Pancreatitis affects gut microbiota via metabolites and inflammatory cytokines: an exploratory two-step Mendelian randomisation study.

IF 2.3 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yi-Fan Qiu, Jun Ye, Jin-Jin Xie, Xiao-Tong Mao, Yi-Long Liu, Qian Fang, Yang-Yang Qian, Wen-Bin Zou, Yu Cao, Zhuan Liao
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Abstract

Previous studies have observed relationships between pancreatitis and gut microbiota; however, specific changes in gut microbiota abundance and underlying mechanisms in pancreatitis remain unknown. Metabolites are important for gut microbiota to fulfil their biological functions, and changes in the metabolic and immune environments are closely linked to changes in microbiota abundance. We aimed to clarify the mechanisms of gut-pancreas interactions and explore the possible role of metabolites and the immune system. To this end, we conducted two-sample Mendelian randomisation (MR) analysis to evaluate the casual links between four different types of pancreatitis and gut microbiota, metabolites, and inflammatory cytokines. A two-step MR analysis was conducted to further evaluate the probable mediating pathways involving metabolites and inflammatory cytokines in the causal relationship between pancreatitis and gut microbiota. In total, six potential mediators were identified in the causal relationship between pancreatitis and gut microbiota. Nineteen species of gut microbiota and seven inflammatory cytokines were genetically associated with the four types of pancreatitis. Metabolites involved in glucose and amino acid metabolisms were genetically associated with chronic pancreatitis, and those involved in lipid metabolism were genetically associated with acute pancreatitis. Our study identified alterations in the gut microbiota, metabolites, and inflammatory cytokines in pancreatitis at the genetic level and found six potential mediators of the pancreas-gut axis, which may provide insights into the precise diagnosis of pancreatitis and treatment interventions for gut microbiota to prevent the exacerbation of pancreatitis. Future studies could elucidate the mechanism underlying the association between pancreatitis and the gut microbiota.

胰腺炎通过代谢物和炎症细胞因子影响肠道微生物群:一项探索性两步孟德尔随机研究。
以往的研究已观察到胰腺炎与肠道微生物群之间的关系;然而,胰腺炎中肠道微生物群丰度的具体变化及其内在机制仍不清楚。代谢物对肠道微生物群发挥其生物功能非常重要,代谢和免疫环境的变化与微生物群丰度的变化密切相关。我们旨在阐明肠道与胰腺之间的相互作用机制,并探索代谢物和免疫系统可能发挥的作用。为此,我们进行了双样本孟德尔随机化(MR)分析,以评估四种不同类型的胰腺炎与肠道微生物群、代谢物和炎症细胞因子之间的偶然联系。为了进一步评估代谢物和炎性细胞因子在胰腺炎与肠道微生物群之间因果关系中的可能中介途径,我们进行了两步MR分析。在胰腺炎与肠道微生物群的因果关系中,共发现了六种潜在的介导因素。19种肠道微生物群和7种炎症细胞因子与四种类型的胰腺炎存在遗传关联。参与葡萄糖和氨基酸代谢的代谢物与慢性胰腺炎有遗传相关性,而参与脂质代谢的代谢物与急性胰腺炎有遗传相关性。我们的研究在基因水平上确定了胰腺炎患者肠道微生物群、代谢物和炎症细胞因子的改变,并发现了胰腺-肠道轴的六个潜在介质,这可能为胰腺炎的精确诊断和肠道微生物群的治疗干预提供启示,以防止胰腺炎恶化。未来的研究可以阐明胰腺炎与肠道微生物群之间的关联机制。
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来源期刊
Molecular Genetics and Genomics
Molecular Genetics and Genomics 生物-生化与分子生物学
CiteScore
5.10
自引率
3.20%
发文量
134
审稿时长
1 months
期刊介绍: Molecular Genetics and Genomics (MGG) publishes peer-reviewed articles covering all areas of genetics and genomics. Any approach to the study of genes and genomes is considered, be it experimental, theoretical or synthetic. MGG publishes research on all organisms that is of broad interest to those working in the fields of genetics, genomics, biology, medicine and biotechnology. The journal investigates a broad range of topics, including these from recent issues: mechanisms for extending longevity in a variety of organisms; screening of yeast metal homeostasis genes involved in mitochondrial functions; molecular mapping of cultivar-specific avirulence genes in the rice blast fungus and more.
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