Table 1_Gut microbiota regulates growth retardation in pigs through their metabolites of taurine and butyric acids.docx

Growth retardation of piglets has always been observed in current pig production system. Here we defined these pigs as stunted pigs. Stunted pigs show normal feed intake, but exhibit extremely slow growth speed. This brings a big economic loss to pig industry. Many factors can lead to growth retardation, including gut microbiota which has been reported to play important roles in growth retardation of children. However, whether and which gut microbial taxa are associated with growth retardation of piglets are largely unknown. Here we used 16S rRNA gene and shotgun metagenomic sequencing to identify bacterial taxa associated with growth retardation in 126 pigs including stunted pigs and their pairwise littermates showing normal growth. We identified several Clostridium spp. significantly enriched in the gut of normal growing pigs, including Clostridium symbiosum which was the key biomarker distinguishing stunted pigs and normal growing pigs, while several Bacteroides spp. had higher abundances in stunted pigs. Clostridium spp. was significantly associated with the shifts of functional capacities of the gut microbiome between normal and stunted pigs, e.g., biosynthesis of unsaturated fatty acids. Untargeted serum metabolome analysis found that normal growing pigs had higher concentration of taurine in serum. Increased concentration of serum taurine was associated with increased abundance of Clostridium symbiosum. Furthermore, all metabolites having higher abundances in normal growing pigs were enriched in the pathway of taurine and hypotaurine metabolism. Short-chain fatty acids (SCFAs) analysis identified butyric acid having higher concentration in feces of normal growing pigs in both discovery and validation cohorts, and the changes in the abundances of Clostridium symbiosum was correlated with the shifts of the concentrations of fecal SCFAs. These results suggested that Clostridium spp., especially Clostridium symbiosum improved pig growth by increasing the concentrations of serum taurine and fecal butyric acid, and was an important biomarker associated with pig growth. This study provided important insights into the effect of the gut microbiome on pig growth retardation.