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Microbiome and metabolome features in treatment of early weaned piglets via multi-omics integration analyses across cohorts

ABSTRACT:

BACKGROUND: Diarrhea is common in infants, particularly, children less than 2 years old. Intractable or protracted infancy diarrhea is typically associated with feeding intolerance and malabsorption that is lethal for newborns. This study aimed to evaluate the effectiveness of baizhu shaoyao decoction in reducing functional diarrhea induced by weaning stress, while also delving into its potential mechanisms of action.

RESULTS: Piglets were allocated into 5 groups, with each group receiving designated medication for a continuous 14-day period: control, zaohu powder, as well as low-, medium- and high-dose baizhu shaoyao decoction groups (n = 6 piglets per group). To identify diarrhea-related biomarkers, microbial communities, functions and metabolites were compared between the early-weaned piglets (control group) and those treated with 1.28 g/kg baizhu shaoyao decoction (medium-dose baizhu shaoyao decoction group). Our findings revealed significant shifts in microbial composition, function and metabolic profiles in piglets from the medium-dose baizhu shaoyao decoction group, intricately associated with the host's diarrhea status. Furthermore, carbohydrate metabolism and biosynthesis, lipid and amino acid metabolism, glycan activity and carbohydrate digestive enzymes exhibited downregulation in piglets of the medium-dose baizhu shaoyao decoction group compared to those in the control group. Transcriptome analysis highlighted the pivotal role of the FoxO1/3 transcription factor in mitigating weaning stress, particularly through the augmentation of CD4+/CD8+ T cell proportions. Our findings underscored that baizhu shaoyao decoction's therapeutic effects on weaning stress involve intestinal barrier restoration, modulation of brain-gut peptide expression and a reduction in mast-cell activity in the ileum.

CONCLUSIONS: The key metabolites (chenodeoxycholyglycine, chenodeoxycholyltaurine, dinoprost, chenodeoxyglycocholic acid, glycochenodeoxycholic acid, glycocholic acid, N-choloylglycine, 5-trans-PGE2, Pregnanediol 3-O-glucuronide, spermidine and spermine) exhibited strong correlations with the abundance of Clostridia_bacterium and Lachnospiraceae_bacterium, emphasizing the significance of Clostridia_bacterium and Lachnospiraceae_bacterium in gut metabolism and function. Besides, this study suggests the potential efficacy of baizhu shaoyao decoction in addressing early post-weaning stress-induced diarrhea in infants, showcasing promising prospects for translational and clinical applications.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Yyuan Wei

PROVIDER: MTBLS9292 | MetaboLights | 2024-02-01

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS9292	Other
	FILES	Other
	a_MTBLS9292_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS9292_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt

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Project description:Purpose: RNA-Seq has become a powerful tool for investigating transcriptional profiles in gene expression analysis, which would help to reveal the molecular mechanism of Clostridium perfringens type C infecting the piglets. In this study, we analyzed the transcriptome profiles of the spleen of piglets caused by Clostridium perfringens type Cens type C. Methods: 30 normal 7-day-old piglets (Y x L), without infecting Clostridium perfringens type C, Escherichia coli and Salmonella, were selected as experimental subjects. 25 piglets were randomly selected as the experimental group, which were disposed once a day for 5 days. Each piglet was dosed with 1 ml of bouillon culture-medium inoculated Clostridium perfringens type C at 37℃ for 16h, which approximate to 1 x109 CFU per ml. Then, 5 piglets were randomly selected as the control group (SC), which were taken the equal volume medium for 5 days.Based on total diarrhea scores, 25 piglets were ranked from high to low. The top and last five piglet were considered as sensitive group (SS) and resistant group (SR), respectively. Finally, spleen were collected and sequenced for lncRNA and mRNA. Results: RNA libraries constructed from spleen of piglets caused by Clostridium perfringens type C were sequenced. A total of 1,450,292,484 clean reads were generated. Among them, 2056 novel lncRNA transcripts corresponding to 1561 lncRNA genes were identified, including 1811 intergenic lncRNAs and 245 anti-sense lncRNAs. The identified spleen lncRNAs shared some characteristics, such as fewer exons and shorter length, with the lncRNAs in other animal. Notably, in pairwise comparisons between the libraries of spleen tissue at the different group, a total of 247 lncRNA and 2170 mRNA were differentially expressed (P < 0.05). Function analyses indicated that these differentially expressed lncRNAs and mRNAs play roles in defensing Clostridium perfringens type C, which were enriched in immune-related biological processes, such as the antigen processing and presentation, TNF signaling pathway, NF-kappa B signaling pathway, B cell receptor signaling pathway and MAPK signaling pathway. Conclusions: This study provides the information of spleen-related lncRNAs in swine diarrhea with Clostridium perfringens type C. We also analyzed all lncRNA’s genomic feature and expression. Bioinformatic analysis indicates that some lncRNAs participated in important biological processes associated with defeasing Clostridium perfringens type C, such as antigen processing and presentation, the MHC protein complex and regulation of autophagy.

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Microbiome and metabolome features in treatment of early weaned piglets via multi-omics integration analyses across cohorts

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