Dataset Information

Rapid Gut Adaptation to Preterm Birth Involves Feeding-Related DNA Methylation Reprogramming of Intestinal Genes in Pigs.

ABSTRACT: Following preterm birth, the immature gut function and immunology must rapidly adapt to cope with bacterial colonization and enteral milk feeding. We hypothesized that intestinal epigenetic changes are involved in the gut response to preterm birth and the first feeding. Using piglets as models for infants, preterm, and term pigs were fed total parenteral nutrition (TPN) or partial enteral feeding for 5 days, followed by exclusive enteral feeding with bovine milk until day 26 (weaning age). Intestinal structure, function, microbiome, DNA methylome, and gene expressions were compared between preterm and term pigs on days 0, 5, and 26 (n = 8 in each group). At birth, the intestine of preterm pigs showed villus atrophy and global hypermethylation, affecting genes related to the Wnt signaling pathway. Hypermethylation-associated lowered expression of lipopolysaccharide-binding protein and genes related to the Toll-like receptor 4 pathway were evident during the first 5 days of life, but most early methylation differences disappeared by day 26. Regardless, sucrase and maltase activities (adult-type brush border enzymes) remained reduced, and the gut microbiota altered (fewer Akkermansia, more Lachnoclostridia and Lactobacilli) until day 26 in preterm pigs. During the 0- to 5-day period, many new preterm-term methylation differences appeared, but mainly when no enteral feed was provided (TPN feeding). These methylation differences affected intestinal genes related to cell metabolism, including increased GCK (glucokinase) expression via promoter hypomethylation. In conclusion, the immature intestine has a remarkable capacity to adapt its gene methylation and expression after preterm birth, and only few preterm-related defects persisted until weaning. Early enteral feeding may be important to stimulate the methylation reprogramming of intestinal genes, allowing rapid intestinal adaptation to preterm birth.

SUBMITTER: Pan X

PROVIDER: S-EPMC7174650 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Rapid Gut Adaptation to Preterm Birth Involves Feeding-Related DNA Methylation Reprogramming of Intestinal Genes in Pigs.

Pan Xiaoyu X Thymann Thomas T Gao Fei F Sangild Per T PT

Frontiers in immunology 20200415

Following preterm birth, the immature gut function and immunology must rapidly adapt to cope with bacterial colonization and enteral milk feeding. We hypothesized that intestinal epigenetic changes are involved in the gut response to preterm birth and the first feeding. Using piglets as models for infants, preterm, and term pigs were fed total parenteral nutrition (TPN) or partial enteral feeding for 5 days, followed by exclusive enteral feeding with bovine milk until day 26 (weaning age). Intes ...[more]

PMID: 32351501

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Project description:Objectives: Maternal milk is often absent or in limited supply just after preterm birth. Many preterm infants are therefore fed infant formula as their first enteral feed despite an increased risk of feeding intolerance, necrotizing enterocolitis (NEC), and infection. Using preterm pigs as a model for preterm infants, we hypothesized that bovine colostrum given before or after formula feeding would alleviate formula-induced detrimental effects during the first days after preterm birth. Methods: A total of 74 preterm pigs received gradually increasing volumes of formula (F) or bovine colostrum (C) until day 5, when they were euthanized or transitioned to either C or F for another 4 days, resulting in six groups: C or F until day 5 (C5, F5, n = 11 each), C or F until day 9 (CC, FF n = 12-13 each), C followed by F (CF, n = 14), and F followed by C (FC, n = 13). Results: Systemically, colostrum feeding stimulated circulating neutrophil recruitment on day 5 (C5 vs. F5, P < 0.05). Relative to initial formula feeding, initial colostrum feeding promoted the development of systemic immune protection as indicated by a decreased T-helper cell population and an increased regulatory T-cell population (CC + CF vs. FC + FF, P < 0.01). In the gut, colostrum feeding improved intestinal parameters such as villus heights, enzymes, hexose absorption, colonic goblet cell density, and decreased the incidence of severe NEC (27 vs. 64%), diarrhea (16 vs. 49%), and gut permeability on day 5, coupled with lowered expression of LBP, MYD88, IL8, HIF1A, and CASP3 (C5 vs. F5, all P < 0.05). On day 9, the incidence of severe NEC was similarly low across groups (15-21%), but diarrhea resistance and intestinal parameters were further improved by colostrum feeding, relative to exclusive formula feeding (CC, CF, or FC vs. FF, respectively, all P < 0.05). The expression of MYD88 and CASP3 remained downregulated by exclusive colostrum feeding (CC vs. FF, P < 0.01) and colostrum before or after formula feeding down regulated HIF1A and CASP3 expression marginally. Conclusion: Colostrum feeding ameliorated detrimental effects of formula feeding on systemic immunity and gut health in preterm newborns, especially when given immediately after birth.

