The role of short-chain fatty acids in the progression of non-alcoholic fatty liver disease

T. Krolevets, M. Livzan, M. I. Syrovenko
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Abstract

Introduction. Nowadays, a multifactorial model of the pathogenesis of NAFLD is recognized. It is interesting to study the contribution of changes in the composition of the intestinal microbiota and its metabolites in the development of the disease.Aim. To evaluate the contribution of research into the qualitative composition of the intestinal microbiota in relation to the risk of progression of NAFLD to reduce the loss of health- saving potential of the population.Materials and methods. An open comparative study of 83 mature-aged patients (56.6 years (46–63)) suffering from NAFLD was conducted. The levels of insulin, leptin, its receptor, adiponectin in blood serum, zonulin in feces were studied, and SCFA in feceswas determined. The analysis was carried out depending on the phenotypes of NAFLD: the degree of steatosis (1 – 40 patients, degree 2 – 18 and degree 3 – 25), the presence of NASH (43 patients), the presence of fibrosis (fibrosis was found in 35 patients). The degree of steatosis and fibrosis was assessed using elastometry. The results of the study were analyzed using the Microsoft Excel, STATISTICA 12.0 software package.Results. In patients with NAFLD, the absolute number of all SCFA in the feces was reduced. The anaerobic index was deviated towards sharply negative values (-0,711 (-0,576-(-0,830)). A high level of propionic acid was noted among the patients with fibrosis (p < 0.05). Anaerobic index, relative content of isoC4 + isoC5 + isoC6, relative content of butyric acid had a positive relationship with the St-index (rs = 0.254, rs = 0.269, rs = 0.240, p≤ 0.05). An increase in the relative amount of propionic acid was statistically significantly associated with a decrease of FLI (rs = -0.229, p ≤0.05). A positive correlation was found between the level of insulin and the absolute amount of butyric acid C4 (rs = 0.228, p ≤ 0.05). There was an inverse relationship of the absolute and relative amounts of isoC4+ isoC5 + isoC6 and Iso Cn/Cn with zonulin in the feces (rs = -0.231, p ≤ 0.05, rs = -0.380, p ≤ 0.05 and rs = -0.332, p ≤ 0.05, respectively).Conclusion. There is the anaerobic flora among the patients with NAFLD. Modification of the content of SCFA in feces may affect to the progression of NAFLD. The effect of SCFA on the development and progression of NAFLD may be mediated by the development of insulin and leptin resistance, as well as an integrity violation of the intestinal barrier.
短链脂肪酸在非酒精性脂肪肝进展过程中的作用
导言。如今,非酒精性脂肪肝发病机制的多因素模型已得到认可。研究肠道微生物群的组成及其代谢产物的变化在疾病发展中的作用很有意义。评估研究肠道微生物群的定性组成与非酒精性脂肪肝进展风险的关系对减少人群健康损失潜力的贡献。对 83 名患有非酒精性脂肪肝的成熟年龄患者(56.6 岁(46-63 岁))进行了公开比较研究。研究了血清中的胰岛素、瘦素及其受体、脂肪连通素水平,粪便中的zonulin,并测定了粪便中的SCFA。根据非酒精性脂肪肝的表型进行了分析:脂肪变性程度(1-40 名患者,2-18 名患者,3-25 名患者),是否存在 NASH(43 名患者),是否存在纤维化(35 名患者发现纤维化)。脂肪变性和纤维化程度通过弹性测量法进行评估。研究结果使用 Microsoft Excel、STATISTICA 12.0 软件包进行分析。非酒精性脂肪肝患者粪便中所有 SCFA 的绝对数量减少。厌氧指数急剧偏向负值(-0,711(-0,576-(-0,830))。纤维化患者的丙酸含量较高(p < 0.05)。厌氧指数、异C4 +异C5 +异C6的相对含量、丁酸的相对含量与St-指数呈正相关(rs = 0.254、rs = 0.269、rs = 0.240,p≤ 0.05)。丙酸相对含量的增加与 FLI 的下降有显著的统计学关系(rs = -0.229,p ≤0.05)。胰岛素水平与丁酸 C4 的绝对量之间呈正相关(rs = 0.228,p ≤ 0.05)。粪便中异C4+异C5+异C6和异Cn/Cn的绝对量和相对量与zonulin呈反向关系(rs=-0.231,p≤0.05;rs=-0.380,p≤0.05;rs=-0.332,p≤0.05)。结论:非酒精性脂肪肝患者体内存在厌氧菌群。粪便中 SCFA 含量的变化可能会影响非酒精性脂肪肝的进展。SCFA对非酒精性脂肪肝的发生和发展的影响可能是由胰岛素和瘦素抵抗的发展以及肠道屏障完整性的破坏所介导的。
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