title: The impact of orally administered phages on host immune response and surrounding microbial communities.
abstract: Numerous studies have shown the efficacy of phage therapy in reducing foodborne pathogen carriage in food animals. Fewer studies have focused on host reactions, especially in terms of phage-mediated acute immune responses and effects on the gut microbiome. Here we administeredE. coliO157:H7 phages in low (single dose of 105PFU) or high (single dose of 107PFU) quantities to mice. While there were time points at which cytokine levels in different treatment groups differed from one another, all cytokine levels remained within normal ranges for mice regardless of treatment. Similarly, the patterns of these differences were not dose related, indicating that phage treatment did not result in a strong acute immune response as measured here. In separate experiments, 3-week-old pigs received a diet containing an in-feed antibiotic or daily phage treatment. After two weeks, microbial DNA of ileal, cecal, and fecal contents was characterized using 16S rRNA sequencing. There were no statistical differences in performance among the different groups. Compared to control pigs (no antibiotic, no phage), antibiotic treatment significantly altered ileal microbiome composition (P < 0.05), withBacillibeing most affected (antibiotic treated: 22%; control: 76%; FDR = 0.0572). No significant differences were observed in cecal and fecal microbiome composition between antibiotic-treated and control pigs, and there were no differences in gut microbiome composition between phage treated and control pigs in any intestinal compartment. Significant abundance differences were observed at the OTU level, with OTUs belonging to genera such asLactobacillusandStreptococcusbeing over- or under-represented in either antibiotic or phage treated groups compared to control pigs. Determining whether these changes are deleterious to host, however, requires further study.
authors.affiliation: Department of Animal Sciences, Purdue University , West Lafayette, IN, USA.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Bionformatics Core, Purdue University , West Lafayette, IN, USA.
authors.forename: Jyothi
authors.initials: J
authors.lastname: Thimmapuram
authors.affiliation: Department of Animal Sciences, Purdue University , West Lafayette, IN, USA.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Bionformatics Core, Purdue University , West Lafayette, IN, USA.
authors.forename: Clayton K
authors.initials: CK
authors.lastname: Collings
authors.affiliation: Bionformatics Core, Purdue University , West Lafayette, IN, USA.
authors.forename: Ketaki
authors.initials: K
authors.lastname: Bhide
authors.affiliation: Department of Animal Sciences, Purdue University , West Lafayette, IN, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Schmidt
authors.affiliation: Department of Animal Sciences, Purdue University , West Lafayette, IN, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Ebner
keywords: 16s rRNA; Phage; pig gut microbiome