Intestinal Flora In Rats Research Articles

Altered intestinal microflora and barrier injury in severe acute pancreatitis can be changed by zinc.

To investigate the effect of zinc (Zn) supplementation on intestinal microflora changes and bacterial translocation in rats with severe acute pancreatitis (SAP), the rats were divided into the sham surgery (SS), SAP, SS + Zn, and SAP + Zn groups. Saline (0.1 mL/100g) and 5% sodium taurocholate were injected into the pancreaticobiliary duct of the rats in the SS and SAP + Zn groups, respectively. Intraperitoneal injection of 5 mg/kg Zn was performed immediately after injecting saline or 5% sodium taurocholate into the rats in both groups. Serum amylase and Zn levels, plasma endogenous endotoxin, intestinal permeability, and the positive rate of intestinal bacterial translocation were detected, haematoxylin and eosin (H&E) staining was performed, and the pancreatic tissue scores were calculated for each group. In addition, immunohistochemical (IHC) staining was performed to evaluate the expression of IL-1β and TNF-α. Real-time fluorescence quantitative PCR was used to quantify the gene copy numbers of Escherichia, Bifidobacterium, and Lactobacillus in the cecum. The levels of amylase and plasma endotoxin in the SAP group were significantly higher than those in the SS and SS + Zn groups. Intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were increased in the SAP group. However, the levels of amylase and plasma endotoxin were decreased as a result of zinc supplementation in the SAP group. The expression of IL-1β and TNF-α was also reduced to a greater degree in the SAP + Zn group than in the SAP group. Moreover, alleviated intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were found in the SAP + Zn group. The results of real-time quantitative PCR showed that the gene copy number of Escherichia increased with time, and the gene copy numbers of Lactobacillus and Bifidobacterium decreased over time. Zn supplementation prevented the release of TNF-α and IL-1β, alleviated intestinal permeability and endotoxemia, reduced bacterial translocation, and inhibited changes in pathogenic intestinal flora in rats with SAP.

Effects of continuous intravenous infusion of propofol on intestinal flora in rats

Under normal circumstances, the gut microbiota, host, and external environment establish a dynamic ecological balance and maintain human health. Once this balance is broken, the intestinal flora dysregulation will form, manifested by changes in the diversity, richness, proportion, location and biological characteristics of the gut microbiota. The hypothesis that propofol alters gut microbes was tested in a rat model with continuous intravenous infusion of propofol. Eight male wistar rats underwent tail vein puncture and catheterization respectively, and were continuously pumped with propofol for 3 h. Feces were collected from each rat before and on the 1 st, 3rd, 7th and 14th days after intervention. Finally, the effect of continuous intravenous infusion of propofol on the intestinal flora of rats was analyzed by high-throughput 16S rRNA gene amplification sequencing. Through high-throughput 16S rRNA gene amplicon sequencing analysis, we found that continuous intravenous infusion of propofol had little effect on intestinal flora in rats. Analysis of Alpha (shannon diversity index) showed that group A-7 was different from group P and group A-1 (P = 0.034), and recovered on the 14th day. Although the species diversity analysis showed a significant difference among the five groups (P = 0.049), the distribution of most fecal samples in the PCoA showed a clustered distribution, indicating similarity. In addition, no significant difference was found in the statistical KEGG difference pathway through LEfSe analysis.

Sesamin Modulation of Intestinal Microflora in Rats on High-Fat Diet

The present study aimed to investigate the effects of sesamin on intestinal flora in rats on high-fat diet by in vitro animal fecal anaerobic culture system. Results showed that treatment with sesamin increased the abundance of Lactobacillus acidophilus and inhibited the growth of E. coli. High throughput sequencing analysis showed that treatment with sesamin increased the abundance of probiotics such as Lactobacillus and Flavonifractor, and decreased the abundance of harmful bacteria such as Bacteroides, Enterococcus, Clostridium_XlVa, and Parabacteroides. Moreover, treatment with sesamin increased the concentration of total short chain fatty acids (acetic acid and isovaleric acid). In conclusion, sesamin intervention improved the composition and abundance of intestinal microorganisms of high fat diet rats, which would be beneficial to intestinal health.

Correlations of changes in inflammatory factors, glucose and lipid metabolism indicators and adiponectin with alterations in intestinal flora in rats with coronary heart disease.

