Undernutrition shapes the gut microbiota and bile acid profile in association with altered gut-liver FXR signaling in weaning pigs

Authors: LIN, SEN - Sichuan Agricultural University; YANG, XIAOMIN - Sichuan Agricultural University; YUAN, PEIQIANG - Sichuan Agricultural University; YANG, JIAMENG - Sichuan Agricultural University; WANG, PENG - Sichuan Agricultural University; ZHONG, HEJU - Sichuan Agricultural University; ZHANG, XIAOLING - Sichuan Agricultural University; CHE, LIANQIANG - Sichuan Agricultural University; FENG, BIN - Sichuan Agricultural University; LI, JIAN - Sichuan Agricultural University; ZHUO, YONG - Sichuan Agricultural University; LIN, YAN - Sichuan Agricultural University; XU, SHENGYU - Sichuan Agricultural University; WU, DE - Sichuan Agricultural University; Burrin, Douglas - Doug; FANG, ZHENGFENG - Baylor College Of Medicine

Submitted to: Progress in Lipid Research
Publication Type: Review Article
Publication Acceptance Date: 3/13/2019
Publication Date: 3/13/2019
Citation: Lin, S., Yang, X., Yuan, P., Yang, J., Wang, P., Zhong, H., Zhang, X., Che, L., Feng, B., Li, J., Zhuo, Y., Lin, Y., Xu, S., Wu, D.E., Burrin, D.G., Fang, Z. 2019. Undernutrition shapes the gut microbiota and bile acid profile in association with altered gut-liver FXR signaling in weaning pigs. Progress in Lipid Research. 67(13):3691-3701. https://doi.org/10.1016/j.plipres.2019.02.003.
DOI: https://doi.org/10.1016/j.plipres.2019.02.003

Interpretive Summary: Bile acids made by the liver and secreted into the gut are important for fat digestion. Bile acids also can function as signaling molecules and activate cell receptors, including the farnesoid X receptor FXR and the G protein-coupled bile acid receptor 1 (TGR5). Bile acids secreted into the gut can also be metabolized by bacteria and result in secondary bile acids which can induce intestinal injury. The aim of the current study was to examine how undernutrition that results from weaning stress in neonatal pigs influences bile acid metabolism and signaling of FXR in the gut and liver. Pigs were studied in four groups, including two control groups that were sow-fed at 21 and 28 days of age and two weaning groups that experienced low food intake (undernutrition) or normal food intake (normal nutrition). We found that 7 days after weaning undernourished pigs had lower Lactobacillus abundance and higher concentrations of secondary bile acids in the colon and bloodstream compared to normally nourished pigs. The accumulation of secondary bile acids in the gut were correlated with lower measures of intestinal thickness, which are commonly observed in undernourished weanling pigs. The increase in gut secondary bile acids during undernutrition may explain poor intestinal growth during the weaning process.

Technical 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 'broblast 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.