Beta-defensin 110 (Homo sapiens)

Background: The pathogenesis of infant colic is poorly defined. Gut microbiota seems to be involved, supporting the potential therapeutic role of probiotics. Aims: To assess the rate of infants with a reduction of ≥50% of mean daily crying duration after 28 days of intervention with the probiotic Bifidobacterium animalis subsp. lactis BB-12® (BB-12). Secondary outcomes were daily number of crying episodes, sleeping time, number of bowel movements and stool consistency. Methods: Randomized controlled trial (RCT) on otherwise healthy exclusively breastfed infants with infant colic randomly allocated to receive BB-12 (1 × 109 CFU/day) or placebo for 28 days. Gut microbiota structure and butyrate, beta-defensin-2 (HBD-2), cathelicidin (LL-37), secretory IgA (sIgA) and faecal calprotectin levels were assessed. Results: Eighty infants were randomised, 40/group. The rate of infants with reduction of ≥50% of mean daily crying duration was higher in infants treated with BB-12, starting from the end of 2nd week. No infant relapsed when treatment was stopped. The mean number of crying episodes decreased in both groups, but with a higher effect in BB-12 group (-4.7 ± 3.4 vs -2.3 ± 2.2, P < 0.05). Mean daily stool frequency decreased in both groups but the effect was significantly higher in the BB-12 group; stool consistency was similar between the two groups. An increase in Bifidobacterium abundance (with significant correlation with crying time reduction), butyrate and HBD-2, LL-37, sIgA levels associated with a decrease in faecal calprotectin level were observed in the BB-12 group. Conclusions: Supplementation with BB-12 is effective in managing infant colic. The effect could derive from immune and non-immune mechanisms associated with a modulation of gut microbiota structure and function.

To evaluate the administration of Bifidobacterium animalis subsp. lactis, BB-12® (BB-12) on infant colic in breastfed infants, a double-blind, placebo-controlled randomised study was conducted in Chengdu, China from April 2016 to October 2017 with 192 full-term infants less than 3 months of age and meeting the ROME III criteria for infant colic. After a 1-week run-in the infants were randomly assigned to receive daily BB-12 (1×109 cfu/day) or placebo for 3 weeks. Crying/fussing time were recorded using a 24 h structured diary. The primary endpoint was the proportion of infants achieving a reduction in crying and fussing time of ≥50% from baseline. Parent's/caregiver's health related quality of life was measured using a modified PedsQL™ 2.0 Family Impact Module and immunological biomarkers were evaluated from faecal samples at baseline and after the 21-day intervention. The percentage of infants achieving a reduction in the daily crying/fussing time ≥50% after the 21-day intervention was significantly higher in the infants supplemented with BB-12 (P<0.001). The mean number of crying episodes was significantly reduced in the BB-12 group compared to the placebo group (10.0±3.0 to 5.0±1.87 vs 10.5±2.6 to 7.5±2.8, respectively) (P<0.001) and the mean daily sleep duration was markedly increased from baseline to end of intervention in the BB-12 group compared to the infants in the placebo group (60.7±104.0 vs 31.9±102.7 min/day, respectively) (P<0.001). The faecal levels of human beta defensin 2, cathelicidin, slgA, calprotectin and butyrate were statistically higher in the BB-12 group compared to the placebo group after the 21-day intervention. At the end of the intervention the parent's/caregiver's physical, emotional and social functioning scores were significantly higher for the BB-12 group compared to the placebo group (all P<0.05). Supplementation of BB-12 is effective in reducing crying and fussing in infants diagnosed with infant colic.

Background: Spontaneous preterm birth (sPTB) is a major contributor to infant mortality and its etiology remains poorly understood. Host immunity and maternal stress may play a role in the pathogenesis of sPTB but mechanisms are poorly delineated. Antimicrobial proteins in the cervicovaginal space, such as beta defensins, modulate immune responses to bacteria and have been shown to modulate the risk of sPTB from non-optimal microbiota. While stress is known to induce immunological changes, no study has examined the interplay between maternal stress and the immune response in association with sPTB. Objectives: Our objectives were to determine whether psychosocial stress was associated with a mediator of the immune system in the cervicovaginal space, beta defensin-2, and to examine the combined impact of high stress and low cervicovaginal beta defensin-2 levels on the odds of sPTB. Study design: From the Motherhood & Microbiome cohort study (n=2000), we performed a secondary, nested case-control study, frequency matched by race/ethnicity, of 519 pregnant women (110 sPTB and 409 term). Stress and cervicovaginal beta defensin-2 levels were measured at 16-20 weeks of gestation. Stress was dichotomized at a score of 30 on Cohen's Perceived Stress Scale (PSS-14). We measured cervicovaginal beta defensin-2 levels with ELISA and dichotomized at the median. We modeled associations of high stress and low cervicovaginal beta defensin-2 levels using multivariable logistic regression. We also compared the proportion of women with high stress and low cervicovaginal beta defensin-2 levels among women with spontaneous preterm and term births using Chi-Square tests. We modeled adjusted associations of stress and cervicovaginal beta defensin-2 levels with odds of sPTB using logistic regression. Results: The majority of the study population was non-Hispanic black (72.8%), insured by Medicaid (51.1%), and had a PSS-14 score < 30 (80.2%). High stress was associated with reduced adjusted odds of low beta defensin-2 levels (aOR 0.63, 95% CI: 0.38 -0.99). In a model adjusted for race and smoking, both high stress (aOR 1.72, 95% CI: 1.03-2.90) and low beta defensin-2 (aOR 1.58, 95% CI: 1.004-2.49) were associated with increased odds of sPTB. We then built a model of the four possible combinations of low and high stress and low and high beta defensin-2 levels with the odds of sPTB. Women with either high stress (aOR 1.37, 95% CI: 0.68 - 2.78) or low beta defensin-2 (aOR 1.40, 95% CI: 0.83-2.34), had slightly elevated but not significantly increased odds of sPTB compared to women with neither exposure. However, women with both high stress and low beta defensin-2 had significantly elevated odds of sPTB compared to women with neither exposure (aOR 3.16, 95 % CI: 1.46 - 6.84). Conclusion: High perceived stress and low cervicovaginal beta defensin-2 levels are associated with higher odds of sPTB, and when present concurrently, they result in the highest odds of sPTB in a largely non-Hispanic black cohort. Our findings warrant further work to examine social determinants of health and the host cervicovaginal immune responses that may modulate the pathogenesis of sPTB.