Chinese Medicine Regulates Intestinal Flora to Treat Ulcerative Colitis in Patients with Syndrome of Large Intestine Dampness-heat： A Review / 中国实验方剂学杂志

The clinical changes of ulcerative colitis （UC） with the main syndrome of large intestine dampness-heat and the alterations of intestinal flora in UC were summarized to reveal the underlying mechanism. After review of the treatment methods for UC with the syndrome of large intestine dampness-heat， we identified the representative traditional Chinese medicines and compound prescriptions and explored the treatment mechanisms. Furthermore， we probed into the associations of UC and the treatment methods with the intestinal flora. The related articles were retrieved from China National Knowledge Infrastructure （CNKI）. The available studies have shown that Akkermansia muciniphila， Escherichia coli， Enterococcus， and probiotics such as Bifidobacterium and Lactobacillus are closely associated with Chinese medicines in UC patients with the syndrome of large intestine dampness-heat. However， due to the shortcomings in clinical research and the susceptibility of intestinal flora to diverse factors， it is still challenging to accurately characterize the intestinal flora changes associated with diseases. Additionally， the research on the mechanisms of Chinese medicines in regulating intestinal flora in UC patients with the syndrome of large intestine dampness-heat remains to be improved. The feasibility of using Chinese medicines and compound prescriptions for precise regulation of intestinal flora in these patients is still debatable. In this regard， scientific issues such as the biological connotation of UC with the syndrome of large intestine dampness-heat and the correlation between syndrome and intestinal flora have become primary research tasks. Additionally， attention should also be paid to the interactions between the intestinal lumen exposure profile of Chinese medicines and intestinal flora. Finally， the thinking of traditional Chinese medicine （TCM） and the concepts of modern medicine should be combined for the research on the formulation of TCM regimens for regulating intestinal flora in treating UC.

Modified Liuwei Dihuangtang Combined with Losartan Potassium Regulates ACE1/AngⅡ/AT1R Axis and Intestinal Flora in Rat Model of Diabetic Kidney Disease / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of modified Liuwei Dihuangtang in preventing and treating renal injury in diabetic kidney disease （DKD） via the angiotensin-converting enzyme 1 （ACE1）/angiotensin Ⅱ （AngⅡ）/angiotensin Ⅱ type 1 receptor （AT1R） axis. MethodFifty male SD rats were randomized into a normal group （n=8） and a modeling group （n=42）. The rats in the modeling group were fed with a high-sugar and high-fat diet for 6 weeks and intraperitoneally injected with 35 mg·kg-1 streptozotocin （STZ） to establish the model of DKD. After successful modeling， the rats were randomized into model， traditional Chinese medicine （modified Liuwei Dihuangtang granules 21 g·kg-1）， western medicine （losartan potassium， 33 mg·kg-1）， and integrated Chinese and western medicine （losartan potassium 33 mg·kg-1 combined with modified Liuwei Dihuangtang granules 21 g·kg-1） groups. The levels of fasting blood glucose （FBG）， urinary protein （Up）， blood urea nitrogen （Bun）， and serum creatinine （SCr） were measured in each group after 8 consecutive weeks of drug intervention. Enzyme-linked immunosorbent assay was employed to determine the serum levels of ACE1， AngⅡ， and AT1R. Western blot was employed to measure the protein levels of ACE1， AngⅡ， and AT1R in the renal tissue. The pathological and morphological changes of the renal tissue were observed after hematoxylin-eosin （HE） staining， Masson staining， and periodic acid Schiff 's （PAS） staining. The fecal samples of rats in each group were collected for 16S rDNA high-throughput sequencing. ResultCompared with the normal group， the model group showed elevated levels of Up， FBG， Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01）， serious lesions in the renal tissue， up-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.01）， increased Firmicutes/Bacteroidetes （F/B） ratio， decreased relative abundance of Lactobacillus， and increased relative abundance of Moralella and Bifidobacteria. Compared with the model group， drug intervention lowered the levels of Bun， SCr， ACE1， AngⅡ， and AT1R （P<0.01） and alleviated the pathological changes in the renal tissue. Chinese medicine and integrated Chinese and western medicine lowered the levels of Up and FBG （P<0.01）， and western medicine and integrated Chinese and western medicine down-regulated the protein levels of ACE1， AngⅡ， and AT1R. In addition， Chinese medicine down-regulated the protein levels of AngⅡ （P<0.01） as well as ACE1 and AT1R （P<0.05）. Chinese medicine and integrated Chinese and western medicine decreased the F/B ratio， and western medicine and Chinese medicine increased the relative abundance of Blautia. Chinese medicine and integrated Chinese and western medicine increased the relative abundance of Lactobacillus， Ruminococcus undetermined genera， and Bifidobacteria， decreased the relative abundance of Moralella， and increased the Chao 1 and Ace indexes （P<0.05）. Compared with the western medicine group， the integrated Chinese and western medicine group showed lowered levels of Up （P<0.01）， Bun （P<0.05）， and ACE1 and AT1R （P<0.01）， down-regulated protein levels of ACE1， AngⅡ， and AT1R （P<0.05）， alleviated pathological changes in the renal tissue， increased relative abundance of Bifidobacteria， and increased Chao 1 and Ace indexes （P<0.05）. ConclusionModified Liuwei Dihuangtang combined with losartan potassium can mitigate renal fibrosis by regulating the ACE1/AngⅡ/AT1R axis， increasing the relative abundance of Lactobacillus and Bifidobacterium， reducing the relative abundance of Moralella， improving the richness and evenness of intestinal flora， and alleviating pathological damage in the renal tissue.

Improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis and its mechanism / 中国药房

OBJECTIVE To investigate the improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis （UC） and its mechanism. METHODS UC rat models were established， and 70 rats with successful modeling were randomly divided into model group， limonin low-， medium-， and high-dose groups （12.5， 25， 50 mg/kg）， and sulfasalazine group （positive control group，500 mg/kg）， with 14 rats in each group. Another 14 rats were selected as the control group. After modeling， each group was given the corresponding drug or equal amount of normal saline， once a day， for 2 weeks. Twenty-four hours after the last administration， the general condition of rats was observed and the body weight was measured， and colon tissue was collected for colonic mucosal damage index （CMDI） scoring； the levels of interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in colon tissue were detected； the pathological changes of colon tissue were observed； the protein expressions of Claudin-1， Occludin， ZO-1， high mobility group protein B1 （HMGB1） and receptor for advanced glycation end products （RAGE） in colon tissue were detected； fecal 16S rRNA sequencing was used to detect the relative abundance of zhangxiaxia5287@163.com intestinal microbiota in rats. RESULTS Compared with the control group， the rats in the model group were in poor mental state， with darker fur， irritable mood， disordered arrangement of colon glands， inflammatory cell infiltration， cell necrosis and edema； CMDI score， the levels of IL-1β， IL-6 and TNF-α， protein expressions of HMGB1 and RAGE in colon tissue， the relative abundance of Proteobacteria and Bacteroidetes were significantly increased （P＜0.05）； body weight， the protein expressions of Claudin-1， Occludin and ZO-1 in colon tissue， the relative abundance of Firmicutes in the intestine were significantly decreased （P＜0.05）. Compared with the model group， general situation and pathological damage of colonic tissue in limonin groups were improved， the levels of the above indicators were significantly reversed （P＜0.05）， and in a dose-dependent manner （P＜0.05）； there was no significant difference in various indexes between sulfasalazine group and limonin high-dose group （P＞0.05）. CONCLUSIONS Limonin can improve intestinal injury and intestinal flora disturbance in UC model rats， the mechanism of which may be associated with the down-regulation of HMGB1/RAGE signaling pathway.

Chinese Medicine in Treatment of Ulcerative Colitis by Regulating Intestinal Flora： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） is a chronic， non-specific inflammatory bowel disease. The pathogenesis of this disease is complex and is attributed to multiple factors. Intestinal mucosal barrier damage is the basic pathological change of UC， and intestinal flora disorder is one of the important characteristics of UC. Intestinal flora plays a key role in the pathological process of UC by regulating intestinal mucosal immunity and inflammatory response to repair the damaged intestinal mucosal barrier. At present， western medicine has the advantages of rapid action onset and significant short-term efficacy， but the curative effect of long-term use is not good， accompanied by many adverse reactions， causing great physical and mental pain to patients. Therefore， it is urgent to explore new treatment methods with definite long-term efficacy and mild adverse reactions. A large number of studies have shown that Chinese medicine can regulate intestinal flora through multiple targets in an all-around way， restore the homeostasis of the flora， and repair the damaged intestinal mucosal barrier， thereby inhibiting the progression of UC. Numerous studies have shown that the active components， monomers， and compounds of Chinese medicine can effectively antagonize UC by regulating the intestinal flora to improve the intestinal mucosal immunity， reduce the inflammatory response of the intestinal mucosa， and restore the normal physiological function of the intestinal mucosal barrier， providing a new strategy for UC prevention and treatment. Although there are some studies of the regulation of intestinal flora by Chinese medicine to prevent and treat UC， those studies have the shortcomings of systematic and comprehensive inadequacy. Therefore， based on the research status of UC， intestinal flora， and Chinese medicine treatment， this study reviewed the relationship between intestinal flora and UC and clarified the key role of intestinal flora in the occurrence and development of UC. At the same time， this paper comprehensively summarized the Chinese medicine that targeted the regulation of intestinal flora for the treatment of UC in the past five years to provide new strategies and ideas for UC treatment.

Clinical Efficacy of Modified Banxia Xiexintang Combined with Vedolizumab in Treatment of Crohn's Disease with Syndrome of Cold and Heat in Complexity / 中国实验方剂学杂志

ObjectiveTo evaluate the clinical efficacy of modified Banxia Xiexintang combined with vedolizumab （VDZ） in the treatment of active moderate to severe Crohn's disease （CD） with the syndrome of cold and heat in complexity and the effect of the therapy on intestinal flora. MethodEighty patients were randomized based on the random number table method into a control group （40 cases） and an observation group （40 cases）. The control group was treated with VDZ， and the observation group was treated with modified Banxia Xiexintang （1 bag per day） combined with VDZ. The treatment in both groups lasted for 14 weeks and the follow-up lasted until the 52th weeks. The CD activity index （CDAI）， CD simplified endoscopic score （SES-CD）， inflammatory bowel disease questionnaire （IBDQ） score， and syndrome score of cold and heat in complexity were assessed before treatment， after treatment， and at the end of follow-up. The levels of hemoglobin （HGB）， hematocrit （HCT）， albumin （ALB）， C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-17 （IL-17）， and fecal calprotectin （FC） were measured before and after treatment. Intestinal flora was examined before and after treatment. The safety of the therapy was evaluated. ResultCompared with those before treatment， the scores of CDAI， SES-CD， and the syndrome of cold and heat in complexity decreased （P<0.05） and the IBDQ score increased after treatment （P<0.05）. Compared with those before treatment， the scores of CDAI， SES-CD， and the syndrome of cold and heat in complexity increased （P<0.05） and the IBDQ score decreased （P<0.05） at the end of follow-up. After treatment and at the end of follow-up， the observation group had lower scores of CDAI， SES-CD， and syndrome of cold and heat （P<0.05） and higher IBDQ score （P<0.05） than the control group. Moreover， the observation group had higher clinical remission rate（χ2=4.381，3.962） and response rate（χ2=5.541，4.306） and lower non-response rate（χ2=6.646，4.306） than the control group at the two time points （P<0.05）. The endoscopic remission rate（χ2=4.072，3.985） and response rate（χ2=4.528，5.161） in the observation group were higher than those in the control group （P<0.05）. After treatment， the HGB， HCT， and ALB levels in both groups elevated， and the observation group had higher levels than the control group （P<0.05）. The treatment in both groups lowered the levels of CRP， IL-6， TNF-α， IL-17， and FC （P<0.05）， and the observation group had lower levels of CRP， IL-6， TNF-α， IL-17， and FC than the control group after treatment （P<0.05）. The relative abundance of Bifidobacterium， Lactobacillus， and Prevotella increased （P<0.05）， while that of Proteus， Klebsiella， and Enterococcus decreased （P<0.05） in the two groups after treatment. Moreover， the changes in the relative abundance of these bacteria in the observation group were more obvious than those in the control group （P<0.05）. No adverse reactions related to the modified Modified Banxia Xiexintang were observed during the study period. ConclusionModified Banxia Xiexintang combined with VDZ can play a synergistic role and has good short-term and long-term efficacy. This therapy can improve the nutritional status， regulate intestinal flora， and reduce inflammatory injury in the treatment of moderate to severe active CD patients with the syndrome of cold and heat in complexity without causing severe adverse reactions.

