Probiotic stool secretory immunoglobulin A modulation in children with gastroenteritis: a randomized clinical trial

Abstract

Background We previously conducted the Probiotic Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) study, which identified no improvements in children with acute gastroenteritis (AGE) administered a probiotic. However, the aforementioned study did not evaluate immunomodulatory benefits. Objectives The object of this study was to determine if stool secretory immunoglobulin A (sIgA) concentrations in children with AGE increase more among participants administered a Lactobacillus rhamnosus / helveticus probiotic compared with those administered placebo. Methods This a priori planned multicenter, randomized, double-blinded, placebo-controlled ancillary study enrolled children presenting for emergency care who received a 5-d probiotic or placebo course. Participants submitted stool specimens on days 0, 5, and 28. The primary endpoint was the change in stool sIgA concentrations on day 5 compared with baseline. Results A total of 133 ( n = 66 probiotic, 67 placebo) of 886 PROGUT participants (15.0%) provided all 3 specimens. Median stool sIgA concentrations did not differ between the probiotic and placebo groups at any of the study time points: day 0 median (IQR): 1999 (768, 4071) compared with 2198 (702, 5278) ( P = 0.27, Cohen's d = 0.17); day 5: 2505 (1111, 5310) compared with 3207 (982, 7080) ( P = 0.19, Cohen's d = 0.16); and day 28: 1377 (697, 2248) compared with 1779 (660, 3977) ( P = 0.27, Cohen's d = 0.19), respectively. When comparing measured sIgA concentrations between days 0 and 5, we found no treatment allocation effects [β: −0.24 (−0.65, 0.18); P = 0.26] or interaction between treatment and specimen collection day [β: −0.003 (−0.09, 0.09); P = 0.95]. Although stool sIgA decreased between day 5 and day 28 within both groups ( P < 0.001), there were no differences between the probiotic and placebo groups in the median changes in sIgA concentrations when comparing day 0 to day 5 median (IQR) [500 (−1135, 2362) compared with 362 (−1122, 4256); P = 0.77, Cohen's d = 0.075] and day 5 to day 28 [−1035 (−3130, 499) compared with −1260 (−4437, 843); P = 0.70, Cohen's d = 0.067], respectively. Conclusions We found no effect of an L. rhamnosus / helveticus probiotic, relative to placebo, on stool IgA concentrations. This trial was registered at clinicaltrials.gov as NCT01853124.

Intestinal Microbial Composition of Children in a Randomized Controlled Trial of Probiotics to Treat Acute Gastroenteritis

“…Future studies should capture the role of other microorganisms, such as viruses, bacteriophages, fungi, and protists, as these are also quite likely to have a biological role in human development in both in health and in the context of various disease states ( Milani et al., 2018 ; Rao et al., 2021 ). While our previous work found no relationship between probiotic administration and secretory fecal IgA levels ( Freedman et al., 2021a ), within the same cohort we found in the current study relationships between genus level abundance of Veillonella , Blautia and Alstipes and sIgA that were age specific. A previous study focused on the association of immunoglobulins and the infant gut microbiota identified an association between age and declining IgA levels, which was also linked to changes in gut microbiota diversity ( Janzon et al., 2019 ).…”

“…Severity of the acute illness was assessed by using the Modified Veskari Scale score ( Schnadower et al., 2013 ; Freedman et al., 2018 ; Freedman et al., 2021a ).…”

“…As part of an a priori planned sub-study, levels of secretory IgA in stools were measured using a commercial immunoassay, as previously described ( Freedman et al., 2021a ).…”

Use of Probiotics for the Management of Acute Gastroenteritis in Chilldren : A Systematic Review

“…Freedman, et al (2021) 12 showed median stool sIgA concentrations did not differ between the probiotic and placebo groups at any of the study time points: day 0 median (IQR): 1999 (768, 4071) compared with 2198 (702, 5278) (P = 0.27, Cohen's d = 0.17); day 5: 2505 (1111, 5310) compared with 3207 (982, 7080) (P = 0.19, Cohen's d = 0.16); and day 28: 1377 (697, 2248) compared with 1779 (660, 3977) (P = 0.27, Cohen's d = 0.19), respectively. When comparing measured sIgA concentrations between days 0 and 5, they found no treatment allocation effects [β: −0.24 (−0.65, 0.18); P = 0.26] or interaction between treatment and specimen collection day [β: −0.003 (−0.09, 0.09); P = 0.95].…”

“…Although stool sIgA decreased between day 5 and day 28 within both groups (P < 0.001), there were no differences between the probiotic and placebo groups in the median changes in sIgA concentrations when comparing day 0 to day 5 median (IQR) [500 (−1135, 2362) compared with 362 (−1122, 4256); P = 0.77, Cohen's d = 0.075] and day 5 to day 28 [−1035 (−3130, 499) compared with −1260 (−4437, 843); P = 0.70, Cohen's d = 0.067], respectively. 12 Study on Vietnam showed placebo group had a median time from the first dose of study medication to the beginning of the first 24-hour period without diarrhea of 43 hours (inter-quartile range (IQR): 15-66 hours), while the probiotic group had a median time of 35 hours (IQR: 20-68 hours) (acceleration factor: 1.09; 95% confidence interval: 1.78-1.51; p=1.62) In addition, there was no evidence to suggest that therapy with probiotics was effective in any of the pre-defined subgroups, nor was it substantially linked with any secondary outcome. 13…”