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

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.

Can early surgery improve the outcome of patients with meconium peritonitis? A single-center experience over 16 years

“…Takino T et al [13] pointed that the relative abundance of Firmicutes (including its families, such as Lactobacillaceae ), which supports health and immune function, was increased substantially during the first week after birth. Giri P et al [12] observed that the sympathoadrenal function could be affected by lack of a microbiome or microbial metabolites, leading to inferior health status. In our data, more than three fourths of patients in group A received surgery on the first day after birth, which means that they had more time for the bowel and intestinal microbiome to develop in the neonatal period.…”

“…Early operation leads to earlier repair and restoration, providing additional time for the bowel to recover and develop in the neonatal period. Animal experiments showed that lack of a microbiome could impair adrenal catecholamine, implying that the poor health status of neonates might be caused by immature of intestinal function [12]. However, the choice of surgical method remains controversial.…”

The impact of preterm adversity on cardiorespiratory function

“…Lower systolic blood pressure and pulse pressure, blunted ventilatory responsiveness to hypercapnia and disrupted brainstem neurochemistry were observed in rats after chronic broad-spectrum antibiotic intervention (O'Connor et al, 2019). A recent study by Giri, Hu, La Gamma, and Nankova (2019) reported that mice raised in a germ-free environment with the absence (Hosoi, Okuma, Matsuda, & Nomura, 2005). Interleukin-1 has been shown to cause a vagusdependent decrease in hypoxic ventilatory response in neonatal rat pups (Balan et al, 2011).…”

“…Lower systolic blood pressure and pulse pressure, blunted ventilatory responsiveness to hypercapnia and disrupted brainstem neurochemistry were observed in rats after chronic broad‐spectrum antibiotic intervention (O'Connor et al., ). A recent study by Giri, Hu, La Gamma, and Nankova () reported that mice raised in a germ‐free environment with the absence of a microbiome and, consequently, short‐chain fatty acids had an impaired adrenal catecholamine response to hypoglycaemia. Dysbiosis may influence excitation of cells in the nucleus tractus solitarii, a central processing site in the brain for autonomic function.…”

Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells

“…One previous finding found that the absence of gut microbial colonization selectively impaired catecholamine response to hypoglycemic stress in mice. ( Giri, Hu, La Gamma, & Nankova, 2019 )…”