Differences in gut microbiota and faecal metabolomics characteristics in preterm infants with feeding intolerance.

Feeding intolerance in preterm infants at day 21 postpartum was associated with significantly higher incidence of vomiting, abdominal distension, abnormal intestinal morphology, and gastric residual volume compared to feeding-tolerant infants.

• Study included 49 preterm infants divided into feeding-tolerant (FT, n=34) and feeding-intolerant (FI, n=15) groups based on feeding assessments at day 21 postpartum.
• Incidence of vomiting, abdominal distension, abnormal intestinal morphology, and gastric residual volume >30% or >2 ml kg-1 was significantly higher in the FI group (P<0.001).
• There was no significant difference in the frequency of nasogastric feeding between the two groups (P>0.05).
• Baseline maternal-infant characteristics showed no significant differences between groups (P>0.05).

Gut microbiota composition differed between feeding-tolerant and feeding-intolerant preterm infants, with distinct bacterial genera enriched in each group.

• FT infants showed enrichment of Escherichia (10.92%) and Klebsiella (6.88%).
• FI infants specifically harboured increased Clostridium_P (3.93%), Burkholderia (4.06%), and Limosilactobacillus (4.94%).
• Faecal samples underwent microbiome profiling to identify these differences.
• Infants were admitted to a tertiary maternal and child health hospital in Zhejiang's coastal region from January to June 2024.

Metabolomic profiling identified significant pathway differences between feeding-tolerant and feeding-intolerant preterm infants.

• Significant pathway differences were identified in ATP-binding cassette transporters (ABC transporters), carbohydrate digestion/absorption, and propanoate metabolism.
• Metabolites arginine-proline (Arg-Pro), glutamic acid-arginine (Glu-Arg), and lactaldehyde were among the differentially identified metabolites.
• Faecal samples underwent metabolomic profiling alongside microbiome profiling.

ROC analyses demonstrated that specific metabolites exhibited robust predictive value for feeding intolerance in preterm infants.

• Arginine-proline (Arg-Pro) had an AUC of 0.920.
• Glutamic acid-arginine (Glu-Arg) had an AUC of 0.873.
• Lactaldehyde had an AUC of 0.900.
• These three metabolites were identified as having robust predictive value for FI.

ROC analyses demonstrated that specific bacterial genera exhibited robust predictive value for feeding intolerance in preterm infants.

• Clostridium_P had the highest AUC of 0.947.
• Bifidobacterium had an AUC of 0.851.
• Escherichia had an AUC of 0.765.
• Staphylococcus had an AUC of 0.733.
• Klebsiella showed diagnostic efficacy but was categorized as 'low accuracy', requiring comprehensive evaluation considering research background, sample characteristics, and clinical context.

The study identified multiple potential diagnostic biomarkers for feeding intolerance in preterm infants combining gut microbiota and metabolomics data.

• Bacterial genera Staphylococcus, Clostridium_P, Bifidobacterium, and Escherichia were identified as diagnostic criteria for feeding tolerance.
• Metabolites including Arg-Pro, Glu-Arg, and lactaldehyde were identified as diagnostic criteria for feeding tolerance.
• Patient data analysis incorporated maternal age, gestational age, parity, antibiotic use, pregnancy complications, and neonatal factors including birth weight, Apgar scores, delivery/feeding methods, vomiting, abdominal distension, gastric residuals, kangaroo care, and enema use.