Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR-PI3K/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria.

Bile acids (BAs) have been implicated in regulation of intestinal epithelial signaling and function. This study aimed to investigate the effects of hyodeoxycholic acid (HDCA) on intestinal epithelial cell proliferation and explore the underlying mechanisms. IPEC-J2 cells and weaned piglets were treated with HDCA and the contributions of cellular signaling pathways, BAs metabolism profiles and gut bacteria were assessed. In vitro, HDCA suppressed IPEC-J2 proliferation via the BAs receptor FXR but not TGR5. In addition, HDCA inhibited the PI3K/AKT pathway, while knockdown of FXR or constitutive activation of AKT eliminated the inhibitory effects of HDCA, suggesting that FXR-dependent inhibition of PI3K/AKT pathway was involved in HDCA-suppressed IPEC-J2 proliferation. In vivo, dietary HDCA inhibited intestinal expression of proliferative markers and PI3K/AKT pathway in weaned piglets. Meanwhile, HDCA altered the BAs metabolism profiles, with decrease in primary BA and increase in total and secondary BAs in feces, and reduction of conjugated BAs in serum. Furthermore, HDCA increased abundance of the gut bacteria associated with BAs metabolism, and thereby induced BAs profiles alternation, which might indirectly contribute to HDCA-suppressed cell proliferation. Together, HDCA suppressed intestinal epithelial cell proliferation through FXR-PI3K/AKT signaling pathway, accompanied by alteration of BAs metabolism profiles induced by gut bacteria.

Dietary chenodeoxycholic acid improves growth performance and intestinal health by altering serum metabolic profiles and gut bacteria in weaned piglets.

Nutritional diarrhea and subsequent performance degradation in weaned piglets are major challenges for the pig industry. Bile acids (BA) can be added to the diet as emulsifiers. This experiment was conducted to investigate the effects of chenodeoxycholic acid (CDCA), a major primary BA, on growth performance, serum metabolic profiles and gut health in weaned piglets. A total of 72 healthy weaned piglets were randomly assigned to the control (CON) and the CDCA groups, which were feed a basal diet and the basal diet supplemented with 200 mg/kg CDCA for 30 d, respectively. Our results demonstrated that CDCA significantly increased final BW and average daily gain (ADG), decreased feed-to-gain (F:G) ratio and tended to reduce diarrhea incidence. In addition, CDCA increased the villus height-to-crypt depth (V:C) ratio, elevated goblet cell numbers and the expression of tight junction proteins, suggesting the enhancement of intestinal barrier function. As an emulsifier, CDCA increased jejunal lipase activity and the mRNA expression of pancreatic lipases. CDCA supplementation also altered the serum metabolic profiles, including increasing the levels of indole 3-acetic acid, N'-formylkynurenine and theobromine that were beneficial for gut health. Moreover, the relative abundance of 2 beneficial gut bacteria, Prevotella 9 and Prevotellaceae TCG-001, were increased, whereas the relative abundance of a harmful bacteria, Dorea, was decreased in the gut of weaned piglets supplemented with CDCA. Importantly, the altered serum metabolic profiles showed a strong correlation with the changed gut bacteria. In conclusion, CDCA improved the growth performance of weaned piglets by improving intestinal morphology and barrier function, and enhancing lipid digestion, accompanied by alterations of serum metabolic profiles, and changes in relative abundance of certain gut bacteria.

cis 9, trans 11, but not trans 10, cis 12 CLA isomer, impairs intestinal epithelial barrier function in IPEC-J2 cells and mice through activation of GPR120-[Ca2+]i and the MLCK signaling pathway.

