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.