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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]

Background: As indigestible carbohydrates, milk oligosaccharides possess various benefits for newborns, mainly through intestinal microbiota, among which 2'‐fucosyllactose (2'‐FL) is the most predominant milk oligosaccharide. However, knowledge about the fermentative characteristics of 2'‐FL in the gut remains limited, especially in the small intestine. The aim of this study is to explore the differential fermentability of 2'‐FL by the small and large intestinal microbiota of piglets using fructo‐oligosaccharide (FOS) and lactose as controls in an in vitro batch fermentation experiment. During fermentation, microbial composition was characterized along with gas production and short‐chain fatty acid production. Results: 2'‐Fucosyllactose showed differential fermentability in jejunal and colonic fermentation. Compared with the colon, 2'‐FL produced less gas in the jejunum than in the FOS and lactose groups (P < 0.05). Meanwhile, 2'‐FL exhibited a different influence on the microbial composition and metabolism in the jejunum and colon compared with FOS and lactose. In the jejunum, compared with the FOS and lactose groups, the 2'‐FL group showed a higher abundance of Bacteroides, Prevotella, and Blautia, but a lower abundance of Streptococcus and Lactobacillus (P < 0.05), with a higher level of propionate and a lower level of lactate during fermentation (P < 0.05). In the colon, compared with the FOS and lactose groups, 2'‐FL increased the abundance of Blautia, Faecalibacterium, and Lachnospiraceae FCS020, but decreased the abundance of Prevotella_9, Succinivibrio, and Megasphaera (P < 0.05) with an increase in acetate production (P < 0.05). Conclusion: Overall, the results suggested that the small intestinal microbiota had the potential to ferment milk oligosaccharides. Meanwhile, in comparison with FOS and lactose, 2′‐FL selectively stimulated the growth of propionate‐producing bacteria in the jejunum and acetate‐producing bacteria in the colon. These results demonstrated the differences in fermentation properties of 2'‐FL by small and large intestinal microbiota and provided new evidence for the application of 2'‐FL in optimizing gut microbiota. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Genetically lean and obese individuals have distinct intestinal microbiota and function. However, the underlying mechanisms of the microbiome heterogeneity and its regulation on epithelial function such as intestinal stem cell (ISC) fate remain unclear. Employing pigs of genetically distinct breeds (obese Meishan and lean Yorkshire), this study reveals transcriptome-wide variations in microbial ecology of the jejunum, characterized by enrichment of active Lactobacillus species, notably the predominant Lactobacillus amylovorus (L. amylovorus), and lactate metabolism network in obese breeds. The L. amylovorus-dominant heterogeneity is paralleled with epithelial functionality difference as reflected by highly expressed GPR81, more proliferative ISCs and activated Wnt/β-catenin signaling. Experiments using in-house developed porcine jejunal organoids prove that live L. amylovorus and its metabolite lactate promote intestinal organoid growth. Mechanistically, L. amylovorus and lactate activate Wnt/β-catenin signaling in a GPR81-dependent manner to promote ISC-mediated epithelial proliferation. However, heat-killed L. amylovorus fail to cause these changes. These findings uncover a previously underrepresented role of L. amylovorus in regulating jejunal stem cells via Lactobacillus-lactate-GPR81 axis, a key mechanism bridging breed-driven intestinal microbiome heterogeneity with ISC fate. Thus, results from this study provide new insights into the role of gut microbiome and stem cell interactions in maintaining intestinal homeostasis., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Intestinal stem cells (ISCs) play a pivotal role in gut physiology by governing intestinal epithelium renewal through the precise regulation of proliferation and differentiation. The gut microbiota interacts closely with the epithelium through myriad of actions, including immune and metabolic interactions, which translate into tight connections between microbial activity and ISC function. Given the diverse functions of the gut microbiota in affecting the metabolism of macronutrients and micronutrients, dietary nutrients exert pronounced effects on host-microbiota interactions and, consequently, the ISC fate. Therefore, understanding the intricate host-microbiota interaction in regulating ISC homeostasis is imperative for improving gut health. Here, we review recent advances in understanding host-microbiota immune and metabolic interactions that shape ISC function, such as the role of pattern-recognition receptors and microbial metabolites, including lactate and indole metabolites. Additionally, the diverse regulatory effects of the microbiota on dietary nutrients, including proteins, carbohydrates, vitamins, and minerals (e.g. iron and zinc), are thoroughly explored in relation to their impact on ISCs. Thus, we highlight the multifaceted mechanisms governing host-microbiota interactions in ISC homeostasis. Insights gained from this review provide strategies for the development of dietary or microbiota-based interventions to foster gut health.