Microbiological evaluation of probiotic therapy in patients with pulmonary tuberculosis

L. Otdushkina, Y. Zakharova, Artem A. Kholodov, T. V. Pyanzova
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Abstract

Patients with pulmonary tuberculosis and multiple pathogen resistance (MDR) develop persistent disorders of the intestinal microbiome during prolonged multicomponent chemotherapy requiring correction. However, there is limited data on the use of bacterial drugs in patients with tuberculosis followed by assessing their effectiveness. The aim of the study was to evaluate changes in the intestinal microbiome after a course of probiotics along with anti-tuberculosis chemotherapy in patients with MDR tuberculosis. Materials and methods. The design a prospective small-cohort study (n = 30). Patients with pulmonary tuberculosis received anti-tuberculosis drugs according to the IV or V regimen, the median of the doses taken was 34.5 (30; 57.5); gastrointestinal syndrome was recorded in all study subjects. Probiotic therapy was applied by using a preparation containing Bifidobacterium bifidum and B. animalis and Lactobacillus casei, L. plantarum, L. delbrueckii subsp.bulgaricus, L. acidophilus. The course of therapy comprised 21 days,1 capsule twice a day. Before and 7 days after probiotics therapy, studies on composition of the intestinal microbiota were carried out, the frequency of virulence factors Enterococcus spp., Staphylococcus spp., Candida spp. was examined; fatty acid composition and activity of enterococcal organic acid production were studied. Results. After a course of probiotics, a significant increase in lactobacillus titers was recorded from 5.2 (4.0; 6.0) to 6.1 (6.0; 8.0) lg CFU/g (p = 0.05). The frequency of mucosal colonization by Candida fungi and lactose-negative Escherichia decreased by 2-fold (p = 0.001) and 3-fold (p = 0.05), respectively. The frequency of detected virulent strains significantly decreased: hemolysin-producing staphylococci by 9 times (p = 0.009), enterococci with gelatinase activity by 6 times. E. faecalis membrane oleic acid level significantly increased (C9-C18:1) (p = 0.03). In E. faecium, cis-7-palmitoleic acid (C7-C16:1) and oleic (C9-C18:1) fatty acid level increased by 2-fold (p = 0.05), and for linoleic acid (C18:2) by 4 time (p = 0.04) accompanied by elevated acid formation by 1.5 times. Conclusion. A single course of probiotic therapy in patients with pulmonary tuberculosis leads to qualitative microbiome changes, which are characterized by decreased levels of conditionally pathogenic microorganisms with virulent properties and altered composition of the enterococcal cell membrane accompanied by their increased biochemical activity.
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肺结核患者益生菌治疗的微生物学评价
肺结核和多重病原体耐药(MDR)患者在长时间的多组分化疗期间出现持续的肠道微生物群紊乱,需要纠正。然而,在结核病患者中使用细菌药物并评估其有效性的数据有限。该研究的目的是评估耐多药结核病患者在服用益生菌和抗结核化疗一个疗程后肠道微生物群的变化。材料和方法。设计一项前瞻性小队列研究(n = 30)。肺结核患者按IV或V方案接受抗结核药物治疗,中位剂量为34.5 (30;57.5);所有研究对象均记录了胃肠道综合征。采用含有两歧双歧杆菌、动物双歧杆菌和干酪乳杆菌、植物乳杆菌、德尔布鲁氏乳杆菌亚种的制剂进行益生菌治疗。保加利亚嗜酸乳杆菌。疗程为21天,每日2次,1粒。研究益生菌治疗前和治疗后7 d肠道菌群组成,检测肠球菌、葡萄球菌、念珠菌等毒力因子的出现频率;研究了肠球菌脂肪酸组成及产有机酸活性。结果。经过一个疗程的益生菌治疗后,乳酸菌滴度从5.2 (4.0;6.0)到6.1 (6.0;8.0) lg CFU/g (p = 0.05)。念珠菌和乳糖阴性埃希氏菌的粘膜定植频率分别下降了2倍(p = 0.001)和3倍(p = 0.05)。检测到的毒力菌株频率显著降低:产溶血素葡萄球菌减少了9倍(p = 0.009),具有明胶酶活性的肠球菌减少了6倍。粪肠球菌膜油酸水平显著升高(C9-C18:1) (p = 0.03)。粪肠菌中顺式-7-棕榈油酸(C7-C16:1)和油酸(C9-C18:1)脂肪酸含量增加了2倍(p = 0.05),亚油酸(C18:2)脂肪酸含量增加了4倍(p = 0.04),产酸量增加了1.5倍。结论。肺结核患者单疗程的益生菌治疗可导致定性微生物组变化,其特征是具有毒性的条件致病性微生物水平降低,肠球菌细胞膜组成改变,并伴有生化活性增加。
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