The aim: To study the state of the intestinal microbiota (ІМ) in patients with Nonalcoholic fatty liver disease (NAFLD) and to determine changes in its composition at the level of basic phylotypes. Materials and methods: The study included 114 patients with NAFLD with metabolic disorders and 64 patients of control group. Determination of the composition of the ІМ at the level of major phylotypes was performed by identifying total bacterial DNA and DNA of Bacteroidetes, Firmicutes and Actinobacteria by quantitative polymerase chain reaction (PCR) in real time (qRT-PCR) using universal primers for the 16S rRNA gene and taxon-specific primers of production (Thermo Fisher Scientific). Results: It was defined the weak correlation between the content of Firmicutes and proinflammatory markers (C-reactive protein (CRP) and Tumor necrosis factor (TNF) alpha) (p <0.05) and inverse correlation of CRP with the content of Bacteroidetes (p <0.001). Also have been observed significant changes in the main intestinal phyla in the direction of increasing the content of Firmicutes in patients with NAFLD with a high degree of steatosis and elevated levels of proinflammatory cytokines (p <0.05). Conclusions: IM imbalance leads to excessive synthesis of pro-inflammatory cytokines, promotes the activation of cellular mechanisms, which increases the flow of fatty acids into hepatocytes and increases the degree of hepatic steatosis.
Kontext a cíl výzkumu: Nealkoholické ztukovatění jater (nonalcoholic fatty liver disease, NAFLD) má závažné ekonomické dopady na zdravotnictví celosvětově a na Ukrajině obzvláště. Hlavní příčinou mortality pacientů s NAFLD jsou kardiovaskulární onemocnění (KVO). Za potenciální mechanismus rozvoje ischemické choroby srdeční (ICHS) u pacientů s NAFLD lze považovat změny ve složení střevní mikrobioty. Cílem našeho výzkumu bylo zjistit změny koncentrací hlavních fylotypů střevní mikrobioty, kmenů Bacteroidetes, Firmicutes a Actinobacteria, a kvantifi kovat koncentrace kmenů Firmicutes/Bacteroidetes u pacientů s NAFLD a současně s ICHS. Materiál a metody: Do studie bylo zařazeno 109 jedinců s NAFLD (25 současně s arteriální hypertenzí [AH] a 24 současně s ICHS). Složení střevní mikrobioty bylo hodnoceno metodou qPCR. Výsledky a závěry: U obou podskupin, s ICHS a s AH jako komorbiditami, byl pozorován výrazný trend ke zvyšování koncentrací Bacteroidetes (o 37,11 %, resp. 21,30 %) a snižování koncentrací kmene Firmicutes (o 7,38 %, resp. 7,77 %), přičemž nalezené změny nedosahovaly statistické významnosti. Ve srovnání s pacienty pouze s NAFLD bylo u nemocných s NAFLD plus ICHS zaznamenáno statisticky významné snížení koncentrací kmene Actinobacteria o 41,37 % (p ˂ 0,05). U pacientů s NAFLD plus AH byly koncentrace kmene Actinobacteria nižší o 12,35 % (statisticky nevýznamný rozdíl). Byly nalezeny změny ve složení střevní mikrobioty, konkrétně nižší koncentrace kmene Actinobacteria u pacientů s ICHS; toto zjištění si vyžádá další výzkum.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, with pathogenetic mechanisms involving complex factors, in particular changes in the intestinal microbiota. The development and evaluation of the effectiveness of NAFLD treatment regimens, affecting intestinal microbiota disturbances, presents an urgent issue in modern medicine. Objective — to determine effects of combined therapy, including ursodeoxycholic acid (UDCA) and probiotic preparation (strains of Lactobacillus acidophilus, L. rhamnosus, Streptococcus salivarius subsp. thermophilus, L. delbrueckii subsp. Bulgaricus) on the metabolic disorders and inflammatory processes in liver tissue of patients with NAFLD. Materials and methods. The study included 108 patients with NAFLD with metabolic disorders and 30 people of the control group, who were examined on the basis of the Department of Gastroenterology and Therapy and outpatient department of the GI «L. T. Mala National Institute of Therapy of the NAMS of Ukraine». Women prevailed in both groups. The mean age of patients was 54.6 ± 11.7 years. The patients were randomized into two groups, comparable by gender and age ratio. Both groups received non‑drug therapy. The comparison group (48 patients) received UDCA preparation only, the main group (60 patients) received additional probiotic preparation «Yogurt capsules» (Pharmascience Inc., Canada). The treatment lasted 12 weeks. Patients were examined at the beginning and end of treatment with additional determination of pro‑inflammatory markers: C‑reactive protein CRP and TNF‑α. Statistical analysis was performed with the package Statistica 13.1 using nonparametric methods. Results. Patients’ examination in the dynamics of treatment showed an improvement in NAFLD course due to a decrease in the levels of alanine aminotransferase, aspartate aminotransferase and γ‑glutamyl peptidase (ALT, AST and GGT) in both groups. Moreover, against the background of treatment, the tendency was observed to the decrease of visceral fat percentage, as well as the visceral obesity index, which in group I significantly decreased in almost 1.6 times. In contrast to the carbohydrate metabolism indicators, the dynamics of which did not differ significantly between the groups, a significant effect of the developed therapy on the lipid profile was determined. The triglycerides (TG) levels in the main group decreased 1.3 times, and LDL cholesterol 1.6 times. In addition, the significant decrease in TNF‑alpha levels by 57.51 % was observed under the influence of treatment with the addition of probiotic yogurt. Conclusions. Combined therapy which includes lifestyle modification by means of non‑drug therapy, UDCA with the additional use of a complex probiotic preparation yogurt capsules, has a pathogenetic focus and proven effectiveness in the treatment of NAFLD.
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