Clinical Manifestations of Neonatal Hyperbilirubinemia Are Related to Alterations in the Gut Microbiota

Zhang, Xueli; Zeng, Shujuan; Cheng, Guoqiang; He, Liufang; Chen, Mingqiu; Wang, Mingbang; Zhou, Wenhao; Qiu, Huixian; Wang, Zhangxing

doi:10.3390/children9050764

Cited by 7 publications

(4 citation statements)

References 20 publications

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“…Bilirubin metabolism is predominantly mediated by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), which aids in glucuronidation and thereby facilitates bilirubin's removal from the body. UGT1A1, located on chromosome 2 (2q37), covers an area of approximately 160 kbp [11][12][13][14] . Multiple genetic polymorphisms within the UGT1A1 gene, such as rs8175347, rs4124874, rs4148323, and rs10929302 are known to in uence gene expression, the function of enzymes, and the concentration of bilirubin in the serum.…”

Section: Discussionmentioning

confidence: 99%

UGT1A1 and BLVRA allele and genotype variants in neonatal patients with hyperbilirubinemia in southern China

Liu,

Zhang,

Chen

et al. 2024

Preprint

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We explore the allele and genotype distribution of UGT1A1 and BLVRA variants in individuals affected by neonatal hyperbilirubinemia in southern China. Blood specimens were collected from 240 neonates: 126 cases of hyperbilirubinemia and 114 healthy controls. Serum levels of total protein, albumin, bilirubin (total and direct), urea nitrogen, creatinine, and other biochemical parameters were quantified using a biochemical analyzer. Nine UGT1A1 and five BLVRA genetic variants were genotyped using flight time mass spectrometry. The allele and genotype frequencies of these variants and their associations with neonatal hyperbilirubinemia were analyzed. The genotype frequencies of CC and CG for the UGT1A1 variant rs11888492 in the hyperbilirubinemia group were 90.48% and 9.52%, respectively (P = 0.001), in comparison with the control group. The C and G allele frequencies of rs11888492 in the hyperbilirubinemia group were 95.24% and 4.76%, respectively (P = 0.023). Similarly, in the hyperbilirubinemia group, the genotype frequencies for the UGT1A1 variant rs4148325 were 90.48% CC, 8.73% CT, and 0.79% TT (P = 0.001), with corresponding allele frequencies of 94.84% for C and 5.16% for T (P = 0.002). No notable distinctions were detected for other variants. Newborns carrying the CC genotype of rs11888492 exhibited higher total bilirubin (TBIL) levels than those carrying the GG genotype (P = 0.034), whereas newborns carrying the CC genotype of rs4148325 displayed higher TBIL levels than those carrying the CT genotype (P = 0.003). The presence of the G allele at rs11888492 was found to be significantly correlated with a decreased likelihood of developing neonatal hyperbilirubinemia (odds ratio [OR]: 0.363; 95% confidence interval [CI]: 0.169–0.777). Furthermore, a substantial reduction in the risk of neonatal hyperbilirubinemia associated with the CT genotype of rs4148325 were revealed (OR = 0.242; 95% CI: 0.102–0.574). Additionally, an inverse relationship was identified between TBIL concentration and the quantity of genetic variants. The UGT1A1 variants rs11888492 and rs4148325 are strongly associated with neonatal hyperbilirubinemia in southern China.

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Section: Discussionmentioning

confidence: 99%

UGT1A1 and BLVRA allele and genotype variants in neonatal patients with hyperbilirubinemia in southern China

Liu,

Zhang,

Chen

et al. 2024

Preprint

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“…This implies that if the colonization process starts in utero or during birth, interventions to influence the composition of the infant’s gut microbiota may need to be started early. The importance of an early intervention is emphasized by previous reports that the meconium microbiota has been found to be associated with the subsequent health of the infants, such as neonatal jaundice, 46 , 61 , 62 NEC, 40 , 60 , 63 , 64 allergies and atopy, 65 , 66 disrupted infant growth, 10 , 53 , 67 – 71 early-onset neonatal sepsis (EONS) 60 , 72 , 73 and other conditions. 9 , 60 , 74 – 76 One possible intervention to alter the gut microbiota may be the use of probiotics, which have been found to have a positive effect on the newborn gut.…”

Section: Discussionmentioning

confidence: 99%

Investigating prenatal and perinatal factors on meconium microbiota: a systematic review and cohort study

