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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.
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ObjectiveThis study aims to explore the potential mechanism of Danggui Niantongtang in treating knee osteoarthritis （KOA） by regulating the intestinal flora through 16S rDNA analysis. MethodThirty-six C57BL/6J mice were subjected to anterior cruciate ligament transection （ACLT） to establish a KOA model and were randomly divided into the sham surgery group， model group， low-dose Danggui Niantongtang group （0.819 g·kg-1）， medium-dose Danggui Niantongtang group （1.638 g·kg-1）， high-dose Danggui Niantongtang group （3.276 g·kg-1）， and Meloxicam group （0.975 mg·kg-1）， with 6 mice in each group. Except for the treatment groups， the sham surgery group and model group were given normal saline by gavage. After 4 weeks of continuous intervention， feces and intact knee joints of the mice were collected. Hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining were performed to observe the pathological changes in knee joint tissue morphology. The 16S rDNA sequencing was used to analyze changes in the abundance and diversity of intestinal microorganisms before and after treatment， along with corresponding functional predictions. ResultHigh-dose Danggui Niantongtang and Meloxicam significantly relieved pain symptoms in KOA mice， improved the disorder of joint structure， maintained the integrity of knee articular cartilage， increased the expression of type Ⅱ collagen alpha 1 （Col2a1） in articular cartilage， and decreased the expression of matrix metalloproteinase-13 （MMP-13）. The results of 16S rDNA sequencing showed that high-dose Danggui Niantongtang could adjust the abundance and structure of intestinal microbial species. Compared with the sham surgery group， the abundance of Proteobacteria， Actinobacteria， Ruminococcus， and Bacteroides was significantly increased in the model group （P<0.05）， while in the Danggui Niantongtang group， the abundance of these four flora was significantly reduced compared with the model group. Compared with the sham surgery group， the abundance of Verrucomicrobia， Oscillospira， and Akkermansia was significantly decreased in the model group （P<0.05）， while in the Danggui Niantongtang groups， the abundance of these three flora was significantly increased compared with the model group （P<0.05）. Functional pathway prediction of differential genera revealed that species differences among groups mainly involved metabolic pathways with high abundance associated with biosynthesis and precursors， as well as energy production， including amino acid biosynthesis， nucleotide and nucleoside biosynthesis， cofactors， prosthetic groups， electron carriers， and vitamin biosynthesis. ConclusionDanggui Niantongtang can effectively protect articular cartilage and delay the progression of KOA， possibly by regulating the structure of the intestinal flora， promoting probiotics， and inhibiting the growth of harmful pathogenic bacteria.
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Objective:To explore the effects of acupuncture combined with Buyang Huanwu Decoction on intestinal flora in cerebral blood flow hypo perfusion model rats with carotid artery stenosis.Methods:Totally 40 rats were randomly divided into sham-operation group, model group, TCM treatment group and acupuncture and drug combination treatment group, with 10 rats in each group. Except the sham-operation group, the other groups were prepared cerebral ischemia model by needle control and thread embolism method. TCM treatment group received Buyang Huanwu Decoction 100 mg/kg for gavage, once a day, and the intervention lasted for 2 weeks. In the acupuncture and drug combination group, based on the TCM treatment group, Baihui and its left and right sides of 2 mm were selected for acupuncture, once a day, and continuous intervention was performed for 2 weeks. Neurological function evaluation and behavioral function score were performed 7 and 14 days after administration, respectively. 16S rRNA sequencing was used to comprehensively characterize the structure and composition of fecal microflora of rats in each group. Linear discriminant analysis Effect Size (LEfSe) was used to analyze the difference of intestinal bacteria among groups.Result:On the 7th and 14th day after administration, compared with the model group, the neurological function score in the TCM treatment group and the acupuncture and drug combination group decreased ( P<0.05), and the behavioral function score increased ( P<0.05). Compared with model group, the Shannon index of TCM treatment group and acupuncture and drug combination group increased ( P<0.05). The abundance of Firmicutes increased ( P<0.05), and the abundance of Bacteroidetes and Proteobacteria decreased ( P<0.05); the abundance of Clostridia increased ( P<0.05), and the abundance of Gammaproteobacteria decreased ( P<0.05). The abundance of Escherichia-Shigella and Bacteroides decreased ( P<0.05); the abundance of lactobacillus significantly increased ( P<0.05). Conclusion:Acupuncture combined with Buyang Huanwu Decoction can improve the symptoms of cerebral hypoperfusion model rats with carotid artery stenosis, and the mechanism may be to increase the abundance of probiotics.
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Based on the introduction of gut-brain-skin axis, this article discussed the relationship between psychological behavior, intestinal flora, and atopic dermatitis. By combing the literature on the treatment of atopic dermatitis with TCM, it is found that TCM therapy can regulate the relative abundance of intestinal flora, participate in immune metabolism and restore skin barrier function by intervening in the gut-brain-skin axis, so as to achieve the purpose of treating atopic dermatitis.
