Spaceflight & the Microbiome
In an attempt to protect astronauts from exposure to novel pathogens preflight, several guidelines are carried out. Prelaunch, crew members are limited both in travel and visitors to limit pathogen exposure.[201] Therefore, crew members tend to launch with normal gut microflora and with a reduced risk of gut infection. Items flown to the International Space Station (ISS) are cleaned before loading to limit introducing bacteria to the environment. Once in orbit, all areas in the ISS have ultra-high-efficiency bacterial filters in the air supply ducts to reduce the levels of bacteria and fungi. Finally, cleaning of the surfaces of the modules is a regular 'housekeeping' chore to limit bacterial and fungal growth.[201]
Still, microorganisms exist on the ISS. No matter how much cleaning is done, microorganisms are continuously shed from skin, mucous membranes, gastrointestinal and respiratory tracts or can be released by sneezing, coughing and talking.[40] Specimens were obtained for mycological examination from the skin, throat, urine and feces of the six astronauts who conducted the Apollo 14 and Apollo 15 lunar exploration missions both before and after flight.[41] Analysis of preflight data demonstrated that the process of severely restricting opportunities for colonization for 3 weeks before flight resulted in a 50% reduction in the number of isolated species.[41] Postflight data indicated that exposure to the spaceflight environment for up to 2 weeks resulted in an even greater reduction with a relative increase in the potential pathogen C. albicans.[41,42] The compositions of intestinal,[43] oral[44,45] and nasal[44] flora have been shown to change even during short spaceflights. In one study, a reduction in the number of nonpathogenic bacteria and an increase in the number of opportunistic pathogens has been reported in the nasal flora of cosmonauts.[46] A significant reduction in the number of bacterial species of the intestine has been seen after 2 weeks of spaceflight.[47] These observations were similar to changes seen in ground volunteers who were kept in isolation, in which volunteers were fed only sterilized, dehydrated foods. A significant decrease in the number of bifidobacteria, lactobacilli and other bacteria was seen.[38] In a Russian experiment, a decrease in lactobacilli (and replacement with pathogens) were seen in mouth and throat cavities in all mission members in inflight period.[48] Spaceflights and even the preparation phase before take-off can exert dysbiosis in the human microflora which results in reduction of the defense group of microorganisms (bifidobacteria and lactobacilli) and appearance of opportunistic pathogens such as E. coli, enterobacteria and clostridia.[49] Subsequently, this procedure can lead to accumulation of the potentially pathogenic species and their long-term persistence.[49–51] Colonization resistance is one of the factors that needs to be taken into account to stabilize the microflora of the cosmonauts during space flights. Indigenous microflora are vital for preservation of microecological homeostasis.[7] It has been hypothesized that a regular intake of probiotic foods might be helpful in correcting this change.[38,52,53]
Human microflora functions as a barrier against antigens from microorganisms and food.[54] Alterations in the microbiome composition have been reported in inflammatory bowel disease, inflammatory conditions, ulcerative colitis and more.[55–57] Healthy immunophysiologic regulation in the gut has been hypothesized to depend on the establishment of indigenous microflora that create specific immune responses at the gut and system levels.[58–61] Furthermore, gut microflora has a role in induction and maintenance of oral tolerance in experimental animal models.[62] Changes in the diversity and number of gut microflora have been linked to a deficient immune system[63] as well as immunological dysregulation which is associated with many human noninfectious diseases such as autoimmunity, allergy and cancer.[63] Reinforcing this concept of health symbiosis, studies of germ-free animal showed wide-ranging defects in the development and maturation of gut-associated lymphoid tissues.[54,63–66] Another way of viewing this health interaction comes from the data that ten Salmonella bacteria have been shown to induce infection in germ-free mice, while 109 bacteria are needed to induce infection in a conventional animal possessing intact intestinal microflora.[67] To maintain astronaut health on orbit, an awareness of the importance of a balanced gut microbiome to maintaining the immune homeostasis and resistance to infections is valuable.
Previous studies have shown that important immune parameters are decreased during spaceflight.[68] Reductions in the number and proportion of lymphocytes and their cytokine production, depression of dendritic cells function and T-cell activation, and finally reduction in numbers of monocytes and precursors of macrophages, have been noted.[68] In one study, stresses associated with spaceflight were shown to alter important functions of neutrophils and monocytes.[69] In another study, the astronauts' monocyte functions showed reductions in their ability to engulf E. coli, elicit an oxidative burst and degranulation.[70] Non-MHC-restricted (CD56) killer cell cytotoxicity tends to decrease after short-term spaceflight.[71] In the latter study, the authors examined the age, gender (nine men and one woman), flight experience, mission factors and mission role (e.g., pilot, scientist or crew) of the astronauts and found no correlation between these variables and individual non-MHC killer cell function levels.[71] Therefore, other factors may contribute to the compromised immune system in space. Decreased natural killer cell cytotoxicity in cosmonauts after short- and long-term spaceflights have also been reported.[72–75] Reductions in absolute numbers of lymphocytes, eosinophils and natural killer cells,[76] reduced lymphocyte mitogenic response,[76,77] diminished delayed-type hypersensitivity,[77] changes in CD4+:CD8+ ratios and reduced production of IL-2 and IFN-γ have also been reported.[78]
The immune system changes of astronauts as well as environmental stress may have been a factor in known incidents of infectious illness in crew members. During the Apollo 8 preflight period for instance, all crew members suffered viral gastroenteritis.[42] During flight, the effects of mission duration on the neuroimmune responses in astronauts were studied and changes in plasma cortisol, epinephrine, norepinephrine, total IgE levels, number of white blood cells, polymorphonuclear leukocytes and CD4+ T cells were found at different times.[79] Upper respiratory problems, influenza, viral gastroenteritis, rhinitis, pharyngitis or mild dermatologic problems were among the illnesses that astronauts faced during Apollo spaceflights.[42] Reactivation of varicellas zoster virus,[71] herpes virus[80] and shedding of Epstein–Barr virus[81] was also found in space shuttle crew members. In astronauts of the Mir station, analyses demonstrated a significant number of episodes of microbial infections, including conjunctivitis, acute respiratory events and dental infections.[82]
Future Microbiol. 2012;7(9):1037-1046. © 2012 Future Medicine Ltd.
