Gut microbial alterations in neonatal jaundice pre- and post-treatment.

Neonatal jaundice is a common disease that affects up to 60% of newborns. Herein, we performed a comparative analysis of the gut microbiome in neonatal jaundice and non-neonatal jaundice infants (NJIs) and identified gut microbial alterations in neonatal jaundice pre- and post-treatment. We prospectively collected 232 fecal samples from 51 infants at five time points (0, 1, 3, 6, and 12 months). Finally, 114 samples from 6 NJIs and 19 non-NJI completed MiSeq sequencing and analysis. We characterized the gut microbiome and identified microbial differences and gene functions. Meconium microbial diversity from NJI was decreased compared with that from non-NJI. The genus Gemella was decreased in NJI versus non-NJI. Eleven predicted microbial functions, including fructose 1,6-bisphosphatase III and pyruvate carboxylase subunit B, decreased, while three functions, including acetyl-CoA acyltransferase, increased in NJI. After treatments, the microbial community presented significant alteration-based ß diversity. The phyla Firmicutes and Actinobacteria were increased, while Proteobacteria and Fusobacteria were decreased. Microbial alterations were also analyzed between 6 recovered NJI and 19 non-NJI. The gut microbiota was unique in the meconium microbiome from NJI, implying that early gut microbiome intervention could be promising for the management of neonatal jaundice. Alterations of gut microbiota from NJI can be of great value to bolster evidence-based prevention against 'bacterial dysbiosis'.

Association of serum bilirubin in newborns affected by jaundice with gut microbiota dysbiosis.

BACKGROUND AND AIMS: Breast milk jaundice (BMJ) is common and benign, but neonatal cholestasis (NC) is rare and not benign, so early differentiation between NC and non-NC jaundice is important and may facilitate diagnosis and treatment. Gut microbiota plays an important role in enterohepatic circulation, which in turn plays an important role in the secretion of bilirubin. We aimed to determine the composition of gut microbiota in patients with NC and BMJ, and to identify the gut microbiota composition associated with NC and BMJ. METHODS: Data on age, gender, delivery, feeding mode, serum total bilirubin, direct bilirubin, and liver function were collected for NC patients, BMJ patients and healthy controls, respectively. Shotgun metagenomic sequencing and metagenome-wide association were performed. RESULTS: Forty NC patients, 16 patients affected by BMJ, and 14 healthy controls (CON) without jaundice were enrolled. A significant increase in species richness, especially Bacteroides, was found in NC patients. The abundances of potentially pathogenic species and KEGG orthologies (KOs) of virulence factor genes were positively correlated with serum bilirubin level. The abundances of nine species of Bifidobacterium and three KOs of galactose metabolism were significantly decreased in the jaundice group (NC and BMJ) and were negatively correlated with serum bilirubin level. CONCLUSIONS: The gut microbiota in NC patients is characterized by a significant increase in species richness, possibly due to the proliferation of potentially pathogenic species. Additionally, the gut microbiota in jaundice patients is characterized by a decreased abundance of Bifidobacterium. Decreased Bifidobacterium has been associated with elevated bilirubin and abnormal gut microbiota galactose metabolic pathway. Further, ten bacteria species were identified as potential biomarker of jaundice. KEY POINTS: Question Is there any alteration of gut microbiotain neonatal cholestasis patients? Does gut microbiota have any involvement in the occurrence of neonatal cholestasis or breast milk jaundice? Findings The alteration of gut microbiota in neonatal cholestasis patients mainly manifested as a significant increase in species richness and an increased abundance of potentially pathogenic species, while the main manifestation in jaundice patients was a significant decrease in Bifidobacterium which may be involved in the metabolism of bilirubin through the galactose metabolic pathway. Meaning The results suggest that an imbalance of gut microbiota exist in neonatal cholestasis and breast milk jaundice patients, primarily in the form of a substantial reduction in the abundance of Bifidobacterium, suggesting the possibility of intervention treatment for neonatal cholestasis and breast milk jaundice by supplementing probiotics.

Meconium microbiome associates with the development of neonatal jaundice.

OBJECTIVE: Neonatal jaundice is a common disease that affects up to 60% of newborns. Gut microbiota mediated the excretion of bilirubin from the human body. However, the relationship between early gut microbiome and development of neonatal jaundice is not fully understood. Here we sought to characterize meconium microbiome of newborns and to clarify its association with risk of neonatal jaundice. METHODS: We conducted a nested case-control study with 301 newborns providing meconium samples from 2014 to 2015. The main outcome was the development of neonatal jaundice at 42 day follow-up. 16S rRNA gene sequencing was performed to profile the meconium microbiome. LEfSe was employed to identify different features between control and case groups. Logistic regression was used to estimate the risk effect of early gut microbiome on neonatal jaundice. RESULTS: Logistic regression models suggested that higher ɑ-diversity was significantly associated with lower risk of jaundice in cesarean infants (OR 0.72, 95% CI 0.52-0.98), but not in infants born naturally. Higher relative abundance of Bifidobacterium pseudolongum in newborn meconium was significantly associated with lower risk of jaundice both in cesarean-born infants and in the total subjects (OR 0.24, 95% CI 0.07-0.68; OR 0.55, 95% CI 0.31-0.95, respectively). Spearman's correlations showed that relative abundance of B. pseudolongum was significantly correlated with ɑ-diversity (P < 0.01). CONCLUSION: Preventive and treatment methods implying early gut microbiome intervention could be promising for the management of neonatal jaundice.