The aim of this study was to explore the correlations of changes in inflammatory factors, glucose and lipid metabolism indicators and adiponectin with alterations in intestinal flora in rats with coronary heart disease. A total of 30 male specific pathogen-free rats were randomly assigned into two groups, including: blank group (n=15) and coronary heart disease group (n=15). The rats in the coronary heart disease group were given high-fat diets and pituitrin to establish the model of coronary heart disease. Meanwhile, rats in the blank group were administered with an equal volume of double-distilled water. The alterations in the intestinal flora of rats were detected in the two groups, respectively. In addition, the changes in the levels of inflammatory factors, glucose and lipid metabolism indicators, adiponectin, creatine kinase (CK) and its isoenzyme, as well as troponin, were also examined. Statistically, significant differences in the levels of glucose and lipid metabolism indicators low-density lipoprotein (LDL) (p=0.040), total cholesterol (TC) (p=0.039), high-density lipoprotein (HDL) (p=0.044), triglyceride (TG) (p=0.000) and blood glucose (p=0.046) were observed between the rats in the coronary heart disease group and blank group. The content of all the glucose and lipid metabolism indicators (except HDL) in coronary heart disease group was significantly higher than the blank group (p<0.05). The rats in the coronary heart disease group had evidently higher levels of CK (p=0.000) and its isoenzyme (p=0.019), as well as troponin (p=0.021), than those in the blank group. The level of serum adiponectin in rats in coronary heart disease group was distinctly lower than that in the blank group, showing statistically significant differences (p<0.05). Besides, the levels of the inflammatory factors interleukin (IL)-2 (p=0.011), transforming growth factor (TGF)-β (p=0.048), tumor necrosis factor-α (TNF-α) (p=0.025) and IL-6 (p=0.038) in rats in the coronary heart disease group were dramatically higher than those in blank group. Rats in coronary heart disease group had remarkably more Actinobacteria, Desulfovibrio, Aristipus and Escherichia coli in the intestine. Meanwhile, the abundance of Flavobacterium, Burkhofer and some probiotics increased significantly in the intestine of rats in blank group (p<0.05). The changes in the abundance of Actinobacteria, Desulfovibrio, Aristipus and Escherichia coli in the intestine of rats were probably correlated with increased levels of glucose and lipid metabolism indicators, inflammatory factors and adiponectin in coronary heart disease group. Moreover, the abundance of intestinal probiotics such as Bifidobacterium and Lactobacillus in rats in coronary heart disease group was notably lower than that in blank group (p<0.05). The decline in the abundance of such intestinal probiotics as Bifidobacterium and Lactobacillus was correlated with the changes in the levels of glucose and lipid metabolism indicators, inflammatory factors and adiponectin. In addition, decreased levels of probiotics weakened normal physiological functions of the intestine and promoted disease progression. Inflammatory factors, glucose and lipid metabolism indicators and adiponectin have evident changes in rats with coronary heart disease, which may be correlated with the alterations in the intestinal flora.

Effects of simulated 5 500 m hypobaric and hypoxia on HPT axis and intestinal flora in rats

