Bifidobacterium longum and Lactobacillus helveticus Synergistically Suppress Stress-related Visceral Hypersensitivity Through Hypothalamic-Pituitary-Adrenal Axis Modulation

Abstract

Background/aims: Visceral pain and hypothalamic-pituitary-adrenal axis (HPA) dysregulation is a common characteristic in irritable bowel syndrome (IBS) patients. Previously, we reported that a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) prevents chronic stress-mediated brain function abnormalities by attenuating the HPA axis response. Here, we compared the effect between different probiotic treatments on the perception of visceral pain during colorectal distension (CRD) following a chronic stress and the consequences to the activity of the HPA axis.

Methods: After a 2-week treatment with a combined probiotic formulation, or L. helveticus or B. longum alone in stressed mice, the visceral pain in response to CRD was recorded. The expression of glucocorticoid receptors was determined in the different brain areas involved in the stress response (hypothalamus, hippocampus, and prefrontal cortex). The plasma levels of stress hormones were also measured.

Results: A pretreatment using the combination of probiotic formulation significantly reduces the chronic stress-induced visceral hypersensitivity respectively at 0.06, 0.08, and 0.10 mL CRD volume. However, a single probiotic (B. longum or L. helveticus) administration is less effective in reducing visceral pain in stressed mice. Moreover, the expression of the glucocorticoid receptor mRNA was consistently up-regulated in several brain areas after pretreatment with a combined probiotic, which correlated with the normalization of stress response compared to the inconsistent effects of a single probiotic.

Conclusion: The combination of L. helveticus and B. longum is more effective in regulating glucocorticoid negative feedback on the HPA axis than probiotic alone and subsequently in treating stress-induced visceral pain.

Keywords: Chronic stress; Glucocorticoid receptors; Probiotics; Visceral pain.

Figure 1

Prevention of abdominal pain induced by chronic stress (water avoidance stress [WAS]) depends on the strain probiotic. *P < 0.05 and ^#P < 0.05 are significantly different from control and WAS groups. B. longum, Bifidobacterium longum; L. helveticus, Lactobacillus helveticus.

Figure 2

Probiotic treatments differentially prevent a plasma level of stress hormone markers. *P < 0.05 and ^#P < 0.05 are significantly different from control and water avoidance stress (WAS; chronic stress). B. longum, Bifidobacterium longum; L. helveticus, Lactobacillus helveticus.

Figure 3

Specific probiotic treatment blocks chronic stress-induced decrease of glucocorticoid receptor (GR) gene expression in (A) hypothalamus, (B) hippocampus, and (C) prefrontal cortex. *P < 0.05 and ^#P < 0.05 are significantly different from control and water avoidance stress (WAS; chronic stress). B. longum, Bifidobacterium longum; L. helveticus, Lactobacillus helveticus.