Improving gut health and growth in early life: a protocol for an individually randomised, two-arm, open-label, controlled trial of a synbiotic in infants in Kaffrine District, Senegal.

Introduction: Infants exposed to enteropathogens through poor sanitation and hygiene can develop a subclinical disorder of the gut called environmental enteric dysfunction (EED), characterised by abnormal intestinal histology and permeability. EED can contribute to stunting through reduced digestion and absorption of nutrients, increased susceptibility to infections, increased systemic inflammation and inhibition of growth hormones. EED can be apparent by age 12 weeks, highlighting the need for early intervention. Modulating the early life gut microbiota using synbiotics may improve resistance against colonisation of the gut by enteropathogens, reduce EED and improve linear growth.

Methods And Analysis: An individually randomised, two-arm, open-label, controlled trial will be conducted in Kaffrine District, Senegal. Infants will be recruited at birth and randomised to either receive a synbiotic containing two strains and one strain, or no intervention, during the first 6 months of life. The impact of the intervention will be evaluated primarily by comparing length-for-age z-score at 12 months of age in infants in the intervention and control arms of the trial. Secondary outcome variables include biomarkers of intestinal inflammation, intestinal integrity and permeability, gut microbiota profiles, presence of enteropathogens, systemic inflammation, growth hormones, epigenetic status and episodes of illness during follow-up to age 24 months.

Discussion: This trial will contribute to the evidence base on the use of a synbiotic to improve linear growth by preventing or ameliorating EED in a low-resource setting.

Trial Registration Number: PACTR202102689928613.