Interactions Between Gut Microbiota and Acute Restraint Stress in Peripheral Structures of the Hypothalamic–Pituitary–Adrenal Axis and the Intestine of Male Mice

Abstract

The gut microbiota play an important role in shaping brain functions and behavior, including the activity of the hypothalamus-pituitary-adrenocortical (HPA) axis. However, little is known about the effect of the microbiota on the distinct structures (hypothalamus, pituitary, and adrenals) of the HPA axis. In the present study, we analyzed the influence of the microbiota on acute restraint stress (ARS) response in the pituitary, adrenal gland, and intestine, an organ of extra-adrenal glucocorticoid synthesis. Using specific pathogen-free (SPF) and germ-free (GF) male BALB/c mice, we showed that the plasma corticosterone response to ARS was higher in GF than in SPF mice. In the pituitary, stress downregulated the expression of the gene encoding CRH receptor type 1 (Crhr1), upregulated the expression of the Fkbp5 gene regulating glucocorticoid receptor sensitivity and did not affect the expression of the proopiomelanocortin (Pomc) and glucocorticoid receptor (Gr) genes. In contrast, the microbiota downregulated the expression of pituitary Pomc and Crhr1 but had no effect on Fkbp5 and Gr. In the adrenals, the steroidogenic pathway was strongly stimulated by ARS at the level of the steroidogenic transcriptional regulator Sf-1, cholesterol transporter Star and Cyp11a1, the first enzyme of steroidogenic pathway. In contrast, the effect of the microbiota was significantly detected at the level of genes encoding steroidogenic enzymes but not at the level of Sf-1 and Star. Unlike adrenal Sf-1, the expression of the gene Lrh-1, which encodes the crucial transcriptional regulator of intestinal steroidogenesis, was modulated by the microbiota and ARS and this effect differed between the ileum and colon. The findings demonstrate that gut microbiota have an impact on the response of the pituitary, adrenals and intestine to ARS and that the interaction between stress and the microbiota during activation of glucocorticoid steroidogenesis differs between organs. The results suggest that downregulated expression of pituitary Pomc and Crhr1 in SPF animals might be an important factor in the exaggerated HPA response of GF mice to stress.

Prebiotics Regulation of Intestinal Microbiota Attenuates Cognitive Dysfunction Induced by Surgery Stimulation in APP/PS1 Mice

“…Recently, an expert insight indicated that intestinal microbiota-bile acid-brain axis may participate in the development and progression of AD [68]. Also, the intestinal microbiota plays a role in the regulation of the hypothalamic-pituitary-adrenal axis and is critical for the stress response [69]. Finally, evidences have proved that intestinal microbiota can modulate neuroinflammatory response, and the fact that diseases or the complications with cognitive dysfunction such as AD, PD, depression, as well as postoperative dysfunction in the present study are closely correlated with neuroinflammatory response [65,70,71].…”

Intestinal mycobiota in health and diseases: from a disrupted equilibrium to clinical opportunities

“…(2) hypothalamus-pituitary-adrenal (HPA) axis plays a core role in communication of gut microbiota and the brain; and (3) gut-brain-microbiota axis provides a new treatment target for depression, autism, and Parkinson disease [150][151][152][153][154][155]. A recent study revealed that mycobiota regulates expression of genes in the kynurenine pathway and associated micro-RNAs (miRNAs) in the hippocampus in a sex-depend manner [156], suggesting a possible gut mycobiota-brain axis [5].…”

Restraint Stress in Hypertensive Rats Activates the Intestinal Macrophages and Reduces Intestinal Barrier Accompanied by Intestinal Flora Dysbiosis

“…Essential HTN is strongly correlated with pressure, and strong mental stress is consistently involved in the development of these conditions. 3 , 39 Therefore, we used the restraint stress rat model, that accelerates cardiovascular damage and HTN on account of bondage stress in our study. While mechanisms that regulate intestinal permeability have been widely studied, little is known on how the colon protects itself from restraint stress.…”

“…The main microbiota remains similar among most individuals but there is also slight difference from person to person. Several factors, such as genetics, 60 dietary patterns, 61 , 62 mental stress 39 and geographical region 63 could account for the reason, making them both highly dynamic and susceptible to transient changes. 57 , 62 Previous research has investigated the role of gut microbiota in autoimmune, multiple infectious and metabolic diseases, such as IBD, Clostridium difficile infection and diabetes.…”