关键词: Bacteroides uniformis CaCo-2 Ruminococcus gnavus ankylosing spondylitis biotin metabolome microbiome oxypurinol

Mesh : Humans Spondylitis, Ankylosing / microbiology metabolism immunology Gastrointestinal Microbiome Probiotics Male Female Metabolome Adult Feces / microbiology Metagenomics / methods Middle Aged Prospective Studies Metabolomics Bacteria / metabolism classification isolation & purification Tumor Necrosis Factor Inhibitors / therapeutic use pharmacology

来  源:   DOI:10.3389/fimmu.2024.1369116   PDF(Pubmed)

Abstract:
UNASSIGNED: Previous research has partially revealed distinct gut microbiota in ankylosing spondylitis (AS). In this study, we performed non-targeted fecal metabolomics in AS in order to discover the microbiome-metabolome interface in AS. Based on prospective cohort studies, we further explored the impact of the tumor necrosis factor inhibitor (TNFi) on the gut microbiota and metabolites in AS.
UNASSIGNED: To further understand the gut microbiota and metabolites in AS, along with the influence of TNFi, we initiated a prospective cohort study. Fecal samples were collected from 29 patients with AS before and after TNFi therapy and 31 healthy controls. Metagenomic and metabolomic experiments were performed on the fecal samples; moreover, validation experiments were conducted based on the association between the microbiota and metabolites.
UNASSIGNED: A total of 7,703 species were annotated using the metagenomic sequencing system and by profiling the microbial community taxonomic composition, while 50,046 metabolites were identified using metabolite profiling. Differential microbials and metabolites were discovered between patients with AS and healthy controls. Moreover, TNFi was confirmed to partially restore the gut microbiota and the metabolites. Multi-omics analysis of the microbiota and metabolites was performed to determine the associations between the differential microbes and metabolites, identifying compounds such as oxypurinol and biotin, which were correlated with the inhibition of the pathogenic bacteria Ruminococcus gnavus and the promotion of the probiotic bacteria Bacteroides uniformis. Through experimental studies, the relationship between microbes and metabolites was further confirmed, and the impact of these two types of microbes on the enterocytes and the inflammatory cytokine interleukin-18 (IL-18) was explored.
UNASSIGNED: In summary, multi-omics exploration elucidated the impact of TNFi on the gut microbiota and metabolites and proposed a novel therapeutic perspective: supplementation of compounds to inhibit potential pathogenic bacteria and to promote potential probiotics, therefore controlling inflammation in AS.
摘要:
先前的研究部分揭示了强直性脊柱炎(AS)中独特的肠道微生物群。在这项研究中,我们在AS中进行了非靶向粪便代谢组学,以发现AS中的微生物组-代谢组界面.基于前瞻性队列研究,我们进一步探讨了肿瘤坏死因子抑制剂(TNFi)对AS患者肠道菌群和代谢产物的影响.
为了进一步了解AS中的肠道微生物群和代谢产物,随着TNFi的影响,我们启动了一项前瞻性队列研究.从TNFi治疗前后的29名AS患者和31名健康对照中收集粪便样本。对粪便样本进行了宏基因组和代谢组学实验;此外,验证实验是基于微生物群和代谢物之间的关联进行的.
使用宏基因组测序系统并通过分析微生物群落分类组成对总共7,703个物种进行了注释,而使用代谢物谱分析鉴定了50,046种代谢物。在AS患者和健康对照组之间发现了不同的微生物和代谢产物。此外,证实TNFi部分恢复肠道微生物群和代谢物。进行微生物群和代谢物的多组学分析,以确定差异微生物和代谢物之间的关联,鉴定化合物,如氧嘌呤醇和生物素,这与对病原菌的抑制和对益生菌均匀拟杆菌的促进有关。通过实验研究,进一步证实了微生物与代谢产物的关系,探讨了这两类微生物对肠上皮细胞和炎性细胞因子白细胞介素-18(IL-18)的影响。
总之,多组学探索阐明了TNFi对肠道微生物群和代谢产物的影响,并提出了一种新的治疗观点:补充化合物以抑制潜在的致病菌并促进潜在的益生菌,因此控制AS的炎症。
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