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.
In the gastrointestinal tract (GIT), proteolytic activity is tightly regulated to prevent inappropriate and potentially harmful proteolysis. In IBD this regulation is broken and our recent work has demonstrated that elastolytic activity is significantly increased in colonic epithelium from IBD patients. We have shown that the expression of the only elastase released by epithelial cells, ELA2 is up‐regulated; and the selective elastase inhibitor ELAFIN is severely down regulated in colonic epithelium from IBD patients. We showed that oral treatments with ELAFIN‐expressing L. Lactis bacteria restored proteolytic balance in the inflamed gut and was protective against acute and chronic colitis. ELAFIN is a low‐molecular weight molecule (10‐kDa), which specifically inhibits elastases. At N‐terminal terminus, a cationic helix showed anti‐microbial activities and could interact with phospholipids. Moreover ELAFIN is also able to inhibit NFkB and AP‐1 activation but this domain is not localized on protein. Therefore, several mechanisms of action are thus possible to explain ELAFIN’s protective property.
Objectives
If ELAFIN‐recombinant L. lactis has to be considered as a possible treatment for IBD in human, there is an absolute need to define the mechanisms by which ELAFIN delivery protects against intestinal inflammation.
Methods
We generated and expressed in LAB ELAFIN’s mutants allowing investigation the biological properties of ELAFIN individually. These different forms of ELAFIN‐recombinant LAB were co‐culture with thapsigargin (10mg/ml) and ELAFIN (107 CFU/well). After 6H, cells were additionally exposed to gentamicin (100 mg/ml) to limit bacterial development. The barrier function was measured using FITC‐dextran passage through the epithelial layer. The elastolytic activity and CXCL8 release were quantified from the culture media. Expression of inflammatory mediators was quantified by qPCR.
Results
Addition of thapsigargin for 24H on Caco2 cells induced ER‐stress and disruption of elastolytic balance. ELAFIN expression was decreased with up‐regulation of ELA2, leading to increase of elastolytic activity in medium, disclosed in IBD patients. Concomitantly, barrier function was reduced, and expression of CXCL8, CXCL10 and hBD2 was increased. Co‐culture with ELAFIN expressing‐LAB normalized all these parameters confirming anti‐inflammatory properties of ELAFIN. Neutralization of a‐helix (mutant K44D/K50G) did not modify ELAFIN’s properties. However, disruption of protease inhibitory function (mutant A62G/M63G) led to unability of ELAFIN mutant to modify permeability and inflammatory phenotype induced by exposure of intestinal epithelial cells to thapsigagin.
Conclusion
This suggests that anti‐inflammatory activity of ELAFIN is based on the control of elastase activity released by epithelial cells.
Cervical cancer screening rates in Haiti are concerningly low. Access to health-related information and health literacy may be important determinants of engagement in cervical cancer screening. This study explored the relationship between sociodemographics,literacy, and sources of information on cervical cancer screening among Haitian women. A secondary data analysis was conducted using USAID Demographics and Health Survey Haiti household data from 2016–2017. Univariate logistic regressions identified significant predictor covariates measuring sociodemographics and sources of information in cervical cancer screening uptake.Two multivariate logistic regression models with adjusted odds ratios were developed using the significant predictor variables from the univariate analysis. N = 610 women responded to questions pertaining to cervical cancer screening. The first multivariate model evaluating sociodemographics demonstrated an economic background of poorer (aOR = 4.06, 95% CI [1.16,14.27]) and richest (aOR = 19.10 , 95% CI[2.58,141.57]), higher education levels (aOR 7.58 , 95% CI [1.64,34.97]), and having insurance (aOR = 16.40, [95% CI 2.65, 101.42]) were significant predictors of cervical cancer screening. The second model evaluating literacy and sources of information indicated that access to a television (aOR = 4.28, 95% CI [1.21,9.34]), mobile phone ownership (aOR = 4.44, 95% CI [1.00,5.59]), and reading the newspaper (aOR = 3.57, [95% CI 1.10,11.59]) were significant predictors of cervical cancer screening. Diverse health communication initiatives that are adapted for literacy level and that incorporate multimedia components may effective in raising women’s cervical cancer knowledge and awareness , and increasing intention and uptake of cervical cancer screening in Haiti.
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