Fecal glycoprotein 2 is a marker of gut microbiota dysbiosis and systemic inflammation.

IF 4.3 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Gut Pathogens Pub Date : 2024-10-19 DOI:10.1186/s13099-024-00657-1
Fabian Frost, Stefan Weiss, Johannes Hertel, Malte Rühlemann, Corinna Bang, Andre Franke, Matthias Nauck, Marcus Dörr, Henry Völzke, Dirk Roggenbuck, Peter Schierack, Uwe Völker, Georg Homuth, Ali A Aghdassi, Matthias Sendler, Markus M Lerch, Frank U Weiss
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Abstract

Background: Antimicrobial autoantigenic glycoprotein 2 (GP2) is an important component of the innate immune system which originates from the exocrine pancreas as well as from the small intestines. The relationship of GP2 with the intestinal microbiome as well as the systemic implications of increased fecal GP2 levels are, however, still unclear. Therefore, fecal samples from 2,812 individuals of the Study of Health in Pomerania (SHIP) were collected to determine GP2 levels (enzyme-linked immunosorbent assay) and gut microbiota profiles (16 S rRNA gene sequencing). These data were correlated and associated with highly standardised and comprehensive phenotypic data of the study participants.

Results: Fecal GP2 levels were increased in individuals with higher body mass index and smokers, whereas lower levels were found in case of preserved exocrine pancreatic function, female sex or a healthier diet. Moreover, higher GP2 levels were associated with increased serum levels of high-sensitivity C-reactive protein, loss of gut microbial diversity and an increase of potentially detrimental bacteria (Streptococcus, Haemophilus, Clostridium XIVa, or Collinsella). At the same time, predicted microbial pathways for the biosynthesis of beneficial short-chain fatty acids or lactic acid were depleted in individuals with high fecal GP2. Of note, GP2 exhibited a stronger association to overall microbiome variation than calprotectin.

Conclusion: Fecal GP2 is a biomarker of gut microbiota dysbiosis and associated with increased systemic inflammation. The intestines may be more important as origin for GP2 than pancreatic acinar cells. Future studies need to investigate the potential clinical value in disease specific patient cohorts.

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粪便糖蛋白 2 是肠道微生物群失调和全身炎症的标志物。
背景:抗微生物自身抗原糖蛋白 2(GP2)是先天性免疫系统的一个重要组成部分,它来源于胰腺外分泌和小肠。然而,GP2 与肠道微生物群的关系以及粪便中 GP2 水平升高对全身的影响仍不清楚。因此,我们收集了波美拉尼亚健康研究(SHIP)中 2812 人的粪便样本,以测定 GP2 水平(酶联免疫吸附试验)和肠道微生物群概况(16 S rRNA 基因测序)。这些数据与研究参与者高度标准化的综合表型数据相关联:结果:体重指数较高和吸烟者的粪便中 GP2 水平较高,而胰腺外分泌功能正常、女性或饮食健康者的 GP2 水平较低。此外,GP2 水平升高与血清中高敏 C 反应蛋白水平升高、肠道微生物多样性丧失和潜在有害细菌(链球菌、嗜血杆菌、XIVa 梭状芽孢杆菌或柯林斯菌)增加有关。与此同时,粪便中 GP2 较高的个体中,预测的有益短链脂肪酸或乳酸生物合成的微生物途径被耗尽。值得注意的是,GP2与微生物组整体变化的关系比钙蛋白更密切:结论:粪便 GP2 是肠道微生物群失调的生物标志物,与全身炎症增加有关。肠道作为 GP2 的来源可能比胰腺尖塔细胞更重要。未来的研究需要调查该指标在特定疾病患者群中的潜在临床价值。
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来源期刊
Gut Pathogens
Gut Pathogens GASTROENTEROLOGY & HEPATOLOGY-MICROBIOLOGY
CiteScore
7.70
自引率
2.40%
发文量
43
期刊介绍: Gut Pathogens is a fast publishing, inclusive and prominent international journal which recognizes the need for a publishing platform uniquely tailored to reflect the full breadth of research in the biology and medicine of pathogens, commensals and functional microbiota of the gut. The journal publishes basic, clinical and cutting-edge research on all aspects of the above mentioned organisms including probiotic bacteria and yeasts and their products. The scope also covers the related ecology, molecular genetics, physiology and epidemiology of these microbes. The journal actively invites timely reports on the novel aspects of genomics, metagenomics, microbiota profiling and systems biology. Gut Pathogens will also consider, at the discretion of the editors, descriptive studies identifying a new genome sequence of a gut microbe or a series of related microbes (such as those obtained from new hosts, niches, settings, outbreaks and epidemics) and those obtained from single or multiple hosts at one or different time points (chronological evolution).
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