Objective: To investigate the effects of simulated hypoxia environment at an altitude of 5 500 meters on hypothalamic-pituitary-thyroid (HPT) axis and intestinal flora of rats and the correlation between them. Methods: The hypoxia model of adult male SD rats was established by hypobaric chamber with simulated altitude of 5 500 m. The hypoxia groups were set for 1, 3, 7, 14, 21 and 28 days, and the normoxic recovery group were set for 1 and 3 days after hypoxia (8 rats per group, hypoxia time 24h per day). Daily body weight and food intake of rats were recorded. The serum levels of HPT axis hormones were detected by enzyme-linked immunosorbent assay (ELISA). Intestinal flora was analyzed by 16s rDNA sequencing. The correlation between intestinal flora and serum HPT axis hormone was analyzed by Spearman correlation analysis. Results: Compared with the normoxic group, the body weight and food intake were significantly reduced (P＜0.01). In the 1-day and 3-day groups, the levels of thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) were decreased significantly (P＜0.05), the levels of total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4) and free triiodothyronine (FT3) were increased significantly (P＜0.05), and the abundance of Prevotella was decreased significantly (P＜0.05), while those of Parabacteroides, Lactobacillus, Butyricimonas, Bacteroides, Odoribacter and RC4-4 were increased significantly (P＜0.05). In the 14-day, 21-day and 28-day hypoxia groups, the levels of TRH and TSH were decreased significantly (P＜0.05), and the levels of TT4 and TT3 were increased significantly (P＜0.05), and there was no significant difference in other indexes, the abundance of Parabacteroides, Sphaerochaeta, Akkermansia, Elusimicrobium was increased significantly, but that of Lactobacillus and Sutterella was decreased significantly (P＜0.05). Correlation analysis of intestinal flora and HPT axis hormones showed that Butyricimonas, Elusimicrobium and Sutterella were significantly negatively correlated with TRH and TSH (P＜ 0.05), Prevotella, Bacteroides, Odoribacter and Parabacteroides were significantly correlated with TSH, TT4, TT3 and FT4 (P＜ 0.05), respectively. Lactobacillus was significantly correlated with TRH, TSH and FT4 (P＜0.05). Akkermansia was significantly correlated with TRH and FT4 (P＜0.05). RC4-4 was significantly associated with TSH and TT3 (P＜0.05). Conclusion: Hypoxia stress at an altitude simulating 5500 meters significantly changed the composition of the intestinal flora of SD rats. This may be a change in thyroid function adapted to the hypoxia environment, and the degree of change is related to the time of hypoxia stress. The change of intestinal microflora is significantly correlated with the hormone level of HPT axis.

Rifaximin Improves Visceral Hyperalgesia via TRPV1 by Modulating Intestinal Flora in the Water Avoidance Stressed Rat.

Background Rifaximin is effective in relieving pain symptoms with IBS patients, although the mechanisms were not clear. The aims of the research were to investigate whether the visceral hyperalgesia was alleviated by rifaximin via TRPV1 channel in rats. Methods Rats were subjected to water avoidance stress (WAS) and were pretreated with rifaximin by oral gavage. The visceromotor response to colorectal distension was measured. The changes of TRPV1 in peripheral and central neurons of rats were detected by immunofluorescence, western blot method, and RT-PCR. Bacterial 16S ribosomal DNA in ileal contents was assessed using the Illumina MiSeq platform. The effect of intestinal flora on TRPV1 channel was observed by fecal microbiota transplantation (FMT) methods. Results Rifaximin could relieve the visceral hyperalgesia and reduce the TRPV1 expression of neurons and ileum mucosa in rats induced by WAS. The reduced relative abundance of intestinal flora induced by WAS could be partly prevented by rifaximin. The electromyographical activities and immunoreactivity of TRPV1 in rats could be changed after FMT. Conclusions Rifaximin could improve visceral hyperalgesia via TRPV1 channels of peripheral and central neurons by modulating intestinal flora in rats.

Effects of Paeonol and Gastroretention Tablets of Paeonol on Experimental Gastric Ulcers and Intestinal Flora in Rats.

Paeonol, a major ingredient isolated from Moutan Cort, has various pharmacological effects. Our previous studies have shown that paeonol can exert antioxidant and anti-inflammatory therapeutic effects on ethanol-induced experimental gastric ulcer (GU). Therefore, in this study, we designed two GU models in rats induced by pyloric ligation (PL) and acetic acid and evaluated the protective effects of paeonol and gastroretention tablets of paeonol (GRT-Ps; 24, 48, and 96 mg/kg) on GU in rats and the effect of paeonol (48 mg/kg) on the intestinal flora. In vivo experiments showed that paeonol or GRT-Ps remarkably reduced gastric mucosal damage in a dose-dependent manner in the different types of models and improved the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) content. And in fact, the sustained-release effect of GRT-Ps is more conducive to the improvement of GU compared with the rapid clearance of free drugs. In the PL-induced model, gastric secretion parameters, that is, pH and total acid, showed significant differences compared with the model group. In addition, paeonol treatment can improve the richness and diversity of the intestinal flora and increase the amount of beneficial bacteria, such as Lactobacillus. Paeonol and its stable sustained-release tablet GRT-Ps can promote ulcer healing by inhibiting oxidative stress and regulating the intestinal flora. This study can provide basis for the clinical treatment of GU with paeonol. Graphical Abstract.

