In the last decade, drought has been identified as one of the most relevant climate change factors affecting ecosystem integrity across countries. It can severely affect plant growth in agroecosystems, leading to changes in the trophic potential of nectar and pollen. As a cascade effect, a deficit in the nutritional composition of pollen can weaken pollinators, triggering additional threats to ecosystem stability. In this scenario, understanding the impact of trophic sources on honey bee health remains a significant gap that needs to be addressed. This study aims to correlate pollen of different botanical and geographical origins, and therefore of different trophic potential, with selected honey bee markers: the abundance of core microbial taxa and proteins involved in the immune response detectable in the haemolymph. A comprehensive proteomic approach based on MALDI BeeTyping and SDS-PAGE profiles, together with qPCR for the quantification of target microorganisms, was used to elucidate these interactions in bees fed with pollen deriving from 8 botanical families. Our results show that different pollens do not significantly affect the concentration and the total amount of small and large haemolymph proteins but do significantly affect the core gut microbiome composition. Furthermore, the effect of different diets on the microbiome suggests an indirect effect on the immune system response by modulating and influencing the synthesis of some immune-related peptides. This research confirms the importance of the gut microbiome in honey bee health and may also help to understand the honey bee response to climate changes in a scenario of compromised trophic resources.