Undernutrition Shapes the Gut Microbiota and Bile Acid Profile in Association with Altered Gut-Liver FXR Signaling in Weaning Pigs

Abstract

Bile acids, synthesized in the liver and metabolized by microbiota, have emerged as important signaling molecules regulating immune responses and cell proliferation. However, the crosstalk among nutrition, microbiota, and bile acids remains unclear. Our study indicated that undernutrition in weaning piglets led to intestinal atrophy, increased colonic production, and systemic accumulation of lithocholic acid (LCA), deoxycholic acid (DCA), or their conjugated forms, which might be associated with decreased Lactobacillus abundance. Moreover, undernutrition led to increased portal fibroblast growth factor 19 (FGF19) level, upregulated hepatic heterodimer partner (SHP), and downregulated cholesterol 7a-hydroxylase ( CYP7A1 ) expression. The detrimental effects of DCA and LCA on proliferation and barrier function were confirmed in porcine enterocytes, whereas their roles in weaning piglets warrant further research. In summary, undernutrition in weaning piglets led to increased secondary bile acids production, which might be related to altered gut microbiome and enhanced farnesoid X receptor (FXR) signaling while CYP7A1 expression was suppressed.

Dietary supplementation withLactobacillus plantarummodified gut microbiota, bile acid profile and glucose homoeostasis in weaning piglets

“…The most common secondary BA, LCA and DCA, have been shown to induce cell apoptosis and increase intestinal permeability (5,6,28) and have been correlated with colorectal carcinogenesis (6,29) . Our recent study also revealed the detrimental effect of LCA and DCA on porcine enterocytes including suppression of cell proliferation, impairment of tight junction and inducement of inflammatory responses (22) . In light of the importance of gut microbiota in the production of secondary BA (11,12) , supplementation of probiotics appeared to be a promising nutritional strategy regulating secondary BA production and may thus aid in the improvement of intestinal health.…”

“…An incision was made on the middle abdomen of piglets, and ileum and liver tissue samples were collected and washed with sterile saline and snap-frozen in liquid N 2 . Approximately 2-cm length of duodenum, jejunum and ileum samples were fixed in 4 % paraformaldehyde and used for measurement of morphometry as we previously described in detail (22) .…”

“…Cells were seeded in twelve-well plate. When grown to confluence, 5 μM of LCA or dimethyl sulphoxide was used to treat cells for 12 h and then each well was added with LPS (10 μg/ml) or saline for another 4 h. The concentrations of LCA and LPS used were based on previous studies (22,23) . Cell culture medium was collected for measurement of IL-8.…”

“…Gene expression analysis was performed as we described previously (22) . Total RNA was extracted from tissues and cells using RNAiso Plus (Takara) and then reverse-transcribed to complementary DNA (cDNA) using a PrimeScript ™ RT reagent kit (Takara) according to the manufacturer's instructions.…”

“…Western blotting was performed as we described previously (22) . Briefly, following treatment, cells were washed with PBS for twice and cellular protein was extracted using RIPA lysis buffer containing 1 mM phenylmethylsulfonyl fluoride protease inhibitor (Beyotime Biotech Inc.) and the concentration was then measured using a Pierce BCA protein assay kit (Thermo Fisher Scientific).…”