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.
Highlights
Subtherapeutic levels of antibiotics have been widely used in the swine and poultry industries to improve weight gain and feed conversion efficiency (Cromwell, 2002; Dibner and Richards, 2005)
After 14 days, 10 mice in each group were killed 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 to feed a Tet diet for 14 days; the Natural Restoration (NatR) group which received a basal diet for 14 days; and the Ursolic acid (UA) Therapy (UaT) group which fed a basal diet supplemented with 150 mg/kg UA for 14 days
The NatR and UaT groups remarkably downregulated (P < 0.05) increased colonic TNFα mRNA expression induced by chlortetracycline treatment, but there was no significant difference between NatR and UaT groups (P > 0.05)
Summary
Subtherapeutic levels of antibiotics have been widely used in the swine and poultry industries to improve weight gain and feed conversion efficiency (Cromwell, 2002; Dibner and Richards, 2005). There has been an increasing concern about the health and environmental safety risks of the application of antibiotics, due to the persistence of antibiotic residues and the transmission of antibiotic resistance For these reasons, the use of antibiotics as feed additives has been restricted or even banned in many countries (Diarra and Malouin, 2014). Ursolic acid (UA), a natural pentacyclic triterpenoid, which is widely present in medicinal plants such as bearfruit, hawthorn and fructus ligustri. It has attracted considerable interest in recent years because of various pharmacological activities, such as antiinflammation and antioxidation. The aim of the present study was to investigate the effects of UA on intestinal health and gut flora antibiotic-resistance in antibiotic exposed mice
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