Introduction
Nearly all animals examined to date show complex interactions with their associated microbial communities. It is evident that there are bidirectional interactions between the gut microbiome and the host in humans (Davison et al., 2017; Dayama et al., 2020; Meisel et al., 2018) and animals (Fuess et al., 2021; Muehlbauer et al., 2021; Naya-Catala et al., 2021). These interactions affect a wide range of host phenotypes including metabolism, immunity, and physiology (McFall-Ngai et al., 2013). Recent studies have shown that host genetics can also shape their gut microbiome (Lopera-Maya et al., 2022; Piazzon et al., 2020). The evidence for benefits provided by the gut microbiota is growing for example, gut microbiota can improve nutrition absorption (Krajmalnik-Brown et al., 2012), facilitate resistance against pathogens (Ducarmon et al., 2019), train the immune system and even modify behaviour and mental state (Surana and Kasper, 2017). (4)Moreover, the gut microbiota gain substantial benefits from their host (e.g., available nutrients and suitable habitat) resulting in a mutualistic relationship with the host. This provides the context for a unique coevolved process in which host and their gut microbiome interact in a mutualistic adaptive scenario (Escalas et al., 2021; Groussin et al., 2020). Coevolution is defined as the reciprocal adaptation process experienced by two organisms as the result of their reciprocal selection pressures; it is possible for the microbiome to evolve at the individual species level, as well as a community response to host-mediated selection (Koskella and Bergelson, 2020).
Many studies have shown the importance of the gut microbiome in healthy and diseased host states, which ultimately affects host fitness (Bozzi et al., 2021; Manor et al., 2020; Yao et al., 2018). The gut microbiome has been shown to alter host gene expression (Davison et al., 2017; Nichols and Davenport, 2021), perhaps a mechanism for the effect of the microbiome on the host. However, the mechanisms and direction of these effects is still not clear since the evidence is largely correlational. Does a change in microbiome composition cause changes in host gene expression, and if so, which genes will be most impacted? It is clearly important to characterize the mechanisms through which the microbiome can cause changes in host gene expression.
Fish live in diverse aquatic environments, but they all harbour complex and diverse microbiomes, and those microbial communities start developing when the eggs are laid (Llewellyn et al., 2014). The bidirectional interaction between the host gut and its associated microbes may arguably be better established in fish, relative to terrestrial animals, as fish are in constant direct contact with the aquatic environmental microbiome through their gut, gills, and skin. Moreover, given the long evolutionary history of fish as a group, studying host–microbe co-evolution in fish may provide unique insights into the host–microbe relationships in general (Montalban-Arques et al., 2015). Characterizing the mechanisms of how the gut microbiota and gene expression processes of the host interact in a symbiotic manner will help explain the physiological processes that maintain the balance among these intricate cross-kingdom interactions and ultimately, help attempts to prevent dysbiosis (Nichols and Davenport, 2021).
Most studies on host- microbiome interactions are correlative or associative analyses without clearly defined cause and effect (Surana and Kasper, 2017). To move beyond such studies, we must more directly address causation through perturbation experimental analyses (Xia and Sun, 2017). Using probiotics and antibiotics to alter gut microbiome in healthy hosts can provide valuable experimental insight into the mechanisms of host-microbiome interactions. Antibiotics can be used for antibiotic-induced microbiome depletion (AIMD), this leads to changes in the structure and function of the gut microbial communities (Ferrer et al., 2017). Furthermore, probiotics can also be used to alter the gut microbiome in a controlled manner, as well as stimulate the host intestinal immune system (Lee and Bak, 2011). Experimental perturbations of the gut microbial community with probiotic strains in human and animal disease treatment is well documented (Azad et al., 2018). However, the effect of probiotics in healthy individuals is not as well characterized.
The direction and nature of host-gut microbiome interactions is still an open question in the study of the microbiome, although it is likely bidirectional and experimental analyses of the mechanisms behind these interactions are needed. Here, our goal was to explore a broad range of host gut tissue responses induced by the experimental manipulation of the gut microbiome. We chose Chinook salmon (Oncorhynchus tshawytscha ) as our study organism as they are reared for commercial and conservation purposes and provide logistical advantages for a study such as ours. Specifically, we used antibiotic, probiotic and control diet treatments to manipulate the gut microbiome in families of Chinook salmon. We used 16S rRNA metabarcoding of the gut bacterial community (BC), coupled with host gut tissue transcriptomics to; (i) quantify treatment effects on the host gut and the fish rearing water BC compositions, (ii) determine the response of the host gut tissue transcriptome to the treatments, and (iii) use gene transcriptional profiling TaqmanTM qPCR to characterize the host response to the treatment-altered gut microbiome. Given the long evolutionary history of the relationship between fish and their microbiomes,we expect strong bidirectional effects, but predicted that the effects of the microbiome on the host are more pronounced. We specifically hypothesized that the host transcriptional responses to each treatment could be attributed to the abundance of specific bacterial taxa. The results obtained provide insight into the co-evolved symbiotic relationship between host and its associated microbiome that may inform future studies exploring host-microbiome interactions and evolution. Additionally, our work will help in better using microbiome manipulation (probiotics, antibiotics) to improve health in fishes and potentially in other animals, including humans.