Exploring mechanism of hypolipidemic effect of total Ligustrum robustum (Roxb. ) Blume on hyperlipidemic golden hamsters based on intestinal flora / 中国药理学通报

Aim To evaluate the hypolipidemic effect of the total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) on hyperlipidemic golden hamsters and explore its regulatory effect on intestinal flora. Methods Sixty hamsters were randomly divided into a control group, a model group, a positive drug group, LRTPG-L group, LRTPG-M group, and LRTPG-H group. After the successful induction of the model by high-fat diet, the animals were continuously administered for four weeks, and their blood lipids and liver lipids were detected. The formed feces from the colorectal region of the hamsters in the control group, model group and LRTPG-H group were collected for 16S rDNA sequencing. Results LRTPG reduced serum TG, TC, LDL-C and liver TG, TC concentrations significantly in hyperlipidemic hamsters. The results of the intestinal microbiota sequencing showed that compared to the control group, LRTPG significantly decreased the relative abundance of the phylum Firmicutes and increased the relative abundance of the phylum Bacteroidetes and Verrucomicrobia (P < 0.01) at the phylum level. At the family level, LRTPG significantly increased the relative abundance of Christensenellaceae, Peptococcaceae, and Verrucomicrobiaceae (P < 0.05 or P < 0.01). At the genus level, LRTPG significantly increased the relative abundance of Oscillospira, Oscillibacter, Flavonifractor and Akkermansiaceae (P < 0.05 or P < 0.01). These changes in the flora were beneficial to the hypolipidemic effect of LRTPG. Conclusion LRTPG may exert its hypolipidemic effect by improving the intestinal flora disorder caused by a high-fat diet in golden hamsters.

Traditional Chinese Medicine in Treatment of Constipation Based on 5-HT Signaling Pathway： A Review / 中国实验方剂学杂志

Chronic constipation （CC） is one of the most common functional gastrointestinal diseases. At present， the overall therapeutic effect of CC is still not satisfactory worldwide， which seriously affects the quality of life and social function of patients. The etiology and pathophysiological mechanism of constipation are still unclear. It involves comprehensive factors such as heredity， social psychology， diet， intestinal flora imbalance， intestinal motility disorder， visceral sensitivity change， pelvic floor muscle group dysfunction and enteric nervous system （ENS） disorder. Among them， the abnormal factors of the brain-gut-microbiome axis are particularly significant. The brain-gut-microbiome axis is a complex network of interactions between the intestine and the brain， integrating and coordinating the physiological functions and pathological processes of the gastrointestinal tract. Microorganisms in the intestinal lumen play an important role in it， and can communicate with the intestinal tract and the central nervous system through nerve， endocrine and immune pathways. As a key brain-gut peptide in the regulation pathway of the brain-gut-microbiome axis， 5-hydroxytryptamine （5-HT） is involved in the regulation of gastrointestinal motility， sensation and secretion. The abnormal conduction of the 5-HT signaling pathway is closely related to the occurrence and development of constipation. Traditional Chinese medicine（TCM） is a unique precious resource in China， which has good curative effects and safety. In recent years， it has received extensive attention in the treatment of constipation. TCM and active ingredients， acupuncture and massage specifically regulate 5-HT signal transmission， so that the expressions of related molecules tend to be suitable for individual disease state levels to effectively improve constipation symptoms， with unique advantages. Therefore， this study used ''constipation''， ''intestinal flora''， ''5-HT''， and ''traditional Chinese medicine'' as the keywords to search PubMed， China National Knowledge Infrastructure （CNKI） and other literature databases. The correlation between 5-HT and constipation as well as brain-gut-microbiome axis and the research progress of TCM intervention in the 5-HT signaling pathway in the treatment of constipation were reviewed in order to explore the potential therapeutic value of 5-HT system in this disease and provide references for subsequent research.

Progress on factors affecting gastrointestinal function and drug protection in high altitude hypoxia environment / 药学实践杂志

Due to factors such as low pressure, low oxygen and cold in the plateau environment, people who enter the plateau rapidly are susceptible to digestive system diseases, such as upper abdominal pain, loss of appetite, nausea and vomiting and other gastrointestinal dysfunction, which seriously affect the health and work ability of people who enter the plateau rapidly. The gastrointestinal dysfunction caused by the rapid advance to the plateau is mainly reflected in three aspects: gastrointestinal motility dysfunction, impaired mucosal barrier function, and intestinal flora imbalance. At present, the pathogenesis of gastrointestinal dysfunction is still not very clear, and there are fewer drugs for targeted prevention and treatment. Gastrointestinal hormones, oxygen free radicals, inflammatory factors, intestinal flora and other factors, as well as the protective effects of related drugs were reviewed in this paper to provide treatment options and theoretical basis for the prevention and treatment of the gastrointestinal emergency response caused by entering the plateau.

Effect of Magnolia officinalis Cortex Before and After Sweating on Distribution of Intestinal Flora and Levels of 5-HT and SP in IBS-C Rats / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Magnolia officinalis cortex for constipation-type irritable bowel syndrome（IBS-C） rats before and after sweating. MethodIBS-C rat model was established by gavage of ice water， and rats were randomly divided into the blank group， model group， mosapride group（1 mg·kg-1）， M. officinalis cortex group（10 g·kg-1） and sweated M. officinalis cortex group（10 g·kg-1）. The changes of body weight， fecal number and fecal water content of rats were observed， 16S rRNA sequencing was used to detect the structural changes of fecal intestinal flora in rats， the levels of 5-hydroxytryptamine（5-HT） and substance P（SP） in colonic tissues of rats were determined by enzyme-linked immunosorbent assay（ELISA）. ResultCompared with the model group， the fecal water content and fecal number of mosapride group， M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased（P<0.05）. At the phylum level， the top four species of flora abundance were Firmicutes， Bacteroidetes， Spirochaetes and Proteobacteria. Compared with the blank group， the proportion of Firmicutes in the model group was significantly reduced（P<0.05）， while the proportion of Spirochaetes was significantly increased（P<0.05）. Compared with the model group， the proportion of Firmicutes and Spirochaetes in M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to that in the blank group， and the proportion of Spirochaetes in sweated M. officinalis cortex group was lower than that of M. officinalis cortex group. At the family level， the top four species of flora abundance were Lactobacillaceae， S24_7， Ruminococcaceae， Bacteroidaceae， compared with the blank group， the proportion of Lactobacillaceae in the model group decreased significantly（P<0.05）， and its proportion in the M. officinalis cortex group and sweated M. officinalis cortex group increased significantly after administration（P<0.05）， and the flora structure of the two groups tended to be similar to that of the blank group. At the genus level， the top four species of flora abundance were Lactobacillus， Unspecified_S24_7， Bacteroides and Treponema. Compared with the blank group， the proportion of Lactobacillus in the model group decreased significantly（P<0.05）， while the proportion of Treponema increased significantly（P<0.05）. Compared with the model group， ratio of bacterial structure of Lactobacillus and Treponema in the M. officinalis cortex group and sweated M. officinalis cortex group tended to be similar to those in the blank group， indicating that M. officinalis cortex could restore the intestinal microbial structure of IBS-C rats before and after sweating. Compared with the model group， the 5-HT content in mosapride group was significantly reduced（P<0.05）， the contents of 5-HT and SP in the M. officinalis cortex group and sweated M. officinalis cortex group were significantly increased（P<0.01）， and the sweated M. officinalis cortex group was higher than the M. officinalis cortex group. ConclusionM. officinalis cortex can play a therapeutic role on IBS-C rats by regulating 5-HT pathway and intestinal flora structure before and after sweating.

