Safety and Effect of a Low- and High-Dose Multi-Strain Probiotic Supplement on Microbiota in a General Adult Population: A Randomized, Double-Blind, Placebo-Controlled Study

Abstract

Few studies have focused on dose-response analyses of multi-strain probiotics in the general adult population. This study aimed at comparing how a low- and high-dose of a multi-strain probiotic supplement (containing <i>Lactobacillus helveticus</i> R0052, <i>Lactobacillus rhamnosus</i> R0011, <i>Lactobacillus casei</i> R0215, <i>Pediococcus acidilactici</i> R1001, <i>Bifidobacterium breve</i> R0070, <i>Bifidobacterium longum</i> ssp. <i>longum</i> BB536, <i>Lactobacillus plantarum</i> R1012, <i>Lactococcus lactis</i> ssp. <i>lactis</i> R1058) affected microbiota composition, transit persistence and safety in adults. After a 7-d baseline, participants were randomized to receive capsules containing 5 or 25 billion CFU, or placebo daily for 28 days, followed by a 7-d washout. Digestive health and general wellness were assessed. Fecal microbiota composition was analyzed using 16S rRNA gene amplicon sequencing and strain persistence, by qPCR. Participants' gastrointestinal and general wellbeing were unaffected. No adverse events were associated with either dose. Supplemented strains contributed to the <i>Lactobacillus</i> and <i>Bifidobacterium</i> genera detected in stool, with 0.40 ± 0.11% and 0.51 ± 0.26%, respectively, in the high-dose group. Strain-specific qPCR assays revealed variable levels of post-intervention persistence between strains. Sequencing and composition analyses using the 16S V4 region revealed a decrease in <i>Holdemania</i> and increase in <i>Bacteroidales</i>. The formulation was well tolerated in this sample of the general adult population, even at the higher dose. The strains appear to have influenced microbiota composition minimally, as expected in the absence of dysbiosis, and consistently with the dose administered. Overall, the results provide a rationale to study the effects this formulation on microbiota composition in individuals exhibiting dysbiosis associated with metabolic disorders or obesity.