The Gut Microbiota Affects Corticosterone Production in the Murine Small Intestine

Abstract

Glucocorticoids (GCs) are hormones that are released in response to stressors and exhibit many activities, including immunomodulatory and anti-inflammatory activities. They are primarily synthesized in the adrenal gland but are also produced in peripheral tissues via regeneration of adrenal 11-oxo metabolites or by de novo synthesis from cholesterol. The present study investigated the influence of the microbiota on de novo steroidogenesis and regeneration of corticosterone in the intestine of germ-free (GF) and specific pathogen-free mice challenged with a physical stressor (anti-CD3 antibody i.p. injection). In the small intestine, acute immune stress resulted in increased mRNA levels of the proinflammatory cytokines IL1β, IL6 and Tnfα and genes involved in de novo steroidogenesis (Stard3 and Cyp11a1), as well as in regeneration of active GCs from their 11-oxo metabolites (Hsd11b1). GF mice showed a generally reduced transcriptional response to immune stress, which was accompanied by decreased intestinal corticosterone production and reduced expression of the GC-sensitive marker Fkbp5. In contrast, the interaction between stress and the microbiota was not detected at the level of plasma corticosterone or the transcriptional response of adrenal steroidogenic enzymes. The results indicate a differential immune stress-induced intestinal response to proinflammatory stimuli and local corticosterone production driven by the gut microbiota.

Contaminated meal intake (Aeromonas hydrophila) does not elicit hormonal or immune modulation in bullfrogs (Lithobates catesbeianus)

“…The detection of CORT in the bullfrogs GIT agrees with previous studies showing GIT CORT production in mammals, which suggests that anuran's GIT tissue can produce glucocorticoids as well (Ergang et al, 2021; Kostadinova et al, 2014). However, bullfrog's GIT CORT levels did not increase after contaminated meal intake.…”

Heat-Killed Lactiplantibacillus plantarum LRCC5314 Mitigates the Effects of Stress-Related Type 2 Diabetes in Mice via Gut Microbiome Modulation

“…In this study, HK-LRCC5314 treatment suppressed corticosterone secretion in mice. Corticosterone, a major hormone induced as a stress response and stress mediator, plays a key role in insulin resistance signaling, intestinal inflammatory response, and T2D via stressors [ 59 , 60 ]. In addition, combination of chronic stress exposure and HFD showed increased corticosterone secretion accompanied by elevated HPA activity.…”

“…In addition, combination of chronic stress exposure and HFD showed increased corticosterone secretion accompanied by elevated HPA activity. These conditions were associated with alternation of intestinal bacterial composition and intestinal inflammatory markers [ 60 ]. Previous studies have demonstrated that heat-killed L. casei DKGF7 and L. paracasei treatment reduced serum corticosterone levels along with low inflammatory cytokines in intestine in murine models [ 61 , 62 ].…”

Gut feelings: the microbiota-gut-brain axis on steroids

“…Another potential psychobiotic, Bifidobacterium longum 1714, reduces reported stress and attenuates increases in stress-induced salivary cortisol in healthy volunteers (9). Further, intestinal corticosterone production in response to stress is reduced in germ-free mice (63).…”