Probiotic intervention not beneficial to prevent antibiotic-associated diarrhea in absence of antibiotic-induced microbiome disruption

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the most common uses of probiotics is for prevention of antibiotic-associated diarrhea (AAD). Here we report on the PLAY-ON study (Probiotics: Live and Active Yogurt Cultures for Healthy Children ON Antibiotics) which was a randomized, placebo-controlled, double-blinded study in healthy children who were prescribed antibiotics for acute outpatient upper respiratory illnesses, such as bacterial sinusitis or streptococcal pharyngitis. The treating clinician determined the antibiotic, its dosage and duration. Participants received either a control yogurt or a yogurt containing the probiotic, Bifidobacterium animalis subsp. lactisBB-12. Our primary aim was to determine whether the probiotic prevented AAD. The microbiome of participants was examined longitudinally. Diarrhea rates were nearly identical at 2% (3 cases in the active group, 2 cases in the control group); adverse events were also similar between groups. Thus, our study did not find any differences in the incidence of AAD between those who took the probiotic and the control group. The microbiota of both groups returned to baseline by day 14 and assessment of the microbiome showed no difference in levels or types of antibiotic resistance genes. Broad-spectrum antibiotics are associated with higher rates of adverse events, including AAD, than narrow-spectrum antibiotics, as observed in children taking antibiotics for respiratory tract infections3,4.However, if the antibiotic does not significantly disturb the microbiota there may be no discernable role for the probiotic. This hypothesis is supported by the participants who used broad spectrum penicillins had a significantly higher rate of diarrhea compared to narrow spectrum antibiotic users, 9.1% and 0.51% respectively, (p=0.004)This study suggests that prescribing short-course, narrow spectrum antibiotics can reduce microbiome disruptions, concomitant AAD, and the need for probiotic intervention. . The antibiotics used in our study did not disrupt the microbiome to the extent expected, which likely accounted for the low observed incidence of AAD. Importantly, this observation can inform clinicians’ choice of antibiotic, steering them toward equally therapeutic antibiotics that are less disruptive to the microbiota and better tolerated. Although probiotics are often recommended to prevent AAD, our study demonstrates that in the absence of microbiome disruption, they may not provide benefit.