong Province of China, and the overall survival rate is improving steadily.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China. / è¶ æœªæˆç†ŸåŒèƒŽå„¿ä¸´åºŠæ•‘æ²»ç»“å±€åŠå˜åŒ–åˆ†æžï¼šä¸€é¡¹å¹¿ä¸œçœå¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Short-term outcomes of extremely preterm infants at discharge: a multicenter study from Guangdong province during 2008-2017.

BACKGROUND: An increasing number of extremely preterm (EP) infants have survived worldwide. However, few data have been reported from China. This study was designed to investigate the short-term outcomes of EP infants at discharge in Guangdong province. METHODS: A total of 2051 EP infants discharged from 26 neonatal intensive care units during 2008-2017 were enrolled. The data from 2008 to 2012 were collected retrospectively, and from 2013 to 2017 were collected prospectively. Their hospitalization records were reviewed. RESULTS: During 2008-2017, the mean gestational age (GA) was 26.68 ± 1.00 weeks and the mean birth weight (BW) was 935 ± 179 g. The overall survival rate at discharge was 52.5%. There were 321 infants (15.7%) died despite active treatment, and 654 infants (31.9%) died after medical care withdrawal. The survival rates increased with advancing GA and BW (p < 0.001). The annual survival rate improved from 36.2% in 2008 to 59.3% in 2017 (p < 0.001). EP infants discharged from hospitals in Guangzhou and Shenzhen cities had a higher survival rate than in others (p < 0.001). The survival rate of EP infants discharged from general hospitals was lower than in specialist hospitals (p < 0.001). The major complications were neonatal respiratory distress syndrome, 88.0% (1804 of 2051), bronchopulmonary dysplasia, 32.3% (374 of 1158), retinopathy of prematurity (any grade), 45.1% (504 of 1117), necrotizing enterocolitis (any stage), 10.1% (160 of 1588), intraventricular hemorrhages (any grade), 37.4% (535 of 1431), and blood culture-positive nosocomial sepsis, 15.7% (250 of 1588). The multivariate logistic regression analysis indicated that improved survival of EP infants was associated with discharged from specialist hospitals, hospitals located in high-level economic development region, increasing gestational age, increasing birth weight, antenatal steroids use and a history of premature rupture of membranes. However, twins or multiple births, Apgar ≤7 at 5 min, cervical incompetence, and decision to withdraw care were associated with decreased survival. CONCLUSIONS: Our study revealed the short-term outcomes of EP infants at discharge in China. The overall survival rate was lower than the developed countries, and medical care withdrawal was a serious problem. Nonetheless, improvements in care and outcomes have been made annually.