Altered hepatic metabolism mediates sepsis preventive effects of reduced glucose supply in infected preterm newborns

• DOI: 10.7554/elife.97830.1
• Publication Date: 2024-07-01T13:30:15Z
• Authors: Ole Bæk; Tik Muk; Ziyuan Wu; Yongxin Ye; Bekzod Khakimov; Alessandra Maria ...; Bagirath Gangadharan; Ivan Bilic; Anders Brunse; Per Torp Sangild; Duc Ninh Nguyen
• Keywords: Carbohydrate Metabolism; Gluconeogenesis; Neonatal Sepsis

Preterm infants are susceptible to neonatal sepsis, a syndrome of pro-inflammatory activity, organ damage and altered metabolism following infection. Given the unique metabolic challenges poor glucose regulatory capacity preterm infants, their intake during infection may have high impact on degree dysregulation damage. Using pig model we previously showed that drastic restriction in supply protects against sepsis via suppression glycolysis-induced inflammation, but results severe hypoglycemia. Now explored clinically relevant options reducing decrease risk, without causing hypoglycemia further explore involvement liver these protective effects. We found reduced regime increased survival response, while maintaining normoglycemia. Mechanistically, this intervention enhanced hepatic oxidative phosphorylation possibly gluconeogenesis, dampened both circulating inflammation. However, switching from after debut clinical symptoms did not prevent suggesting conditions at start key driving outcome. Finally, an early therapy with purified human inter-alpha inhibitor protein, derived anti-inflammatory partially reversed effects low parenteral provision, likely by inhibiting neutrophil functions mediate pathogen clearance.Our findings suggest for infected could or delay development vulnerable neonates.