Mechanisms of Yangxin Tongmai Formula for blood stasis syndrome in coronary heart disease rats based on untargeted plasma metabolomics and intestinal flora 16S rRNA sequencing / 数字中医药（英文）

@#【Objective】  To investigate the correlations between intestinal flora, plasma metabolites, and blood stasis syndrome in coronary heart disease (CHD), and the mechanisms of Yangxin Tongmai Formula (养心通脉方, YXTMF) for blood stasis syndrome in CHD rats. 【Methods】  A total of 18 specific pathogen free (SPF) male Sqrague-Dawley (SD) rats were used to establish CHD rat models with blood stasis syndrome, which were then randomized into model, YXTMF, and atorvastatin calcium (AVT) groups, with six rats in each group, and were intervened through gavage for two weeks. Subsequently, additional six rats that received normal diet were included as normal group. The pathological changes in the CHD rat models were identified by hematoxylin-eosin (HE) staining. The electrocardiogram, hemodynamics, and lipid profiles of the rats were detected as well. The untargeted plasma metabolomics of rats were analyzed by liquid chromotography-tandem mass spectrometry (LC-MS/MS), their ileal mucosal flora by 16S rRNA sequencing, and the correlation between the two results were also analyzed. 【Results】  The whole blood viscosity, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of rats in the model group increased compared with those in the control group (P < 0.05). In the model group, the proliferation of endothelial cells in the coronary artery of rats was damaged, with quite a few vacuolated pathological changes observed. However, the endothelial lesions in the coronary artery of rats were alleviated in the intervention groups (YXTMF and AVT groups). With the use of  LC-MS/MS, a total of 33 potential endogenous metabolites were identified in plasma, among which 1-methylhistidine, N-acetylhistamine, progesterone, and deoxycorticosterone were expected to be the differential metabolites in CHD rats with blood stasis syndrome. The 16S rRNA sequencing results showed that improved diversity and abundance of intestinal flora were observed in the YXTMF group. The correlation analysis suggested that Hydrogenophaga, Limnohabitans, and Polaromonas, which were highly related to the formation of blood stasis syndrome in CHD patients, were positively correlated with plasma metabolites such as 5-hydroxyindole, N-acetylhistamine, and progesterone (P < 0.01), but were negatively correlated with plasma metabolites such as L-arginine, homoarginine, and Boc-beta-cyano-L-alanine (P < 0.01). After YXTMF intervention, Lactobacillus, Corynebacterium, and Candidatus Nitrososphaera were positively correlated with plasma metabolites such as Boc-β-cyano-L-alanine, stachydrine, and naringenin (P < 0.05), while negatively correlated with 5-hydroxyindole, N-acetylhistamine, and oleoylethanolamide (P < 0.05). 【Conclusion】  YXTMF could alleviate blood stasis syndrome in CHD rats through improving their plasma metabolisms achieved by regulating the intestinal flora.

Effects of Shaoyao gancao decoction on intestinal flora in rats with acute lung injury / 中国药房

OBJECTIVE To study the improvement effects of Shaoyao gancao decoction （SGD） on acute lung injury （ALI） in rats and its effects on the intestinal flora. METHODS Sixty SD rats were randomly divided into normal group （CON group， normal saline）， model group （MOD group， normal saline）， positive control group （DEX group， 5 mg/kg dexamethasone）， SGD low-dose， medium-dose and high-dose groups （SGD-L， SGD-M， SGD-H groups， 5.8， 11.6， 23.2 g/kg， calculated by crude drug）， with 10 rats in each group. Each group was given relevant medicine 10 mL/kg intragastrically， for 7 consecutive days. Thirty minutes after the last administration， CON group was given constant volume of normal saline via airway infusion， and other groups were given lipopolysaccharide （5 mg/kg） via airway infusion to induce ALI model. After 12 hours of modeling， the lung tissue wet/dry weight ratio was calculated， and the contents of interleukin 1β （IL-1β）， IL-6 and tumor necrosis factor α（TNF-α） in rat bronchial alveolar lavage fluid （BALF） were all detected； the pathological changes of lung tissue were observed after hematoxylin-eosin staining. The intestinal flora of rat feces was analyzed by 16S rRNA sequencing technology， and the correlation of differential bacteria genera with inflammatory factors was also analyzed. RESULTS Compared with MOD group， the infiltration of inflammatory cells in the lung tissue of rats in each SGD dose group was decreased， and the thickening of alveolar septum and pulmonary edema improved； lung tissue wet/dry weight ratio， the levels of IL-1β， IL-6 and TNF-α in BALF significantly decreased （P＜0.05 or P＜0.01）. SGD （low dose） could improve the intestinal flora disorder in ALI rats， restore the diversity and richness of intestinal flora， regulate the structure of flora， reduce the abundance of Lactobacillus， Streptococcus and Escherichia-Shigella， and increase the abundance of Firmicutes， Lachnospira， Ruminococcus， Clostridia，Dubosiella and Akkermansia. Through correlation analysis， it was found that the relative abundance of Lactobacillus， Streptococcus and Escherichia-Shigella was positively related to the levels of inflammatory factor IL-1β， IL-6 and TNF-α （P＜0.05 or P＜0.01）. The relative abundance of Lachnospira， Dubosiella， Firmicutes was significantly negatively correlated with the levels of inflammatory factors mentioned above （P＜0.05 or P＜0.01）. CONCLUSIONS SGD may improve ALI by reducing lung tissue injury and inflammatory response and regulating flora structure in rats.

