The Gut Microbiome of Preterm Infants Treated With Aminophylline Is Closely Related to the Occurrence of Feeding Intolerance and the Weight Gain

Abstract

BackgroundAminophylline is widely used in the treatment of preterm infants, but it can cause feeding intolerance events, in which gut microbial dysbiosis may have a role. This study aims to investigate the relationship between the gut microbiome of preterm infants treated with aminophylline and the occurrence of feeding intolerance and weight gain rate.MethodsThis study included a cohort of 118 preterm infants. Survival analysis and multivariate Cox regression were used to evaluate the relationship between aminophylline treatment and the occurrence of feeding intolerance. 16S rRNA V4 region gene sequencing was used to characterize the microbiome of fecal samples from the cohort. Linear discriminant analysis effect size was used to analyze the differential abundance of bacteria related to aminophylline treatment. Wilcoxon test, Kruskal–Wallis test, Spearman correlation coefficients and generalized linear mixed models were used to analyze the correlation between the differential bacteria and feeding intolerance events as well as the weight gain.ResultsThe results showed that the use of aminophylline could significantly increase the occurrence of feeding intolerance. The relative abundances of Streptococcus and Rothia in the gut microbiome of preterm infants were positively correlated with both the occurrence of feeding intolerance and the use of aminophylline, while the relative abundance of Staphylococcus was negatively correlated. In particular, preterm infants with a lower relative abundance of Rothia were more likely to develop feeding intolerance associated with aminophylline, and this difference existed before the onset of feeding intolerance. Moreover, it took longer for individuals with a lower relative abundance of Streptococcus to reach 2 kg weight. The contribution of Streptococcus to weight gain was greater than that of Bifidobacterium or Lactobacillus.ConclusionThe gut microbiome in preterm infants treated with aminophylline was characterized by a decrease in Streptococcus and Rothia and an increase in Staphylococcus. These microbes, especially Rothia, were positively correlated with the occurrence of feeding intolerance. Streptococcus but not Bifidobacter likely participated in the weight gain of preterm infants in early life.

A systematic review of associations between gut microbiota composition and growth failure in preterm neonates

“…There was some agreement among the 14 studies correlating the relative abundance of specific taxa with growth ( Figure 3 ). Five studies reported positive associations between Streptococcus and growth, 19 , 21 , 24 , 26 , 30 whereas four studies reported negative associations between Staphylococcus and growth. 19 , 21 , 22 , 24 Several taxa were positively correlated with growth in some studies and negatively correlated with growth in other studies; these included Enterobacteriaceae, Streptococcaceae, Acinetobacter , Bacteroides , Enterobacter , Enterococcus , Serratia , and Streptococcus .…”

“…Of the 12 observational studies, 10 were prospective cohort studies, 19–28 one was a nested case-control study, 29 and one was a retrospective cohort study. 30 There was geographic diversity, with five studies conducted in China, 23 , 26–29 four each in Europe 17–19 , 25 and the United States, 20–22 , 30 and one in Brazil. 24 Some studies included only extremely preterm infants (< 28 weeks gestation), whereas others included any preterm infant (< 37 weeks), resulting in a range of extremely low birth weight (< 1000 g) to low birth weight (< 2500 g).…”

“…Interestingly, neonatal growth and Shannon diversity were positively correlated in three studies 18 , 21 , 22 and negatively correlated in three studies. 24 , 26 , 29 Some studies calculated “microbiota maturity” as an index of a neonate’s postnatal acquisition of age-discriminatory taxa (microbes whose proportional representation define gut microbiota assembly within healthy infants sampled in the same cohort). Microbiota maturity and neonatal growth were positively correlated in one study 20 and negatively correlated in another study.…”

Characterization and diagnostic value of the gut microbial composition in patients with minimal change disease

“…The matched cohort was subsequently divided into a discovery cohort and a validation cohort. After comparing the alteration of gut microbiota and profiles of OTUs in the discovery cohort, we used the Wilcoxon rank sum test to determine the significant OTUs ( p < 0.05) for further analysis ( Shen et al, 2022 ). All the key OTUs needed to meet the following conditions: 1) The abundance was greater than 0.5% in at least one sample.…”