Protective mechanism of rhubarb anthraquinone glycosides in rats with cerebral ischaemia\u2013reperfusion injury: interactions between medicine and intestinal flora

BackgroundAnthraquinone glycosides extracted from rhubarb have been proven to have significant therapeutic effects on ischaemic stroke. It is well known that anthraquinone glycosides are not easily absorb. Thus, how can rhubarb anthraquinone glycosides (RAGs) exert protective effects on the brain? Is this protective effect related to interactions between RAGs and intestinal flora?MethodsThe model used in this study was established by middle cerebral artery occlusion (MCAO) and reperfusion. Twenty-seven adult male Sprague–Dawley (SD) rats were randomly divided into 3 groups: the normal group (A) (non-MCAO + 0.5% sodium carboxymethyl cellulose (CMC-Na)), model group (B) (MCAO + 0.5% CMC-Na) and medicine group (C) (MCAO + RAGs (15 mg/(kg day)). The rats were fed by gavage once a day for 7 days. Fresh faeces were collected from the normal group to prepare the intestinal flora incubation liquid. Add RAGs, detect the RAGs and the corresponding anthraquinone aglycones by HPLC–UV at different time points. On the 8th day, the rats were euthanized, and the colonic contents were collected and analysed by high-throughput sequencing. In addition, 12 adult male SD rats were randomly divided into 2 groups: the normal group (D) (non-MCAO + RAGs (15 mg/(kg day)) and model group (E) (MCAO + RAGs (15 mg/(kg day)). The rats were fed by gavage immediately after reperfusion. Blood was collected from the orbital venous plexus, and the RAGs and anthraquinone aglycones were detected by HPLC–UV.ResultsThe abundance and diversity of the intestinal flora in rats decreased after cerebral ischaemia–reperfusion injury (CIRI). RAGs could effectively improve the abundance of the intestinal flora. In addition, in vitro metabolism studies showed that RAGs were converted into anthraquinone aglycones by intestinal flora. In the in vivo metabolism studies, RAGs could not be detected in the plasma; in contrast, the corresponding anthraquinone aglycones could be detected. Absorption of RAGs may be inhibited in rats with CIRI.ConclusionsCIRI may lead to intestinal flora disorder in rats, and after the administration of RAGs, the abundance of intestinal flora can be improved. RAGs can be metabolized into their corresponding anthraquinone aglycones by intestinal flora so that they can be absorbed into the blood.

Effect of acupuncture on serum inflammatory cytokines and intestinal flora in rats with stress-induced gastric ulcer

To investigate the effect of acupuncture on serum inflammatory cytokines and intestinal flora in rats with stress-induced gastric ulcer (SGU), and to explore the mechanism of acupuncture in the treatment of SGU. Sprague-Dawley rats were randomly divided into blank, model, acupuncture, and medication groups, with 7 rats in each group. Restraint water-immersion stress was used to establish the model of SGU. The rats in the acupuncture group were given acupuncture at "Zhongwan"(CV12) and bilateral "Zusanli"(ST36) for 20 min, once a day for 5 days, and those in the medication group were given 2 mL solution of Omeprazole enteric-coated tablets (0.2 mg/kg) by gavage, once a day for 5 days. The Guth method was used to calculate the gastric mucosa damage index, HE staining was used to observe the histopathological changes of the gastric mucosa, ELISA was used to measure the serum levels of interleukin-4 (IL-4) and interleukin-6 (IL-6), and 16S rDNA sequencing method was used to observe the change in intestinal flora. Compared with the blank group, the model group had a significant increase in gastric mucosa damage index (P<0.01), markedly pathological changes of the gastric mucosa shown by HE staining, a significant reduction in the content of serum IL-4 (P<0.01), and a significant increase in the content of serum IL-6 (P<0.01), as well as a significant reduction in Bacteroidetes and Firmicutes at the phylum level. Compared with the model group, the acupuncture group and the medication group had a significant reduction in gastric mucosa damage index (P<0.01, P<0.05). HE staining showed reduced pathological changes of the gastric mucosa, as well as a significant increase in the content of serum IL-4 (P<0.01, P<0.05) and a significant reduction in the content of serum IL-6 (P<0.01, P<0.05). As for the intestinal flora, there was a significant increase in Bacteroidetes. Compared with the medication group, the gastric mucosa damage index was decreased （P<0.05），the content of serum IL-4 was significantly increased （P<0.05）, while the content of serum IL-6 significantly decreased (P<0.05) in the acupuncture group. Acupuncture at CV12 and ST36 can down-regulate the content of serum IL-6, up-regulate the content of serum IL-4, maintain the relative homeostasis of inflammatory cytokines, and regulate the community structure of intestinal flora, and thus help to repair the damage of gastric mucosa.

