Evaluation of probiotics’ effectiveness for correction of dysbiosis and endogenous intoxication in patients with lymphoproliferative diseases
Authors:   Novosibirsk State Medical University, Voitko M.S. , Sorokin O.V. ,   VedaGenetika, LLC, Novosibirsk, Russia, Zinatulin S.N. ,   VedaGenetika, LLC, Novosibirsk, Russia, Skvortsova N.V. ,   Novosibirsk State Medical University, Korotchenko A.A. ,   Novosibirsk State Medical University, Trubnikova A.A. ,   Novosibirsk State Medical University
Published: December 2024

Introduction. The development of gastrointestinal complications of chemoradiotherapy in patients with hematologic malignancies is based on dysbiotic processes characterized by suppression of normal intestinal microflora, activation of opportunistic microorganisms, high risk of their translocation to non-specific biotopes, and endogenous infection. Another etiological factor in the development of intestinal dysbiosis in patients with hematologic malignancies is the use of antibacterial therapy (ABT) amid febrile neutropenia. Thus, the relevance of searching for therapeutic and preventive measures to reduce the number of gastrointestinal complications that arise in antitumor treatment is beyond doubt. The solution to this problem is rational ABT and maintenance therapy with probiotics.
Aim. To evaluate the effectiveness of probiotics in patients with lymphomas at the onset of the disease in order to correct dysbiosis and endogenous intoxication (EI).
Materials and methods. A total of 40 patients with lymphomas were included in a prospective randomized study. The average age of the patients was 45 (34; 54.5) years. The distribution of patients by gender was as follows: 4 men (10%), 36 women (90%). Among the subjects, patients with stages III and IV of the disease predominated
(n = 26, 65%). In order to evaluate the efficacy of a probiotic, the patients were randomly divided into 2 groups: 20 people who, in addition to polychemotherapy (PCT), received the probiotic orally in combination with a metabiotic, and 20 patients with lymphomas from the control group who received only conventional therapy. A comprehensive assessment of the state of the intestinal microbiome was performed using real-time polymerase chain reaction. Statistical data processing was performed using IBM SPSS Statistics 26.0 program.
Results. At the disease onset, a pronounced deficiency of the total bacterial load was observed in 7 patients (17.5%), a deficiency of bifidobacteria – in 29 patients (72.5%), a decrease in the lactobacilli count – in 34 (85%) patients. An imbalance in anaerobic flora prevailed in patients with aggressive B-cell lymphomas compared to patients with indolent tumor (χ2 = 4.1, p = 0.04). The microbiome with abundance of E. coli was more often diagnosed in patients with localized tumors compared to those with stages III and IV of the disease (χ2 = 4.6, p = 0.03). Clinical manifestations of intestinal dysbiosis at the onset of the disease were characterized by the following symptoms: abdominal pain (n = 4, 10%), flatulence (n = 6, 15%), a feeling of incomplete evacuation (n = 2, 5%), diarrhea (n = 8, 20%). In patients receiving probiotics as maintenance therapy, the count of Bifidobacterium spp. (p = 0.000005), Lactobaccilus spp. (p = 0.00007) and Faecalibacterium prausnitzii (p = 0.003) was significantly higher compared to the results of patients who received only standard courses of polychemotherapy. Comparative assessment of median concentrations of biochemical parameters demonstrated that in patients receiving the probiotic, the concentration of lactate dehydrogenase (p = 0.000001) and C-reactive protein (p = 0.04) was significantly lower compared to the control group who did not receive pro- and metabiotics. More pronounced leukocytosis (p = 0.0005) and accelerated erythrocyte sedimentation (p = 0.002) were noted in patients from the control group. At the same time, it was found that in the group of patients who received the probiotic before the start of antitumor treatment, nausea (χ2 = 10.9, p = 0.0009), flatulence (χ2 = 4.3, p = 0.03), and diarrhea (χ2 = 4.2, p = 0.04) associated with chemotherapy were significantly less common.
Conclusion. Intestinal dysbiosis in patients with hematologic malignancies has a multifactorial nature, caused by destructive processes in the body due to growth and spread of tumor, disorder of the functional state of various organs, empiric antibacterial therapy and the administration of high doses of cytostatic drugs. The use of probiotics as part of combined therapy for patients with lymphomas will significantly reduce the severity of intestinal dysbiosis and improve polychemotherapy results.