Natural Pig Plasma Immunoglobulins Have Anti-Bacterial Effects: Potential for Use as Feed Supplement for Treatment of Intestinal Infections in Pigs

Hedegaard, Chris J.; Strube, Mikael L.; Hansen, Marie B.; Lindved, Bodil K.; Lihme, Allan; Boye, Mette; Heegaard, Peter M. H.

doi:10.1371/journal.pone.0147373.g001 In vivo study Piglets were infected experimentally with E. coli O149:F4 with (group C) and without (group B) ppIgG supplementation in the feed. A non-infected non-ppIgG-feed group (group A) served as a negative control for infection. The feed was generally well tolerated by the piglets; however on average the animals did not gain weight during the course of the study, irrespectively of experimental group (see Table 1 ) most probably due to a discernible reluctance of the weaners of all groups to feed for the first days after arrival. The infection did not cause clinical disease, however shedding of the E. coli inoculation strain was 10 5 and 10 4 times higher at day 3 and day 5 after infection, respectively, in the two infected groups compared to the control group (Fig 3A) , indicating intestinal colonization by the challenge bacterium. The mathematical model describing the shedding pattern shows that the infection was cleared significantly faster in group C (infection + ppIgG) compared to group B (infection only)(p = 0.0007), even if onset of infection was faster in group C than in group B (p = 0.0017). The effect of ppIgG on the intestinal microbial colonisation was further investigated by deep sequencing of the ileal microbiota ( Fig 3B) . This showed a significantly lowered (p<0.001) colonisation of the family Enterobacteriaceae in the ileum as compared to both the non-infected control (group A) and the infected control group (group B, Fig 3B) . Collectively the data presented in Fig 3 suggest that ppIgG inhibits adhesion of bacteria from the family Enterobacteriaceae, including E. coli. Conversely, the families Enterococcoceae and Streptococcaceae were significantly (p<0.01) increased in the ppIgG group compared to both other groups, and compared to the uninfected group only, respectively (Fig 4) . Lactobacillus, Bifidobacterium and other bacterial families generally viewed as health promoting did not differ significantly between groups (Fig 4) . Furthermore, the diversity (Shannon Index) was significantly (p<0.05) higher in the 'Infected + ppIgG' group than in the infected (no ppIgG) control group (S4A Fig) and in a multivariate analysis by NMDS, there was limited separation between groups, mainly by the 'Infected + ppIgG' group being slightly separated from the control groups on the first axis (S4B Fig).