From ontogenesis to homeostasis, the phenotypes of complex organisms are shaped by the bidirectional interactions between the host organisms and their associated microbiota. Current technology can reveal many such interactions by combining multi-omic data from both hosts and microbes. However, exploring the full extent of these interactions requires careful consideration of study design for the efficient generation and optimal integration of data derived from (meta)genomics, (meta)transcriptomics, (meta)proteomics, and (meta)metabolomics. In this perspective, we introduce the holo-omic approach that incorporates multi-omic data from both host and microbiota domains to untangle the interplay between the two. We revisit the recent literature on biomolecular host-microbe interactions and discuss the implementation and current limitations of the holo-omic approach. We anticipate that the application of this approach can contribute to opening new research avenues and discoveries in biomedicine, biotechnology, agricultural and aquacultural sciences, nature conservation, as well as basic ecological and evolutionary research.

Background: Due to its central role in animal nutrition, the gut microbiota is likely a relevant factor shaping dietary niche shifts. We analysed both the impact and contribution of the gut microbiota to the dietary niche expansion of the only four bat species that have incorporated fish into their primarily arthropodophage diet.Results: We first compared the taxonomic and functional features of the gut microbiota of the four piscivorous bats to that of 11 strictly arthropodophagous species using 16S rRNA targeted amplicon sequencing. Second, we increased the resolution of our analyses for one of the piscivorous bat species, namelyMyotis capaccinii,and analysed multiple populations combining targeted approaches with shotgun sequencing. To better understand the origin of gut microorganisms, we also analysed the gut microbiota of their fish prey (Gambusia holbrooki). Our analyses showed that piscivorous bats carry a characteristic gut microbiota that differs from that of their strict arthropodophagous counterparts, in which the most relevant bacteria have been directly acquired from their fish prey. This characteristic microbiota exhibits enrichment of genes involved in vitamin biosynthesis, as well as complex carbohydrate and lipid metabolism, likely providing their hosts with an enhanced capacity to metabolise the glycosphingolipids and long-chain fatty acids that are particularly abundant in fish.Conclusions: Our results depict the gut microbiota as a relevant element in facilitating the dietary transition from arthropodophagy to piscivory.