Table 3.
Details of studies on immunity and natural defenses.
| Reference [Language] |
Study Dates | Population | Study Design Arms, n |
Probiotic Regimen | Results (vs. Control) | Adverse Events |
|---|---|---|---|---|---|---|
| Chen, 2007 [27] [Chinese] |
Not stated | Children 0–48 months old Healthy with low salivary sIgA |
Randomized, controlled Probiotic, n = 20 No Intervention, n = 8 |
1 sachet BID Orally. For 14 days |
Increase in salivary sIgA compared to baseline in probiotic but not in controls. No statistical analyses reported. |
n.r. |
| Cazzola, 2010 [31] [English] | December 2006–March 2007 | Children 3–7 years old ≥ 3 infections (ENTI, URTI, GI illness) in past winter. |
Randomized, double-blind, placebo-controlled Probiotic, n = 62 Placebo, n = 73 |
1 sachet QD Orally. For 3 months |
Lower incidence of ENTI, URTI, or GI health events (51.6% vs. 68.5%; p = 0.044), representing a 25% reduction in RR. Less participants experienced school day losses for sickness (25.8% vs. 42.5%; p = 0.0443). |
2 SAEs; 1 abdominal pain in placebo and 1 otitis media in Probiotic. 24 AEs in 20 children (9 in placebo, 11 in Probiotic), most were expected respiratory or GI events. |
| Pantovic, 2013 [29] [English] | Not stated | Children 6–42 months old low IgA levels hospitalized for URTI or ENTI |
Open-label, uncontrolled before–after study Probiotic, n = 31 |
1 sachet QD Orally. For 6 months |
Increase in serum IgA levels in 35% of the children after 3 months and 81% after 6 months (p < 0.05), normalized to normal range. Clinical improvement in URTI after 3 months, and no infections diagnosed between 3 and 6 months. |
n.r. |
| Liu, 2015 [18] [Chinese] |
May 2011–May 2014 | Children 3–38 months old Non-infectious diarrhea |
Randomized, controlled Smecta® + Probiotic, n = 75 Smecta®, n = 75 |
<12 months: 0.33 sachet TID 13–24 months: 0.5 sachet BID 24–36 months: 1 sachet BID Orally. For 3 days |
Lower serum levels of pro-inflammatory cytokines IL-6 and IL-17 (p < 0.05). Higher levels of salivary sIgA (p < 0.05). |
n.r. |
| Stojkovic, 2016 [32] [English] | Not stated. | Children <5 years Hospitalized during the past year for respiratory diseases |
Open label, before–after Probiotic, n = 78 Divided into 3 groups based on medical history: G1: URTI + wheezing, n = 50 G2: URTI w/o wheezing, n = 17 G3: Wheezing w/o URTI, n = 11 |
1 sachet QD Orally. For 9 months |
Decrease in URTI and wheezing after 3 months (p < 0.01), reaching 0% after 6 months. No recurrence of URTI or wheezing (0%) in all groups) at 9 months. Increase in serum IgA from 3 months onwards (p < 0.01). Increase in serum IgG from 3 months onwards (p < 0.01). Decrease in serum IgE at 9 months (p < 0.01). |
None observed. |
| Manzano, 2017 [13]; De Andres, 2018 [28] [English] |
August 2014–December 2016 | Children 3–12 months old Healthy |
Randomized, double-blind, placebo-controlled L. helveticus Rosell®-52, n = 52 B. infantis Rosell®-33, n = 53 B. bifidum Rosell®-71, n = 51 Placebo, n = 52 |
3 × 109 CFU of each single strain QD Orally. For 8 weeks |
Increased IL10/IL12 ratio (anti-inflammatory) in B. infantis (p < 0.01). Increased TNFα/IL10 ratio (pro-inflammatory) in L. helveticus and placebo (p < 0.01). Placebo group showed a microbiota composition related to the weaning process, while the probiotics groups were similar to 4-month-old un-weaned infants. |
No difference between groups for the number and severity of adverse events (mild) nor in behavioral and anthropometric parameters. No SAEs observed. |
| Xiao, 2019 [14] [English] |
December 2014–November 2015 | Children 3.5–6 months old Healthy |
Randomized, placebo-controlled Probiotic, n = 66 Placebo, n = 66 |
1 sachet QD Orally, in formula. For 4 weeks |
Maintained higher fecal sIgA levels at the end of the four-week treatment period (p < 0.05). | All AEs reported were minor and more frequent in the placebo group. Probiotic: 37 AEs; 21 respiratory, 12 GI, 4 dermatological. Placebo: 69 AEs; 38 respiratory, 15 GI, 16 dermatological. No effect on growth rate. |
| Qiu, 2020 [30] [Chinese] |
September 2017–May 2018 | Full-term neonates with hyperbilirubinemia | Randomized, controlled Blue light photo- therapy + Probiotic, n = 32 Blue light photo- therapy, n = 32 |
1 sachet BID, for 5 days |
Reduction in IL-6 vs. controls (p < 0.05). Reduction in IL-6 and IL-8 at day 3 and 5 vs. baseline (p < 0.05). Increase in IL-10 at day 5 vs. baseline (p < 0.05). Increase in serum catalase levels at day 5 vs. baseline (p < 0.05). |
n.r. |
BID, twice a day; CFU, colony-forming unit; ENTI, ear-nose-throat infection; GI, gastrointestinal; n.r., not reported; QD, once daily; sIgA, secretory immunoglobulin A; TID, three times per day; URTI, upper respiratory tract infection.