Upper respiratory tract infections (URTI) are highly prevalent worldwide. Although probiotics have shown potential in preventing URTI, evidence in healthy adults remains limited. Lacticaseibacillus rhamnosus CRL 1505 is a strain with immunomodulatory effects in preclinical studies and benefits in healthy children. Based on this evidence, a randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted in healthy adults, receiving either L. rhamnosus CRL 1505 (1 bln/day) or placebo for 12 weeks, with a 4-week follow-up. The primary endpoint was the proportion of participants experiencing URTI episodes (at least one, two, or three episode(s)). The secondary endpoints included: number and duration of URTI episodes, URTI-free time, symptom severity, use of symptomatic medication, salivary IgA levels, and safety outcomes. Results show that L. rhamnosus CRL 1505 significantly reduced the number of participants experiencing ≥3 URTI episodes at 16 weeks compared with placebo. The probiotic group experienced fewer URTI episodes per participant, a shorter cumulative duration of URTIs, and a higher URTI-free time rate. Probiotic supplementation significantly reduced the use of symptomatic medications. In conclusion, daily supplementation with L. rhamnosus CRL 1505 reduced the burden of URTI in healthy adults, specifically of those experiencing more episodes, by decreasing infection frequency, duration, and medication use.

The two probiotic bacteria Lactobacillus helveticus MIMLh5 and L. acidophilus NCFM exhibit homology, are both equipped with an S-layer made up of highly homologous proteins and are capable of stimulating Th1-inducing signals in dendritic cells. In this study, we aimed to compare the two strains as regards the thickness of the S-layer and their capacity to induce the production of the two Th1-inducing cytokines IL-12 and IFN-β. For both bacteria, stimulation with an increasing number of bacteria led to the higher and prompter production of IL-12 and IFN-β, but at all MOIs tested, the IL-12 response induced by NCFM was always the strongest. For both bacteria, the induction of IL-12 peaked at a multiplicity of infection (MOI) of 2–5, while IL-10, known to inhibit the induction of IL-12 cytokines, was induced more slowly and continued to increase at a higher MOI. By employing specific inhibitors, MIMLh5 and NCFM were also shown to activate different MAP kinase pathways. Endocytosed MIMLh5 showed higher survival in the DCs compared to NCFM. In the presence of mannan, previously shown to accelerate endosomal killing of Gram-positive bacteria, the survival of MIMLh5 was strongly decreased, and IL-12 increased to a level close to that induced by NCFM without the addition of mannan, indicating the importance of rapid endosomal degradation for a strong IL-12 response. When measuring the S-layer thickness, MIMLh5’s S-layer appeared to be more than twice the thickness of NCFM and exhibited an elastic modulus approximately twice as high, which is a measure of a cell’s resistance to an applied mechanic stress. When the two strains were depleted of S-layer protein, the elastic modulus was comparable. Together, our data suggests that the thicker S-layer of MIMLh5 compared to NCFM may contribute to its endosomal survival, thus reducing its capacity to induce IL-12. This may constitute an important parameter in the selection of probiotic bacteria for specific purposes.