Changes of gut microbiota and tricarboxylic acid metabolites may be helpful in early diagnosis of necrotizing enterocolitis: A pilot study

Abstract

PurposeWe aimed to explore the value of gut microbiota and tricarboxylic acid (TCA) metabolites in early diagnosis of necrotizing enterocolitis (NEC) among infants with abdominal manifestations.MethodsThirty-two preterm infants with abdominal manifestations at gestational age ≤ 34 weeks were included in the study and were divided into non-NEC (n = 16) and NEC (n = 16) groups. Faecal samples were collected when the infants were enrolled. The gut microbiota was analysed with high-throughput sequencing, and TCA metabolites were measured with multiple reaction monitoring (MRM) targeted metabolomics. Receiver operating characteristic (ROC) curves were generated to explore the predictive value of the obtained data.ResultsThere was no significant difference in alpha diversity or beta diversity between the two groups (p > 0.05). At the phylum level, Proteobacteria increased, and Actinomycetota decreased in the NEC group (p < 0.05). At the genus level, Bifidobacterium and Lactobacillaceae decreased significantly, and at the species level, unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis decreased in the NEC group (p < 0.05). Further Linear discriminant analysis effect sizes (LEfSe) analysis showed that the change in Proteobacteria at the phylum level and Lactobacillaceae and Bifidobacterium at the genus level scored higher than 4. The concentrations of succinate, L-malic acid and oxaloacetate in the NEC group significantly increased (p < 0.05), and the areas under the ROC curve for these metabolites were 0.6641, 0.7617, and 0.7344, respectively.ConclusionDecreased unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis at the species level as well as the increase in the contents of some TCA metabolites, including succinate, L-malic acid and oxaloacetate, have potential value for the early diagnosis of NEC.

Metabolomics in NEC: An Updated Review

“…Finally, Du et al [ 79 ] investigated the intestinal microbiota and the metabolites of tricarboxylic acids (TCA) in the early diagnosis of NEC. 32 preterm infants’ samples were analyzed, of which 16 were NEC and 16 were non-NEC.…”

Case Report: The impact of severe cryptosporidiosis on the gut microbiota of a pediatric patient with CD40L immunodeficiency

“…Similarly, pathways which feed into the TCA cycle, including mevalonate degradation and glycine cleavage, were also enriched in the patient compared to CTRLs, which is also consistent with an increase in TCA metabolic intermediates found in stool samples from infected patients ( Ng et al., 2012 ). Furthermore, an increase in TCA intermediates has been described in many pathological contexts, including necrotizing enterocolitis ( Du et al., 2023 ) and colorectal cancer ( Telleria et al., 2022 ). Finally, we found an enrichment in purine nucleotide salvage pathways, including the superpathway of purine nucleotides, adenine and adenosine salvage, UDP-β-L-arabinose biosynthesis I (from UDP-α-D-xylose), and urate conversion to allantoin II ( Figure 4 ).…”