Project description:<p>Background In large-scale poultry farming, broilers of the same breed, sharing a common genetic background and identical management conditions, nevertheless exhibit considerable individual variation in body weight. Multitudinous stressors can profoundly influence the host microbiota, thereby modulating overall health and growth. This study employed multi-omics approaches to elucidate the underlying factors contributing to the disparities between high- and low-weight broilers and to evaluate the effects of Lactobacillus aerosolization on growth performance and systemic inflammation in these animals.</p><p>Results This study identified distinct plasma proteomic profiles between high- and low-weight broilers, with the latter exhibiting a systemic inflammatory response. Gut microbiota differences were minimal, and fecal microbiota transplantation did not alter broiler body weight. However, lung microbiota analysis revealed a higher relative abundance of Lactobacillus in high-weight broilers, linked to altered plasma tryptophan metabolism. Aerosolized Lactobacillus reuteri C501, Lacticaseibacillus rhamnosus UA260, and their combination enhanced growth and mitigated LPS-induced inflammation. This intervention increased L-Tryptophan (L-Trp), indoleacrylic acid (IAA), and indole-3-carboxaldehyde (I3C) levels in plasma and bronchoalveolar lavage fluid (BALF). Mechanistic studies showed that IAA and I3C activated the AHR pathway, promoting SOCS3 expression in macrophages, inhibiting JAK2/STAT3 signaling, and alleviating LPS-induced inflammation.</p><p><strong>Conclusions</strong> Aerosolization of Lactobacillus enhances broiler performance and alleviates LPS-induced stress responses. This effect is mediated through the modulation of tryptophan metabolism, which interacts with the AHR/SOCS3 axis to inhibit JAK2/STAT3 signaling, thereby reducing both pulmonary and systemic inflammation. Our findings provide insights into the interaction between poultry production and lung microbiota, establishing Lactobacillus aerosolization as a promising strategy to combat systemic inflammation and improve poultry health and performance.</p>
Project description:Microbial dysbiosis is a colorectal cancer (CRC) hallmark and contributes to inflammation, tumor growth, and therapy response. Gut microbes signal via metabolites, but how the metabolites impact CRC is largely unknown. We interrogated fecal metabolites associated with mouse models of colon tumorigenesis with varying mutational load. We found that microbial metabolites from healthy mice or humans were growth-repressive, and this response was attenuated in mice and patients with CRC. Microbial profiling revealed that Lactobacillus reuteri and its metabolite, reuterin were downregulated in mouse and human CRC. Reuterin altered redox balance, and reduced survival, and proliferation in colon cancer cells. Reuterin induced selective protein oxidation, and inhibited ribosomal biogenesis and protein translation. Exogenous Lactobacillus reuteri restricted mouse colon tumor growth, increased tumor reactive oxygen species, and decreased protein translation in vivo. Our findings indicate that a healthy microbiome and specifically, Lactobacillus reuteri, is protective against CRC through microbial metabolite exchange.
Project description:<p>In large-scale poultry farming, broilers of the same breed share a common genetic background and identical management conditions, yet substantial individual variation in body weight persists. In this study, we identified distinct plasma proteomic profiles between high and low weight broilers, with low weight broilers exhibiting a heightened systemic inflammatory response. The gut microbiome differences between groups were minimal, and fecal microbiota transplantation from high or low weight broilers did not significantly affect body weight. However, lung microbiome analysis revealed that high weight broilers had a significantly higher abundance of Lactobacillus, associated with altered plasma tryptophan metabolism. Aerosolized<em> Lactobacillus rhamnosus</em>, <em>Lactobacillus reuteri</em>, and their combination were administered to modulate the lung microbiota. This intervention significantly enhanced production performance and alleviated LPS-induced systemic inflammation. Aerosolization of Lactobacillus strains elevated metabolites such as L-tryptophan (Trp), indoleacrylic acid (IAA), and indole-3-carboxaldehyde (I3C) in plasma and lung tissues. Mechanistic explorations elucidate that IAA and I3C activated the aryl hydrocarbon receptor (AHR) pathway, promoting nuclear translocation and upregulating SOCS3 expression in macrophages. This inhibited the JAK2/STAT3 signaling pathway, mitigating LPS-induced inflammation. Our findings provide insights into the interaction between poultry production and lung microbiota, establishing Lactobacillus aerosolization as a promising strategy to combat systemic inflammation and improve poultry health and performance.</p>
2025-06-10 | MTBLS12390 | MetaboLights
Project description:Effects of dietary supplementation of Lactobacillus reuteri postbiotics on growth performance, intestinal flora structure and plasma metabolome of weaned piglets
Project description:This SuperSeries is composed of the following subset Series: GSE11860: The impact of glycerol on the metabolism of Lactobacillus reuteri - Exploratory experiment GSE11861: The impact of glycerol on the metabolism of Lactobacillus reuteri - Main experiment Refer to individual Series
