Absence of gut microbial colonization attenuates the sympathoadrenal response to hypoglycemic stress in mice: implications for human neonates

• Published in: Pediatric research 2019-03, Vol.85 (4), p.574-581
• Main Authors: Giri, Priyadarshani, Hu, Furong, La Gamma, Edmund F., Nankova, Bistra B.
• Format: Article
• Language: English
• Subjects: Adrenal glands; Adrenal Glands - physiopathology; Animals; Basic Science Article; Corticosterone - blood; Epinephrine - urine; Gastrointestinal Microbiome; Gene expression; Glucagon - blood; Humans; Hypoglycemia; Hypoglycemia - microbiology; Hypoglycemia - physiopathology; Infant, Newborn; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Microbiota; Pediatric Surgery; Pediatrics; Sympathetic Nervous System - physiopathology
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1038/s41390-018-0270-y

ABSTRACT Background Gut microbiota plays an important role during early development via bidirectional gut–brain signaling. Catecholamines provide a survival advantage allowing adaptation to common postnatal stressors. We aimed to explore the potential link between gut microbiota/gut-derived metabolites and sympathoadrenal stress responsivity. Methods The effect of insulin-induced hypoglycemia was compared in mice with (control, adapted control) and without microbiome (germ-free, GF). Counter-regulatory hormones were analyzed in urine and plasma. Adrenal gene expression levels were evaluated and correlated to cecal short chain fatty acids (SCFA) content. Results There was a significant association between absent microbiota/SCFA and epinephrine levels at baseline and after stress. Corticosterone (hypothalamic-pituitary-adrenal axis) and glucagon release (parasympathetic signaling) were similar in all groups. Hypoglycemia-induced c- Fos (marker of trans-synaptic neuronal activation) in both conditions. Delayed increases in adrenal tyrosine hydroxylase and neuropeptide Y messenger RNA were observed in GF mice. Transcriptome analysis provided insight into underlying mechanisms for attenuated epinephrine production and release. Conclusion Lack of microbiome selectively impaired adrenal catecholamine responses to hypoglycemia. We speculate that absent/delayed acquisition of flora (e.g., after antibiotic exposure) may compromise sympathoadrenal stress responsivity. Conversely, controlled manipulation of the intestinal microflora may provide a novel therapeutic opportunity to improve survival and overall health in preterm neonates.