Evaluation of the state of small intestinal microbiota, pro- and anti-inflammatory cytokines, short-chain fatty acids in metabolic dysfunction-associated steatotic liver disease in patients with immune response to SARS-CоV-2

Background. The intestinal microbiota and its metabolites have a significant impact on the pathophy­siology of liver diseases, it plays an important role in human metabolism, supports the intestinal mucosal barrier and interacts with the immune system. The COVID-19 epidemic has led to a significant increase in the number of patients in Ukraine suffering from metabolic dysfunction-associated steatotic liver disease (MASLD). One of the unresolved problems associated with MASLD is the identification of pathogenetic links that affect the risk of rapid progression of the disease and the development of irreversible changes in the liver. An imbalance in the intestinal microbiota is a trigger for the launch of a pathological reaction in the liver. The purpose: to study the features of the content of pro- and anti-inflammatory cytokines and short-chain fatty acids in MASLD in patients with an immune response to SARS-CoV-2 depending on the small intestinal bacterial overgrowth (SIBO). Materials and methods. The study included 61 patients with MASLD, 41 men and 20 women aged 18 to 73 years, mean age (46.4 ± 1.5) years. All patients underwent determination of IgG specific to SARS-CoV-2, cytokine content (IL-6, IL-10, TNF-α) in serum by enzyme-linked immunosorbent assay. For the diagnosis of SIBO, a hydrogen breath test (HBT) with glucose was performed. Evaluation of short-chain fatty acids in faeces was performed on a chromatograph using the Guohua Zhao method. Results. In 44.3 % of patients with MASLD and an immune response to SARS-CoV-2, SIBO was diagnosed. The median value of IL-6 level in SIBO significantly exceeded the control values by 13.7 times (p < 0.001), the median of TNF-α was significantly higher by 18.5 times (p < 0.001). In SIBO group, the levels of TNF-α and IL-6 were, accordingly, 2 (p = 0.01) and 3.3 times (p = 0.004) higher compared to patients without SIBO. The median acetic acid (C2) level in the group with SIBO statistically significantly excee­ded the control value by 1.5 times (p = 0.021). The median concentration of propionic acid (C3) was significantly higher by 1.4 times (p = 0.003) in the faeces of patients with SIBO than in those without it. At the same time, in the presence of SIBO, a decrease in the median of butyric acid (C4) was observed by 2.2 times (p = 0.021) compared to the group of patients without SIBO. Direct correlations were found between the levels of IgG specific to SARS-CoV-2 and TNF-α (r = 0.304, p = 0.016); the HBT index at 45 min and the level of TNF-α (r = 0.269, p = 0.041), IL-6 (r = 0.443, p = 0.002), the median of propionic acid (C3) content (r = 0.400, p = 0.006). At the same time, an inverse correlation was found between the level of butyric acid (C4) and the HBT index at 60 min (r = –0.332, p = 0.040). Conclusions. In patients with MASLD with an immune response to SARS-CoV-2 and SIBO, there was a significant increase in the production of proinflammatory cytokines, in contrast to patients without SIBO. An increased content of acetic acid and a decrease in butyric acid in the faeces of patients with MASLD with an immune response to SARS-CoV-2 in the presence of SIBO were found. Disturbance in the microbial composition of the small intestinal microbiota, hyperproduction of proinflammatory cytokines and impaired synthesis of short-chain fatty acids are distinctive features of MASLD in patients with an immune response to SARS-CoV-2.