Fecal filtrate transplantation in neonatal pigs induces gut microbiota changes and reduces mortality and diarrhea

Background Enteritis and gut dysbiosis are leading causes of morbidity and mortality in suckling and weanling pigs. We hypothesized that fecal filtrate transplantation (FFT) from a healthy donor to neonatal piglet recipients would stabilize postnatal gut colonization, prevent diarrhea and enhance survival and growth until the post-weaning stage.Methods Blood baseline characteristics associated with the birth process and postnatal immunization, were collected for each pig. Next FFT was given orally to piglets (FFT, n=150) once daily the first six days, and a control group was given placebo at the same timepoints (CON, n=150). We assessed colon microbiota composition via 16S rRNA and metagenomic sequencing on day 27 (the day before weaning) and day 41 (13 days after weaning), together with resistome analysis, blood parameters and gut mucosal enzymatic activity. Growth, diarrhea, and survival were monitored throughout the study.Results Baseline characteristics including birth weight, lactate, and IgG were similar between the two groups indicating proper randomization. The FFT group showed lower prevalence of post-weaning diarrhea (days 27, 32-37, and 41), and all cause-mortality rate was lower for FFT vs CON both pre- and post-weaning (p<0.05). This was associated with differences in the colon microbiome composition between FFT and CON both pre- and post-weaning, as indicated by an enrichment in FFT of metagenome-assembled genomes (MAG) associated with beneficial bacterial families such as Oscillospiraceae and Lachnospiraceae. Resistome analysis revealed no significant effect of FFT on the overall abundance of resistance genes or on the quantity of specific genes of relevance to public health. Body weights were higher for FFT piglets during the suckling period but similar to CON piglets during the post-weaning period. Mucosal disaccharidase and aminopeptidase activity per gram tissue were lower in FFT piglets on day 41 (p<0.05), whereas plasma concentration of intestinal fatty-acid binding protein was similar between the groups.Conclusion Provision of oral FFT after birth induced changes in the gut microbiome lasting at least to the postweaning stage. FFT had a substantial reducing effect on post-weaning diarrhea and all-cause mortality, albeit with only small effects on growth and mucosal function. Oral provision of FFT was well tolerated and appeared safe.