Metabolome, microbiome, and gene expression alterations in the colon of newborn piglets with intrauterine growth restriction

Abstract

Newborn animals with intrauterine growth restriction (IUGR) are characterized by impaired intestinal structure and function; however, their intestinal microbiota and metabolome profiles have not been fully identified. The present study investigated the differences in colonic microbiota, metabolomics, and barrier function-related gene expression profiles between the IUGR and normal birth weight (NBW) piglets at 7, 21, and 28 days of age. Forty-eight piglets (24 NBW and 24 IUGR) from 24 litters were assigned to assess the differences in colonic microbiota, metabolomics, and gene expression between IUGR and NBW piglets. Compared with the NBW piglets, IUGR piglets showed decreased Shannon index and increased Simpson index at 7 days of age and Chao1 index at 21 days of age (p < 0.05). The IUGR piglets had lower abundances of Firmicutes, Subdoligranulum, Ruminococcaceae_UCG-002, and Ruminococcaceae_UCG-003 at 7 days of age, and Bacteroidetes, Phascolarctobacterium, and Ruminococcaceae_UCG-005 at 21 days of age, when compared with the NBW piglets (p < 0.05). Metabolomics analysis showed significant changes in 147 metabolites mainly involved in organic acids and their derivatives in the colon. Six differential metabolic pathways were significantly enriched, including purine metabolism, amino sugar/nucleotide sugar metabolism, ubiquinone/other terpenoid-quinone biosynthesis, phenylalanine/tyrosine/tryptophan biosynthesis, phenylalanine metabolism, and histidine metabolism. Spearman’s correlation analysis further demonstrated significant correlations between colonic microbiota and metabolites. In addition, colonic isobutyrate at 7 days of age, isovalerate and total short-chain fatty acids (SCFAs) at 21 days of age, and acetate, propionate, butyrate, and total SCFAs levels at 28 days of age were lower and isovalerate was higher at 28 days of age in the IUGR piglets than in the NBW piglets (p < 0.05). Furthermore, the mRNA expression of zonula occludens (ZO)-1 at 7 days of age, ZO-1, occludin, and interleukin (IL)-4 at 21 days of age were down-regulated in the IUGR piglets, whereas tumor necrosis factor (TNF)-α and nuclear factor-kappa B (NF-κB) at 28 days of age were up-regulated, when compared with the NBW piglets (p < 0.05). The findings suggest that the IUGR pigs present abnormal microbiota and nutrient metabolism in the colon, which may further affect the intestine barrier function by regulating gene expressions.

Unraveling hepatic consequences of intrauterine growth restriction and catch- up growth: Insights from histological, biochemical, and metabolomic analysis in rats

“…Phenylalanine and tyrosine metabolism are closely interconnected, with phenylalanine being metabolized into acetoacetic acid and fumaric acid via tyrosine. Previous research by Tang et al(Tang et al 2022) has also reported upregulated phenylalanine and tyrosine metabolisms in the IUGR piglet groups corroborating our ndings. Additionally, Faverzani et al(Faverzani et al 2021) highlighted the potentially detrimental effects of elevated phenylalanine levels and its keto acid derivatives, including DNA oxidative damage in glial cells.…”

Intrauterine Growth Restriction Affects Colonic Barrier Function via Regulating the Nrf2/Keap1 and TLR4-NF-κB/ERK Pathways and Altering Colonic Microbiome and Metabolome Homeostasis in Growing–Finishing Pigs

“…Early intestinal microbiota establishment is crucial for intestinal physiology and regulation throughout adult life. Our previous studies found significant alterations in the small intestinal and colonic microbiome and metabolome profiles of IUGR piglets during the suckling and weaning stages [ 15 , 17 ]. However, the effects of IUGR on colonic microbiota colonization and metabolism in pigs during the growing-finishing stages remained unclear.…”

“…The changes in intestinal function, microbiota composition, and metabolic activity induced by IUGR persisted throughout the life of rats [ 7 ]. Our previous studies showed that IUGR altered the colonic metabolome and microbiome in pre-weaning piglets and reduced the abundances of Firmicutes, Proteobacteria, and Lactobacillus in growing-finishing pigs [ 14 , 15 ]. In addition, IUGR decreased the colonic expressions of zonula occludens (ZO)-1 and occludin, activated nuclear factor-kappa B (NF-κB), and increased inflammatory factor levels in pre-weaning piglets [ 15 ].…”

“…Our previous studies showed that IUGR altered the colonic metabolome and microbiome in pre-weaning piglets and reduced the abundances of Firmicutes, Proteobacteria, and Lactobacillus in growing-finishing pigs [ 14 , 15 ]. In addition, IUGR decreased the colonic expressions of zonula occludens (ZO)-1 and occludin, activated nuclear factor-kappa B (NF-κB), and increased inflammatory factor levels in pre-weaning piglets [ 15 ]. However, the effects of IUGR on the colonization and metabolic profiles of the colonic microbiota and the barrier function in growing-finishing pigs remain unclear.…”

Metabolic and fecal microbial changes in adult fetal growth restricted mice

“…Disturbances in gut microbial composition have been reported in FGR piglets, 25 , 61 rats, 26 and in human neonates. 27 In our mouse model, FGR resulted in persistent fecal microbial changes into adulthood.…”