Characteristics of intestinal flora in patients with cerebral infarction complicated with Type 2 diabetes mellitus / 中南大学学报(医学版)

OBJECTIVES@#The intestinal microbial characteristics of patients with simple cerebral infarction (CI) and CI complicated with Type 2 diabetes mellitus (CI-T2DM) are still not clear. This study aims to analyze the differences in the variable characteristics of intestinal flora between patients simply with CI and CI-T2DM.@*METHODS@#This study retrospectively collected the patients who were admitted to the Affiliated Hospital of Putian University from September 2021 to September 2022. The patients were divided into a CI group (n=12) and a CI-T2DM group (n=12). Simultaneously, 12 healthy people were selected as a control group. Total DNA was extracted from feces specimens. Illumina Novaseq sequencing platform was used for metagenomic sequencing. The Knead Data software, Kraken2 software, and Bracken software were applied for sequencing analysis.@*RESULTS@#At phylum level, the average ratio of Firmicutes, Bacteroidetes, and Proteobacteria in the CI-T2DM group were 33.07%, 54.80%, and 7.00%, respectively. In the CI group, the ratios of each were 14.03%, 69.62%, and 11.13%, respectively, while in the control group, the ratios were 50.99%, 37.67%, and 5.24%, respectively. There was significant differences in the distribution of Firmicutes (F=6.130, P=0.011) among the 3 groups. At the family level, compared with the CI group, the relative abundance of Eubacteriaceae (t=8.062, P<0.001) in the CI-T2DM group was significantly increased, while Corynebacteriaceae (t=4.471, P<0.001), Methanobacteriaceae (t=3.406, P=0.003), and Pseudomonadaceae (t=2.352, P=0.028) were decreased significantly. At the genus level, compared with the CI group, there was a relative abundance of Cutibacterium (t=6.242, P<0.001), Eubacterium (t=8.448, P<0.001), and Blautia (t=3.442, P=0.002) in the CI-T2DM group which was significantly increased. In terms of Methanobrevibacter (t=3.466, P=0.002), Pyramidobacter (t=2.846, P=0.009) and Pseudomonas (t=2.352, P=0.028), their distributions were decreased significantly in the CI-T2DM group. At the species level, compared with the CI group, the relative abundance of Cutibacterium acnes (t=6.242, P<0.001) in the CI-T2DM group was significantly increased, while Pseudomonas aeruginosa (t=2.352, P=0.028) was decreased significantly. Still at the genus level, linear discriminant analysis effect size (LEfSe) analysis showed that the distributions of Pseudomonas and Blautia were determined to be the most significantly different between the CI-T2DM and the CI group. At the species level, the total number of operational taxonomic units (OTUs) in the 3 groups was 1 491. There were 169, 221, and 192 kinds of OTUs unique to the CI-T2DM, CI, and control group, respectively.@*CONCLUSIONS@#From phylum level to species level, the composition of intestinal flora in the patients with CI-T2DM is different from those in the patients simply with CI. The change in the proportion of Firmicutes, Bacteroidetes and Proteus compared with the healthy population is an important feature of intestinal flora imbalance in the patients with CI and with CI-T2DM. Attention should be paid to the differential distribution of Bacteroides monocytogenes and butyrate producing bacteria.

Intervention of Renal Fibrosis with Traditional Chinese Medicine by Regulating Intestinal Microecology Based on "Combination of State and Target" / 中国实验方剂学杂志

Renal fibrosis is the main pathological foundation of chronic kidney diseases progressing to end-stage renal diseases. With complex pathogenic factors and prolonged disease course， it threatens the quality of life of patients and brings about heavy financial burden to medical care. In the instance of intestinal flora disturbance， the internal homeostasis is broken， resulting in various "imbalances". The "combination of state and target" endows the syndrome differentiation-based treatment of renal fibrosis with new connotation from the perspective of intestinal flora reconstruction and microbial diversity restoration. In addition， traditional Chinese medicine （TCM）-targeted intervention of intestinal microecology has unique advantages under the principle of "treating different diseases with the same method"， which can guide the diagnosis and treatment of renal fibrosis. To be specific， TCM emphasizes macroscopic regulation of state and microscopic targeting. In view of the inflammatory response， accumulation of endotoxin， and excessive deposition of extracellular matrix （ECM） in the process of renal fibrosis， the strategies for treating this disease have been developed， such as alleviating dampness，removing turbid toxin， and relieving deficiency and stasis. Famous prescriptions in ancient books or compound Chinese medicine prescriptions， classical formulas， Chinese medicine monomers， or active components of Chinese medicine target intestinal microecology. Therefore， from the perspective of common pathogenic factors of renal diseases （renal fibrosis） or pathological product-intestinal microecological imbalance， this article combines TCM basic theory with modern medical pathogenesis， and summarizes the research on TCM intervention of renal fibrosis by regulating intestinal microecology and the scientific connotation of renal fibrosis， which is expected to provide ideas and methods for the product development and related preparations and in-depth molecular biological research.

Integrated Metagenomics and UPLC-Q-TOF-MS/MS to Explore the Mechanism of Dexamethasone on Pneumonia in Rats / 中山大学学报(医学科学版)

ObjectiveUsing multi-omics technology， we conducted the present study to determine whether dexamethasone has therapeutic effect on pneumonia rats through the regulation of intestinal flora and metabolites. MethodsTotally 18 Sprague-Dawley rats were randomly divided into 3 groups （n = 6 each）： Control group， Model group and Dexamethasone （Dex） group. Lipopolysaccharide （LPS） was continuously injected intraperitoneally into rats at a dose of 4 mg/kg for 7 days to induce pneumonia except the Control group. Then the Dex group was given Dex at a dose of 2 mg/kg via oral gavage for 12 days， and both the other two groups received continuously equal volume of sterile PBS buffer for 12 days. On the 19th day， lung， plasma， feces and intestinal contents of rat were collected. Hematoxylin-eosin （H&E） staining and Bio-plex suspension chip system were applied to evaluate the effect of Dex on pneumonia. Furthermore， metagenomic sequencing and UPLC-Q-TOF-MS/MS technology were employed to determine the intestinal flora and metabolites of rats， respectively. ResultsH&E staining results showed that the lung tissue of the Model group was infiltrated with inflammatory cells， the alveolar septum was increased， alveolar hemorrhage， and histological lesions were less severe in Dex group than in the model group. The levels of 3 inflammatory cytokines including TNF-α （P < 0.000 1）， IL-1α （P = 0.009 6） and IL-6 （P < 0.000 1） in the Model group were increased compared with the Control group， while Dex treatment reduced the levels of the three inflammatory factors. Taken together， Dex treatment effectively reversed the features of pneumonia in rats. Metagenomic analysis revealed that the intestinal flora structure of the three groups of rats was changed. In contrast with the Model group， an increasing level of the Firmicutes and an elevated proportion of Firmicutes/Bacteroidetes were observed after Dex treatment. Dex-treated rats possessed notably enrichment of Bifidobacterium， Lachnospiraceae and Lactobacillus. Multivariate statistical analysis showed a great separation between Model group and Dex group， indicating metabolic profile changes. In addition， 69 metabolites （P < 0.05） were screened， including 38 up-regulated in the Model group and 31 elevated in the Dex group， all of which were mainly involved in 3 metabolic pathways： linoleic acid metabolism， tryptophan metabolism and primary bile acid biosynthesis. ConclusionsIn summary， we demonstrate the beneficial effects of Dex on the symptoms of pneumonia. Meanwhile， integrated microbiome-metabolome analysis reveals that Dex improves LPS-induced pneumonia in rats through regulating intestinal flora and host metabolites. This study may provide new insights into the mechanism of Dex treatment of pneumonia in rats.

