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Updated: Jun 29, 2025
A Murine Model of Fetal Exposure to Maternal Inflammation to Study the Effects of Acute Chorioamnionitis on Newborn Intestinal Development
Published on: June 24, 2020
Intestinal microbiota modulates neuroinflammatory response and brain injury after neonatal hypoxia-ischemia
Alexander Drobyshevsky1, Sylvia Synowiec1, Ivan Goussakov1
1Department of Pediatrics, NorthShore University HealthSystem, Evanston, IL, USA.
Insights
Neonatal gut microbiota impacts brain injury severity in premature infants. Modulating the gut microbiome, particularly with beneficial bacteria like B. infantis, may reduce brain inflammation and injury.
Area of Science:
- Neuroscience
- Microbiology
- Immunology
Background:
- Premature infants often have disrupted gut microbiota.
- Perinatal hypoxic-ischemic (HI) brain injury is a major cause of long-term deficits in infants.
- The link between gut microbiota and HI brain injury is not fully understood.
Purpose of the Study:
- To investigate how neonatal gut microbiota composition influences the immune response and severity of hypoxic-ischemic (HI) brain injury.
- To explore potential therapeutic interventions targeting the gut microbiome for neonatal brain injury.
Main Methods:
- Neonatal C57BL/6J mice underwent a hypoxic-ischemic (HI) protocol.
- Microbial manipulation involved antibiotic treatment, with or without E. coli or B. infantis gavage.
- Brain injury extent and inflammatory gene expression were assessed using MRI and gene expression analysis.
Main Results:
- The E. coli group showed significantly higher brain injury volumes compared to B. infantis and control groups.
- Pro-inflammatory cytokine and toll-like receptor gene expression was elevated in the E. coli group post-HI.
- Gut microbiota composition significantly affected brain injury and neuroinflammation.
Conclusions:
- Neonatal intestinal microbiota composition modulates the neuroinflammatory response and brain injury severity following hypoxia-ischemia.
- Targeting early gut microbial colonization and development presents a promising therapeutic strategy for neonatal brain injury.
Abstract:
Premature infants lack a normal intestinal microbial community and also at risk of perinatal hypoxic-ischemic (HI) brain injury, which is considered to be one of the major factors for motor, sensory, and cognitive deficits. We hypothesized that neonatal gut microbiota composition modulated the immune reaction and severity of neonatal H-I brain injury. Neonatal C57BL/6J mouse pups were exposed to H-I protocol consisting of permanent left carotid artery ligation, followed by 8% hypoxia for 60 min. Microbial manipulation groups included 1) antibiotic treatment, E18 (maternal) to P5; 2) antibiotic treatment E18 to P5 + E. coli gavage; 3) antibiotic treatment E18 to P5 + B. infantis gavage; and 4) saline to pups with dams getting fresh water. The extent of brain injury and recovery was measured on MRI. Edematous injury volume was significantly higher in E. coli group than that in B. infantis group and in fresh water group. Gene expression in brains of pro-inflammatory cytokines (IL1β, IL6, IL2, TNF-α and toll-like receptors 2-6) were elevated to a greater extent in the E. coli group at P10, no injury, and at P13, 72 hours after H-I relative to sham control and B. infantis groups. Significant effects of microbiome and brain injury and interaction of these factors were found in abundance of major phyla. The neuroinflammatory response and brain injury after neonatal hypoxia-ischemia are affected by intestinal microbiota, providing opportunities for therapeutic intervention through targeting the early colonization and development of the gut microbiota.
