RESUMO
BACKGROUND AND AIMS: Dietary fat intake is associated with increased risk of colorectal cancer (CRC). We examined the role of high-fat diet (HFD) in driving CRC through modulating gut microbiota and metabolites. METHODS: HFD or control diet was fed to mice littermates in CRC mouse models of an azoxymethane (AOM) model and Apcmin/+ model, with or without antibiotics cocktail treatment. Germ-free mice for fecal microbiota transplantation were used for validation. Gut microbiota and metabolites were detected using metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Gut barrier function was determined using lipopolysaccharides level and transmission electron microscopy. RESULTS: HFD promoted colorectal tumorigenesis in both AOM-treated mice and Apcmin/+ mice compared with control diet-fed mice. Gut microbiota depletion using antibiotics attenuated colon tumor formation in HFD-fed mice. A significant shift of gut microbiota composition with increased pathogenic bacteria Alistipessp.Marseille-P5997 and Alistipessp.5CPEGH6, and depleted probiotic Parabacteroides distasonis, along with impaired gut barrier function was exhibited in HFD-fed mice. Moreover, HFD-modulated gut microbiota promotes colorectal tumorigenesis in AOM-treated germ-free mice, indicating gut microbiota was essential in HFD-associated colorectal tumorigenesis. Gut metabolites alteration, including elevated lysophosphatidic acid, which was confirmed to promote CRC cell proliferation and impair cell junction, was also observed in HFD-fed mice. Moreover, transfer of stools from HFD-fed mice to germ-free mice without interference increased colonic cell proliferation, impaired gut barrier function, and induced oncogenic genes expression. CONCLUSIONS: HFD drives colorectal tumorigenesis through inducing gut microbial dysbiosis, metabolomic dysregulation with elevated lysophosphatidic acid, and gut barrier dysfunction in mice.
Assuntos
Bactérias/metabolismo , Colo/microbiologia , Neoplasias Colorretais/microbiologia , Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Antibacterianos/farmacologia , Azoximetano , Bactérias/efeitos dos fármacos , Translocação Bacteriana , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/ultraestrutura , Colo/metabolismo , Colo/ultraestrutura , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/ultraestrutura , Modelos Animais de Doenças , Disbiose , Transplante de Microbiota Fecal , Fezes/microbiologia , Genes APC , Vida Livre de Germes , Humanos , Lisofosfolipídeos/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Permeabilidade , Células Tumorais CultivadasRESUMO
We announce the draft genome sequence of amikacin- and kanamycin-resistant Mycobacterium tuberculosis MT433, which has been previously described as the strain carrying an unknown resistance mechanism.
RESUMO
We present the draft genome sequence of DS-16780, with a rare spoligo-international type (SIT) 523 (777777777777771) genotype, which reveals an extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) phenotype. The isolate is a representative of clonal XDR-TB from the western part of Thailand.
RESUMO
Infections with the Beijing family of Mycobacterium tuberculosis occur worldwide and are endemic in Asian countries. We present the draft genome sequence of DS6701, a multidrug-resistant M. tuberculosis Beijing strain of sequence type 10. The isolate is a representative of strains isolated from a multidrug-resistant tuberculosis outbreak in Thailand.