Background. Changes in the human oral microbiota is an adaptive process. Infections will be particularly manifest in extreme conditions, especially during a long stay in space flight, where the astronaut is exposed to various nonspecific stresses. Aim - the aim of the work is to estimate the complex influence of 14-day isolation conditions of human being in sealed environment on the state of natural barriers of periodontal colonization. Methods. During the experiment 6 volunteer subjects (4 men and 2 women) aged 24 to 45 years old were confined for 14 days to an air-tight space simulating a spaceship capsule. Then from 6 to 18 days after leaving the experiment the experimental group (4 people) received Lactobacillus spp. autoprobiotics once a day on an empty stomach in the morning. During this period the control group (2 persons) took Linex (Lebenin®: Lactobacillus acidophilus (species L. gasseri) - 300 mg, Bifidobacterium infantis - 300 mg, Enterococcus faecium - 300 mg, lactose - 50 mg). Qualitative and quantitative changes of oral microbiota, concentration of immunoglobulins (sIgA, IgA, IgM) and cytokines (IL-6, IL-8, IL-1β, IL-4, INFγ, TNFα) in periodontal samples were recorded. The number of periodontopathogens and regional blood flow in the periodontium under conditions of prolonged confinement and hypokinesia were studied. Results. In comparison with the background period during the time of isolation, a quantitative growth of obligate periodontopathogens was observed in the subjects. This was accompanied by increased levels of immunoglobulins (IgM, IgA, sIgA) and pro-inflammatory cytokines (IL-1, IL-6, IL-8). There was an increase in blood flow in the arteriolo- venular part of the microcirculatory channel of periodontal tissues after leaving isolation. Subsequently, there was a tendency to optimize microbiocenosis through the use of probiotic and autoprobiotic agents. Along with this, there was a decrease of anti-inflammatory interleukin IL-4 practically to the initial values on the 18th day. © 2022 Izdatel'stvo Meditsina. All rights reserved.