Is screening for urine infection in well infants with prolonged jaundice required? Local review and meta-analysis of existing data.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) neonatal jaundice guidance recommends a urine culture for investigation of babies with prolonged jaundice. However, the evidence cited for this guidance is limited. We aimed to review local data and the existing literature to identify evidence to either support or refute this guidance. METHOD: We retrospectively reviewed 3 years of urine cultures from our outpatient prolonged jaundice clinic. We then conducted literature review with meta-analysis of studies presenting original data on urine tract infection (UTI) rates in jaundiced and prolonged jaundiced babies. RESULTS: From our local data, none of the 279 patients met our unit clinical criteria for UTI. Literature review revealed considerable differences worldwide in UTI rates in both jaundiced and prolonged jaundiced cases. Using pooled data from our literature review and our local population, the incidence of UTI in prolonged jaundiced babies is 0.21% (95% CI 0.0% to 0.73%) in the UK. This is significantly lower than the figure indicated from the data from elsewhere in the world, 8.21% (95% CI 4.36% to 13.0%). CONCLUSIONS: The findings both from our local data and the current literature do not support the practice of routine screening for urine infection in well babies with prolonged jaundice. In view of the above, we no longer include urine culture in screening of well infants with prolonged jaundice. We hope that NICE will re-examine the evidence and recommend changes to their guidance on the role of routine screening for urine infection in babies with prolonged jaundice.

Breast milk jaundice: effect of bacteria present in breast milk and infant feces.

OBJECTIVE: Breast milk is an important source of bacteria in establishing the infantile intestinal microbiota that appear to influence the enterohepatic circulation of bilirubin. The aim of the present study was to evaluate the effect of breast milk's microbiological content on the development of breast milk jaundice (BMJ). METHODS: A total number of 60 mother-infant pairs enrolled to the study. Two groups were defined: BMJ group (n=30), full-term otherwise healthy newborns who were considered BMJ; control group (n=30), full-term healthy newborns without jaundice. All newborns in the study were exclusively breast-fed. The breast milk samples and the feces of infants were evaluated for content of selected bacterial populations (Bifidobacterium, Lactobacillus, Clostridium, Staphylococcus, and Streptococcus species) with real-time polymerase chain reaction. RESULTS: Bifidobacterium bifidum content in the breast milk and B adolescentis, B bifidum, and B longum content in the fecal samples were higher in the control group than in the BMJ group. The milk and fecal concentrations of B bifidum were significantly correlated. The concentrations of breast milk B bifidum and fecal B bifidum, B adolescentis, and B longum were found to be negatively correlated with bilirubin levels. CONCLUSIONS: Our results suggest that Bifidobacterium species in breast milk may protect against BMJ.

Urinary tract infections in infants: comparison between those with conjugated vs unconjugated hyperbilirubinaemia.

AIMS: The aim was to investigate conjugated and unconjugated hyperbilirubinaemia in association with urinary tract infection (UTI) in young infants. METHODS: Fifty infants aged <3 mths who developed prolonged jaundice among 2128 infants with UTI from 1984 to 2004 were enrolled retrospectively. They were divided into conjugated (n=22) and unconjugated (n=28) hyperbilirubinaemia groups and the clinical variables between the two were compared. RESULTS: Compared with the unconjugated group, the conjugated hyperbilirubinaemia group had statistically significantly lower haemoglobin (1.57 vs 1.80 micromol/L), higher aspartate aminotransferase (96 vs 32.5 U/L) and alanine aminotransferase (81.5 vs 16 U/L), were older on admission (48.0 vs 32.5 days), had a longer duration of jaundice before treatment (43.5 vs 30 days) and a higher incidence of E. coli infections (19/22 vs 15/28). The direct/total bilirubin ratio was linearly correlated with duration of jaundice before treatment (p=0.004). The most significant cut-off value for the duration of jaundice vis-à-vis the type of jaundice was 38 days (p=0.007). Patients who on presentation had had jaundice for >44 days (p=0.007) were unlikely to have unconjugated hyperbilirubinaemia. CONCLUSIONS: Infants with UTI may present with unconjugated hyperbilirubinaemia in the early stage. After 6 weeks, it is always conjugated hyperbilirubinaemia and is frequently associated with anaemia, elevated hepatic aminotransferases and E. coli infections.

The impact of intestinal microflora on serum bilirubin levels.

