Lactobacillus frumenti mediates energy production via fatty acid ß-oxidation in the liver of early-weaned piglets.

BACKGROUND: Early-weaning of piglets is often accompanied by severe disorders, especially diarrhea. The gut microbiota and its metabolites play a critical role in the maintenance of the physiologic and metabolic homeostasis of the host. Our previous studies have demonstrated that oral administration of Lactobacillus frumenti improves epithelial barrier functions and confers diarrhea resistance in early-weaned piglets. However, the metabolic response to L. frumenti administration remains unclear. Then, we conducted simultaneous serum and hepatic metabolomic analyses in early-weaned piglets administered by L. frumenti or phosphate-buffered saline (PBS). RESULTS: A total of 100 6-day-old crossbred piglets (Landrace × Yorkshire) were randomly divided into two groups and piglets received PBS (sterile, 2 mL) or L. frumenti (suspension in PBS, 108 CFU/mL, 2 mL) by oral administration once per day from 6 to 20 days of age. Piglets were weaned at 21 days of age. Serum and liver samples for metabolomic analyses were collected at 26 days of age. Principal components analysis (PCA) showed that L. frumenti altered metabolism in serum and liver. Numerous correlations (P < 0.05) were identified among the serum and liver metabolites that were affected by L. frumenti. Concentrations of guanosine monophosphate (GMP), inosine monophosphate (IMP), and uric acid were higher in serum of L. frumenti administration piglets. Pathway analysis indicated that L. frumenti regulated fatty acid and amino acid metabolism in serum and liver. Concentrations of fatty acid ß-oxidation related metabolites in serum (such as 3-hydroxybutyrylcarnitine, C4-OH) and liver (such as acetylcarnitine) were increased after L. frumenti administration. CONCLUSIONS: Our findings suggest that L. frumenti regulates lipid metabolism and amino acid metabolism in the liver of early-weaned piglets, where it promotes fatty acid ß-oxidation and energy production. High serum concentrations of nucleotide intermediates, which may be an alternative strategy to reduce the incidence of diarrhea in early-weaned piglets, were further detected. These findings broaden our understanding of the relationships between the gut microbiota and nutrient metabolism in the early-weaned piglets.

A Microbiota-Derived Bacteriocin Targets the Host to Confer Diarrhea Resistance in Early-Weaned Piglets.

Alternatives to antibiotics for preventing diarrhea in early-weaned farm animals are sorely needed. CM piglets (a native Chinese breed) are more resistant to early-weaning stress-induced diarrhea than the commercial crossbred LY piglets. Transferring fecal microbiota, but not saline, from healthy CM into LY piglets by oral administration prior to early weaning conferred diarrhea resistance. By comparing the relative abundance of intestinal microbiota in saline and microbiota transferred LY piglets, we identified and validated Lactobacillus gasseri LA39 and Lactobacillus frumenti as two bacterial species that mediate diarrhea resistance. Diarrhea resistance depended on the bacterial secretory circular peptide gassericin A, a bacteriocin. The binding of gassericin A to Keratin 19 (KRT19) on the plasma membrane of intestinal epithelial cells was essential for enhancement of fluid absorption and decreased secretion. These findings suggest the use of L. gasseri LA39 and L. frumenti as antibiotic alternatives for preventing diarrhea in mammals.

Lactobacillus frumenti Facilitates Intestinal Epithelial Barrier Function Maintenance in Early-Weaned Piglets.

Increased intestinal epithelial barrier function damages caused by early weaning stress have adverse effects on swine health and feed utilization efficiency. Probiotics have emerged as the promising antibiotic alternatives used for intestinal barrier function damage prevention. Our previous data showed that Lactobacillus frumenti was identified as a predominant Lactobacillus in the intestinal microbiota of weaned piglets. However, whether the intestinal epithelial barrier function in piglets was regulated by L. frumenti is still unclear. Here, piglets received a PBS vehicle or PBS suspension (2 ml, 108 CFU/ml) containing the L. frumenti by oral gavage once a day during the period of 6-20 days of age prior to early weaning. Our data demonstrated that oral administration of L. frumenti significantly improved the intestinal mucosal integrity and decreased the serum endotoxin and D-lactic acid levels in early-weaned piglets (26 days of age). The intestinal tight junction proteins (including ZO-1, Occludin, and Claudin-1) were significantly up-regulated by L. frumenti administration. The serum immunoglobulin G (IgG) levels, intestinal secretory immunoglobulin A (sIgA) levels, and interferon-γ (IFN-γ) levels were significantly increased by L. frumenti administration. Furthermore, our data revealed that oral administration of L. frumenti significantly increased the relative abundances of health-promoting microbes (including L. frumenti, Lactobacillus gasseri LA39, Parabacteroides distasonis, and Kazachstania telluris) and decreased the relative abundances of opportunistic pathogens (including Desulfovibrio desulfuricans and Candida humilis). Functional alteration of the intestinal bacterial community by L. frumenti administration was characterized by the significantly increased fatty acids and protein metabolism and decreased diseases-associated metabolic pathways. These findings suggest that L. frumenti facilitates intestinal epithelial barrier function maintenance in early-weaned piglets and may be a promising antibiotic alternative used for intestinal epithelial barrier function damage prevention in mammals.