BACKGROUND: Heat-inactivated probiotics (HPs) may provide an effective alternative to live probiotics (P) by avoiding their risks (eg, probiotic sepsis) while retaining the benefits. We assessed the safety and efficacy of a HP in very preterm (VP: gestation <
32 weeks) infants. METHODS: VP infants were randomly allocated to receive a HP or P mixture ( RESULTS: 86 VP infants were randomised to HP or P group (n=43 each). Total FCP and SCFA were comparable between HP and P groups within 7 days (T1) and between day 21 and 28 (T2) after supplementation. At T2, median (range) FCP was 75 (8-563) in the HP group and 80 (21-277) in the P group (p=0.71). Propionate was significantly raised in both groups, while butyrate was significantly raised in the HP group (all p<
0.01). Bacterial richness and diversity increased but was comparable between HP and P (p>
0.05). Beta diversity showed similar community structures in both groups (all p>
0.05). Changes in faecal Actinobacteria, Bacteroidetes and Bifidobacteriacae levels were comparable in both groups at T1 and T2. There was no probiotic sepsis. CONCLUSIONS: HP was safe and showed no significant difference in FCP as compared with a live probiotic. Adequately powered trials are needed to assess the effects of HP on clinically significant outcomes in preterm infants. TRIAL REGISTRATION NUMBER: ACTRN12618000489291.