Dataset Information

Effects of Early Intervention with Antibiotics and Maternal Fecal Microbiota on Transcriptomic Profiling Ileal Mucusa in Neonatal Pigs.

ABSTRACT: This study aimed to investigate the effects of early intervention with antibiotics and maternal fecal microbiota on ileal morphology and barrier function, and transcriptomic profiling in neonatal piglets. Piglets in the amoxicillin (AM), fecal microbiota transplantation (FMT), and control (CO) groups were orally administrated with amoxicillin solution (6.94 mg/mL), maternal fecal microbiota suspension [>109 colony forming unit (CFU)/mL], and physiological saline, respectively. Compared with the CO group, early intervention with AM or FMT significantly decreased ileal crypt depth on day 7 and altered gene expression profiles in ileum on days 7 and 21, and especially promoted the expression of chemokines (CCL5, CXCL9, and CXCL11) involved in the toll-like receptor signaling pathway on day 21. FMT changed major immune activities from B cell immunity on day 7 to T cell immunity on day 21 in the ileum. On the other hand, both AM and FMT predominantly downregulated the gene expression of toll-like receptor 4 (TLR4). In summary, both early interventions modulated intestinal barrier function and immune system in the ileum with a low impact on ileal morphology and development.

SUBMITTER: Xu R

PROVIDER: S-EPMC7168243 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Effects of Early Intervention with Antibiotics and Maternal Fecal Microbiota on Transcriptomic Profiling Ileal Mucusa in Neonatal Pigs.

Xu Rongying R Wan Jiajia J Lin Chunhui C Su Yong Y

Antibiotics (Basel, Switzerland) 20200118 1

This study aimed to investigate the effects of early intervention with antibiotics and maternal fecal microbiota on ileal morphology and barrier function, and transcriptomic profiling in neonatal piglets. Piglets in the amoxicillin (AM), fecal microbiota transplantation (FMT), and control (CO) groups were orally administrated with amoxicillin solution (6.94 mg/mL), maternal fecal microbiota suspension [>10<sup>9</sup> colony forming unit (CFU)/mL], and physiological saline, respectively. Compare ...[more]

PMID: 31963653

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Project description:The establishment of a stable bacterial flora in early life is associated with host metabolism. Studies of fecal microbiota transplantation (FMT) and antibiotics on neonatal pig mainly focused on intestinal development and mucosal immunity, but the information on metabolism is lacking. The objective of this study was to investigate the responses of metabolome and transcriptome in the livers of neonatal piglets that were orally inoculated with maternal fecal bacteria suspension and amoxicillin (AM) solution. Five litters of Duroc × Landrace × Yorkshire neonatal piglets were used as five replicates and nine piglets in each litter were randomly assigned to the control (CO), AM or FMT groups. Neonatal piglets in three groups were fed with 3 mL saline (0.9%), AM solution (6.94 mg/mL) or fecal bacteria suspension (>109/mL), respectively, on days 1-6. At the age of 7 and 21 days, one piglet from each group in each litter was sacrificed, and the serum and liver were collected for analysis. The RNA sequencing analysis showed that the mRNA expressions of arachidonate 12-lipoxygenase (ALOX12), acetyl-CoA acyltransferase 2 (ACAA2), cytochrome P450 family 1 subfamily A member 2 (CYP1A2), glutamic-pyruvic transaminase 2 (GPT2) and argininosuccinate synthase 1 (ASS1) were downregulated (P < 0.05) by AM on day 7, and that the mRNA expressions of arachidonate 15-lipoxygenase (ALOX15), CYP1A2 and GPT2 were downregulated (P < 0.05) by FMT on day 7. GC-MS analysis showed that AM and FMT treatments mainly affected fatty acid metabolism and amino acid metabolism on days 7 and 21. AM and FMT both reduced (P < 0.05) the blood levels of triglycerides and low density lipoprotein cholesterol (LDL-C) on day 7. AM reduced (P < 0.05) the blood level of cholesterol on day 21, and FMT reduced the blood levels of cholesterol, triglycerides and LDL-C on day 21. These results indicate that early intervention with FMT or AM can reduce fatty acid oxidative catabolism and amino acid biosynthesis of neonatal piglets, which provides a reference for regulation host metabolism through early intervention in animal production and even human health.

