Naturally Occurring TPE-CA Maintains Gut Microbiota and Bile Acids Homeostasis via FXR Signaling Modulation of the Liver–Gut Axis

Abstract

Antibiotics-induced changes in intestinal flora (dysbiosis) may have various effects on the host. Dysbiosis is associated with numerous metabolites including bile acids, which are produced in the liver from cholesterol and metabolized in the gut by intestinal microbiota. Total phenolic extracts of Citrus aurantium L. (TPE-CA) are rich in dietary flavanones and their glycosyl derivatives, including flavones, flavonols, polymethoxyflavones and coumarins, which exert positive health effects on the microbiota. The aim of this study is to elucidate the interplays between the intestinal microbiota and bile acids metabolism attributed to antibiotics. Mice were exposed to broad-spectrum antibiotics, such as ampicillin, streptomycin and clindamycin, for 14 days. This exposure resulted in reduced bacterial diversity and richness, and destroyed intestinal permeability. The homeostasis of bile acids was also affected. Subsequent TPE-CA administration, counteracted most of the dysbiosis, and reshaped intestinal permeability, these effects occurred via upregulation of zonula occludens 1 and occludin associated proteins and downregulation of serum endotoxin compared to the antibiotics group. TPE-CA maintained the homeostasis of bile acids via modulation of the liver-gut axis related farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF15) pathway and FXR-targeted protein. Our findings indicated that TPE-CA exerted a protective effect on the restoration of intestinal microbiota composition, reshaped barrier integrity and maintained bile acid homeostasis via the liver-gut axis with antibiotics-induced dysbiosis.

Citrus flavonoids and the intestinal barrier: Interactions and effects

“…This unbalanced condition, however, might be a precursor to MetS (Chávez‐Talavera, Tailleux, Lefebvre, & Staels, 2017; Saad, Santos, & Prada, 2016). A very recent study established an antibiotics‐induced mice model of dysbiosis, paralleled by BAs dysmetabolism and the intestinal dysfunction, to evaluate the metabolically modulatory effect of CFs in vivo (Liu et al., 2020). Results showed that the CFs‐rich extract from Citrus aurantium L .…”

“…counteracted the dysbiosis and recovered the intestinal permeability. This function of CFs was demonstrated to be associated with its capacity to reshape the homeostasis of BAs via up‐regulation of the liver‐gut axis related farnesoid X receptor (FXR)/fibroblast growth factor 15 (FGF15) pathway (Liu et al., 2020). FXR is a major BAs‐sensing receptor, whose activation leads to alterations in energy metabolism‐related pathways and therefore known as a key regulator of whole‐body energy metabolism (Teodoro, Rolo, & Palmeira, 2011).…”

Methanolic Extract of Lysimachia Candida Lindl. Prevents High-Fat High-Fructose-Induced Fatty Liver in Rats: Understanding the Molecular Mechanism Through Untargeted Metabolomics Study

“…A previous study reported that the levels of bile acid were found to be low in carbon tetrachloride (CCl4) induced fatty liver rats (Zhang et al, 2019). When there is a disruption in the bile acid metabolism, it leads to a decrease in the activation of nuclear receptors such as FXR (farnesoid X receptor) and dysregulation in these receptors leads to NAFLD (Parséus et al, 2017;Chen et al, 2019;Liu et al, 2020). Chenodeoxycholic acid, muricholic acid and other cholic acids are primary bile acids produced in the liver as derivatives of cholesterol and secreted in the intestine as taurine and glycine conjugates.…”

EEN Yesterday and Today … CDED Today and Tomorrow

“…Liu (2020) [35] C57BL/6J mice Increase in ZO-1 and proteins associated with occludin and reduction in serum endotoxin. FXR stimulation with reduced hepatic synthesis of bile acids.…”