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The intestinal flora and gut barrier function are of great significance for gut function and human health. When the intestinal flora is disrupted and the gut barrier structure is disrupted, it can lead to bacterial translocation, endotoxin influx into the bloodstream, and the production of pro-inflammatory factors, leading to various tissue damage in the body. Tongfu method in TCM can affect the intestinal environment by regulating intestinal permeability and immune response, restoring normal intestinal movement, and regulating the structure and metabolites of intestinal flora, thereby maintaining intestinal homeostasis and body health. The research on regulating intestinal flora and improving intestinal barrier function by Tongfu method can provide reference for further research on the relationship between TCM and intestinal microecology, and provide ideas for clinical treatment.
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Objective To observe the regulating effect and mechanism of Yichang Sanjie Granules on intestinal flora and immune function in mice with colon cancer.Methods Sixty mice were randomly divided into six groups,i.e.,the normal group,the model group,the low-,medium-and high-dose groups of Yichang Sanjie Granules,and the overexpression of melanoma absent gene 2(AIM2)plasmid(pcDNA-AIM2)intervention group,with 10 mice in each group.Colorectal cancer model was prepared by oxidized azomethine(AOM)/dextran sulfate sodium(DSS)induction method in all groups except normal group.After drug administration,the survival curves of mice in each group were plotted and the tumor volume was calculated;serum levels of immunoglobulin(Ig)G,IgM,interleukin(IL)-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA);peripheral blood levels of CD3+,CD4+,CD8+ T cells were detected by flow cytometry;the splenic index was determined;Hematoxylin-eosin(HE)staining was used to observe the pathological changes in colon tissues;16S-rDNA intestinal flora sequencing was used to detect the α-diversity of intestinal flora and the structure of intestinal flora communities;and protein immunoblotting(Wetsern Blot)was used to detect the protein expressions of AIM2,apoptosis-associated speckled-like protein containing a CARD(ASC),and cystatinase-1(caspase-1)in colon tissues.Results Compared with the normal group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the model group were significantly decreased,and the tumor volume,serum levels of IL-1β and IL-18,peripheral blood level of CD8+,and splenic index were significantly increased(all P＜0.05),and the HE staining results showed the characteristic manifestations of colon cancer;compared with the model group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group were significantly increased,and the tumor volume,serum levels of IL-1β and IL-18,level of peripheral blood CD8+,and splenic index were significantly decreased(all P＜0.05),and the HE staining results showed the manifestations of colon cancer were improved.Compared with the normal group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group,and Ruminiclostridium in the model group were significantly decreased,while the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was increased in the model group(P＜0.05);compared with the model group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group and Ruminiclostridium were significantly increased,and the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was decreased in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group(all P＜0.05).Conclusion Yichang Sanjie Granules can increase autoimmunity and improve intestinal flora structure in mice with colon cancer,and its mechanism is related to the activation of AIM2 inflammatory vesicles.
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Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.
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Antibiotic-associated diarrhea(AAD)in children is a type of diarrhea that occurs after the use of antibiotics in children,and its pathogenesis is closely related to the intestinal flora.The medication of antibiotics can affect the metabolic function of the intestinal flora and the immune function of the body,and then leads to the occurrence of AAD.In the view of Chinese medicine,AAD in children is mainly involved the spleen,and the etiology of the disease is due to the weakness of the spleen and stomach of the body constitution together with the attack of the pestilential pathogen and the accumulation of drug toxin.The pathogenesis of ADD in children is characterized by spleen deficiency with predominant dampness,deficiency of spleen qi,and insufficiency of spleen yang.Spleen deficiency is the root cause of pediatric AAD,and spleen and intestinal flora have commonality,so the treatment of pediatric AAD can be performed from the perspective of the spleen.The treatment of pediatric ADD from the spleen follows the principle of strengthening and activating the spleen,and the regulation of the spleen for achieving the purpose of treating the disease from the root can be achieved by the methods of strengthening spleen and draining dampness,strengthening spleen and replenishing qi,and strengthening spleen and warming yang separately with the fundamental prescriptions of Shenlin Baizhu Powder,Sijunzi Decoction,and Fuzi Lizhong Pills.