Effect of Danggui Niantongtang on Intestinal Flora in Adjuvant-induced Arthritis Rats of Wind-dampness-heat Arthralgia：Based on 16S rDNA Sequencing / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Danggui Niantongtang （DGNTT） against adjuvant-induced arthritis （AA） in rats with wind-dampness-heat arthralgia （FSR） based on the variation of intestinal flora. MethodA total of 60 SD rats were randomized into normal （control） group， FSR group， low-， medium-， and high-dose DGNTT （5.67， 11.34， 22.68 g·kg-1） groups， and methotrexate （MTX） group （1.35 mg·kg-1）， with 10 rats in each group. The rats， except the control group， were injected with Mtb adjuvant and then exposed to artificial climatic chamber （hot and humid with wind） for 64 h for modeling. The rats were treated with water， DGNTT or MTX for 28 days from the day of injection. Arthritis index （AI） of rats was measured and paw volume was determined with a volume meter. The morphology of synovial tissues of the knees was observed based on hematoxylin-eosin （HE） staining and the changes of intestinal flora were analyzed based on 16S rRNA sequencing. ResultDGNTT can alleviate the hyperplasia of synovial tissue and inflammation of AA rats with FSR and inhibit the formation of pannus. The results of 16S rRNA sequencing showed that the relative abundance of Firmicutes， Lactobacillus， Prevotella 9， and Alloprevotella decreased （P<0.05， P<0.01） and the relative abundance of Bacteroidetes and Bacteroides increased （P<0.01） in FSR group compared those in the control group. Compared with the FSR group， all DGNTT groups and MTX group had high relative abundance of Lactobacillus （P<0.05， P<0.01） and low relative abundance of Bacteroidetes （P<0.01） and medium-dose and high-dose DGNTT groups and MTX group showed high abundance of Firmicutes， Prevotella 9， and Alloprevotella and low abundance of Bacteroides （P<0.05， P<0.01）. Spearman's correlation analysis suggested that the abundance of Bacteroides and Helicobacter was in positive correlation with AI （P<0.05）， while the abundance of Prevotella 9 and Candidatus Saccharimonas was in negative correlation with AI （P<0.01， P<0.05）. There was a negative correlation between the abundance of Prevotella 9 and paw volume （P<0.01）， and the abundance of Ruminococcaceae NK4A214 group， Christensenellaceae R-7 group， and Bacteroides was in negative correlation with spleen index （P<0.05）. The abundance of Prevotella 9 was in negative correlation with spleen index （P<0.01）. ConclusionDGNTT is effective for arthritis with FSR， as it can regulate the composition of intestinal flora in AA rats by increasing the abundance of probiotics and inhibiting the growth of pathogenic bacteria. The mechanism is the likelihood that it improves intestinal immune metabolism to ensure intestinal homeostasis.

Biological Connotation of Pathogenesis of Ulcerative Colitis with Liver Depression and Spleen Deficiency Based on Bile Acid-intestinal Flora Axis / 中国实验方剂学杂志

Ulcerative colitis （UC） is one of the chronic refractory inflammatory bowel diseases characterized by abdominal pain， diarrhea， and mucus， pus and blood in the stool. In recent years， with changes in human life style and improvements of the diagnosis， the incidence and prevalence of UC have been increasing. The pathogenesis of UC is closely related to intestinal mucosal immune dysfunction， intestinal flora disturbance， and abnormal bile acid secretion. Patients with UC have abnormal bile acid secretion and intestinal flora imbalance. A large number of studies have found that abnormal bile acid secretion inhibits immune function， affects signal transduction， and destroys the intestinal mucosal barrier. Intestinal flora disturbance has an important impact on the occurrence and development of inflammation， immune homeostasis， and stress. Bile acids indirectly or directly affect the structure and function of intestinal flora， and at the same time， they produce secondary bile acids under the modification of intestinal flora， entering the liver through enterohepatic circulation. Therefore， the complex dialogue mechanism of bile acid-intestinal flora axis is closely related to the occurrence and development of UC. Based on the basic theory of traditional Chinese medicine（TCM） and clinical research， it is found that emotion is an important factor that induces this disease， spleen and stomach weakness is the root of the disease， and liver depression and spleen deficiency are the key pathogenesis of UC. Combined with modern medicine and molecular biology research， it is believed that abnormal secretion of bile acids is a microscopic manifestation of liver depression in TCM， and intestinal flora disturbance is the biological basis of spleen deficiency. In the pathogenesis of UC， the imbalanced bile acid-intestinal flora axis is consistent with the pathogenesis of liver depression and spleen in TCM. The exploration of the biological connotation of the pathogenesis of UC with liver depression and spleen deficiency from the perspective of bile acid-intestinal flora axis can better explain the scientific nature of its pathogenesis， which provides new clinical solutions and reliable references for studying the pathogenesis of UC with liver depression and spleen deficiency and finding representative prescriptions to prevent and treat this disease.