Project description:All mammals must breathe and breathe continuously from birth. Similarly, all mammals, including infants, have high functional demands for feeding. However, the pathway that food takes through the pharynx interrupts respiration. The coordination between swallowing and breathing is therefore critical for all infant mammals. Clinically, this coordination differs between term and preterm infants. However, the neurological mechanisms underlying this coordination and how it matures as infants grow are poorly understood. Here, we integrate high-resolution data from multiple physiologic processes across a longitudinal time frame to study suck-swallow-breathe dynamics in a preterm animal model, the infant pig. In doing so, we test the hypothesis that preterm birth will have an impact on some, but not all, behaviors associated with suck-swallow-breath performance. We hypothesize that coordination will be disrupted, reflecting incomplete connections in the brainstem. We found that preterm pigs became rhythmic and mature in sucking and swallowing behaviors, suggesting substantial postnatal maturation in the coordination of these behaviors. However, their ability to coordinate swallowing and breathing never developed. These results have implications for the nature of clinical care of human infants, as well as for how feeding processes develop in mammals. Clinically, they provide a foundation for developing interventions for preterm infants. Additionally, these results suggest that the lack of coordination between swallowing and breathing may be a significant factor in determining the minimum gestation time across mammals. NEW & NOTEWORTHY Preterm infants face a variety of challenges associated with safe feeding, but obtaining high-resolution longitudinal data to understand these challenges in humans is challenging. We used a pig model to acquire high-speed videofluoroscopic and respiratory inductance plethysmograph data throughout the nursing period to show that preterm birth does not have substantial impacts on the ability of infants to perform isolated behaviors. However, it does decrease the ability of preterm infants to coordinate among behaviors during feeding.

Project description:The objective of this study was to elucidate the impacts of irregular eating patterns on gut microbiota and transcriptomic responses in a pig model with different feeding regimens. The experiment involved 24 growing pigs (Duroc × Landrace × Large White, 48 days of age) which were randomly allocated to one of three feeding patterns: one-meal (M1), three-meals (M3), or five-meals (M5) per day with the same daily feed intake. The results showed that different feeding frequencies had no significant effects on the microbial composition of ileal digesta, colonic digesta, colon mucosa, as well as the concentration of SCFAs in colonic digesta. Mucosa transcriptomic profiling data showed the pathways related to vitamin metabolism were enriched in the ileum and colon of pigs in the pairwise comparison between M3 and M1 groups. On the other hand, the pathways related to lipid metabolism were enriched in the ileum and colon of pigs in the pairwise comparison between M5 and M1 groups. Lastly, the pathways related to protein metabolism were enriched in the colon in the pairwise comparison between M3 and M1 groups, M5 and M1 groups, M5 and M3 groups, while the ileum was not enriched. Differentially expressed genes (DEG) related to metabolism showed that carbohydrate transport was suppressed in the ileum and enhanced in the colon in M5 and M3 groups compared with the M1 group. Compared with the M3 group, carbohydrate transport in the ileum was enhanced in the M5 group, while in the colon was inhibited. With the increase of feeding frequency, the catabolism, biosynthesis, and transport of lipid in the ileum were suppressed, while those in the colon were enhanced. Compared with the M1 group, amino acid transport in the ileum and colon in the M3 group was enhanced. Amino acid catabolism in the ileum in the M5 group was enhanced compared with M1 and M3 groups. In summary, different feeding frequencies affected the transport of carbohydrate, lipid, and amino acid in the ileum and colon, and affected the catabolism and biosynthesis of lipid in the ileum and colon with a low impact on intestinal microbiota.

Project description:This study investigated the use of carbadox in the diet of nursery pigs. Ten pens of weanling piglets were assigned to 2 treatments: one containing carbadox and another without it. From days 21 to 35 of age, the first group of piglets was fed carbadox at 55 mg/kg of diet; followed by 27.5 mg/kg from days 36 to 49; and 0 mg/kg from days 50 to 63. The second group of pigs was fed a control diet without carbadox from days 21 to 63 of age. On days 35, 49, and 63, fecal samples were collected directly from the rectum of 2 piglets in each pen, and the samples were subjected to microbial DNA sequencing and metagenomic functional analysis using the 16S rRNA gene. Feed conversion from days 21 to 63 was improved (P = 0.04) in the group of piglets fed carbadox. Faith's phylogenetic diversity was similar (P = 0.89) for both groups of piglets on day 35, but it was diminished (P = 0.01) in the carbadox-fed group on day 49; however, following the complete removal of carbadox from their diets, this microbial diversity index was once again found to be similar (P = 0.27) in both groups on day 63. Likewise, abundances of Slackia, Peptococcus, Catenibacterium, Coprococcus, and Blautia were all similar between the two groups (P ≥ 0.40) on day 35, but were smaller in the carbadox group (P ≤ 0.05) on day 49; however, on day 63, abundances of all these genera were once again similar (P ≥ 0.29). Metabolic pathways involved in cellular growth, death, and genetic information processing (translation) were found to be similarly expressed in the microbiota of piglets from both groups on day 35 (P ≥ 0.52), but decreased in the carbadox group on day 49 (P ≤ 0.05), and were similar again in both groups on day 63 (P ≥ 0.51). These results revealed that feeding carbadox to piglets during the first 4 weeks after weaning significantly affected their fecal microbiotas; however, 2 weeks after the removal of carbadox, those changes tended to disappear, indicating that the shifts were carbadox-dependent.

Dataset Information

Rapid Gut Adaptation to Preterm Birth Involves Feeding-Related DNA Methylation Reprogramming of Intestinal Genes in Pigs.

Publications

Rapid Gut Adaptation to Preterm Birth Involves Feeding-Related DNA Methylation Reprogramming of Intestinal Genes in Pigs.

Similar Datasets

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