Evidence for beneficial effects of corticotropin releasing hormone (CRH) antagonists in abdominal and pelvic organs is emerging in preclinical studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement a compilation of preclinical studies using CRH receptor antagonists as a treatment for abdominal and pelvic disease was carried out. The Animal Research: Reporting of In Vivo Experiments (ARRIVE) essential 10 guidelines were used to determine quality of the included studies. A total of 40 studies from the last 15 years studying irritable bowel syndrome, inflammatory bowel disease, endometriosis, enteritis, stress impact on gastrointestinal processes and exogenous CRH administration effects were included. Blockage of the CRH receptor 1 was mainly associated with beneficial effects while that of CRH receptor 2 worsened studied effects. However, time of administration, route of administration and the animal model used, all had an impact on the beneficial outcomes. Frequency of drugs administered indicated that astressin-2B, astressin and antalarmin were among the most utilized antagonists. Of concern, studies included were predominantly carried out in male models only, representing a gender discrepancy in preclinical studies compared to the clinical scenario. The ARRIVE score average was 13 with ~60% of the studies failing to randomize or blind the experimental units. Despite the failure to date of the CRH antagonists in moving across the clinical trials pipeline, there is evidence for their beneficial effects beyond mood disorders. Future pre-clinical studies should be tailored towards effectively predicting the clinical scenario, including reduction of bias and randomization.

Background/Objective: Probiotic and vitamin D supplements are widely studied in clinical and animal studies as potential treatments for inflammatory bowel disease. However, their potential synergistic or additive effect in ameliorating colitis development is still poorly understood. The aim of this study was to investigate the potential beneficial enhancement of combining a mixed-strain probiotic with vitamin D supplementation in a colitis animal model. Method: After 5 days of acclimation, C57BL/6 mice received Vivomixx probiotic (at least 1 × 10⁹ Colony-Forming Units) and/or vitamin D (5 IU/g) in drinking water and chow, respectively, for 7 days prior to intracolonic TNBS-induced colitis and until sacrifice. On day 10, animals were sacrificed, and colons were collected to assess colonic damage, cytokine and chemokine expression, total M1 macrophage phenotype, and neutrophil recruitment. Serum and fecal samples were collected to assess vitamin D levels and microbiome composition. Results: Administration of probiotic and vitamin D alone or combined decreased colonic damage and neutrophil recruitment and activity. This effect was associated with an increase in the active form of vitamin D in serum and mucosal barrier integrity. However, administration of probiotics and/or vitamin D did not modulate macrophage infiltration or the M1 pro-inflammatory phenotype. Conclusions: These results suggest that combined probiotic and vitamin D supplementation attenuates TNBS-induced colitis by targeting neutrophil infiltration while enhancing the mucosal barrier. This alternative approach may offer protective potential for IBD management.