Future Perspective: Considering Probiotics as a Countermeasure
On Earth, probiotics have been shown to improve both innate and adaptive immune responses.[83] Oral bacteriotherapy with probiotic bacterial strains is believed to improve the intestine's immunologic barrier, particularly through intestinal IgA responses and alleviation of inflammatory reactions.[83] A gut-stabilizing effect seems to occur through a balance between proinflammatory and anti-inflammatory cytokines. Lactobacillus rhamnosus GG has been shown to inhibit TNF-α-induced IL-8 secretion of human colon adenocarcinoma (HT29) cells and to reduce elevated fecal concentration of TNF-α in patients with atopic dermatitis and cow milk allergy.[84] On the other hand, ingestion of lactobacilli in fermented milk products or as live-attenuated bacteria potentiated the IFN-γ production by peripheral blood mononuclear cells.[85,86] Oral administration of lactobacilli increased the systemic and mucosal IgA response to dietary antigens.[59,60,87] Oral supplementation with Bifidobacterium bifidum and Bifidobacterium breve enhanced the antibody response to ovalbumin[88] and stimulated the IgA response to cholera toxin in mice.[89] An increase in the humoral immune response including an increase in rotavirus-specific antibody-secreting cells in the IgA class was also detected in children[60] and individuals receiving L. rhamnosus GG.[90]
Isolauri et al. reported that infants receiving a reassortant live oral rotavirus vaccine in conjunction with L. rhamnosus GG had a higher frequency of rotavirus-specific IgM class antibody-secreting cells.[91] An increased incidence of rotavirus-specific IgA antibody class seroconversion compared with placebo subjects was also seen.[91] IgA+ cells and IL-6-producing cells increased in number after 7 days of Lactobacillus casei administration.[92] In another study, administration of lactic acid bacteria stimulated the gut immune cells to release inflammatory cytokines such as TNF-α, IFN-γ and IL-12, and regulatory cytokines like IL-4 and IL- 10 in a dose- and strain-dependent manner.[93] Several lactobacilli strains have been shown to promote the immunopotentiator capacity of cells of the innate immune system, including macrophages.[94] Examples of probiotics that can modulate the gut immune system are abundant and have been reviewed extensively.[95–98]
Buckley et al. have suggested that consumption of soy-based fermented products (containing lactic acid bacteria) can prevent the health problems of astronauts associated with long-term space travel.[99] Assessment of soy-based fermented products by in vitro challenge system (using TNF-α) with human intestinal epithelial and macrophage cell lines has demonstrated the ability of the intervention to downregulate production of the proinflammatory cytokine IL-8.[99]
Considering the importance of the human gut in healthy digestion, nutrient absorption and exposure to pathogens across its large surface area, a healthy digestive tract is important to a healthy human. Diet, lifestyle, antibiotic therapy, different kinds of stressful conditions and so on, can exert alterations in an astronaut's gut microbiome in space (Figure 1). Considering potential immune system alterations from gut microflora changes, antibiotic use in orbit and changes of increased virulence and antibiotic resistance of bacteria in space, physicians who care for astronauts must remember the importance of the intestinal microbiome to their health status. From this perspective, an impaired digestive system might endanger the mission as well as the health of the astronaut. One countermeasure to be considered would be replenishing the astronaut's intestinal microflora by introducing immune-enhancing probiotic bacteria periodically during the mission.
Figure 1.
Diet, lifestyle, antibiotic therapy and various environmental stresses, and so on, can exert alterations in an astronaut's gut microbiome in space and impair their immune system.
Although single probiotics have sometimes been shown to promote health, the human microbiome is composed of more than 400 microbial species, most of which remain uncultured and have as yet unknown functions.[100] The Human Microbiome Project will certainly pave the way for us to increase our understanding of these microbial entities.[4] Thus, providing only a single probiotic might not be the answer. Contrary to numerous previous investigations and clinical trials in which only effects of single or a couple of probiotics have been studied, we think multiprobiotic therapy and/or designing individualized probiotic kits seems a more reasonable option. A series of experiments need to be launched to confirm the efficacy and safety of using probiotics in space. Safety studies are of equal importance as efficacy studies, since astronauts are immunocompromised (although as discussed above, much of this may return to washing out of microflora in space). These studies can be carried out initially in ground-based space analogs and further followed in actual space (first on animal models and then on humans). The lifestyle of astronauts can be simulated in these studies and after interventions, the composition of microbiota (including opportunistic pathogens) along with immunological markers should be determined. Both short- and long-term confinement and actual spaceflight studies can be designed. The administration and/or consumption of probiotics is supposed to have immune-enhancing effects, hinder alterations in the human microbiome to a large extent and prevent colonization of potential pathogens. Upon observation of possible benefits, probiotics can be incorporated into astronauts' food or supplied periodically as a probiotic kit. This line of research can be followed by NASA scientists and other space agencies to enhance the quality of life of astronauts and to contribute to human presence in space.
Surprisingly, this may bring a future where astronauts utilize probiotic bacteria to counteract the potential effect of pathogenic bacteria during spaceflight.
Acknowledgement
The authors are sincerely grateful to S Saei, who contributed in editing the manuscript.
Future Microbiol. 2012;7(9):1037-1046. © 2012 Future Medicine Ltd.
