Dataset Information

Alterations in the Gut Microbiome and Cecal Metabolome During Klebsiella pneumoniae-Induced Pneumosepsis.

ABSTRACT: Klebsiella (K.) pneumoniae is a common cause of pneumonia-derived sepsis in human and is associated with high morbidity and mortality. The microbiota promotes and maintains host immune homeostasis during bacterial infections. However, the mechanisms by which the gut microbiota affects immune responses in the lung still remain poorly understood. Here, we performed cecal metabolomics sequencing and fecal 16s rRNA sequencing in K. pneumoniae-infected mice and uninfected controls and showed that K. pneumoniae infection led to profound alterations in the gut microbiome and thus the cecal metabolome. We observed that the levels of Lactobacillus reuteri and Bifidobacterium pseudolongum were significantly decreased in K. pneumoniae-infected mice. Spearman correlation analysis showed that alterations in the richness and composition of the gut microbiota were associated with profound changes in host metabolite concentrations. Further, short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, were detected in cecal contents and serum by gas chromatography-mass spectrometry (GC-MS). We observed that the concentrations of these three SCFAs were all lower in the infected groups than in the untreated controls. Lastly, oral supplementation with these three SCFAs reduced susceptibility to K. pneumoniae infections, as indicated by lower bacterial burdens in the lung and higher survival rates. Our data highlight the protective roles of gut microbiota and certain metabolites in K. pneumoniae-pneumonia and suggests that it is possible to intervene in this bacterial pneumonia by targeting the gut microbiota.

SUBMITTER: Wu T

PROVIDER: S-EPMC7411141 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Alterations in the Gut Microbiome and Cecal Metabolome During Klebsiella pneumoniae-Induced Pneumosepsis.

Wu Ting T Xu Fangming F Su Cong C Li Hongru H Lv Na N Liu Yanyan Y Gao Yufeng Y Lan Yanhu Y Li Jiabin J

Frontiers in immunology 20200731

Klebsiella (K.) pneumoniae is a common cause of pneumonia-derived sepsis in human and is associated with high morbidity and mortality. The microbiota promotes and maintains host immune homeostasis during bacterial infections. However, the mechanisms by which the gut microbiota affects immune responses in the lung still remain poorly understood. Here, we performed cecal metabolomics sequencing and fecal 16s rRNA sequencing in K. pneumoniae-infected mice and uninfected ...[more]

PMID: 32849494

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Project description:Antibiotic overuse in poultry husbandry poses a potential threat to meat safety and human health. Lauric acid (LA) is a primary medium-chain fatty acid (MCFA) with a strong antibacterial capacity. The goal of this study was to evaluate the beneficial effects of LA on the growth performance, immune responses, serum metabolism, and cecal microbiota of broiler chickens. One-day-old male Ross 308 broilers were randomly divided into 4 groups: CON, fed a basal diet; ANT, a basal diet supplemented with 75 mg/kg antibiotic; LA500, a basal diet supplemented with 500 mg/kg LA; LA1000, a basal diet supplemented with 1000 mg/kg LA. The feeding period was 42 d. The results showed that LA significantly improved broiler growth and immune functions, as evidenced by increased body weight (BW) and average daily gain (ADG), enhanced intestinal mucosal barrier, upregulated immunoglobulins (IgA, IgM, and IgY), and downregulated inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-4, and IL-10) (P < 0.05). HPLC/MS-based metabolome analysis revealed that the serum metabolites in the LA group differed from those of CON and ANT groups. LA markedly decreased the abundance of phosphatidylcholines (PCs), increased lysophosphatidylcholines (LysoPCs), and inhibited the sphingolipid metabolism pathway, indicating its capacity to modulate lipid metabolism. 16S rRNA sequencing indicated that LA significantly altered cecal microbiota composition by reducing Phascolarctobacterium, Christensenellaceae_R-7_group, and Bacteroides, and increasing Faecalibacterium and Ruminococcaceae_UCG-014 (P < 0.05). Furthermore, Spearman correlation analysis revealed that changes in metabolism and microbiota were highly correlated with the growth and immune indices; strong links were also found between lipid metabolism and microbial composition. Taken together, LA promotes broiler growth and immune functions by regulating lipid metabolism and gut microbiota. The above findings highlight the substantial potential of LA as a supplement in poultry diets and provide a new strategy to reduce antibiotic usage and improve food safety.

Project description:ObjectiveWe explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI.MethodsFecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman's rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage.ResultsThe abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-β1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-β1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice.ConclusionsThe interactions between the gut microbiota, serum metabolites, and serum TGF-β1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-β1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.

Dataset Information

Alterations in the Gut Microbiome and Cecal Metabolome During Klebsiella pneumoniae-Induced Pneumosepsis.

Publications

Alterations in the Gut Microbiome and Cecal Metabolome During <i>Klebsiella pneumoniae</i>-Induced Pneumosepsis.

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