Dataset Information

Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer.

ABSTRACT: BACKGROUND:The aim was to evaluate the changes of 16S rDNA sequencing and LC-MS metabolomics in breast cancer and explore the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii. RESULTS:Total 49 significantly different flora and 26 different metabolites were screened between two groups, and the correlation was calculated. Relative abudance of Firmicutes and Bacteroidetes were decreased, while relative abundance of verrucomicrobla, proteobacteria and actinobacteria was increased in breast cancer group. Differentially expressed metabolites were mainly enriched in pathways such as linoleic acid metabolism, retrograde endocannabinoid signaling, biosynthesis of unsaturated fatty acids, choline metabolism in cancer and arachidonic acid metabolism. Lipid upregulation was found in breast cancer patients, especially phosphorocholine. The abundance of Faecalibacterium was reduced in breast cancer patients, which was negatively correlated with various phosphorylcholines. Moreover, Faecalibacterium prausnitzii, the most well-known species in Faecalibacterium genus, could inhibit the secretion of interleukin-6 (IL-6) and the phosphorylation of Janus kinases 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) in breast cancer cells. Faecalibacterium prausnitzii also suppressed the proliferation and invasion and promoted the apoptosis of breast cancer cells, while these effects disappeared after adding recombinant human IL-6. CONCLUSIONS:Flora-metabolites combined with the flora-bacteria (such as Faecalibacterium combined with phosphorocholine) might a new detection method for breast cancer. Faecalibacterium may be helpful for prevention of breast cancer. Faecalibacterium prausnitzii suppresses the growth of breast cancer cells through inhibition of IL-6/STAT3 pathway.

SUBMITTER: Ma J

PROVIDER: S-EPMC7144064 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer.

Ma Ji J Sun Lingqi L Liu Ying Y Ren Hui H Shen Yali Y Bi Feng F Zhang Tao T Wang Xin X

BMC microbiology 20200409 1

<h4>Background</h4>The aim was to evaluate the changes of 16S rDNA sequencing and LC-MS metabolomics in breast cancer and explore the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii.<h4>Results</h4>Total 49 significantly different flora and 26 different metabolites were screened between two groups, and the correlation was calculated. Relative abudance of Firmicutes and Bacteroidetes were decreased, while relative abundance of verrucomicrobla, proteobacteria and actinobac ...[more]

PMID: 32272885

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Project description:UnlabelledFaecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified on the basis of human clinical data. The mechanisms underlying its beneficial effects are still unknown. Gnotobiotic mice harboring F. prausnitzii (A2-165) and Escherichia coli (K-12 JM105) were subjected to 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute colitis. The inflammatory colitis scores and a gas chromatography-time of flight (GC/TOF) mass spectrometry-based metabolomic profile were monitored in blood, ileum, cecum, colon, and feces in gnotobiotic mice. The potential anti-inflammatory metabolites were tested in vitro. We obtained stable E. coli and F. prausnitzii-diassociated mice in which E. coli primed the gastrointestinal tract (GIT), allowing a durable and stable establishment of F. prausnitzii. The disease activity index, histological scores, myeloperoxidase (MPO) activity, and serum cytokine levels were significantly lower in the presence of F. prausnitzii after TNBS challenge. The protective effect of F. prausnitzii against colitis was correlated to its implantation level and was linked to overrepresented metabolites along the GIT and in serum. Among 983 metabolites in GIT samples and serum, 279 were assigned to known chemical reactions. Some of them, belonging to the ammonia (?-ketoglutarate), osmoprotective (raffinose), and phenolic (including anti-inflammatory shikimic and salicylic acids) pathways, were associated with a protective effect of F. prausnitzii, and the functional link was established in vitro for salicylic acid. We show for the first time that F. prausnitzii is a highly active commensal bacterium involved in reduction of colitis through in vivo modulation of metabolites along the GIT and in the peripheral blood.ImportanceInflammatory bowel diseases (IBD) are characterized by low proportions of F. prausnitzii in the gut microbiome. This commensal bacterium exhibits anti-inflammatory effects through still unknown mechanisms. Stable monoassociated rodents are actually not a reproducible model to decipher F. prausnitzii protective effects. We propose a new gnotobiotic rodent model providing mechanistic clues. In this model, F. prausnitzii exhibits protective effects against an acute colitis and a protective metabolic profile is linked to its presence along the digestive tract. We identified a molecule, salicylic acid, directly involved in the protective effect of F. prausnitzii. Targeting its metabolic pathways could be an attractive therapeutic strategy in IBD.

Project description:Liver cirrhosis (LC) has been associated with gut microbes. However, the strain diversity of species and its association with LC have received little attention. Here, we constructed a computational framework to study the strain heterogeneity in the gut microbiome of patients with LC. Only Faecalibacterium prausnitzii shows different single-nucleotide polymorphism (SNP) patterns between the LC and healthy control (HC) groups. Strain diversity analysis discovered that although most F. prausnitzii genomes are more deficient in the LC group than in the HC group at the strain level, a subgroup of 19 F. prausnitzii strains showed no sensitivity to LC, which is inconsistent with the species-level result. The functional differences between this subgroup and other strains may involve short-chain fatty acid production and chlorine-related pathways. These findings demonstrate functional differences among F. prausnitzii subgroups, which extend current knowledge about strain heterogeneity and relationships between F. prausnitzii and LC at the strain level. IMPORTANCE Most metagenomic studies focus on microbes at the species level, thus ignoring the different effects of different strains of the same species on the host. In this study, we explored the different microbes at the strain level in the intestines of patients with liver cirrhosis and of healthy people. Previous studies have shown that the species Faecalibacterium prausnitzii has a lower abundance in patients with liver cirrhosis than in healthy people. However, our results found multiple F. prausnitzii strains that do not decrease in abundance in patients with liver cirrhosis. It is more sensitive to select the appropriate strains as indicators to distinguish between the disease and the control samples than to use the entire species as an indicator. We clustered multiple F. prausnitzii strains and discuss the functional differences of different clusters. Our findings suggest that more attention should be paid to metagenomic studies at the strain level.

Dataset Information

Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer.

Publications

Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer.

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