Effects of a live versus heat-inactivated probioticBifidobacteriumspp in preterm infants: a randomised clinical trial

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 ( Bifidobacterium breve M-16V, Bifidobacterium longum subsp. infantis M-63, Bifidobacterium longum subsp. longum BB536, total 3×10 9 CFU/day) assuring blinding. Primary outcome was faecal calprotectin (FCP) levels were compared after 3 weeks of supplementation. Secondary outcomes included faecal microbiota and short chain fatty acid (SCFA) levels. 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.