Dicks Leon M T
Department of Microbiology, Stellenbosch University, Stellenbosch 7600, South Africa.
Int J Mol Sci. 2024 Apr 17;25(8):4431. doi: 10.3390/ijms25084431.
With genetic information gained from next-generation sequencing (NGS) and genome-wide association studies (GWAS), it is now possible to select for genes that encode reporter molecules that may be used to detect abnormalities such as alcohol-related liver disease (ARLD), cancer, cognitive impairment, multiple sclerosis (MS), diabesity, and ischemic stroke (IS). This, however, requires a thorough understanding of the gut-brain axis (GBA), the effect diets have on the selection of gut microbiota, conditions that influence the expression of microbial genes, and human physiology. Bacterial metabolites such as short-chain fatty acids (SCFAs) play a major role in gut homeostasis, maintain intestinal epithelial cells (IECs), and regulate the immune system, neurological, and endocrine functions. Changes in butyrate levels may serve as an early warning of colon cancer. Other cancer-reporting molecules are colibactin, a genotoxin produced by polyketide synthetase-positive strains, and spermine oxidase (SMO). Increased butyrate levels are also associated with inflammation and impaired cognition. Dysbiosis may lead to increased production of oxidized low-density lipoproteins (OX-LDLs), known to restrict blood vessels and cause hypertension. Sudden changes in SCFA levels may also serve as a warning of IS. Early signs of ARLD may be detected by an increase in regenerating islet-derived 3 gamma (REG3G), which is associated with changes in the secretion of mucin-2 (Muc2). Pro-inflammatory molecules such as cytokines, interferons, and TNF may serve as early reporters of MS. Other examples of microbial enzymes and metabolites that may be used as reporters in the early detection of life-threatening diseases are reviewed.
借助从下一代测序（NGS）和全基因组关联研究（GWAS）中获得的遗传信息，现在有可能筛选出编码报告分子的基因，这些报告分子可用于检测诸如酒精性肝病（ARLD）、癌症、认知障碍、多发性硬化症（MS）、糖尿病肥胖症和缺血性中风（IS）等异常情况。然而，这需要全面了解肠-脑轴（GBA）、饮食对肠道微生物群选择的影响、影响微生物基因表达的条件以及人体生理学。细菌代谢产物如短链脂肪酸（SCFAs）在肠道稳态中起主要作用，维持肠道上皮细胞（IECs），并调节免疫系统、神经和内分泌功能。丁酸盐水平的变化可能是结肠癌的早期预警信号。其他癌症报告分子包括多酮合成酶阳性菌株产生的基因毒素大肠杆菌素和精胺氧化酶（SMO）。丁酸盐水平升高还与炎症和认知障碍有关。肠道微生物群失调可能导致氧化型低密度脂蛋白（OX-LDLs）生成增加，已知OX-LDLs会使血管收缩并导致高血压。SCFA水平的突然变化也可能是IS的预警信号。ARLD的早期迹象可能通过再生胰岛衍生3γ（REG3G）的增加来检测，REG3G与粘蛋白-2（Muc2）分泌的变化有关。细胞因子、干扰素和肿瘤坏死因子等促炎分子可能是MS的早期报告分子。本文综述了其他可在危及生命疾病早期检测中用作报告分子的微生物酶和代谢产物的实例。
