Bees are one of the best-known and, at the same time, perhaps the most enigmatic insects on our planet, known for their organization and social structure, being essential for the pollination of agricultural crops and several other plants, playing an essential role in food production and the balance of ecosystems, being associated with the production of high-value-added inputs, and a unique universe in relation to bees’ microbiota. In this review, we summarize information regarding on different varieties of bees, with emphasis on their specificity related to microbial variations. Noteworthy are fructophilic bacteria, a lesser-known bacterial group, which use fructose fermentation as their main source of energy, with some strains being closely related to bees’ health status. The beneficial properties of fructophilic bacteria may be extendable to humans and other animals as probiotics. In addition, their biotechnological potential may ease the development of new-generation antimicrobials with applications in biopreservation. The concept of “One Health” brings together fundamental and applied research with the aim of clarifying that the connections between the different components of ecosystems must be considered part of a mega-structure, with bees being an iconic example in that the healthy functionality of their microbiota is directly and indirectly related to agricultural production, bee health, quality of bee products, and the functional prosperity for humans and other animals. In fact, good health of bees is clearly related to the stable functionality of ecosystems and indirectly relates to humans’ wellbeing, a concept of the “One Health”.