СОСТОЯНИЕ КИШЕЧНОЙ МИКРОБИОТЫ У ДЕТЕЙ С ТУБЕРКУЛЕЗОМ ОРГАНОВ ДЫХАНИЯ

Abstract

Aim: to study the structure and species composition, incidence of gut microbiota dysbiotic disorders using a new technique based on real-time polymerase chain reaction (PCR) – enteroflor®Kiddy – in children with pulmonary TB on TB treatment. Materials and methods. The study enrolled 63 children aged 2–12 years. We carried out a one-step cross-sectional study of gut microbiota in 49 patients (the median age was 5 years [3; 8]) with newly diagnosed active pulmonary TB: 13 children were examined before, and 36 children – at various time points of TB treatment; 14 children without focal TB did not receive TB treatment (the median age was 7.5 years [5,5; 10]). A specialized study of gut microbiota was performed using the enteroflor®Kiddy test system. Results. There was no difference in gut microbiota composition and incidence of dysbiotic disorders between children without focal TB and children with TB before TB treatment. We determined differences in gut microbiota in children with TB before TB treatment and during treatment monitoring: lower frequency of detection of Bifidobacterium spp. (100 and 61.1%, p < 0.05); Butyricimonas spp. (92.3 and 58.3%, p < 0.05); Desulfovibrio spp. (100 and 50.0%, p < 0.05); Clostridium perfringens gr. (92.3 and 22.2%, p < 0.001), higher frequency of detection of markers for pathogenicity and resistance of Clostridioides difficile (7.7 and 38.9%, p < 0.05), and lower frequency of detection of Staphylococcus aureus (23.1 and 0%, p < 0.05), respectively. We established that increased duration of TB treatment (more than 3 months vs. 2-3 months) led to higher frequency of gut microbiota dysbiotic disorders: complete absence of normobiota species Bifidobacterium spp. and Coriobacteriia was established in 52.4% and 14.3% of cases, respectively; pathogenic microbiota species Clostridioides difficile were detected 2.4 times more frequently (47.6%), Candida spp. fungi were detected 1.7 times more frequently (р > 0.05). In children on TB treatment containing second-line drugs as compared to children only receiving first-line drugs dysbiotic disorders associated with Bifidobacterium spp. were significantly more frequent (69.2 and 30% respectively) (χ2 = 4.573, р = 0.05), up to complete absence in 50% of children receiving second-line drugs; and pathogenic microbiota species Clostridioides difficile were detected 4.6 times more frequently (46.2 and 10%, р = 0.059); cdtA, cdtB were detected twice as often (46.2 and 20.0%, р > 0.05). The Candida genus fungi Candida spp. (р > 0.05) were detected twice as often in the microbiota of children only receiving first-line drugs. Conclusion. TB treatment produces pronounced negative effect on gut microbiota. The increase in chemotherapy duration and inclusion of second-line drugs leads to increasing incidence of dysbiotic changes of specific representatives of normobiota, their decreasing amount, and significant increase in detection of markers for pathogenicity and resistance.