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

Abstract

Background/AimsVisceral 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. MethodsAfter 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. ResultsA 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. ConclusionThe 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.

Hypothesis: Caco‐2 cell rotational 3D mechanogenomic turing patterns have clinical implications to colon crypts

“…HES1 is responsible for maintaining gut homeostasis via preventing microbial dysbiosis in the mouse, and HES1‐knockout altered colon crypt morphology . The probiotic combination of Lactobacillus helveticus and Bifidobacterium longum helped reverse WA‐stress‐induced changes in the mouse hypothalamic‐pituitary‐adrenal axis and WA stress‐induced visceral hyperalgesia by blocking decrease of NR3C1 in the hypothalamus, hippocampus and prefrontal cortex . These reports support the potential of HES1‐CLDN1 and NR3C1 acting as equilibrium maintaining gene circuits consists of three genes that regulate each other in a cyclical manner and their potential roles in homeostasis of the Microbiota‐Gut‐Brain Axis.…”

“…These reports support the potential of HES1‐CLDN1 and NR3C1 acting as equilibrium maintaining gene circuits consists of three genes that regulate each other in a cyclical manner and their potential roles in homeostasis of the Microbiota‐Gut‐Brain Axis. Future advances in personalized probiotics based, in part, on 4D Nucleome algorithms represent a potentially promising therapeutic area …”

“…We anticipate the programmable “gut‐on‐a‐chip” methodology will demonstrate epithelium morphology similar to the colon lumen surface. This system can be used to study the topology of colon epithelium in response to morphogens including FGF2/glucocorticoids/microbiome, etc . High‐throughput “gut‐on‐a‐chip” array methods allow automated experimental designs incorporating various chemical, medicinal and mechanical morphogen conditions.…”

“…24 The probiotic combination of Lactobacillus helveticus and Bifidobacterium longum helped reverse WA-stress-induced changes in the mouse hypothalamic-pituitary-adrenal axis and WA stress-induced visceral hyperalgesia by blocking decrease of NR3C1 in the hypothalamus, hippocampus and prefrontal cortex. 25 These reports support the potential of HES1-CLDN1 and NR3C1 acting as equilibrium maintaining gene circuits consists of three genes that regulate each other in a cyclical manner and their potential roles in homeostasis of the Microbiota-Gut-Brain Axis. Future advances in personalized probiotics based, in part, on 4D Nucleome algorithms represent a potentially promising therapeutic area.…”

Gut Microbiota-Brain Axis Modulation by a Healthier Microbiological Microenvironment : Facts and Fictions

“…Authors found that one month intake of fermented milk product with probiotic in healthy women was associated with alteration in activity of brain regions that control central processing of emotion and sensation. In this issue of the Journal of Neurogastroenterology and Motility, 16 authors from France, Canada, Sweden studied the comparative effects of treatment of mice with different probiotics (B. longum and L. helveticus) for 2 weeks on the perception of visceral pain induced by colorectal distension after chronic stress and on the activity of the HPA axis. The authors concluded that the combination of the 2 probiotics showed greater efficacy than either alone in regulating glucocorticoid induced negative feedback on the HPA axis; hence, they suggested that this observation may have implication in the treatment of stress-induced visceral pain.…”