Heat-Killed Lactobacillus acidophilus Promotes Growth by Modulating the Gut Microbiota Composition and Fecal Metabolites of Piglets

Probiotics can improve animal growth performance and intestinal health. However, understanding the effects of paraprobiotics on the growth performance and gut microbiota of piglets and how the paraprobiotics exert their impact are still limited. The present study was conducted to investigate the effects of heat-killed <i>Lactobacillus acidophilus</i> IFFI 6005 supplementation on the growth performance, intestinal microbiota, and fecal metabolites of piglets. First, a feed-additive sample of heat-killed <i>Lactobacillus acidophilus</i> IFFI 6005 was prepared by culture. Second, 96 (initial BW = 14.38 ± 0.67 kg, weaning age of 40 days) healthy piglets were selected and randomized into four treatment groups. Each treatment group consisted of three replicates (<i>n</i> = 8). Pigs were fed a basal diet (NC), basal diet plus antibiotics (PC), basal diet plus <i>Lactobacillus acidophilus</i> IFFI 6005 at 600 g/t (LA, 1.0 × 10¹⁰ cfu/g), and basal diet plus heat-killed <i>Lactobacillus acidophilus</i> IFFI 6005 at 600 g/t (HKLA), respectively; the trial lasted for 30 days. The results showed that the ratios of feed to gain (F:G) and diarrhea rate of both the HKLA and PC groups were significantly lower compared with the NC and LA groups (<i>p</i> < 0.05); however, there was no significant difference between the HKLA and PC group (<i>p</i> > 0.05). In addition, the average daily weight gain (ADG) of the HKLA group was significantly higher (<i>p</i> < 0.05) than that of the other three groups in terms of growth performance. Finally, 16S rRNA sequencing and metabolome analysis based on fecal samples further elaborated that the addition of heat-killed <i>Lactobacillus acidophilus</i> IFFI 6005 to the feed improved the intestinal microbial diversity and abundance (<i>p</i> < 0.05) and reduced the abundance of pathogenic bacteria (<i>p</i> < 0.05), but it did not affect the abundance of <i>Lactobacillus</i> (<i>p</i> > 0.05). Through the comparison of microbial abundance and metabolite content between the two groups (NC_vs_HKLA), the largest differences were found in six microorganisms and 10 metabolites in the intestine (<i>p</i> < 0.05). These differential metabolites were involved in the digestion, absorption and utilization of protein and starch, as well as in oxidative stress. In summary, addition of heat-killed <i>Lactobacillus acidophilus</i> IFFI 6005 as a new feed additive in piglets has beneficial effects on the growth performance, intestinal bacteria and metabolites, and can be used as an alternative to antibiotics.