Turunen,

Tejesvi,

Paalanne

et al. 2023

Pediatr Res

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Background The first-pass meconium has been suggested as a proxy for the fetal gut microbiota because it is formed in utero. This systematic review and cohort study investigated how pre- and perinatal factors influence the composition of the meconium microbiota. Methods We performed the systematic review using Covidence by searching PubMed, Scopus, and Web of Science databases with the search terms “meconium microbiome” and “meconium microbiota”. In the cohort study, we performed 16 S rRNA gene sequencing on 393 meconium samples and analyzed the sequencing data using QIIME2. Results Our systematic review identified 69 studies exploring prenatal factors, immediate perinatal factors, and microbial composition in relation to subsequent health of infants but gave only limited comparative evidence regarding factors related to the composition of the meconium microbiota. The cohort study pointed to a low-biomass microbiota consisting of the phyla Firmicutes, Proteobacteria and Actinobacteriota and the genera Staphylococcus, Escherichia-Shigella and Lactobacillus, and indicated that immediate perinatal factors affected the composition of the meconium microbiota more than did prenatal factors. Conclusions This finding supports the idea that the meconium microbiota mostly starts developing during delivery. Impact It is unclear when the first-pass meconium microbiota develops, and what are the sources of the colonization. In this systematic review, we found 69 studies exploring prenatal factors, immediate perinatal factors, and microbial composition relative to subsequent health of infants, but there was no consensus on the factors affecting the meconium microbiota development. In this cohort study, immediate perinatal factors markedly affected the meconium microbiota development while prenatal factors had little effect on it. As the meconium microbiota composition was influenced by immediate perinatal factors, the present study supports the idea that the initial gut microbiota develops mainly during delivery.

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“…Neonatal hyperbilirubinemia (NH) is a common clinical phenomenon in newborns[ 1 ]. The condition from a metabolic imbalance between the production and elimination of bilirubin[ 2 ]. NH is generally benign and transient, but about one in ten neonates are likely to develop clinically severe hyperbilirubinemia[ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D metabolic pathway genes polymorphisms and vitamin D levels in association with neonatal hyperbilirubinemia in China: a single-center retrospective cohort study

et al. 2023

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Background Neonatal hyperbilirubinemia (NH) is a major cause of hospitalization after birth. Previous studies indicated that vitamin D deficiency might play an important role in NH susceptibility, but the results were controversial. Meanwhile, there has been limited description of the association between vitamin D related genes single nucleotide polymorphisms (SNP) and NH susceptibility. We aimed to investigate the vitamin D metabolic pathway genes polymorphisms and vitamin D levels with NH susceptibility. Methods We retrospectively analyzed the clinical data, vitamin D levels and its metabolic pathway gene polymorphisms of 187 NH neonates and 149 controls at Tianjin Children’s Hospital/Tianjin University Children’s Hospital between April 2019 and August 2022. Vitamin D levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and the genetic polymorphism of NADSYN1/DHCR7, GC, CYP2R1, CYP24A1 and CYP27B1 was detected by high resolution melting (HRM) analysis. Results The frequency of vitamin D deficiency (25(OH)D < 15 ng/mL) was significantly increased in the NH group compared to controls. TT genotype of rs12785878 and GT genotype of rs10877012 were protective factors of vitamin D deficiency and NH, and GT genotype and dominant model carriers of rs12785878 had a higher risk of severe NH than the GG genotype carriers (GT genotype: OR: 2.43; 95% CI: 1.22–4.86; P = 0.012, dominant model: OR: 1.97; 95% CI: 1.04–3.73; P = 0.037). GC gene haplotype was associated with vitamin D deficiency. No significant SNP-SNP and SNP-vitamin D levels interaction combinations were found. Conclusions There were associations among NH, vitamin D deficiency and NADSYN1/DHCR7 and CYP27B1 polymorphisms, TT genotype of rs12785878 and GT genotype of rs10877012 could reduce the risk of vitamin D deficiency and NH. Furthermore, rs12785878 was significantly associated with severe NH.

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Clinical Manifestations of Neonatal Hyperbilirubinemia Are Related to Alterations in the Gut Microbiota

Cited by 7 publications

References 20 publications

UGT1A1 and BLVRA allele and genotype variants in neonatal patients with hyperbilirubinemia in southern China

UGT1A1 and BLVRA allele and genotype variants in neonatal patients with hyperbilirubinemia in southern China

Investigating prenatal and perinatal factors on meconium microbiota: a systematic review and cohort study

Vitamin D metabolic pathway genes polymorphisms and vitamin D levels in association with neonatal hyperbilirubinemia in China: a single-center retrospective cohort study

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