Impairments of the intestinal microbiota in the acute period of infectious diarrhea in children and comparative analysis of the effects of nifuroxazide and cephalosporins
Authors:   Central Research Institute of Epidemiology, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Moscow, Russian Federation, Usenko D.V. , Gorelov A.V. ,   Central Research Institute of Epidemiology, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Moscow, Russian Federation, Odintsova V.E. ,   Atlas Biomed Group – Knomics LLC, Москва, Russian Federation,   Atlas Biomed Group – Atlas LLC, London, Great Britain, Kashtanova D.A. ,   Atlas Biomed Group – Atlas LLC, London, Great Britain,   Center for Strategic Planning and Management of Medical and Biological Health Risks, Federal Medical and Biological Agency, Moscow, Russian Federation, Koshechkin S.I. ,   Atlas Biomed Group – Knomics LLC, Москва, Russian Federation, Tyakht A.V. ,   Atlas Biomed Group – Knomics LLC, Москва, Russian Federation,   Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Moscow, Russian Federation, Krikun V.S. ,   Central Research Institute of Epidemiology, Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Moscow, Russian Federation
Published: December 2020

The intestinal microbiota (IM) plays an important role in maintaining homeostasis in the human organism. Changes in the IM are associated with many diseases, for example, IM is involved in the pathogenesis of inflammation during acute intestinal infections (AIIs). Medications have different effects on the quantitative and qualitative composition of the microbial community and can therefore indirectly affect the course of recovery. Objective. To evaluate the IM composition in the acute period of infectious diarrhea in children and to assess the effect of therapy with nifuroxazide and cephalosporins on it. Patients and methods. This study included 21 children with invasive AIIs. Twelve patients received nifuroxazide (IN group), whereas 9 patients were treated with third-generation cephalosporins (IC group). There was also a control group comprised of 10 healthy children (group C). The duration of the course of antibacterial therapy was 5–7 days. We analyzed the microbial composition of fecal specimens from all study participants using 16S rRNA gene high-throughput sequencing. Data analysis was performed using the Knomics-Biota platform and the R Programming Environment. Results. We observed reduced alpha diversity (an integral characteristic of a microbial community which estimates the number of species in it and their proportion) already in the early period of invasive AII in children. We also found an increased total proportion of opportunistic bacteria in children with AIIs compared to controls, particularly species of Fusobacteriacea. Restoration of alpha diversity was achieved only in patients receiving nifuroxazide. Differences in the dynamics of the proportion of opportunistic microflora in the intervention groups were associated with the initial differences in the microbiome composition between the groups due to small number of patients in them. In the IN group, the proportion of Fusobacteriaceae species before treatment was higher than that in healthy controls; however, immediately after treatment completion and one month later, there were no differences in the IM composition between the IN group and controls. Patients from the IC group had higher proportion of opportunistic bacteria than healthy children; by the end of the treatment course, this parameter was normalized and was similar to that in the control group. Conclusion. The use of nifuroxazide in children with invasive AIIs was associated with restoration of alpha diversity and the reduction in the proportion of opportunistic species (in particular, Fusobacteriaceae). Children receiving cephalosporins also demonstrated the reduction in this proportion, but their alpha diversity was not restored. Keywords: acute intestinal infections, children, antibacterial therapy, nifuroxazide, cephalosporins, intestinal microbiota, 16S rRNA gene sequencing