Assessment Trial of the Effect of Enteral Insulin on the Preterm Infant Intestinal Microbiota

Background Insulin might be associated with changes in infant gastrointestinal microbiota. The objective of this randomized controlled trial was to assess the efficacy of two doses of recombinant human(rh) enteral insulin administration compared to placebo in intestinal microbiota. Methods 19 preterm patients were recruited at the NICU of La Paz University Hospital (Madrid, Spain). Subjects received 2000 µIU of rh enteral insulin/ml( n = 8), 400 µIU of rh enteral insulin/ml( n = 6) or placebo( n = 5) for 28 days administered once per day. Extracted DNA from fecal samples collected at the beginning and end of treatment were analyzed. The 16S rRNA V4 region was amplified and sequenced in a Miseq(Illumina®) sequencer using 2 × 250 bp paired end. Resulting reads were filtered and analyzed using Qiime2 software. Metabolic activity was assessed by GC. Results Gestational age and birth weight did not differ between groups. At the phylum level, both insulin treated groups increased the relative abundance of Bacillota, while Pseudomonadota decreased. No change was observed in infants receiving placebo. At the genus level, insulin at both doses showed enriching effects on Clostridium . We found a significant increase in concentrations of fecal propionate in both rh insulin treated groups. Conclusion Rh insulin may modify neonatal intestinal microbiota and SCFAs in preterm infants. Impact statement Decrease of Pseudomonadota (former Proteobacteria phylum) and increase of Bacillota (former Firmicutes phylum) obtained in this study are the changes observed previously in low-risk infants for NEC. The administration of recombinant enteral insulin may modify the microbiota of preterm new-borns and SCFAs. Modulation of the microbiota may be a mechanism whereby insulin contributes to neonatal intestinal maturation and/or protection.