Tolerability and Functional Assessment of a Novel Children's Synbiotic

Overview

Recent data support the use of specific probiotic strains in a pediatric population. However, given the wide number of commercial products available, and contradictory data in the literature, healthcare providers and consumers are uncertain about whether or not to use probiotics in children and which one(s) to choose. While much progress has been made in understanding the gastrointestinal microbiota and its role in the balanced development of the infant immune system, the tolerability and efficacy of introducing beneficial microbes into the pediatric gastrointestinal tract remain underexplored. The purpose of this study is to investigate the effect of a 9 strain synbiotic consortium comprised of strains with previous pediatric clinical data for use in modulating airway sensitivity, gastrointestinal discomfort, dermatological inflammation, and reduction in the duration and severity of upper respiratory tract infections in a pediatric population.

During infancy and childhood, environmental factors including the maternal vaginal and skin microbiomes, breast milk microbiota, breast milk, geographic location, and use of antibiotics will exert significant influence over the offspring's microbiota and have a determinant impact on their health later in life. Unfavorable environmental exposures, coupled with an immature immune system in early life can, therefore, confer suboptimal immune responses that can lead to the development of extra-gastrointestinal conditions such as allergic rhinitis, asthma, and atopic dermatitis-which affects 15-20% of the world's population. Furthermore, while the indiscriminate use of antibiotics has decreased, they remain standard-of-care for most childhood infections, and unfortunately, often result in short- or long-term disruption of the patient's microbiome. Constipation is a common childhood gastrointestinal disorder, with a worldwide prevalence between 0.7-29.6%. Its etiology is multifactorial and usually not due to underlying conditions. Few studies have explored the implications of the intestinal or fecal microbiota in childhood constipation, yet some have shown benefits of various probiotic compositions in reducing transit time and improving bowel movement frequency. Dysbiosis of the gut microbiome may play an important role in functional constipation. PDS-08™ is a novel synbiotic, comprised of nine probiotic bacterial strains and fructooligosaccharide with inulin (FOS-inulin) as a prebiotic. A synbiotic is defined as a probiotic ("live microorganisms that, when administered in adequate amounts, confer a health benefit on the host") plus an established prebiotic ("a substrate that is selectively utilized by host microorganisms conferring a health benefit")-or, an untested live microbe co-administered with a substrate that it selectively utilizes. The selected probiotics and prebiotic in the PDS-08 formulation have shown to improve antibiotic-associated diarrhea, gastrointestinal and respiratory tract infections, allergic rhinitis, atopic dermatitis, irritable bowel syndrome (IBS) symptoms, and/or microbiota modulation. The positive outcomes of these respective studies warrants further investigation of the strains as part of a probiotic consortium with the potential to modulate the microbiota, regulate dysbiosis, and confer a benefit to host health. There is a need for additional systematic studies on probiotic administration in pediatric populations, with a focus on measuring shifts in the fecal microbiota and markers of gut health and function. Therefore, the objective of this study is to assess the efficacy, tolerability, and safety of a novel synbiotic in healthy children with occasional constipation, over 12 weeks, as compared to a sensory-matched placebo. This is a randomized, 12-week study to compare the efficacy and tolerability of PDS-08 in a cohort of 100 healthy children with constipation. 50 subjects will receive PDS-08™ over 12 weeks, and 50 subjects will receive a placebo. Subjects will provide stool samples at baseline and week 12. Safety is a paramount concern in the study design and will be monitored carefully throughout the study. Parents or direct relative guardians of study subjects will receive extensive education on synbiotic use.