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