Effects of Ursolic Acid on Intestinal Health and Gut Bacteria Antibiotic Resistance in Mice

Abstract

Ursolic acid (UA), a natural pentacyclic triterpenoid, has been widely reported to exert anti-oxidant and anti-inflammatory properties. However, the effects of UA on the intestinal homeostasis and gut microbiota were rarely explored. The aim of the present study was to investigate the effects of UA on intestinal health and gut microflora antibiotic-resistance in antibiotic-exposed mice. Kunming mice (n = 80) were randomly allocated into three groups and fed with one of the following diets, respectively: Cont group (n = 20), the basal diet; UA group (n = 20), the basal diet supplemented with 150 mg/kg UA; Tet group (n = 40), the basal diet supplemented with 659 mg/kg chlortetracycline. After 14 days, 10 mice in each group were euthanatized and the remaining 30 mice in the Tet group were randomly allocated into three sub-groups (n = 10 per group) as follows: the Tet group which were kept feeding a Tet diet for 14 days; the Natural Restoration (NatR) group which received a basal diet for 14 days; and the UA therapy (UaT) group which fed a basal diet supplemented with 150 mg/kg UA for 14 days. Throughout the experiment, the weight and the food intake of each mouse were recorded once weekly. Serum LPS and diamine oxidase (DAO), jejunal morphology, jejunal tight junction proteins and nutrient transporters, colonic inflammatory cytokines, gut microbiota and its antibiotic resistance gene (ARG) were examined at euthanasia. The results showed that UA treatment significantly increased average daily food intake (ADFI) of mice. Notably, UA increased the jejunal villi height, decreased the jejunal crypt depth and promoted the expression of jejunum nutrient transporters. UaT group had higher villi height, lower crypt depth and higher nutrient transporter mRNA expression in jejunum than NatR group. Besides, UA decreased serum DAO content, upregulated mRNA expression of ZO-1, claudin-1 and occludin and downregulated TNF-α and IL-6. The mRNA abundances of ZO-1, claudin-1 and occludin and TNF-α and IL-6 in UaT group were, respectively upregulated and downregulated than NatR group. Furthermore, an analysis of 16S rDNA sequences demonstrated that UA increased the abundance of beneficial bacteria in the gut. And the results of ARG test showed that UA downregulated the expression of antibiotic-induced resistance genes. The UaT group inhibited the increase of harmful bacteria abundance and suppressed the mRNA abundances of ARG compared to the NatR group. In conclusion, considering the positive effects of UA on the growth performance and intestinal mucosal barrier, we anticipate that these findings could be a stepping stone for developing UA as a novel substitute of antibiotics.

Algal oil alleviates antibiotic-induced intestinal inflammation by regulating gut microbiota and repairing intestinal barrier

“…Occludin, a key member of transmembrane protein, mainly regulate the permeability of TJs and maintain the polarity of epithelial cells ( 57 ). Consistent with previous studies ( 58 ), the protein concentration of Occludin and ZO-1 decreased after CS treatment in this experiment. Occludin protein did not display significant differences between CS group with YE or with RSM group, while both two kinds of algal oil improved the expression of ZO-1 in colon tissue compared with CS group.…”

Ursolic acid regulates gut microbiota and corrects the imbalance of Th17/Treg cells in T1DM rats

“…In contrast, recent studies have reported that gut microbiota dysbiosis and differentiation of Th17/Treg cells contribute to T1DM progression [ 11 , 17 , 42 ]. In addition, UA modulates the abundance and diversity of intestinal flora and inhibits Th17 cells differentiation [ 43 , 44 ]. However, whether UA has similar protective and ameliorative effects in T1DM remains unknown.…”

Early flora colonization affects intestinal immunoglobulin G uptake in piglets, which may be mediated by NF-κB-FcRn pathway

“…Gene expression was determined on a real-time quantitative PCR system, using SYBR Green Premix Pro Taq HS qPCR kit (Accurate Biotechnology, Hunan, China). Relative quantification of the target gene expression was calculated as previously described methods ( Peng et al, 2021 ).…”