Environmental microbes determine macrophage response towards saponin-induced inflammation in zebrafish larvae

The microbial consortium within an organism is crucial for its development and immune status. Alteration of the host microbiome by antibiotics or antinutritional factors may contribute to increased disease susceptibility. Here, we investigated whether exposure to different microbes could influence zebrafish larval microbiota composition and modulate their immune response towards a saponin challenge. Adult zebrafish were exposed to the antibiotic oxytetracycline (OxyT) or control tank water and their intestinal content was harvested after 30 ​h (24 ​h exposure, 6 ​h wash-out). Subsequently, zebrafish embryos were exposed to either OxyT-treated content or non-treated content from 3 to 6 days post fertilization (dpf). At 6 dpf part of the group received a saponin challenge until 8 dpf. Zebrafish larvae exposed to OxyT-treated adult gut content (3–6 dpf) showed an altered microbiota composition compared to controls. Interestingly, larvae exposed to saponin-treated OxyT-content showed fewer macrophages (as visualized by fluorescent microscopy using mpx:GFP¹¹⁴;mpeg:mCherry transgenic fish) in the overall fish as well as around the gut area than saponin-treated control-exposed larvae. Fewer macrophages were associated with a decreased expression of interleukin 22 (il22) in larvae exposed to saponin-treated OxyT-content compared to controls. Overall, this study shows that exposure to different microbial environments early in life might affect disease susceptibility of larval zebrafish.