Distinct Adrenal Medulla Activity in Germ-Free Versus Conventional Male Rats Under Acute and Chronic Stress

Area of Science:

• Neuroendocrinology
• Microbiome Research
• Stress Physiology

Background:

• Gut microbiota is known to influence neuroendocrine stress responses, particularly the hypothalamic-pituitary-adrenocortical (HPA) axis.
• The impact of gut microbiota on adrenomedullary catecholamine production under stress remains underexplored.

Purpose of the Study:

• To investigate the differential regulation of adrenal corticosterone and catecholamine biosynthesis in germ-free (GF) versus specific pathogen-free (SPF) rats under various stress conditions.
• To explore the role of gut microbiota in modulating the adrenomedullary response to chronic mild stress, acute metabolic stress, or combined stress.

Main Methods:

• Comparison of adrenal gland weight, corticosterone and catecholamine levels, and gene expression in GF and SPF male rats subjected to different stress paradigms.
• Analysis included assessment of enzymes involved in corticosterone and catecholamine biosynthesis, such as Pnmt, tyrosine hydroxylase, and dopamine β-hydroxylase.

Main Results:

• Both GF and SPF rats exhibited increased adrenal gland weight under chronic stress.
• Corticosterone levels and biosynthesis enzyme gene expression remained unchanged across groups and stress conditions.
• GF rats showed significantly increased Pnmt gene expression and epinephrine concentration under combined stress, unlike SPF rats, which displayed reduced norepinephrine and epinephrine levels, correlating with gut microbiota alterations.

Conclusions:

• Gut microbiota plays a significant role in regulating adrenomedullary activity and catecholamine release in response to stress.
• Chronic stress alters gut microbiota composition and function, impacting peripheral stress hormone levels.
• This study elucidates a novel interaction between the gut microbiota and the central stress circuitry via the adrenomedullary pathway.