Effect of Durio zibethinus rind polysaccharide on functional constipation and intestinal microbiota in rats

The prevalence of constipation increases rapidly with the increased pressure of some people’s life, which seriously affects the quality of life in related patients. In this study, the improvement of functional constipation by Durio zibethinus Murr rind polysaccharide (DZMP) and the effects of DZMP on intestinal microbiota were investigated in a constipation model of Sprague-Dawley (SD) rats established by loperamide hydrochloride. Results showed that DZMP at 200 mg/kg could significantly (P < 0.05) increase the intestinal transit rate, motilin, gastrin, substance P levels and concentration of short-chain fatty acids (SCFAs), reduce the somatostatin levels and improve the gastrointestinal peristalsis of rats. Sequencing showed that the Lachnospiraceae-NK4A136-group in the rats given 200 mg/kg DZMP (16.07%) was significantly higher than that of the model group (10.13%), while the Desulfovibrio was lower (2.99%) than that of the model group (4.19%). Principal co-ordinates analysis (PcoA) revealed a significant difference in intestinal microbiota composition between the model group and the high-dose DZMP group (200 mg/kg). The results demonstrated that DZMP has a regulatory effect of treating functional constipation and regulating intestinal flora in rats.

Effect of acupuncture on intestinal flora in rats with stress gastric ulcer

To observe the effect of acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36) on intestinal flora in rats with stress gastric ulcer (SGU) , and to explore the mechanism of acupuncture promoting SGU recovery. Thirty-one SPF SD rats were randomly divided into a control group (7 rats), a model control group (8 rats), an acupuncture group (8 rats) and a medication group (8 rats). The rats in the model group, acupuncture group and medication group were selected to applied the improved restraint water-immersion stress method to establish the SGU model. After modeling, the rats in the control group and model group were fixed and restrained for 20 min every day for a total of 5 days; the rats in the acupuncture group were intervented with acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36), once a day, 20 min each time, and twisting needle for 30 s every 5 min for a total of 5 days; the rats in the medication group were gavaged by solution of omeprazole enteric-coated tablet (200 mg/mL), 2 mL for each rat, once a day. Guth method was used to calculate the gastric mucosal damage index (GMDI), HE staining was used to observe the pathological changes of gastric mucosa, and 16SrDNA identification was used to detect the structural abundance of intestinal flora. Compared with the control group, the GMDI of rats in the model group was increased (P<0.01), the gastric mucosal pathological changes were significant, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all decreased (P<0.05), the diversity index Simpson was increased (P<0.05). Compared with the model group, the GMDI of rats in the acupuncture group and medication group was reduced (P<0.01, P<0.05), the gastric mucosal damage degree was reduced, and the intestinal flora richness index Chao1, Observed species and diversity index Shannon were all increased (P<0.05) and the diversity index Simpson decreased (P<0.05). Compared with the medication group, the GMDI of rats in the acupuncture group was reduced (P<0.01), the recovery of gastric mucosal injury was better than that of the medication group. Acupuncture can effectively improve gastric mucosal injury of SGU, and the mechanism may be related to increasing the diversity of intestinal flora and promoting the correction of the disordered intestinal flora.

Effects of Hetiao Jianpi Decoction on Intestinal Injury and Repair in Rats with Antibiotic-Associated Diarrhea.

BackgroundThrough observing the changes of indexes of the intestinal mucosal barrier and intestinal flora in rats, we explored the mechanism by which Hetiao Jianpi Decoction (HTJPD) treats antibiotic-associated diarrhea (AAD) by repairing intestinal mucosal injury and regulating intestinal flora.Material/MethodsSamples of colon tissues were collected for HE staining. Enzyme-linked immunosorbent assay (ELISA) was used to assess levels of diamine oxidase (DAO) and D-lactic acid in rat plasma and the expression of secretory immunoglobulin A (SIgA) in colon tissue. We assessed the abundance of intestinal contents by high-throughput sequencing of the 16S rRNA gene.ResultsCompared with the Model group, the muscle layer and intestinal mucosal edema were improved, and the continuity was restored; the levels of DAO and D-lactic acid in plasma decreased, and the SIgA level were increased in the HTJPD group. The structure of the intestinal flora changed, as indicated by increased levels of certain beneficial bacteria (Verrucomicrobia, Actinobacteria, CF231, and Akkermansia), decreased levels of pathogenic bacteria (Spirochaetes and Treponema), and increased species diversity.ConclusionsBy improving the permeability and immune function of the intestinal mucosa, Hetiao Jianpi decoction prevented the occurrence of AAD by repairing the intestinal mucosal damage and regulating the structure and diversity of intestinal flora.

