Abstract
ObjectiveCatch-up growth (CUG) in small for gestational age (SGA) leads to increased risk of metabolic syndrome and cardiovascular diseases in adults. It remains unclear if microbiota could play an important role in CUG-SGA independent of genetic or nutritional factors. The present study explored the role of gut microbiota in, and its association with, metabolic disorders during CUG-SGA.MethodsAn SGA rat model was established by restricting food intake during pregnancy, and the rats were divided into catch-up growth (CUG-SGA) and non-catch-up growth (NCUG-SGA) groups based on body weight and length at the fourth postnatal week. High-throughput sequencing of 16S rRNA was conducted to detect the diversity and composition of the gut microbiota. Fecal short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry. Transcriptome sequencing of liver tissue was performed and verified using real-time PCR. Concentrations of insulin and total cholesterol were determined using enzyme-linked immunosorbent assay.ResultsThe composition of gut microbiota in CUG-SGA rats differed from that of NCUG-SGA rats, with reduced abundance of Lactobacillus in the CUG-SGA group. The decrease in Lactobacillus was significantly associated with increased body weight and upregulated insulin and total cholesterol levels. Five SCFAs and two branched chain fatty acids were significantly higher in the CUG-SGA group than in the NCUG-SGA group. Additionally, SCFAs were positively associated with clinical indices such as weight, body mass index, insulin, and total cholesterol. Transcriptomic data revealed that insulin-like growth factor-2 expression was significantly decreased in CUG-SGA rats and was associated with a decrease in Lactobacillus bacteria.Conclusion Lactobacillus and SCFAs were associated with the metabolic disorders during CUG in SGA. Gut microbiome may play a certain role on metabolic disorders during catch-up growth in small-for-gestational-age.
Highlights
Small for gestational age (SGA) refers to newborns whose birth weight and/or length are at least 2 standard deviations (SDs) below the mean for the gestational age (≤−2 SD) [1]
As described in the methods above, SGA rats are defined as body weight and body length -2SD below the rats from control group at birth, i.e. rats appropriate for gestational age at birth
NCUG-SGA rats were identified by week 4, when their body weights were -2SD lower than those in the normal group, and the rest of the SGA rats were defined as catch-up growth (CUG)-SGA
Summary
Small for gestational age (SGA) refers to newborns whose birth weight and/or length are at least 2 standard deviations (SDs) below the mean for the gestational age (≤−2 SD) [1]. Newborns with SGA often require additional medical care, including temperature-controlled incubators, tube feeding, and monitoring of blood glucose levels. With advances in medical care, the mortality rate of newborns with SGA has significantly decreased. Worldwide epidemiological data have revealed that CUG of SGA infants may contribute to insulin resistance [6]. Eriksson et al found that some SGA infants caught up rapidly after birth, reaching or exceeded the normal body mass index level of children of the same age by 7 years, but with a high death rate associated with cardiovascular disease [7]. A cohort study in India found similar results. They found that insulin resistance indicators, total lipoproteins, and low-density lipoproteins were higher in such group of infants [8].
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