This study investigated the influence of gut microbiome composition in modulating susceptibility to Mycoplasma hyopneumoniae in pigs. Thirty-two conventional M. hyopneumoniae free piglets were randomly selected from six different litters at 3 weeks of age and were experimentally inoculated with M. hyopneumoniae at 8 weeks of age. Lung lesion scores (LS) were recorded 4 weeks post-inoculation (12 weeks of age) from piglet lungs at necropsy. Fecal bacterial community composition of piglets at 3, 8 and 12 weeks of age were targeted by amplifying the V3-V4 region of the 16S rRNA gene. The LS ranged from 0.3 to 43% with an evident clustering of the scores observed in piglets within litters. There were significant differences in species richness and alpha diversity in fecal microbiomes among piglets within litters at different time points (p < 0.05). The dissimilarity matrices indicated that at 3 weeks of age, the fecal microbiota of piglets was more dissimilar compared to those from 8 to 12 weeks of age. Specific groups of bacteria in the gut that might predict the decreased severity of M. hyopneumoniae associated lesions were identified. The microbial shift at 3 weeks of age was observed to be driven by the increase in abundance of the indicator family, Ruminococcaceae in piglets with low LS (p < 0.05). The taxa, Ruminococcus-2 having the highest richness scores, correlated significantly between litters showing stronger associations with the lowest LS (r = -0.49, p = 0.005). These findings suggest that early life gut microbiota can be a potential determinant for M. hyopneumoniae susceptibility in pigs.
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