Role of short chain fatty acids in evaluation of gut microbiocenosis disorders and their correction in patients with NAFLD of different stages

Aim of investigation: to study the content and qualitative profile of shot-chain fatty acids in feces and blood serum in patients with NAFLD of different stages as indicators of intestinal microbiocenosis status and systemic lipid metabolism, and to evaluate the effectiveness of course antibacterial (rifaximin) and prebiotic (psyllium) therapy in the period of 6 months for the correction of gut microbiocenosis disorders. Material and methods: The survey included 115 patients (82 (71,3%) men, 33 (28,7%) women) with NAFLD of different stages (steatosis - 40 people, nonalcoholic steatohepatitis (NASH) of minimal activity - 30 people, NASH of moderate activity - 30 people, liver cirrhosis class A Child-Pugh - 15 people) at the average age of 51,83±8,48 years old. All the patients were examined by research of short-chain fatty acids (SCFA) using gas-liquid chromatographic analysis in various biological substrates (blood serum and feces). According to the management scheme, the patients with NAFLD were divided into 3 groups. The first group of 30 people (on the background of lifestyle modification) received a 6-month intake of psyllium. The second group of 35 people in addition to lifestyle modification received a 7-day course of rifaximin (7 - days/800 mg/d) and psyllium during the period of observation (6 months). The third group of 35 people received standard therapy of NAFLD without pharmacotherapy aimed to correction of gut microbiocenosis disorders. In the course of treatment the frequency and severity of clinical manifestations of intestinal bacterial overgrowth syndrome (SIBO) reduced in patients of groups 1 and 2 (in group 1 the complaints on abdominal pain and flatulence decreased by 11%, in group 2 - by 37%, the normalization of stool occurred in both groups), SIBO was not detected according to the results of the hydrogen breath test with lactulose, the level of total endotoxin was determined within normal values. Negative dynamics was noted in group 3: the increase in the number of complaints of abdominal pain by 16%, flatulence and unstable stool - by 10%, the frequency of registration of SIBO increased by 20%, increased level of total endotoxin was detected in 5.7% of patients. Results. The absolute concentration of SCFA in feces in patients with NAFLD (steatosis) is reduced, in patients with NASH of minimal activity, NASH of moderate activity and liver cirrhosis is increased, in the profile of C2-C4 acids there was the increase in the share of propionic and butyric acids and the decline in the share of acetic acid, the anaerobic index (AI) deflected in the region of strongly negative values, the total relative content of isoacids increased in all groups of patients, worsening with the severity of the pathological process (at normal Σ(C2-C6)=10.51±2.50 mg/g, C2=0.634±0.004, C3=0.189±0.001, C4=0.176±0.004, AI= -0.576(±0.012), Σ(isoCn)=0.068±0.004). The obtained results indicate marked changes in the qualitative and quantitative composition of the microflora, the decrease in the number and activity of obligate microorganisms and the increase in facultative and residual anaerobic bacteria. These changes in the microbial landscape lead to the marked disorders in the intestinal phase of lipid metabolism. The absolute concentration of SCFA in serum in patients with NAFLD (steatosis) is reduced, in patients with NASH of minimal activity, NASH of moderate activity is increased, in the profile of C2-C4 acids there is the decrease in the share of propionic acid and the increase in the share of butyric acid, most pronounced in steatosis and NASH of minimal activity. In patients with liver cirrhosis, the absolute concentration of SCFA in serum is increased, in the profile of C2-C4 acids, the share of acetic acid is sharply reduced with an increase in the share of propionic and butyric acids and the total relative content of isoacids. The content of caproic and isocaproic acids is increased in all groups (at normal Σ (C2-C6)=0.195±0.011 mg/g, C2=0.902±0.006, C3=0.071±0.004, C4 = 0.027±0.002, Σ (isoCn)=0.040±0.007, isoC6+C6=0.025±0.004). This fact can be explained by the changes in the functional state of hepatocytes, and, consequently, in the metabolic function of the liver (in particular with respect to lipid metabolism). The clinical efficacy of therapeutic management with the use of drugs aimed at the relief of the intestinal microflora disorders (course of rifaximin (if SIBO is identified) on the background of prolonged ingestion of psyllium) in patients with NAFLD of different stages, is supported by the normalization of the content and profile of SCFA in various biological substrates. In patients of group 3 there was noted the negative dynamics of estimated parameters SCFA. Thus, the results of the undertaken research of the parameters of SCFA in various biosubstrates indicate the marked changes in the intestinal microbiocenosis and their contribution to the development and enhancement of systemic metabolic processes. The inclusion of means aimed at correcting the microecological status disorders in the complex management of NAFLD is not only effective, but also pathogenetically necessary.