The microgravity environment during space flight imposes numerous adverse effects on animal and microbial physiology. It is unclear, however, how microgravity impacts those cellular interactions between mutualistic microbes and their hosts. Here, we used the symbiosis between the host squid Euprymna scolopes and its luminescent bacterium Vibrio fischeri as a model system. We examined the impact of simulated microgravity on the timeline of bacteria-induced development in the host light organ, the site of the symbiosis. To simulate the microgravity environment, host squid and symbiosis-competent bacteria were incubated together in high-aspect ratio rotating wall vessel bioreactors and examined throughout the early stages of the bacteria-induced morphogenesis. The host innate immune response was suppressed under simulated microgravity; however, there was an acceleration of bacteria-induced apoptosis and regression in the host tissues. These results suggest that the space flight environment may alter the cellular interactions between animal hosts and their natural healthy microbiome.