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Objective To explore the effect of omeprazole combined with different probiotics on regulating intestinal flora in reducing functional dyspepsia(FD)in children.Methods Two hundreds children with FD admitted to the Pediatric Department of Foshan Maternal and Child Health Hospital from January 2022 to February 2023 were se-lected as the study subjects.They were randomly divided into omeprazde(omep)group,groups of omeprazole+yeast(yeast group),+clostridium butyricum(clos group),and+bifidobacterium(bifi group)respectively.Results After treatment,serum level of IL-6,TNF-α,IL-1β,hs-CRP,VIP,SS,Enterobacter and Enterococcus in all groups significantly decreased as compared with the finding before treatment(P<0.05).Those targets in the three combined treatment groups were significantly lower compared to the ome group;After treatment,the serum MOT level,bifidobacteria,and lactobacilli in each group were significantly increased(P<0.05),and the results from three combined treatment groups demonstrated notably higher levels compared to the omep group(P<0.05);The scores of symptoms in all groups showed a significant alleviation after the treatment(P<0.05).Additionally,the three combined treatment groups exhibited significantly lower symptom scores than the group treated with omeprazole alone(P<0.05).There was no difference in the incidence of adverse reactions during treatment among the groups.Conclusions Omeprazole combined with different probiotics have achieved good results in the treatment of FD in children.
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When refractory diarrhea comes on,it greatly affects the life and daily work of patients,and there is no unified treatment.Patients with refractory diarrhea have varying degrees of intestinal flora disorder,so rebuilding the intestinal micro ecosystem may be an effective way to treat refractory diarrhea.Fecal microbiota transplantation(FMT)has the potential to be an effective treatment for refractory diarrhea as a therapy that reconstructs normal intestinal flora.In recent years,FMT has been applied to the treatment of some refractory diarrhea related to intestinal flora imbalance,such as recurrent clostridium difficile infection,inflammatory bowel disease,irritable bowel syndrome,and has achieved good results,but some problems have not been properly solved so far.This article reviews the mechanism of action of FMT in the treatment of refractory diarrhea,its clinical application,research progress and current problems.
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Objective To explore the role of TMAO from gut microbiota in non-alcoholic fatty liver disease(NAFLD),we detected the serum level of TMAO and its precursor metabolites in NAFLD,as well as the expression level of Eubacterium rectum,Bacteroidetes multiforme,Lactobacillus and bifidobacterium in the intestinal flora.Methods We collected 118 subjects and divided into NAFLD group(86 cases)and healthy control group(32 cases)randomly.We also detected the serum level of TMAO and its precursor metabolites in subjects by high performance liquid chromatography tandem mass spectrometry detection(LC-MS),and the expression of target bacterial DNA was detected by qRT-PCR.Results Serum TMAO,TMA and choline levels were significantly increased in NAFLD(P<0.05),and liver fat content was positively correlated with TMAO(P<0.05).The expression level of Lactobacillus and Eubacterium rectum in NAFLD group were increased(P<0.05);the expression level of Bifidobacterium and Bacteroides multiform were decreased(P<0.05).The serum TMAO level was positively correlated with Eubacterium rectum(r=0.280,P<0.05),and negatively correlated with Bifidobacterium(r=-0.332,P<0.05).Conclusion The level of TMAO in serum shows a positive correlation with NAFLD.The structure of intestinal flora in individuals with NAFLD is altered and linked to TMAO.This suggests that the intestinal flora may have a significant impact on the development of NAFLD through TMAO.
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BACKGROUND:Gut microbiota is closely related to host energy balance and metabolism.The metabolites of intestinal flora can regulate the occurrence and development of obesity and can be a new target for the prevention and treatment of obesity. OBJECTIVE:To summarize the interaction between the intestinal flora and obesity,as well as the specific mechanism underlying regulation of obesity by metabolites of intestinal flora,thereby providing a new reference and basis for the prevention and treatment of obesity. METHODS:"Intestinal microbiota,intestinal bacteria,intestinal microbiota metabolites,short-chain fatty acids,bile acids,ipopolysaccharide,trimethylamine N-oxide,medium-chain fatty acids,tryptophan derivatives,obesity"were used as search terms in Chinese and English.Literature related to obesity from 1990 to 2022 was retrieved in PubMed and CNKI databases.According to inclusion and exclusion criteria,88 articles were finally selected. RESULTS AND CONCLUSION:Intestinal flora is closely related to the occurrence and development of obesity.For example,changes in the Firmicutes to Bacteroidetes ratio can be used as a biomarker for the diagnosis of obesity,and the occurrence of obesity can be delayed by the colonization of probiotics such as Bifidobacterium breve,Lactobacillus and Akkermansia.Intestinal flora is mainly mediated by the metabolites of intestinal flora to participate in the regulation of obesity.For example,short-chain fatty acid can regulate adipogenesis by regulating signaling pathways such as G protein-coupled receptors 41,43 and peroxisome proliferator-activated receptor γ,thus delaying the occurrence and development of obesity.Bile acids can increase insulin sensitivity and body energy expenditure by promoting the activation of G protein-coupled receptor 5 and farnesol X receptor.In addition,lipopolysaccharide,trimethylamine oxide,medium-chain fatty acids and tryptophan derivatives are also widely involved in the occurrence and development of obesity through various signaling pathways.Further studies have found that metabolites of the same bacterial community exert heterogeneous effects in the specific process of regulating obesity via different signaling pathways.For example,under the influence of high-fat diet,acetic acids can activate the parasympathetic nervous system,leading to hyperphagia and liver insulin resistance and thus accelerating the physiological course of obesity.
