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.
Highlights
The gut microbiota is an indispensable “metabolic organ” that participates in nutrient processing and the production of essential compounds, such as short-chain fatty acids and bile acids, and it contributes to gastrointestinal system maturation and immune system shaping (Lin et al, 2018)
Standard substances of cholic acid (CA), chenodeoxycholic acid (CDCA), beta-muricholic acid, glycolithocholic acid (GLCA), ursodeoxycholic acid (UDCA), hyodeoxycholic acid (HDCA), deoxycholic acid (DCA), tauroursodeoxycholic acid (TUDCA), glycocholic acid (GCA), taurolithocholic acid (TLCA), glycochenodeoxycholic acid (GCDCA), taurocholic acid (TCA), lithocholic acid (LCA), glycohyodeoxycholic acid (GHDCA), and glycoursodeoxycholic acid (GUDCA), taurochenodeoxycholic acid (TCDCA), ampicillin, streptomycin and clindamycin were purchased from Shanghai Source Leaf Biological Technology Co., Ltd. (Shanghai, China)
Probiotic was obtained from Guangzhou Baiyunshan Pharmaceutical Holdings Company Limited (Guangzhou, China) Anti-Cholesterol 7a-hydroxylation (CYP7A1), anti-Sterol 12a-hydroxylase (CYP8B1), anti-Organic anion transporters (OATPs), anti-SLC10A1 (NTCP, ab131084), anti-ABCB11 (BSEP, ab155421), anti-NR1H4 (FXR, ab235094), anti-FGf15, anti-Zonula occludens 1, anti-occludin and antiGAPDH antibodies were obtained from Abcam (USA)
Summary
The gut microbiota is an indispensable “metabolic organ” that participates in nutrient processing and the production of essential compounds, such as short-chain fatty acids and bile acids, and it contributes to gastrointestinal system maturation and immune system shaping (Lin et al, 2018). Numerous endogenous and exogenous factors affect microbial composition, such as the host's physiology, immunity, diet, antibiotics and environmental factors. Intestinal barrier integrity prevents microbiota endotoxin product translocation from the intestinal to the liver. Antibiotics were used increased the incidence of gastrointestinal diseases, and interferes with the intestinal homeostasis and disrupts intestinal barrier integrity (Deng et al, 2018). Restoring the composition of microorganisms and strengthening of intestinal barrier integrity are essential to restore intestinal homeostasis. The metabolism of bile acids is consecutively disturbed due to intestinal bacteria alterations (Swann et al, 2011b). Emerging dietary strategies such as probiotics, prebiotics, and polyphenols recommended modulation of the composition of the human gut microbiota (Lee et al, 2006)
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