Isovitexin, A new metabolite, was found in the metabolites of co-cultured five flavonoids isolated from Ziziphus jujuba Mill var. spinosa seeds by rat intestinal flora

Background: Ziziphus jujubaMill var. spinosa seeds (ZSS) is one of the most popular traditional Chinese herbs. It shows several pharmacological effects, such as anti-anxiety, antidepressant, neuroprotection, and cardiotonic, and prevents insomnia. The primary biologically active flavonoids derived from ZSS are 6´´´-feruloyl spinosin, 6´´´-p-coumaroyl spinosin, spinosin, swertisin, and isovitexin. Objectives: The primary objective of this study was to investigate the mechanism of degradation of co-cultured flavonoids, namely 6´´´-feruloyl spinosin, 6´´´-p-coumaroyl spinosin, spinosin, swertisin, and isovitexin, in the intestinal flora of rats under in vitroconditions. Materials and Methods: In this study, we co-cultured the five flavonoids in the intestinal flora of rats under in vitro conditions and determined the degradation of these five flavonoids via high-performance liquid chromatography with tandem mass spectrometry (MS/MS). Results: The degradation rate of the 6´´´-feruloyl spinosin, 6´´´-p-coumaroyl spinosin, and swertisin was affected by the concentration of the sample and conforms to the first-order kinetic model. According to our results, the 6´´´-feruloyl spinosin and 6´´´-p-coumaroyl spinosin may be degraded to spinosin and swertisin, and spinosin continued to decompose into swertisin. These results were consistent with their individual experiments. Moreover, by comparing the structures of isovitexin and swertisin, isovitexin was first found to be the product of the seventh demethylation reaction of the flavonoid core structure, demonstrating that isovitexin is a metabolite of ZSS flavonoids following spinosin and swertisin. Conclusion: Taken together, the results of this study explain the metabolic and interrelation of these five main flavonoids in vitro.

Effects of soluble dietary fiber from soybean residue fermented by Neurospora crassa on the intestinal flora in rats.

In this study, soluble dietary fiber (SDF, including oligosaccharides and polysaccharides) of soybean residue (SR) fermented by Neurospora crassa was used as a research object. In vitro fermentation technology was used to analyze the fermentation properties of SDF from fermented soybean residue (FSR). Moreover, the effects of SDF from FSR on the composition and diversity of intestinal microflora of rats were studied by high-throughput sequencing technology. Results showed that the SDF content of fermented soybean residue was 27.21%. The addition of SDF in the range 2 to 10 g L-1 could increase the levels of gas production and short-chain fatty acids (SCFAs), as well as decrease the pH and ammonia N concentration after 24 h fermentation in the fermentation broth compared with the control group (p < 0.05). The animal-based experiments showed that Bacteroidetes and Firmicutes were the major dominant phyla in all the groups. Compared with the control group, oligosaccharides and polysaccharides of FSR changed the relative abundance and diversity of the bacterial community, and increased the numbers of beneficial flora, such as Prevotellaceae and Lactobacillales. It was shown that SDF of SR fermented by Neurospora crassa had great effects on the intestinal environment and the composition of intestinal flora in rats.

