Ratajczak Weronika, Rył Aleksandra, Mizerski Arnold, Walczakiewicz Kinga, Sipak Olimpia, Laszczyńska Maria
Department of Histology and Developmental Biology, Pomeranian Medical University, Szczecin, Poland.
Department of Medical Rehabilitation and Clinical Physiotherapy, Pomeranian Medical University, Szczecin, Poland.
Acta Biochim Pol. 2019 Mar 4;66(1):1-12. doi: 10.18388/abp.2018_2648.
Intestinal microbiota is an element of the bacterial ecosystem in all mammalian organisms. These microorganisms play a very important part in the development, functioning, and modulation of the immune system from the moment of birth. In recent years, owing to the use of modern sequencing techniques, the microbiome composition in healthy people has been identified based on bacterial 16S rRNA analysis. Currently, more and more attention is being given to the influence of microorganisms on the host's cellular metabolism. Analysis of microbial metabolites, among them short-chain fatty acids (SCFAs), and disruption of intestinal microbiota homeostasis in terms of their effects on molecular regulatory mechanisms of immune reactions will surely improve the understanding of the etiology of many common diseases. SCFAs, mainly butyrate, propionate, and acetate, occur in specific amounts, and their proportions can change, depending on the diet, age and diseases. The levels of SCFAs are substantially influenced by the ratio of commensal intestinal bacteria, the disturbance of which (dysbiosis) can lead to a disproportion between the SCFAs produced. SCFAs are regarded as mediators in the communication between the intestinal microbiome and the immune system. The signal they produce is transferred, among others, in immune cells via free fatty acid receptors (FFARs), which belong to the family of G protein-coupled receptors (GPCRs). It has been also confirmed that SCFAs inhibit the activity of histone deacetylase (HDAC) - an enzyme involved in post-translational modifications, namely the process of deacetylation and, what is new, the process of histone crotonylation. These properties of SCFAs have an effect on their immunomodulatory potential i.e. maintaining the anti/pro-inflammatory balance. SCFAs act not only locally in the intestines colonized by commensal bacteria, but also influence the intestinal immune cells, and modulate immune response by multi-protein inflammasome complexes. SCFAs have been confirmed to contribute to the maintenance of the immune homeostasis of the urinary system (kidneys), respiratory system (lungs), central nervous system, and the sight organ.
肠道微生物群是所有哺乳动物机体细菌生态系统的一个组成部分。从出生那一刻起，这些微生物就在免疫系统的发育、功能和调节中发挥着非常重要的作用。近年来，由于使用了现代测序技术，已通过细菌16S rRNA分析确定了健康人的微生物群组成。目前，微生物对宿主细胞代谢的影响受到越来越多的关注。对微生物代谢产物（其中包括短链脂肪酸）的分析，以及从其对免疫反应分子调节机制的影响方面对肠道微生物群稳态破坏的分析，必将增进对许多常见疾病病因的理解。短链脂肪酸主要包括丁酸、丙酸和乙酸，它们以特定的量存在，其比例会因饮食、年龄和疾病而变化。短链脂肪酸的水平受到共生肠道细菌比例的显著影响，共生肠道细菌比例的紊乱（生态失调）会导致所产生的短链脂肪酸之间比例失调。短链脂肪酸被视为肠道微生物群与免疫系统之间通讯的介质。它们产生的信号通过游离脂肪酸受体（FFARs）在免疫细胞等细胞中传递，游离脂肪酸受体属于G蛋白偶联受体（GPCRs）家族。还已证实，短链脂肪酸可抑制组蛋白脱乙酰酶（HDAC）的活性，组蛋白脱乙酰酶是一种参与翻译后修饰（即去乙酰化过程）以及新发现的组蛋白巴豆酰化过程的酶。短链脂肪酸的这些特性影响其免疫调节潜能，即维持促炎/抗炎平衡。短链脂肪酸不仅在共生细菌定植的肠道局部起作用，还影响肠道免疫细胞，并通过多蛋白炎性小体复合物调节免疫反应。已证实短链脂肪酸有助于维持泌尿系统（肾脏）、呼吸系统（肺）、中枢神经系统和视觉器官的免疫稳态。
