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Abstract
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 3×109 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.
- Neonatology
- Microbiology
- Intensive Care Units, Neonatal
- Gastroenterology
Data availability statement
Data are available upon reasonable request. Data are available on reasonable request to corresponding author. The protocol and pre-print are freely available on public domain.
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Data availability statement
Data are available upon reasonable request. Data are available on reasonable request to corresponding author. The protocol and pre-print are freely available on public domain.
Footnotes
X @GayatriJape
Contributors GA-J contributed to data acquisition, infant recruitment, ethics, governance and TGA application, funding application, setting up the clinical trial including liaising with pharmacy, ordering trial equipment for storage of faecal samples, supervision of project running, data interpretation, writing first and final draft of manuscript, revision of manuscript for critically important intellectual content. ME contributed to analysis and interpretation of data including bio-informatics details, critical revision of manuscript for important intellectual content. SP contributed to conception and design, data interpretation, revision of manuscript for critical important intellectual content, supervision of project running and manuscript writing. SP is responsible for overall content as the guarantor. SP accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. EN and DD contributed to statistical input into design, analysis and interpretation of clinical and SCFA data, revision of manuscript for critical important intellectual content. ES and LC contributed to sample analysis for metagenomic sequencing, data interpretation. CK contributed as research assistant, and for data collection, data cleaning, participant recruitment, sample collection and preparation for storage. PC and SS contributed to critical revision of manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Funding Telethon Channel Seven Trust (SF719) and the Stan Perron Charitable Foundation (51018400); GA-J was the recipient of both grants. The manufacturer, Morinaga Milk Industry Co, Japan and funders (Telethon Channel Seven Trust and Stan Perron Charitable Foundation) had no role in the design, conduct and reporting of this study. The views expressed are those of the authors and not necessarily those of the funders.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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