Abstract Body: Background:
The microbiome and the metabolites it produces, influences homeostasis in the host. A disruption of gut biome composition, or dysbiosis, can be a risk factor or a consequence of disease. The maternal biome is known to play a vital role in brain and immune development of the offspring by shaping the metabolic environment during early development. Neonatal hypoxic ischemic encephalopathy (nHIE) is one of the leading causes of death and disability among neonates. We investigated if the presence of an aged dysbiotic maternal biome influenced the response to neonatal nHIE in offspring and worsened outcomes after injury.
Method:
Young female C57B6 mice 3-month (M) of age had their host gut bacteria cleared via antibiotic treatment prior to recolonization via fecal microbiome transplants with the microbiota from 3M (control), or 14M (middle aged) female mice. The dams were subsequently bred with a young male and delivered pups. At 10 days post birth, the pups received either a sham surgery or were subjected to the Rice-Vannucci model of nHIE and were monitored 7 days post-surgery. The pups were aged to 2-3 months for behavioral testing and longitudinal fecal samples collection.
Results:
The maternal biome had a significant impact on offspring biome and on recovery from nHIE during both the acute and chronic phases of recovery. From Day 3 post-surgery to Day 7, 14M male sham mice had a significant increase in their weight from baseline compared to 3M HIE males and 14M HIE males (p< 0.05, 0.01). 14M females had a significantly higher percent change from baseline weights on Day 1, Day 3 and Day 7 post surgery compared 3M HIE females and 14M HIE shams (p= 0.0132, 0.0495, and 0.0025 respectively). At 2-3 months of age, HIE males from dams recolonized with 14M biome weighed significantly less than HIE males from dams recolonized with 3M biome (p= 0.0305); females had no significant weight differences at this time. Upon assessment of chronic motor functional impairment, HIE males born from dams recolonized with 14M biome had significantly lower grip strength compared to 3M HIE males (p= 0.469). This was also seen in female offspring from dams recolonized with 14M biome, HIE females had significantly lower grip strength compared to HIE females from dams with 3M biome (p= 0.0021).
Conclusion:
The maternal biome had a significant impact on offspring recovery from nHIE during both the acute and chronic phases of recovery. Sex and injury specific changes were seen.