## 4 Interactions between Vaccine Administration and Gut Microbiome Status
### Gut Dysbiosis and Its Influence on Vaccine Efficacy in Poultry
Additionally, in ovo probiotic supplementation could aid in the developing chick's microbiota while effectively minimizing _Salmonella_ colonization [81]. However, minimization of colonization by pathogenic bacteria, such as avian pathogenic _E. coli_, through in ovo probiotic supplementation is not consistently observed [82]. Moreover, there is currently no clear management strategy that defines how to effectively apply probiotics in a manner that universally benefits vaccine efficacy in poultry flocks. Vaccine Administration and Its Influence on Gut Microbiome Status in Poultry and Other Non-Human Hosts  
The state of the gut microbiota at the time of vaccination can influence the immunogenicity of a wide variety of vaccines [5; 6]. Recent research has discovered that vaccines may influence the host microbiome as it mounts an inflammatory response and develops an antigen-specific memory following vaccine administration. Investigations regarding the effects of commercial vaccine administration regimens on gut microbiome status among poultry flocks are limited (Table 2), although there is a collection of investigations in other monogastric animal models. For example, [PERSON] et al. [14] discovered that pigs vaccinated for influenza A virus had no changes in microbial diversity or abundance in fecal samples after primary and secondary vaccinations. However, vaccinated pigs had a higher abundance of lactic acid-producing microbes (_Lactobacillus_ genus) at the time of the secondary immunization, and microbial families associated with fiber fermentation (_Lachospiraceae_) and short-chain fatty acid generation (_Ruminococcaceae_) were enriched one week after the secondary vaccination. Additionally, pigs that exhibited weak immune responses to the influenza A vaccine had greater levels of microbes associated with enteric inflammation (including _Helicobacter_ and _Escherichia-Shigella_) after primary vaccination [14]. Alternatively, [PERSON] et al. [69] observed that 15-day-old broilers vaccinated for coccidiosis, an enteric protozoan, had an increased abundance of the _Enterococcus_ genus, which is associated with bacteriocin production but also foodborne disease outbreaks in humans [83]. Unlike the results from [PERSON] et al. [14], several reports have indicated that vaccine administration does not negatively or positively alter gut microbiota. [PERSON] et al. [84] determined that vaccination with a trivalent avian influenza vaccine combined with an anthelmintic treatment in red-crowned cranes triggered temporary deviations in stool microbiota populations. After vaccine administration, lactic acid-secreting microbes (_Lactobacillus_ genus) decreased while microbes associated with fortification of the mucosal barrier (genera within the Proteobacteria and Actinobacteria phyla) increased. Even with these responsive changes, microbiota homeostasis began to be re-established in the red-crowned creanes by 15 days post-vaccination and anthelmitic treatment [84]. In SPF chicks, [PERSON] et al. [85] evaluated immune responses and cecal microbiome status following oral administration of an H9N2 recombinant protein as a vaccine candidate attached to a yeast (_Saccharomyces cerevisiae_) vector. There was higher richness and more diverse microbial community composition in the cecal contents of chicks vaccinated with the recombinant protein attached to yeast when compared to the control (PBS) vaccination. Additionally, the Firmicutes phylum was enriched while the abundance of the _Lactobacillus_ genus was not altered when comparing recombinant protein-vaccinated chicks to those of the PBS-vaccinated control [85]. Similar results were observed when candidate and commercial non-typhoidal _Salmonella_ vaccines were applied to broiler [86, 87] and egg-type chickens [68, 88]. [PERSON] et al.