Background: Vairimorpha (Nosema) ceranae is the most common eukaryotic gut pathogen in honey bees, Apis mellifera. Infection is typically chronic but may result in mortality. Additional factors may be involved in mortality, including the honey bee gut microbiota. Previous studies of V. ceranae and gut microbiota identified positive associations between core bacteria and V. ceranae infection. These possibly synergistic or mutualistic associations are often disregarded because some core bacteria act as probiotic symbionts. Methods: To clarify the effects caused by the positive associations, we added isomaltooligosaccharide (IMO), a prebiotic also found in honey, to alter the interactions between V. ceranae and gut bacteria. Mortality and sugar consumption of the caged bees were monitored. Infection intensities and gut bacteria were examed after 12 days post inoculation, the plateau phase of infection. The gut bacteria were evaluated using both qPCR and 16S rDNA sequencing.Results: We confirmed that V. ceranae infections alone significantly enhance several core bacterial populations, including Bifidobacterium spp., Snodgrassella alvi, and Gilliamella apicola in the honey bee hindgut microbiota. Moreover, the qPCR results suggested that V. ceranae infected bees had significantly higher bacterial microbiota populations. In addition to the enhanced core bacteria, Commensalibacter and Bartonella were significantly increased in the fecal microbiome. Infected bees fed IMO had significantly higher V. ceranae spore counts but lower mortality; however, infected bees fed IMO did not have significant changes in gut bacteria populations compared to those fed only sucrose, but feeding IMO further reduced the fecal microbiome alpha-diversity. Conclusions: The microbiota alterations caused by infection were similar to the microbiota differences found between summer bees and winter bees, the latter of which have longer lifespans, and feeding IMO increased this similarity. Our results indicated that the interactions between gut bacteria and V. ceranae not only enhanced both the pathogen and bacteria populations but also sustained the host survival. This mutualistic interaction potentially enhances disease transmission and avoids social immune responses of the honey bee hosts.