Effect of Bufeitang on Lung-gut Axis in Rats with Lung Qi-deficiency Syndrome of Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Bufeitang on intestinal flora of rats with lung Qi-deficiency syndrome of chronic obstructive pulmonary disease（COPD）， and to explore the mechanism of traditional Chinese medicine in regulating intestinal flora and thus restoring the balance of lung-gut axis. MethodA total of 84 rats were randomly divided into 7 groups， including blank group， model group， fecal bacterial transplantation（FMT） group， dexamethasone group and low， medium and high dose groups of Bufeitang， 12 rats in each group. Except for the blank group， cigarette and sawdust fumigation combined with intratracheal instillation of lipopolysaccharide（LPS） were used to establish the COPD rat model with lung Qi-deficiency syndrome in all other groups. The low， medium and high dose groups of Bufeitang were intragastric administrated with Bufeitang（3.645， 7.29， 14.58 g·kg-1）， the FMT group was given fecal bacteria liquid enema（10 mL·kg-1）， dexamethasone group was given dexamethasone acetate tablet suspension by gavage（0.135 mg·kg-1）， the blank group and model group were given equal amount of distilled water. Fresh feces were collected after 28 d of continuous intervention for 16S rRNA gene sequencing. Lung and colon tissues were stained with hematoxylin-eosin（HE） for pathomorphological observation， and enzyme-linked immunosorbent assay （ELISA） was performed to detect the contents of tumor necrosis factor-α（TNF-α） and interleukin-8（IL-8） in lung tissues. ResultCompared with the blank group， the model group showed severe abnormal lung tissue structure with alveolar atrophy and collapse accompanied by severe inflammatory cell infiltration. Compared with the model group， the extent of injury was significantly improved， and inflammatory cell infiltration was reduced with basically normal alveolar structure in the high dose group of Bufeitang. Compared with the blank group， the model group had severely abnormal colonic tissue structure， the epithelial cells in the mucosal layer were eroded and shed， the number of inflammatory cells increased， the submucosal layer was edematous and the gap was enlarged. Compared with the model group， the extent of damage was significantly improved in the medium and high dose groups of Bufeitang， the epithelial cells in the mucosal layer were neatly and closely arranged， with only a small amount of inflammatory cell infiltration and no significant degeneration. Compared with the blank group， the TNF-α and IL-8 levels of lung tissue in the model group were significantly increased（P<0.01）. Compared with the model group， the TNF-α and IL-8 levels of lung tissues in the low， medium and high dose groups of Bufeitang were significantly decreased（P<0.01）. Bufeitang significantly modulated the number of bacteria species as well as alpha and beta diversity of model rats， corrected the return of intestinal flora to normal abundance and diversity， and positively regulated 4 differential phyla（such as Firmicutes， Proteobacteria） and 13 differential genera（such as Turicibacter， Lactobacillus， Anaerobiospirillum， Intestinimonas） in COPD model rats with lung Qi-deficiency syndrome， and down-regulated 2 carbohydrate metabolic pathway functions， including the pentose phosphate pathway（non-oxidative branch） Ⅰ and the Calvin-Benson-Bassham cycle. ConclusionBufeitang can modulate the abundance and diversity of intestinal flora species， affect the function of metabolic pathways， repair the structure of lung and colon tissues， regulate the level of inflammatory factors， and thus improve COPD with lung Qi-deficiency syndrome. The mechanism may be related to its regulation of inflammation-related intestinal flora to restore the balance of lung-gut axis in COPD with lung Qi-deficiency syndrome.

Effect of Huangqintang on Intestinal Flora in Mice with Ulcerative Colitis and Its Protective Mechanism on Intestinal Mucosal Barrier / 中国实验方剂学杂志

ObjectiveTo evaluate the pharmacodynamic effect of Huangqintang （HQT） on ulcerative colitis （UC） model mice and investigate its protective effect against UC by regulating intestinal flora. MethodMale Balb/c mice were randomly divided into control group，model group， high-， medium-， and low-dose HQT groups （20， 10， 5 g·kg-1）， flora interference group， flora interference model group， and flora interference-drug treatment group （HQT， 20 g·kg-1）. The flora interference model was constructed through intragastric administration of antibiotics （200 mg·kg-1 bacitracin and 200 mg·kg-1 vancomycin） for 8 d， and the UC model was constructed by allowing mice with free access to 3% dextran sulfate sodium （DSS） solution for 7 d. HQT was administered for 7 d. After the experiments， the mice were sacrificed， and blood， colon， and feces were collected. Hematoxylin-eosin （HE） staining was performed to observe the colonic lesions. The serum levels of interleukin （IL）-4， IL-6， IL-10， and tumor necrosis factor （TNF）-α were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression of Claudin1， MUC1， Occludin， and zonula occludens-1（ZO-1） in colon tissues was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The fecal DNA of mice was extracted and analyzed by high-throughput sequencing. ResultCompared with the normal group， the model group showed increased serum content of IL-4， IL-6， and TNF-α （P<0.05， P<0.01） and decreased IL-10 （P<0.05）. Compared with the model group， the HQT groups displayed decreased serum levels of IL-4， IL-6， and TNF-α （P<0.05， P<0.01）， increased IL-10 content （P<0.01）， increased mRNA and protein expression levels of Claudin1， MUC1， Occludin， and ZO-1 （P<0.05， P<0.01）. After flora interference， the diversity and abundance of intestinal bacteria decreased. To be specific， Proteobacteria increased （P<0.01）， and Firmicutes and Bacteroidetes decreased （P<0.01）. After UC induction by DSS， Bacteroidetes and Tenericutes decreased （P<0.05）. The high-， medium-， and low-dose HQT groups showed increased Bacteroidetes and Tenericutes （P<0.05， P<0.01） and decreased Firmicutes （P<0.05）. Additionally， the abundance of Lactobacillus， Lachnospiraceae NK4A136 group， Escherichia-Shigella， and Helicobacteris was positively proportional to the dose of HQT. ConclusionHQT can inhibit the inflammatory response of UC mice， restore the imbalance of intestinal flora， and repair the damaged intestinal mucosal barrier.