Effects of inulin and isomalto-oligosaccharide on diphenoxylate-induced constipation, gastrointestinal motility-related hormones, short-chain fatty acids, and the intestinal flora in rats

The prebiotics inulin (INU) and isomalto-oligosaccharide (IMO) influence intestinal health and immunity, but their effects on constipation are not clearly established. We evaluated the effects of INU and IMO in a rat model of diphenoxylate-induced constipation. Twenty-four male rats were divided into four groups: basal diet (Con), 40 mg kg-1 diphenoxylate (PCon), 20 g kg-1 INU and treated with 40 mg kg-1 diphenoxylate, and 20 g kg-1 IMO and treated with 40 mg kg-1 diphenoxylate. INU and IMO increased the number, weight, and water content of fecal pellets, and decreased the time to the first black stool in rats with constipation. Serum levels of the gastrointestinal motility-related hormones adrenocorticotropic hormone (ACTH), motilin (MTL), and Substance P (SP) were higher and corticosterone (CORT), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP) were lower in rats treated with prebiotics than in untreated rats. Colon tissue levels of MTL and SP were increased, and VIP and CGRP were decreased by prebiotics. Furthermore, in rats with constipation, INU and IMO increased the colonic contents of short-chain fatty acids. The relative abundance of Bacteroidetes was lower in the prebiotics groups than in the Con and PCon groups. Lactobacillus was more abundant in the INU and IMO groups than in PCon rats. Lactobacillus reuteri and Lactobacillus intestinalis were more abundant in the IMO group than in the PCon group (P < 0.01), and L. intestinalis was more abundant in the INU group than in the PCon group (P < 0.01). In summary, INU and IMO improved constipation and altered the intestinal microbiota in a rat model of constipation.

Effect of Moxibustion on the Intestinal Flora of Rats with Knee Osteoarthritis Induced by Monosodium Iodoacetate.

In this study, a knee osteoarthritis (KOA) rat model induced by monosodium iodoacetate (MIA) was used to study the effect of moxibustion on improving knee cartilage damage and its effect on the intestinal flora. The experimental rats were divided into the normal group (N), model group (M), moxibustion treatment group (MS), and diclofenac sodium treatment group (DS). After 4 weeks, cartilage pathological damage in the knee joint was evaluated using hematoxylin-eosin and safranin O-fast green staining analysis. ELISAs and Western blots were used to detect the expression levels of IL-1β and TNF-α in the serum and cartilage, respectively. The total DNA of the fecal samples was extracted and subjected to high-throughput sequencing of the V3-V4 region of the 16S rRNA gene to analyze the changes in the intestinal flora. In the model group, the cartilage was obviously damaged, the expression levels of IL-1β and TNF-α in the serum and cartilage were increased, and the abundance and diversity of the intestinal flora were decreased. Moxibustion treatment significantly improved the cartilage damage and reduced the concentration of inflammatory factors in the serum and cartilage. The high-throughput sequencing results showed that compared to the model group, the moxibustion treatment regulated some specific species in the intestinal microorganisms rather than the α diversity. In conclusion, our findings suggest that moxibustion treatment may work through two aspects in rats. On one hand, it directly acts on knee cartilage to promote repair, and on the other hand, it regulates the composition of the intestinal flora and reduces the production of inflammatory factors.

Gut Microbiota-Mediated Drug-Drug Interaction between Amoxicillin and Aspirin

The effects of antibiotics on the intestinal flora can create potential drug-drug interactions. The combination of amoxicillin and aspirin is high and there is a high probability of interaction. We used 16S rRNA, incubation experiments and liquid chromatography-tandem mass spectrometry to analyze rat biological samples to characterize the effect of amoxicillin on the pharmacokinetics of aspirin metabolites. We first discovered that amoxicillin reduced the species and number of intestinal flora in rats, such as reducing the abundance of Helicobacter pylori and Prevotella_copri. After 12, 24, and 36 hours of incubation, the remaining amount of aspirin in the aspirin and amoxicillin treatment groups decreased, and salicylic acid production increased, suggesting that aspirin is metabolized by the intestinal flora, and the main metabolite is salicylic acid. As the incubation time prolonged, the reduction of aspirin and the production of salicylic acid in the amoxicillin treatment group were slower. It is indicated that the metabolic activity of aspirin through the intestinal flora is slowed down after administration of amoxicillin. The pharmacokinetic experiments showed that after administration of amoxicillin, the area under the salicylic acid curve increased by 91.38%, the peak concentration increased by 60.43%, and the clearance rate decreased by 43.55%.The results demonstrated that amoxicillin affected the pharmacokinetics of aspirin active metabolite salicylic acid by slowing down the metabolic activity of intestinal flora on aspirin. The interaction between amoxicillin and aspirin mediated by the intestinal flora may affect the efficacy of aspirin and cause more significant adverse effects.

