Supplemental probiotic fermented milk as a gut modulator can improve growth performance for weaned piglets by promoting the development of the small intestine in digestion and immune function. The effect on colon health might also play a considerable part in the favourable role of probiotic fermented milk in the growth performance improvement of weaned piglets; however, it has yet to be reported. This study aimed to investigate the effects of supplementation with lactic acid bacteria-fermented formula milk (LFM) on colonic morphology, microbiota composition, and mucosal transcriptome profile in weaned piglets. A total of 24 male weaned piglets were randomly divided into two groups: a control (CON) treatment or the LFM-supplemented treatment. Each group consisted of six replicates (cages) with two piglets per cage, and each piglet in the LFM group was supplemented with 80mL LFM three times a day for 21 d, while the CON group was treated with the same amount of drinking water. Results showed that supplementation of LFM reduced the colonic histological damage scores and significantly increased the number of goblet cells per crypt. Furthermore, LFM consumption decreased the levels of pro-inflammation cytokines in the colonic mucosa. LFM downregulated the expression of inflammatory genes (CXCL9 and CXCL10) involving Toll-like receptor signalling pathway, immune response, and response to bacterium, and up-regulated two active genes (S100A8 and S100A9) involving the IL-17 signalling pathway and Toll-like receptor 4 binding. In addition, LFM could increase the potential probiotic genera containing Lachnospira and Anaerorhabdus furcosa group, which were positively related to short-chain fatty acid (SCFA) production. Correspondingly, LFM-fed piglets had higher total bacterial load and total SCFA concentration in the colonic digesta compared with the CON group. These novel findings support the benefits of LFM in enhancing intestinal homoeostasis and ameliorating weaning stress for weaned piglets, which is associated with the modulation of gut microbiota composition and immune-related genes.
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