Project description:BACKGROUND:Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans. OBJECTIVES:The aim of this study was to test the effects of a flaxseed lignan supplement (50 mg secoisolariciresinol diglucoside/d) compared with placebo on host gene expression in colon biopsies and exfoliated colonocyte RNA in feces and fecal microbial community composition, and to compare responses in relation to ENL excretion. METHODS:We conducted a 2-period randomized, crossover intervention in 42 healthy men and women (20-45 y). We used RNA-seq to measure differentially expressed (DE) genes in colonic mucosa and fecal exfoliated cells through the use of edgeR and functional analysis with Ingenuity Pathway Analysis. We used 16S ribosomal RNA gene (V1-V3) analysis to characterize the fecal microbiome, and measured END and ENL in 24-h urine samples by gas chromatography-mass spectrometry. RESULTS:We detected 32 DE genes (false discovery rate <0.05) in the exfoliome, but none in the mucosal biopsies, in response to 60 d of lignan supplement compared with placebo. Statistically significant associations were detected between ENL excretion and fecal microbiome measured at baseline and at the end of the intervention periods. Further, we detected DE genes in colonic mucosa and exfoliome between low- and high-ENL excreters. Analysis of biopsy samples indicated that several anti-inflammatory upstream regulators, including transforming growth factor ? and interleukin 10 receptor, were suppressed in low-ENL excreters. Complementary analyses in exfoliated cells also suggested that low-ENL excreters may be predisposed to proinflammatory cellular events due to upregulation of nuclear transcription factor ?B and NOS2, and an inhibition of the peroxisome proliferator-activated receptor ? network. CONCLUSIONS:These results suggest that ENL or other activities of the associated gut microbial consortia may modulate response to a dietary lignan intervention. This has important implications for dietary recommendations and chemoprevention strategies. This study was registered at clinicaltrials.gov as NCT01619020.

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Project description:Diarrhea is a leading cause of increased mortality in neonatal and young piglets. Aberration of the gut microbiota is one important factor in the etiology of piglet diarrhea. However, information regarding the structure and function of the gut microbiome in diarrheic neonatal piglets is limited. To investigate the composition and functional potential of the fecal microbiota in neonatal piglets, we performed 16S rRNA gene sequencing on 20 fecal samples from diarrheic piglets and healthy controls, and metagenomics sequencing on a subset of six samples. We found striking compositional and functional differences in fecal microbiota between diarrheic and healthy piglets. Neonatal piglet diarrhea was associated with increases in the relative abundance of Prevotella, Sutterella, and Campylobacter, as well as Fusobacteriaceae. The increased relative abundance of Prevotella was correlated with the reduction in Escherichia coli and the majority of beneficial bacteria that belonging to the Firmicutes phylum (e.g., Enterococcus, Streptococcus, Lactobacillus, Clostridium, and Blautia) in diarrheic piglets. The differentially functional gene abundances in diarrheic piglets were an increase in bacterial ribosome, and contributed primarily by the genera Prevotella, this indicates a growth advantage of the Prevotella in diarrheic conditions. Additional functional gene sets were associated with the reduction of polyamine transport, monosaccharide and sugar-specific PTS transport, amino acid transport, and two-component regulatory system. These profiles likely impact the ability to transport and uptake nutrients, as well as the ability to fight microbial infections in the piglet gut ecosystem. This work identifies a potential role for Prevotella in the community-wide microbial aberration and dysfunction that underpins the pathogenesis of piglet diarrhea. Identification of these microbial and functional signatures may provide biomarkers of neonatal piglet diarrhea.

Dataset Information

Effects of Early Intervention with Antibiotics and Maternal Fecal Microbiota on Transcriptomic Profiling Ileal Mucusa in Neonatal Pigs.

Publications

Effects of Early Intervention with Antibiotics and Maternal Fecal Microbiota on Transcriptomic Profiling Ileal Mucusa in Neonatal Pigs.

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