Interwoven processes in fish development: microbial community succession and immune maturation

Fishes are hosts for many microorganisms that provide them with beneficial effects on growth, immune system development, nutrition and protection against pathogens. In order to avoid spreading of infectious diseases in aquaculture, prevention includes vaccinations and routine disinfection of eggs and equipment, while curative treatments consist in the administration of antibiotics. Vaccination processes can stress the fish and require substantial farmer’s investment. Additionally, disinfection and antibiotics are not specific, and while they may be effective in the short term, they have major drawbacks in the long term. Indeed, they eliminate beneficial bacteria which are useful for the host and promote the raising of antibiotic resistance in beneficial, commensal but also in pathogenic bacterial strains. Numerous publications highlight the importance that plays the diversified microbial community colonizing fish (i.e., microbiota) in the development, health and ultimately survival of their host. This review targets the current knowledge on the bidirectional communication between the microbiota and the fish immune system during fish development. It explores the extent of this mutualistic relationship: on one hand, the effect that microbes exert on the immune system ontogeny of fishes, and on the other hand, the impact of critical steps in immune system development on the microbial recruitment and succession throughout their life. We will first describe the immune system and its ontogeny and gene expression steps in the immune system development of fishes. Secondly, the plurality of the microbiotas (depending on host organism, organ, and development stage) will be reviewed. Then, a description of the constant interactions between microbiota and immune system throughout the fish’s life stages will be discussed. Healthy microbiotas allow immune system maturation and modulation of inflammation, both of which contribute to immune homeostasis. Thus, immune equilibrium is closely linked to microbiota stability and to the stages of microbial community succession during the host development. We will provide examples from several fish species and describe more extensively the mechanisms occurring in zebrafish model because immune system ontogeny is much more finely described for this species, thanks to the many existing zebrafish mutants which allow more precise investigations. We will conclude on how the conceptual framework associated to the research on the immune system will benefit from considering the relations between microbiota and immune system maturation. More precisely, the development of active tolerance of the microbiota from the earliest stages of life enables the sustainable establishment of a complex healthy microbial community in the adult host. Establishing a balanced host-microbiota interaction avoids triggering deleterious inflammation, and maintains immunological and microbiological homeostasis.