BACKGROUND/AIMS: Intestinal microflora plays an important role in the pathogenesis of neonatal jaundice by inhibiting enterosystemic circulation of bilirubin. The present study aimed to investigate the influence of intestinal microflora on serum bilirubin levels in hyperbilirubinemic Gunn rats. METHODS: After a baseline phase Gunn rats received oral antibiotics (either clindamycin/neomycine or co-trimethoxazole for four days, phase II). Intestinal colonization was carried out either with a bilirubin-reducing strain of C. perfringens or C. pasteurianum incapable of reducing bilirubin (phase III). Serum bilirubin and fecal bile pigments were determined at the end of each phase. RESULTS: Oral administration of clindamycin/neomycine resulted in the disappearance of fecal urobilinoids. Simultaneously, serum bilirubin increased dramatically (186+/-31 vs. 289+/-35 micromol/l, P=0.004). Intestinal colonization with C. perfringens led to reappearance of fecal urobilinoid production accompanied with a partial decrease of serum bilirubin (289+/-35 vs. 239+/-17 micromol/l, P=0.013), whereas the effect of C. pasteurianum on bile pigment metabolism was negligible. Co-trimethoxazole therapy had no effect on serum and intestinal metabolism of bilirubin. CONCLUSIONS: Intestinal microflora greatly affects intravascular metabolism of bilirubin. Prolonged use of certain antibiotics in man may lead to an increase in serum bilirubin levels, while the enhancement of intestinal catabolism may have an opposite effect.

[The Amben correction of disorders in the intestinal microbial colonization of newborn infants with perinatal pathology]. / Korrektsiia ambenom narushenii mikrobnoi kolonizatsii kishechnika u novorozhdennykh detei s perinatal'noi patologiei.

The examination of 49 newborn infants revealed that at the early neonatal period the character of the microbial colonization of the intestine depended on the kind of perinatal pathology: in lesions of the central nervous system and conjugation jaundice the deficiency of Bifidobacterium and Escherichia was detected; in hemolytic disease opportunistic bacteria were dominant simultaneously with the deficiency of lactoflora. The study of these infants, divided into two groups differing in the administration of Amben (an inhibitor of proteolytic enzymes), showed the efficiency of Amben which stimulated the growth and development of resident microflora in the intestine, thus contributing to the maintenance of eubiosis in a given group of infants with perinatal pathology.

The first isolate of Tatumella ptyseos in Malaysia.

Tatumella ptyseos, the type species for the genus Tatumella, is a newly established member of the Family Enterobacteriaceae. It is a Gram-negative, oxidase negative, fermentative rod that grows on Mac Conkey agar. This first isolate was obtained from the blood culture of a neonate having neonatal jaundice with presumed sepsis. The organism was in vitro sensitive to Gentamicin, Chloramphenicol, Cotrimoxazole and Ampicillin. The patient was treated with Ampicillin and Gentamicin and recovered uneventfully.

[Jaundice associated with urinary infection in the first three months of life. Study of 66 cases (author's transl)]. / Ictericia asociada a infección urinaria en el primer trimestre de la vida. Revisión de 66 casos.

Sixty-six infants aged 8 days to 3 months presented jaundice as a sign of urinary infection during a ten-year period 1968-1977. The main clinical and biochemical aspects are described. "E.coli" grew in 49 urine cultures (74.2%), but other bacteria were also found ("Klebsiella", "Proteus", "Pseudomonas", "A. aerogenes"). Hepatic function tests seem to prove that intrahepatic colostasis is the main mechanism involved, although hemolysis was also found in some cases. The importance of considering urinary infection in the diagnosis of jaundice during infancy is stressed.

Antigenic analysis of human cytomegalovirus isolates from Japanese women and infants.

The antigenic differences among human cytomegalovirus (CMV), two laboratory strains (Davis, AD 169), isolates from pregnant women's cervical secretions, mother's milk, infants' throat swabs and urine were analyzed by means of the plaque reduction assay using human sera which were assumed to contain monotypic antibodies by primary infection and boosted antibodies by reinfection or reactivation of the latent virus. In the cross-neutralization tests, there were no remarkable differences among the CMV strains examined. Moreover, in the neutralization kinetics, normalized kappa values among the strains constantly exceeded 80. Therefore, it is suggested that the human CMV strains examined in the study were serologically identical or very closely related.

[Neonatal jaundice occurring during infection with a Coxsackie B4 virus]. / Ictere neonatal au cours d'une infection a virsu Coxsackie B4

An infant, born at term, presented at the 3rd day of life an hepatitis with hepatospleomegaly, intense icterus and abnormal activities on the coagulation test. Coxsackie B 4 virus could be isolated from the urine, and later on the infant developed specific antibodies of increasing titers. The child recovered and encephalitic or myocardial involvements were not observed. The literature is reviewed and the authors underline the relative rarity but also the severity of Coxsackie B 4 infection in the neonatal period.