Preventive Effect of Cow's Milk Fermented with Lactobacillus paracasei CBA L74 on Common Infectious Diseases in Children: A Multicenter Randomized Controlled Trial

Abstract

Background: Fermented foods have been proposed to prevent common infectious diseases (CIDs) in children attending day care or preschool.

Objectives: To investigate the efficacy of dietary supplementation with cow's skim milk fermented with the probiotic Lactobacillus paracasei CBA L74 in reducing CIDs in children attending day care or preschool. Methods: Multicenter, randomized, double-blind, placebo-controlled trial on healthy children (aged 12-48 months) consuming daily 7 grams of cow's skim milk fermented with L. paracasei CBA L74 (group A), or placebo (maltodextrins group B) attending day care or preschool during the winter season. The main outcome was the proportion of children who experienced ≥1 episode of CID during a 3-month follow-up. Fecal biomarkers of innate (α- and β-defensins, cathelicidin) and acquired immunity (secretory IgA) were also monitored. Results: A total of 126 children (71 males, 56%) with a mean (SD) age of 33 (9) months completed the study, 66 in group A and 60 in group B. At intention to treat analysis, the proportion of children presenting ≥1 CID was 60% in group A vs. 83% in group B, corresponding to an absolute risk difference (ARD) of -23% (95% CI: -37% to -9%, p < 0.01). At per-protocol-analysis (PPA), the proportion of children presenting ≥1 CID was 18% in group A vs. 40% in group B, corresponding to an absolute risk difference (ARD) of -22% (95% CI: -37% to -6%, p < 0.01). PPA showed that the proportion of children presenting ≥1 acute gastroenteritis (AGE) was significantly lower in group A (18% vs. 40%, p < 0.05). The ARD for the occurrence of ≥1 AGE was -22% (95% CI: -37% to -6%, p < 0.01) in group A. Similar findings were obtained at PPA regarding the proportion of children presenting ≥1 upper respiratory tract infection (URTI), which was significantly lower in group A (51% vs. 74%, p < 0.05), corresponding to an ARD of -23% (95% CI: -40% to -7%, p < 0.01). Significant changes in innate and acquired immunity biomarkers were observed only in subjects in group A. Conclusions: Dietary supplementation with cow's skim milk fermented with L. paracasei CBA L74 is an efficient strategy in preventing CIDs in children.

Keywords: acquired immunity; acute gastroenteritis; gut microbiota; immunonutrition; innate immunity; probiotics; upper respiratory tract infections.

Figure 1

The design of the study.

Figure 2

The flow of children through the study, Group A: Cow’s milk fermented milk with L. paracasei CBA L74; Group B: Placebo.

Figure 3

The proportion of children presenting at least one common infectious disease during the study period (intention-to-treat analysis). Group A: Cow’s milk fermented with L. paracasei CBA L74; Group B: Placebo. p = 0.002, chi-square test p < 0.01, absolute risk difference: −23% (95% CI: −37% to −9%, binomial regression).

Figure 4

The proportion of children requiring medication use (i.e., antibiotics, antipyretics, steroids) during the study period. Group A: Cow’s milk fermented with L. paracasei CBA L74; Group B: Placebo.

Figure 5

Determination of innate and acquired immunity biomarkers at enrolment and after 3-month treatment in children evaluated in the two study groups. Panel a: α-defensin; panel b: β-defensin; panel c: LL-37; panel d: sIgA. Values are means and 95% confidence intervals from random effect linear regression with correction for baseline. Group A: Cow’s milk fermented with L. paracasei CBA L74; Group B: Placebo.