Shaoming Zhou1, Zhangxing Wang2, Fusheng He3, Huixian Qiu4, Yan Wang3, Huihui Wang5, Jianli Zhou6, Jiaxiu Zhou7, Guoqiang Cheng8, Wenhao Zhou8, Ruihuan Xu9, Mingbang Wang10. 1. Division of Gastroenterology, Shenzhen Children's Hospital, Shenzhen, Guangdong, 518038, China. Electronic address: zhousm15d@aliyun.com. 2. Division of Neonatology, Shenzhen Longhua People's Hospital, Guangdong, 518109, China. 3. Imunobio, Shenzhen, Guangdong, China, 518001. 4. Division of Neonatology, Longgang Central Hospital of Shenzhen, Guangdong, 518116, China. 5. Division of Clinical Nutrition, Shenzhen Children's Hospital, Shenzhen, Guangdong, 518038, China. 6. Division of Gastroenterology, Shenzhen Children's Hospital, Shenzhen, Guangdong, 518038, China. 7. Division of Psychology, Shenzhen Children's Hospital, Shenzhen, Guangdong, 518038, China. 8. Division of Neonatology, Children's Hospital of Fudan University, National Center for Children's Health, Shanghai, 201102, China. 9. Clinical Laboratory, Longgang Central Hospital of Shenzhen, Guangdong, 518116, China. Electronic address: xrh69@126.comand. 10. Xiamen Branch, Shanghai Key Laboratory of Birth Defects, Division of Neonatology, Children's Hospital of Fudan University, National Center for Children's Health, Shanghai, 201102, China. Electronic address: Mingbang.wang.bgi@qq.com.
Abstract
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.
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 jaundicepatients 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 cholestasispatients? Does gut microbiota have any involvement in the occurrence of neonatal cholestasis or breast milk jaundice? Findings The alteration of gut microbiota in neonatal cholestasispatients mainly manifested as a significant increase in species richness and an increased abundance of potentially pathogenic species, while the main manifestation in jaundicepatients 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 jaundicepatients, 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.