The relationship between intestinal microbiota and systemic inflammation in patients with non-alcoholic fatty liver disease

Abstract

Objective — to determine the relation of the main phylotypes of the intestinal microbiota (IM) with markers of systemic inflammation and the degree of hepatic steatosis in patients with non‑alcoholic fatty liver disease (NAFLD) with metabolic disorders.
 Materials and methods. The study included 114 patients with NAFLD with excessive body mass and obesity and 30 people as a control group, who were investigated on the basis of the Department of Gastroenterology and Therapy of the Polyclinics of the L. T. Mala National Therapy Institute of NAMS of Ukraine. The mean age of the investigated subjects was (52.56 ± 11.70) years. Anthropometric measurements were carried out with the calculation of the body mass index (BMI), determination of the percentage of visceral adipose tissue (VAT) using the OMRON BF‑511 body composition monitor. To determine the VAT dysfunction, the visceral obesity index (VOI) was calculated by the M. C. Amato method. Determination of CRP and TNF‑alpha levels was carried out by enzyme immunoassay. The assessment of the degree of steatosis was carried out by determining the wave attenuation coefficient (WAC) and shear wave elastometry. Determination of the composition of the intestinal microbiota at the level of the main phylotypes was carried out by identifying the total bacterial DNA and DNA of Bacteroidetes, Firmicutes, and Actinobacteria by the method of quantitative polymerase chain reaction (PCR) in real time.
 Results. The NAFLD patients displayed significantly increased levels of CRP and TNF‑alpha in comparison with the control group. A weak direct correlation has been established between CRP, TNF‑alpha and Firmicutes (r = 0.24 (p = 0.0029) and r = 0.17 (p = 0.0350), respectively), and an inverse correlation dependence of CRP on Bacteroidetes (r` = – 0.29 (p = 0.0003)). Analysis of the dependence of the ratio of the main intestinal phyla (Firmicutes/Bacteroidetes) on markers of systemic inflammation in NAFLD patients with different activity of visceral adipose tissue (VAT) revealed an increase in the ratio of the main phyla of IM with an increase in VAT activity. In the group of NAFLD patients with high VAT activity maximum values of the Firmicutes/Bacteroidetes ratio have been defined. Patients with increased levels of CRP an TNF‑alpha displayed an increase in the Firmicutes/Bacteroidetes ratio. Patients with advanced steatosis showed more significant changes in the main phyla of IM towards an increase in Firmicutes.
 Conclusions. The dependence of the Firmicutes/Bacteroidetes ratio from the markers of systemic inflammation and VAT activity has been established. The maximum values of the index (Firmicutes/Bacteroidetes) were observed in NAFLD patients with a high degree of visceral obesity index and hepatic steatosis as well as elevated CRP and TNF‑alpha levels.