Cefpirome Treatment Results in Limited Selection of Stable Derepressed Enterobacter cloacae Mutants in the Intestinal Flora of Rats Treated for an Experimental Klebsiella pneumoniae Pulmonary Infection.

Background: Fourth-generation cephalosporins have been developed to improve their potency, that is, low minimal inhibitory concentrations (MICs) and to prevent resistance selection of derepressed AmpC-producing mutants in comparison to third-generation cephalosporins as ceftazidime. Objectives: We investigated the role of the administered cefpirome dose on the efficacy of treatment of a Klebsiella pneumoniae lung infection as well as in the selection of resistant Enterobacter cloacae isolates in the intestines of rats treated for a K. pneumoniae lung infection. Materials and Methods: Rats with K. pneumoniae lung infection received therapy with cefpirome doses of 0.4 to 50 mg/kg/day b.i.d. for 18 days. Resistance selection in intestinal E. cloacae was monitored during 43 days. Mutants were checked for β-lactamase activity, mutations in their structural ampC gene, ampD gene, and omp39-40 gene. Results: A 45% and 100% rat survival rate was obtained by administration of 3.1 and 12.5 mg/kg b.i.d. of cefpirome. A significant correlation was demonstrated in the reduction of the susceptible E. cloacae isolates with %fT>MIC at days 7, 14, 22, and 29. Cefpirome E. cloacae mutants, with increased cefpirome MICs, were obtained in only four rats. Conclusions: The treatment with cefpirome resulted in less selection of derepressed mutants in comparison to ceftazidime as shown by their low number per gram of feces and in a limited number of animals.

Lactobacillus paracasei Jlus66 extenuate oxidative stress and inflammation via regulation of intestinal flora in rats with non alcoholic fatty liver disease.

The nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease that affects the health of people in an increasing rate. In the current research, we investigated the beneficial effect of a novel probiotic strain L. paracasei Jlus66 (Jlus66) on rats with high‐fat diet (HFD)‐induced NAFLD. The intestinal flora of rats was analyzed based on V3‐V4 region 16S rDNA sequencing. Moreover, we measured the oxidative stress and inflammation factors in the liver using commercial ELISA kit, and the lipopolysaccharide (LPS) in serum with chromogenic end‐point tachypheus amebocyte lysate. Compared with the HFD‐induced group, Jlus66 treatment significantly decreased the malondialdehyde (MDA) level in the serum (p < 0.05). Additionally, Jlus66 significantly enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) in the liver and serum (p < 0.05). Jlus66 administration also reduced the levels of tumor necrosis factor (TNF‐α) and interleukin‐6 (IL‐6), and inversely increased the interleukin‐10 (IL‐10) level in serum (p < 0.05). Intestinal flora analysis results showed that Jlus66 can improve intestinal flora structure by increasing the abundance of gram‐positive flora such as Firmicutes, and decreasing gram‐negative flora such as Bacteroidetes, Proteobacteria, and Fusobacteria, and then reduced LPS concentration in the serum. So we concluded that Jlus66 can improve NAFLD by modulating the intestinal flora and followed reduction of oxidative stress (OxS) and inflammation.

Effect of long-term intake of ginseng extracts on gut microbiota in rats

As a traditional Chinese medicine in China, ginseng has a wide range of medicinal and health value. At present, the nutritional value of ginseng as a medicinal food has been a hotspot in studies. Intestinal flora plays an important role in the organism, which has been confirmed by many researchers. In order to find out the effect of long-term intake of ginseng extracts on the gut microbiota structure of rats, MiSeq sequencing platform was applied in macro gene sequencing of cecal contents in the long-term use of ginseng extracts modelin rats. According to the findings, after long-term administration with ginseng extracts, probiotics such as Bifidobacterium, Lactobacillus, Allobaculum and Clostridium, in the intestinal flora of rats were significantly increased, suggesting that long-term intake of ginseng extracts could facilitate the growth of probiotics. Meanwhile, some pathogenic bacteria, such as Butyricimonas, Parabacteroides, Alistipes, Helicobacter, were significantly down-regulated, indicating that long-term intake of ginseng extracts may have a positive effect in inhibiting the colonization of pathogenic bacteria. In conclusion, this study provided an important basis for the research on the effect of long-term use of ginseng extracts on the intestinal flora of rats.