Administration of probiotics and synbiotics and systemic inflammation in Kenyan infants: an open label, randomised, phase II trial

Environmental enteric dysfunction (EED) in early life, caused by gut pathogen colonisation, contributes to chronic systemic inflammation (CSI) which impairs growth and organ development and increases non-communicable disease risk. Pro/synbiotics may prevent or ameliorate EED, and thereby reduce CSI, through boosting colonisation resistance against enteropathogens and provide other intestinal and immune benefits. We evaluated three pro/synbiotics consisting of live, multi-strain Bifidobacterium spp. and Lactobacillaceae in reducing CSI. In this open-label, randomised, four-arm, phase II trial, 600 healthy Kenyan newborns (1–3 days old, birthweight ≥2000g) were allocated 1:1:1:1, stratified by HIV exposure, to receive Labinic synbiotic, Lab4b synbiotic or Lab4b probiotic or no intervention daily for ten days, then weekly until six months. The primary outcome was CSI (plasma α ₁ -acid glycoprotein > 1g/L) at six months with blinded laboratory assessments. At six months, CSI occurred in 60/138 (43%) controls versus 4/144 (3%; relative risk (RR) 0.06, 95% CI 0.02–0.17; p < 0.0001) infants in the Labinic synbiotic, 3/132 (2%; RR = 0.05, 0.02–0.16; P < 0.0001) in the Lab4b synbiotic, and 3/141 (2%; RR = 0.05, 0.02–0.15; P < 0.0001) in the Lab4b probiotic arm. Serious adverse events and mortality over 0–24 months were similar across study arms. Pro/synbiotics safely and markedly reduced CSI in this disadvantaged population, warranting investigation of health impacts.