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Plasma non-targeted metabolome of high- and low-body-weight broilers

ABSTRACT:

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 Lactobacillus rhamnosus, Lactobacillus reuteri, 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.

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

PROVIDER: MTBLS12390 | MetaboLights | 2025-06-10

REPOSITORIES: MetaboLights

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			Action	DRS
	NEG_Fk14High_plasma_1.raw	Raw
	NEG_Fk14High_plasma_10.raw	Raw
	NEG_Fk14High_plasma_2.raw	Raw
	NEG_Fk14High_plasma_3.raw	Raw
	NEG_Fk14High_plasma_4.raw	Raw

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Project description: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.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.Conclusions 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.

Project description:Background: Artemisia argyi is a traditional medicinal herb with established anti-inflammatory and immunomodulatory properties. Its aqueous extract (AEAA), enriched in water-soluble bioactive constituents, exhibits favorable safety and bioavailability; however, its potential protective effects against acute lung injury (ALI) and its associations with systemic immunometabolic regulation remain incompletely understood. Methods: An LPS-induced ALI mouse model was established following 28 days of AEAA pretreatment. Lung histopathology, pulmonary edema, and inflammatory cytokines were evaluated. Integrated multi-omics analyses—including gut microbiota profiling, untargeted metabolomics of colonic contents and serum, and lung transcriptomics—were performed to characterize treatment-associated microbial, metabolic, and transcriptional alterations. Results: AEAA pretreatment dose-dependently alleviated lung injury, reduced pulmonary edema, and suppressed pro-inflammatory cytokines while restoring anti-inflammatory IL-10 levels. AEAA treatment was associated with partial reversal of LPS-induced gut dysbiosis, characterized by reduced abundance of inflammation-associated taxa and enrichment of beneficial genera, particularly Akkermansia and Lactobacillus. Metabolomic analyses revealed treatment-associated normalization of intestinal and systemic metabolic disturbances, including increased homeostasis-related metabolites and reduced inflammation-associated metabolites. Lung transcriptomic profiling suggested attenuation of LPS-associated transcriptional signatures related to NF-κB, MAPK, Toll-like receptor, and PI3K–AKT signaling pathways. Cross-omics integration further revealed coordinated associations among microbial shifts, metabolic remodeling, and pulmonary inflammatory gene expression. Conclusion: These findings suggest that aqueous Artemisia argyi extract is associated with mitigation of LPS-induced acute lung injury, accompanied by coordinated alterations in gut microbiota composition, host metabolic profiles, and pulmonary inflammatory gene expression. Although causal relationships were not established, this integrated multi-omics analysis provides a systems-level, hypothesis-generating framework supporting the potential of AEAA as a multi-target botanical candidate for ALI.

Project description:BACKGROUND AND PURPOSE: The microbiota dysfunction aggravated the severity of acute pancreatitis (AP), but the relationship between microbiota dysfunction and metabolites alteration was not fully explained. This study aimed to explore the crosstalk between microbiota and metabolites in AP mice.METHODS: Experimental AP models were established by caerulein for 7 times plus lipopolysaccharide (LPS) for once in C57/BL mice. To reveal systemic disturbance of AP, metagenomics and untargeted metabolomics were applied to reveal systemic disturbance of microbiota and metabolites in AP progress, respectively.RESULTS: Gut microbiota from AP mice was mainly composed of Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria, and presented a 'core microbiota' characterized by an expansion in Proteobacteria as well as a decrease in Actinobacteria. Kyoto encyclopedia of genes and genomes (KEGG) analysis found that the significantly differential microbiota was involved in several signaling networks. Moreover, 872 metabolites were identified from untargeted metabolomics. Among them, lipids and lipid-like molecules were majorly affected. The integrated analysis of metagenomics and metabolomics showed that acetate kinase (Acka) was associated with various gut microbiota, including Alistipes, Butyricimonas and Lactobacillus. Particularly, Acka was tightly correlated with the metabolite daphnoretin. Besides, the functional gene of O-acetyl-L-serine sulfhydrylase (Cysk) was correlated with Alistipes, Jeotgalicoccus and Lactobacillus, and which was associated with metabolites of bufalin and Phlorobenzophenone.CONCLUSION: Our study uncovered the relationship between gut microbiota and metabolites during AP, especially the Lactobacillus, Alistipes and Butyricimonas associated functional genes (Acka and Cysk) was tightly correlated to anti-inflammation and anti-tumor metabolites (daphnoretin and bufalin).

Project description:Multipotent stromal cells (MSCs) are currently in clinical trials for a number of inflammatory diseases. Recent studies have demonstrated the ability of MSCs to attenuate inflammation in rodent models of acute lung injury (ALI) suggesting that MSCs may also be beneficial in treating ALI. To better understand how human MSCs (hMSCs) may act in ALI, the lungs of immunocompetent mice were exposed to lipopolysaccharide (LPS) and 4 hr later bone marrow derived hMSCS were delivered by oropharyngeal aspiration (OA). Administration of hMSCs significantly reduced the expression of pro-inflammatory cytokines, neutrophil counts and total protein in bronchoalveolar lavage. There was a concomitant reduction in pulmonary edema as indicated by a decrease in lung wet/dry weight ratio. The anti-inflammatory effects of hMSCs were not dependent on localization to the lung, as intraperitoneal administration of hMSCs also attenuated LPS-induced inflammation in the lung. Microarray analysis revealed significant induction of TNF-α-induced protein 6 (TSG-6) expression by hMSCs 12 hr after OA delivery to LPS-exposed lungs. Knockdown of TSG-6 expression in hMSCs by RNA interference abrogated most of their anti-inflammatory effects. In addition, intra-pulmonary delivery of recombinant human TSG-6 reduced LPS-induced inflammation in the lung. These results show that hMSCs recapitulate the observed beneficial effects of rodent MSCs in animal models of ALI and suggest that the anti-inflammatory properties of hMSCs in the lung are explained, at least in part, by activation of hMSCs to secrete TSG-6. Eight- to 10-week-old female BALB/C mice were treated with either 1 mg/kg lipopolysaccharide (LPS) in 100 μl PBS or an equal volume of PBS, as vehicle control, by oropharyngeal aspiration (OA). Four hours after LPS exposure, 250,000 human multipotent stromal cells in 100 μl of PBS were given by OA and 30 min later a second dose of equal concentration was administered, for a total of 500,000 hMSC. As a control, 200 μl PBS was delivered as described above. After 12 h, total RNA was isolated from (A) lungs of LPS-exposed mice treated with either hMSCs (LPS+MSC) or PBS (LPS+PBS), and (B) lungs of PBS-exposed mice treated with hMSCs (PBS+MSC). To obtain additional controls, hMSCs were mixed in vitro with either LPS- (LPS+MSC in vitro mix) or PBS-exposed (PBS+MSC in vitro mix) mouse lungs just before RNA isolation. RNA samples containing mouse and human RNA were first analyzed for amount of human RNA based on human GAPDH signal from real-time RT PCR. Samples with similar human RNA content were used for both mouse and human microarrays

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Plasma non-targeted metabolome of high- and low-body-weight broilers

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