This study aimed to investigate the effects of conjugated linoleic acid (CLA) on intestinal epithelial barrier function and explore the underlying mechanisms. IPEC-J2 cells and mice were treated with different CLA isomers. The intestinal epithelial barrier function determined by transepithelial electrical resistance (TEER), the expression of tight junction proteins, and the involvement of G-protein coupled receptor 120 (GPR120), intracellular calcium ([Ca2+]i) and myosin light chain kinase (MLCK) were assessed. In vitro, c9, t11-CLA, but not t10, c12-CLA isomer, impaired epithelial barrier function in IPEC-J2 by downregulating the expression of tight junction proteins. Meanwhile, c9, t11-CLA isomer enhanced GPR120 expression, while knockdown of GPR120 eliminated the impaired epithelial barrier function induced by c9, t11-CLA isomer. In addition, c9, t11-CLA isomer increased [Ca2+]i and activated the MLCK signaling pathway in a GPR120-dependent manner. However, chelation of [Ca2+]i reversed c9, t11-CLA isomer-induced MLCK activation and the epithelial barrier function impairment of IPEC-J2. Furthermore, inhibition of MLCK totally abolished the impairment of epithelial barrier function induced by c9, t11-CLA. In vivo, dietary supplementation of c9, t11-CLA rather than t10, c12-CLA isomer decreased the expression of intestinal tight junction proteins and GPR120, increased intestinal permeability, and activated the MLCK signaling pathway in mice. Taken together, our findings showed that c9, t11-CLA, but not t10, c12-CLA isomer, impaired intestinal epithelial barrier function in IPEC-J2 cells and mice through activation of GPR120-[Ca2+]i and the MLCK signaling pathway. These data provided new insight into the regulation of the intestinal epithelial barrier by different CLA isomers and more references for CLA application in humans and animals.

Chenodeoxycholic Acid (CDCA) Protects against the Lipopolysaccharide-Induced Impairment of the Intestinal Epithelial Barrier Function via the FXR-MLCK Pathway.

Chenodeoxycholic acid (CDCA), a primary bile acid, has been demonstrated to play important roles as a signaling molecule in various physiology functions. However, the role of CDCA in regulating intestinal barrier function remains largely unknown. This study aimed to investigate the effects of CDCA on the lipopolysaccharide (LPS)-impaired intestinal epithelial barrier function and explore the underlying mechanisms. In IPEC-J2 cells, CDCA reversed the LPS-induced increase in transepithelial electrical resistance and decrease in tight junction protein expression. In addition, we found that farnesoid X receptor (FXR) but not Takeda G-protein receptor 5 was responsible for the CDCA-improved epithelial barrier function impaired by LPS. Furthermore, CDCA blocked LPS-induced activation of the myosin light chain kinase (MLCK) pathway in a FXR-dependent manner and elicited similar effects to MLCK inhibition. In mice, CDCA supplementation restored LPS-induced elevation of intestinal permeability and MLCK expression and reduction of tight junction protein expression, thus alleviating LPS-induced intestinal barrier impairment. In conclusion, CDCA protected against the LPS-induced impairment of the intestinal epithelial barrier function via the FXR-MLCK pathway.

Ulcer disease prophylaxis in koi carp by bath immersion with chicken egg yolk containing anti-Aeromonas salmonicida IgY.

Ulcer disease, caused by atypical Aeromonas salmonicida, is a serious concern in ornamental koi carp, because it induces skin ulceration, disfiguring ornamental fish and causing economic loses. The present study aimed to establish a novel prophylaxis with chicken egg yolk immunoglobulin, IgY, against ulcer disease and to assess its feasibility in the ornamental fish industry. Addition of egg yolk powder containing anti-A. salmonicida IgY to rearing water provided significant protection against an A. salmonicida bath infection, whereas administration of non-specific IgY did not. Consecutive immersion of fish into rearing water containing specific IgY completely prevented ulcer disease resulting from cohabitation infection, indicating that this prophylaxis could prevent infection from such type of contact. Thus, passive immunization induced by immersing fish into aquarium water containing specific IgY is a prospective prophylaxis against diseases caused by pathogens that invade the skin and gills.