Discussion
ADVERSE EVENTS
To our knowledge this is the first clinical trial to evaluate structural and functional fecal microbiome response to this 14-strain probiotic intake by shotgun metagenomics in healthy individuals. The results presented here showed that alpha- and beta-diversity of the fecal microbiota structure was not significantly altered in response to probiotic intake. However, significant changes were observed when functional genes were assessed. Abundance of certain genes involved in several functional pathways, including phenylalanine metabolism, O-antigen nucleotide sugar biosynthesis, bacterial chemotaxis, and flagellar assembly were significantly altered following probiotic intake. No significant changes in stool frequency or consistency, fecal biochemistry, or breath tests of methane and hydrogen were observed.It has been widely observed that, in healthy individuals, the alpha- and beta diversity of gut microbiome composition tend to be stable in response to probiotic intervention. A systematic review conducted in 2016 by Kristensen et al. assessed seven RCTs investigating the effect of probiotic supplementation on the gut microbiota of healthy adults and concluded that probiotic supplementation did not affect composition in healthy adults (Despite the stability of the overall microbial composition among healthy adults, probiotic supplementation has been shown to support many aspects of health and well-being. Previous studies based on metabolic pathway analysis have reported a dissociation between microbiota structure and function, demonstrating that functionality can change in response to dietary intervention with minimal compositional changes (Another interesting result from this trial is the product specific species analysis of the fecal sample. The data showed that the number of individuals presenting with product specific species after 8 weeks of intervention depended on the species and individual. The main limitation to consider here was that the data was not analyzed at strain level. The differential contribution of product specific probiotic strains on host health is an interesting angle that should be explored further. This though is a hugely complex task given the complex bacterial consortia that makes up the multi-strain probiotic product. It should be noted that some product specific species had a lower prevalence (bacteria present in less than 50% of the samples) in the fecal microbiome of health adults, this should be further assessed.There were no serious adverse events reported and only few mild and transient adverse events recorded. Consistent with other studies, the consumption of multi strain probiotics at a dose of 8x10Despite these limitations the data provided here in terms of composition, diversity, and functional gene alterations in fecal microbiome of healthy individuals offer an important foundation for our understanding of intestinal microbiome dynamics in response to multi-strain probiotic intake.