Jujubae Fructus alleviates intestinal injury caused by toxic medicinals in Shizao Decoction based on correlation between intestinal flora and host metabolism / 中国中药杂志

Genkwa Fols, Kansui Radix, and Euphorbiae Pekinensis Radix in Shizao Decoction(SZD) are toxic to intestinal tract. Jujubae Fructus in this prescription can alleviate the toxicity, but the mechanism is still unclear. Therefore, this study aims to explore the mechanism. To be specific, 40 normal Sprague-Dawley(SD) rats were classified into the normal group, high-dose and low-dose SZD groups, and high-dose and low-dose SZD without Jujubae Fructus(SZD-JF) groups. The SZD groups were given(ig) SZD, while SZD-JF groups received the decoction without Jujubae Fructus. The variation of body weight and spleen index were recorded. The patho-logical changes of intestinal tissue were observed based on hematoxylin and eosin(HE) staining. The content of malondialdehyde(MDA) and glutathione(GSH) and activity of superoxide dismutase(SOD) in intestinal tissue were measured to evaluate the intestinal injury. Fresh feces of rats were collected to detect intestinal flora structure by 16S ribosomal RNA gene(16S rDNA) sequencing technology. The content of fecal short chain fatty acids and fecal metabolites was determined by gas chromatography-mass spectrometer(GC-MS) and liquid chromatography-mass spectrometer ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometer(UFLC-Q-TOF-MS), separately. Spearman's correlation analysis was employed to analyze the differential bacteria genera and differential metabolites. RESULTS:: showed that high-dose and low-dose SZD-JF groups had high content of MDA in intestinal tissue, low GSH content and SOD activity, short intestinal villi(P<0.05), low diversity and abundance of intestinal flora, variation in the intestinal flora structure, and low content of short chain fatty acids(P<0.05) compared with the normal group. Compared with high-dose and low-dose SZD-JF groups, high-dose and low-dose SZD groups displayed low content of MDA in intestinal tissue, high GSH content and SOD activity, recovery of the length of intestinal villi, increased abundance and diversity of intestinal flora, alleviation of dysbacteria, and recovery of the content of short chain fatty acids(P<0.05). According to the variation of intestinal flora and fecal metabolites after the addition of Jujubae Fructus, 6 differential bacterial genera(Lactobacillus, Butyricimonas, Clostridia＿UCG-014, Prevotella, Escherichia-Shigella, Alistipes),4 differential short chain fatty acids(such as acetic acid, propionic acid, butyric acid, valeric acid) and 18 differential metabolites(such as urolithin A, lithocholic acid, and creatinine) were screened out. Beneficial bacteria such as Lactobacillus were in positive correlation with butyric acid and urolithin A(P<0.05). The pathogenic bacteria such as Escherichia-Shigella were in negative correlation with propionic acid and urolithin A(P<0.05). In summary, SZD-JF caused obvious intestinal injury to normal rats, which could lead to intestinal flora disorder. The addition of Jujubae Fructus can alleviate the disorder and relieve the injury by regulating intestinal flora and the metabolites. This study discusses the effect of Jujubae Fructus in relieving the intestinal injury caused by SZD and the mechanism from the perspective of intestinal flora-host metabolism, which is expected to serve as a reference for clinical application of this prescription.

Difference of lipid-lowering efficacy of "Xinjianqu" before and after fermentation and its mechanism based on LKB1-AMPK pathway and 16S rDNA sequencing technology / 中国中药杂志

On the basis of establishing the prescription of Xinjianqu and clarifying the increase of the lipid-lowering active ingredients of Xinjianqu by fermentation, this paper further compared the differences in the lipid-lowering effects of Xinjianqu before and after fermentation, and studied the mechanism of Xinjianqu in the treatment of hyperlipidemia. Seventy SD rats were randomly divided into seven groups, including normal group, model group, positive drug simvastatin group(0.02 g·kg~(-1)), and low-dose and high-dose Xinjianqu groups before and after fermentation(1.6 g·kg~(-1) and 8 g·kg~(-1)), with ten rats in each group. Rats in each group were given high-fat diet continuously for six weeks to establish the model of hyperlipidemia(HLP). After successful modeling, the rats were given high-fat diet and gavaged by the corresponding drugs for six weeks, once a day, to compare the effects of Xinjianqu on the body mass, liver coefficient, and small intestine propulsion rate of rats with HLP before and after fermentation. The effects of Xinjianqu before and after fermentation on total cholesterol(TC), triacylglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN), creatinine(Cr), motilin(MTL), gastrin(GAS), and the Na~+-K~+-ATPase levels were determined by enzyme-linked immunosorbent assay(ELISA). The effects of Xinjianqu on liver morphology of rats with HLP were investigated by hematoxylin-eosin(HE) staining and oil red O fat staining. The effects of Xinjianqu on the protein expression of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK), liver kinase B1(LKB1), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase(HMGCR) in liver tissues were investigated by immunohistochemistry. The effects of Xinjianqu on the regulation of intestinal flora structure of rats with HLP were studied based on 16S rDNA high-throughput sequencing technology. The results showed that compared with those in the normal group, rats in the model group had significantly higher body mass and liver coefficient(P<0.01), significantly lower small intestine propulsion rate(P<0.01), significantly higher serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2(P<0.01), and significantly lower serum levels of HDL-C, MTL, GAS, Na~+-K~+-ATP levels(P<0.01). The protein expression of AMPK, p-AMPK, and LKB1 in the livers of rats in the model group was significantly decreased(P<0.01), and that of HMGCR was significantly increased(P<0.01). In addition, the observed＿otus, Shannon, and Chao1 indices were significantly decreased(P<0.05 or P<0.01) in rat fecal flora in the model group. Besides, in the model group, the relative abundance of Firmicutes was reduced, while that of Verrucomicrobia and Proteobacteria was increased, and the relative abundance of beneficial genera such as Ligilactobacillus and Lachnospiraceae＿NK4A136＿group was reduced. Compared with the model group, all Xinjianqu groups regulated the body mass, liver coefficient, and small intestine index of rats with HLP(P<0.05 or P<0.01), reduced the serum levels of TC, TG, LDL-C, ALT, AST, BUN, Cr, and AQP2, increased the serum levels of HDL-C, MTL, GAS, and Na~+-K~+-ATP, improved the liver morphology, and increased the protein expression gray value of AMPK, p-AMPK, and LKB1 in the liver of rats with HLP and decreased that of LKB1. Xinjianqu groups could regulate the intestinal flora structure of rats with HLP, increased observed＿otus, Shannon, Chao1 indices, and increased the relative abundance of Firmicutes, Ligilactobacillus(genus), Lachnospiraceae＿NK4A136＿group(genus). Besides, the high-dose Xinjianqu-fermented group had significant effects on body mass, liver coefficient, small intestine propulsion rate, and serum index levels of rats with HLP(P<0.01), and the effects were better than those of Xinjianqu groups before fermentation. The above results show that Xinjianqu can improve the blood lipid level, liver and kidney function, and gastrointestinal motility of rats with HLP, and the improvement effect of Xinjianqu on hyperlipidemia is significantly enhanced by fermentation. The mechanism may be related to AMPK, p-AMPK, LKB1, and HMGCR protein in the LKB1-AMPK pathway and the regulation of intestinal flora structure.