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The infant gut microbiome is increasingly recognized as a reservoir of antibiotic resistance genes, yet the assembly of gut resistome in infants and its influencing factors remain largely unknown. We characterized resistome in 4132 metagenomes from 963 infants in six countries and 4285 resistance genes were observed. The inherent resistome pattern of healthy infants (N = 272) could be distinguished by two stages: a multicompound resistance phase (Months 0-7) and a tetracycline-mupirocin-β-lactam-dominant phase (Months 8-14). Microbial taxonomy explained 40.7% of the gut resistome of healthy infants, with Escherichia (25.5%) harboring the most resistance genes. In a further analysis with all available infants (N = 963), we found age was the strongest influencer on the resistome and was negatively correlated with the overall resistance during the first 3 years (p

Background: The hypothalamus plays a crucial role in the health and productivity of dairy cows, yet studies on its functionality and its impact on peripheral circulation in these animals are relatively scarce, particularly regarding dietary interventions. Therefore, our study undertook a comprehensive analysis, incorporating both metabolomics and transcriptomics, to explore the effects of a grain-based diet on the functionality of the hypothalamus, as well as on blood and milk in dairy cows. Results: The hypothalamic metabolome analysis revealed a significant reduction in prostaglandin E2 (PGE2) level as a prominent response to the grain-based diet introduction. Furthermore, the hypothalamic transcriptome profiling showed a notable upregulation in amino acid metabolism due to the grain-based diet. Conversely, the grain-based diet led to the downregulation of genes involved in the metabolic pathway from lecithin to PGE2, including phospholipase A2 (PLA2G4E, PLA2G2A, and PLA2G12B), cyclooxygenase-2 (COX2), and prostaglandin E synthase (PTGES). Additionally, the plasma metabolome analysis indicated a substantial decrease in the level of PGE2, along with a decline in adrenal steroid hormones (tetrahydrocortisol and pregnenolone) following the grain-based diet introduction. Analysis of the milk metabolome showed that the grain-based diet significantly increased uric acid level while notably decreasing PGE2 level. Importantly, PGE2 was identified as a critical metabolic marker in the hypothalamus, blood, and milk in response to grain intervention. Correlation analysis demonstrated a significant correlation among metabolic alterations in the hypothalamus, blood, and milk following the grain-based diet. Conclusions: Our findings suggest a potential link between hypothalamic changes and alterations in peripheral circulation resulting from the introduction of a grain-based diet. [ABSTRACT FROM AUTHOR]

Simple Summary: Bacteriophages (phages) are viruses specifically infecting bacteria, and have been considered as a prospective substitute for antibiotics. It is necessary to evaluate the impact of phages on overall body health before phage application. This study suggests that the effects of phages on body health are complex, especially regarding immune status. Our results are informative and further improve the implementation and supervision of phage therapy. Numerous studies have demonstrated that bacteriophages (phages) can effectively treat intestinal bacterial infections. However, research on the impact of phages on overall body health once they enter the intestine is limited. This study utilized weaned piglets as subjects to evaluate the systemic effects of an orally administered phage cocktail on their health. Twelve 21-day-old weaned piglets were divided into control (CON) and phage gavage (Phages) groups. The phage cocktail consisted of five lytic phages, targeting Salmonella enterica serovar Choleraesuis (S. choleraesuis), Enteropathogenic Escherichia coli (EPEC), and Shiga tox-in-producing Escherichia coli (STEC). The phages group received 10 mL of phage cocktail orally for 20 consecutive days. The results show that the phage gavage did not affect the piglets' growth performance, serum biochemical indices, or most organ indices, except for the pancreas. However, the impact on the intestine was complex. Firstly, although the pancreatic index decreased, it did not affect the secretion of digestive enzymes in the intestine. Secondly, phages increased the pH of jejunum chyme and relative weight of the ileum, and enhanced intestinal barrier function without affecting the morphology of the intestine. Thirdly, phages did not proliferate in the intestine, but altered the intestinal microbiota structure and increased concentrations of microbial metabolites isobutyric acid and isovaleric acid in the colonic chyme. In addition, phages impacted the immune status, significantly increasing serum IgA, IgG, and IgM, as well as serum and intestinal mucosal IFN-γ, IL-1β, IL-17, and TGF-β, and decreasing IL-4 and IL-10. They also activated toll-like receptors TLR-4 and TLR-9. Apart from an increase in basophil numbers, the counts of other immune cells in the blood did not change. This study indicates that the impact of phages on body health is complex, especially regarding immune status, warranting further attention. Short-term phage gavage did not have significant negative effects on health but could enhance intestinal barrier function. [ABSTRACT FROM AUTHOR]