Causal associations between gut microbiota and inflammatory factors in neonatal jaundice: a Mendelian randomization study

BACKGROUND: Neonatal jaundice is a common clinical condition, affecting approximately 60% of full-term infants and 80% of preterm infants. The majority of neonatal jaundice represents benign physiological hyperbilirubinemia that resolves spontaneously, yet a subset progresses to clinically significant hyperbilirubinemia (CSH), defined as elevated serum bilirubin requiring phototherapy or exchange transfusion to prevent permanent neurotoxic injury. The gut microbiota plays a crucial role in human health and disease, with inflammatory mediators frequently contributing to the body's response to illness or injury, often through their modulation of immune system function. As a result, the interplay between gut microbiota, inflammatory factors, and neonatal jaundice has garnered considerable research interest. Investigating the involvement of gut microbiota and inflammatory factors in neonatal jaundice holds the potential to inform the development of novel therapeutic strategies. METHODS: This study employed Mendelian Randomization (MR) to investigate the causal relationships between 418 gut microbiota taxa, 91 inflammatory factors, and clinically significant neonatal hyperbilirubinemia. Instrumental variables (IVs) genetic variants used as proxies for the exposure were selected from genome-wide association study (GWAS) summary statistics according to stringent criteria. Five well-established MR methods-namely, inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, and weighted mode-were applied to evaluate the causal associations between gut microbiota composition and susceptibility to neonatal jaundice. Sensitivity analyses and tests for pleiotropy were performed on the MR results to assess the robustness and reliability of the findings. RESULTS: and three inflammatory markers: β-nerve growth factor (NGF), C-X-C motif chemokine 1 (CXCL1), and interleukin-6 (IL-6). CONCLUSION: This study provides evidence supporting associations between specific gut microbiota taxa and neonatal jaundice, as well as potential links with inflammatory markers. These findings are hypothesis-generating and should be interpreted cautiously, especially because the gut microbiome instruments were derived from adult cohorts rather than neonatal cohorts. They do not support immediate clinical recommendations regarding probiotics or antibiotics in newborns, but may help guide future mechanistic and pediatric validation studies.