RESUMEN
BACKGROUND: Exclusive enteral nutrition (EEN) is an important alternative strategy for patients with Crohn's disease (CD), and during this process, microbiota alterations have been observed. However, the underlying mechanisms by which EEN reduces intestinal inflammation are currently unclear. METHODS: The therapeutic potential of enteral nutrition (EN) was assessed using various mouse models. Fecal full-length 16S rDNA sequencing analysis and several CD metagenome datasets were used to identify the candidate therapeutic bacteria Faecalibaculum rodentium (F. rodentium). Whole genome sequencing of F. rodentium and widely-targeted metabolome analysis of the supernatant showed that EN-induced F. rodentium accumulation protected against colitis via histidine biosynthesis. FINDINGS: The therapeutic potential of EN therapy was observed in both dextran sulfate sodium (DSS)-induced colitis and Il10-/- spontaneous colitis mouse models. Accumulation of F. rodentium after EN therapy was determined using full-length 16S rDNA sequencing and verified with several metagenome datasets from patients with CD. Colonization of an isolated F. rodentium could reduce colitis in Il10-/- mice. Significant histidine enrichment was observed in the F. rodentium culture supernatant, and a series of histidine biosynthesis genes were observed in the F. rodentium genome. Engineered Escherichia coli Nissle 1917 (EcN), encoding the heterologous hisG of F. rodentium (EcN-hisG), which was a key driver of histidine biosynthesis in F. rodentium, was found to protect against colitis. INTERPRETATION: This study suggests that EN-induced F. rodentium accumulation protects against colitis in mice via gut bacteria-mediated histidine biosynthesis. FUNDING: A full list of funding bodies can be found in the Acknowledgements section.
Asunto(s)
Colitis , Enfermedad de Crohn , Firmicutes , Humanos , Animales , Ratones , Nutrición Enteral , Interleucina-10/genética , Histidina , Colitis/etiología , Colitis/terapia , Enfermedad de Crohn/microbiología , Bacterias/genética , Modelos Animales de Enfermedad , ADN RibosómicoRESUMEN
Inflammatory bowel disease (IBD) is a predisposing factor for colitis-associated cancer (CAC). The association between bile acids and the gut microbiota has been demonstrated in colon neoplasia; however, the effect of ursodeoxycholic acid (UDCA) on gut microbiota alteration in development of colitis and CAC is unknown. Our analysis of publicly available datasets demonstrated the association of UDCA treatment and accumulation of Akkermansia. UDCA-mediated alleviation of DSS-induced colitis was microbially dependent. UDCA treatment significantly upregulated Akkermansia colonization in a mouse model. Colonization of Akkermansia was associated with enhancement of the mucus layer upon UDCA treatment as well as activation of bile acid receptors in macrophages. UDCA played a role in CAC prevention and treatment in the AOM-DSS and ApcMin/+-DSS models through downregulation of inflammation and accumulation of Akkermansia. This study suggests that UDCA intervention could reshape intestinal gut homeostasis, facilitating colonization of Akkermansia and preventing and treating colitis and CAC.
Asunto(s)
Neoplasias Asociadas a Colitis , Colitis , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Ratones , Animales , Ácido Ursodesoxicólico/efectos adversos , Neoplasias Asociadas a Colitis/complicaciones , Colitis/inducido químicamente , Colitis/complicaciones , Colitis/tratamiento farmacológico , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , ColonRESUMEN
Centipeda minima is a traditional Chinese medicine with wide applications and diverse pharmacological effects. Scholars have conducted extensive studies on its relevant clinical applications, especially its remarkable efficacy in cancer treatment. This paper thoroughly investigates the chemical composition and identification, pharmacological effects, and toxicity, along with the safety of Centipeda minima, so as to lay the foundation for corresponding clinical applications and product development. Furthermore, as global scholars have conducted extensive research on such clinical applications and made significant progress, the future development and utilization of Centipeda minima's active ingredients to create novel drugs are of great clinical significance.