Project description:Necrotic enteritis (NE) in broiler chickens, caused by the overgrowth of toxin-producing strains of Clostridium (C.) perfringens, results in the development of necrotic lesions, compromised intestinal health, and significant economic losses in poultry production. This study aims to analyze the blood proteome of broiler chickens affected by NE, providing insights into the host's response to the infection. Using MS/MS-based proteomics, blood plasma samples from broilers with necrotic lesions of different severity were analyzed and compared to healthy controls. A total of 412 proteins were identified, with 63 showing significant differences and (for some of those) correlating with disease severity. Gene Set Enrichment Analysis (GSEA) revealed that proteins affected by NE were predominantly associated with the immune and signaling processes and extracellular matrix (ECM) structures. Notably, regulated proteins were significantly involved in bioprocesses related to complement activation, acute phase reaction, proteolysis and humoral immune response. The findings suggest that the changes in plasma proteins in response to NE are driven by the host's intensified efforts to counteract the infection, demonstrating a.o. a notable reduction in peptides from ECM-related proteins in the blood of NE-affected birds. Overall, proteomics results underscored the attempts of the host to manage tissue damage and inflammation, indicating a coordinated effort to mitigate the pathogenic impact of C. perfringens. This study provides a deeper understanding of the host-pathogen interactions and potential targets for therapeutic intervention.
Project description:Lactobacillus reuteri 100-23 is an autochthonous inhabitant of the rodent gastrointestinal system that adheres to the non-secretory epithelium of the forestomach and forms biofilms. Microarray analysis of the expression profile of L. reuteri 100-23 cells harvested from the stomach of ex-Lactobacillus-free mice, compared to those of L. reuteri 100-23 in laboratory culture, revealed an in vivo upregulation of a urease gene cluster by greater than 50-fold. Genes for urease production were absent in all publically available Lactobacillus genome sequences except L. reuteri 100-23 and have recently been identified as specific to rodent strains of L. reuteri (Frese et al. 2011). In the current study, the urease enzyme was shown to be functional. Supplementation with 2% urea allowed L. reuteri 100-23 to increase the pH of the culture medium. A mutant strain of L. reuteri 100-23 was developed by insertional inactivation of the ureC gene, which encodes the largest subunit of the urease enzyme. The mutant strain was unable to hydrolyze urea to increase the pH of culture medium, and did not survive acid stress at pH 2.5 for 6 h, even in the presence of urea. In contrast, the wild type strain was still viable after 6 h when 2% urea supplementation was included. When mice free of lactobacilli were inoculated with a mixture of equal numbers of wild type L. reuteri 100-23 and ureC mutant cells, the wild type constituted 99% of the resulting Lactobacillus population in the stomach, caecum and jejunum after one week (108 cells/gram of sample). This study has therefore shown the importance of a functional urease enzyme in the ecological fitness of L. reuteri 100-23.
Project description:The intestinal microbiome forms dynamic ecosystem whose balanced composition and functioning are essential for maintaining overall gut health and well-being in living organisms. In broilers, dysbiosis disrupts the microbiota-host balance, often without obvious clinical symptoms but with intestinal inflammation, leading to impaired animal performance and significant economic losses. This study utilizes an in vivo model of dysbiosis to investigate the blood proteome response of broilers to intestinal imbalance. Microscopic histological changes in the gut (shorter villi, increased crypt depth, p<0.0001) were observed in the duodenal and jejunal tissue of challenged birds. Elevated levels of permeability markers faecal ovotransferrin (p < 0.0001) and serum iohexol (p= 0.0009) additionally indicated increased intestinal permeability in challenged group compared to control. The MS/MS-based proteomics analysis was performed on broilers’ blood plasma enabling identification of 388 proteins, 25 of which demonstrated significant difference between the groups. Functional analysis showed activation of immune response, signalling, and interspecies interaction, while proteins related to cellular physiology, cell-cell communication, and extracellular matrix (ECM) processes were suppressed. Protein-protein interaction (PPI) analysis revealed two clusters of downregulated proteins involved in ECM organization and cell adhesion. These results suggest that the dysbiosis challenge alters plasma protein expression as the host prioritizes immune defense over structural maintenance. The activation of immune processes and suppression of ECM pathways highlight potential biomarkers and therapeutic targets for addressing dysbiosis.
Project description:Purpose: Analyze gene expression of necrotic enteritis C. perfringens in intestinal chicken loops comparing with in vitro conditions