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BACKGROUND:Exercise has a regulatory effect on intestinal flora dysbiosis,which can effectively protect the beneficial flora and improve the intestinal environment.However,the effect of treadmill exercise on the structure and diversity of intestinal microbial community in Parkinson's disease and the specific mechanism are not clear. OBJECTIVE:Using 16S rDNA technique to analyze the effect of treadmill exercise on the structure and diversity of the intestinal flora of rats with Parkinson's disease,and to investigate the mechanism of non-pharmacological treadmill exercise to improve Parkinson's disease. METHODS:Twelve of the 18 Sprague-Dawley rats were randomly selected to make animal models of Parkinson's disease using unilateral 2-point nigrostriatal injection of 6-hydroxydopamine.The remaining six rats were used as sham-operation group,which were injected with the same dose of saline containing 0.2%ascorbic acid using the same positioning and injection method.After successful modeling,12 rats with Parkinson's disease were randomly divided into model group and treadmill exercise group(n=6 per group).The treadmill exercise group was subjected to a middle and low intensity tread mill exercise,10 m/min,30 minutes per day,5 days per week for 4 weeks.Fresh feces were collected and stored in liquid nitrogen 24 hour after the last exercise session,and the changes in fecal flora were analyzed by 16S rDNA sequencing technique. RESULTS AND CONCLUSION:Treadmill exercise significantly improved behavior and nigrostriatal tyrosine hydroxylase-positive cell expression in rats with Parkinson's disease model and alleviated changes in the structure and diversity of the gut microbial community caused by Parkinson's disease,increased the number of operational taxonomic units and modulated Alpha and Beta diversity in rats.At the phylum and genus levels,the abundance ratio of Firmicutes/Bacteroidetes in the model group decreased compared with the sham-operated group,while beneficial bacteria such as Prevotella,Bacteroides,and Clostridium_XlV increased significantly after treadmill exercise.To conclude,treadmill exercise has a significant modulating effect on behavioral abnormalities,toxic damage to dopaminergic neurons and gut microbial imbalance caused by Parkinson's disease,alleviates the symptoms of flora-related diseases,and has a positive effect on the improvement of Parkinson's disease.
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BACKGROUND:Intestinal flora and its metabolites can participate in the pathological process of osteoporosis and play an important role in the diagnosis and treatment of osteoporosis.In addition,exercise can regulate the intestinal flora and thus affect the occurrence and development of osteoporosis. OBJECTIVE:To summarize the effects and mechanism of intestinal flora on osteoblasts,osteoclasts,and bone marrow mesenchymal stem cells,and the potential role of exercise-mediated intestinal flora in regulating osteoporosis. METHODS:"Intestinal flora,intestinal bacteria,metabolites of intestinal flora,bone metabolism,osteoporosis,exercise"were selected as keywords.Literatures from 1990 to 2023 were retrieved from PubMed and CNKI databases. RESULTS AND CONCLUSION:Changes in the abundance and diversity of intestinal flora and changes in the levels of intestinal flora metabolites such as trimethylamine oxide and bile acid can be used as biomarkers for the diagnosis of osteoporosis.The imbalance of intestinal flora can lead to intestinal barrier dysfunction and excessive production of lipopolysaccharides and trimethylamine oxide,induce the secretion of tumor necrosis factor-α and other inflammatory cytokines,activate the nuclear factor κB signaling pathway and aggravate oxidative stress,thus promoting osteoclast differentiation,inducing osteoblast apoptosis and affecting bone marrow mesenchymal cell migration.Remodeling intestinal flora homeostasis can inhibit inflammatory response,downregulate oxidative stress,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate the osteogenic migration of bone marrow mesenchymal cells to prevent and treat osteoporosis.Exercise can regulate intestinal flora homeostasis,improve intestinal barrier function,promote the secretion of short-chain fatty acids and bile acids,down-regulate serum lipopolysaccharide level,reduce oxidative stress,and then inhibit osteocyte apoptosis,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate osteocyte nutrient metabolism to exert the potential of preventing and treating osteoporosis.
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BACKGROUND:Osteonecrosis of the femoral head is a common and disabling disease,which is mainly characterized by microcirculation disorders and bone cell metabolism disorders.Luzhongjiangu decoction was developed by Shandong Academy of Chinese Medicine and used in the form of soup in the clinic,which has good efficacy in the treatment of osteonecrosis of the femoral head.However,its mechanism of action has not been clarified. OBJECTIVE:To study the effect mechanism of Luzhongjiangu decoction on intestinal flora in rats with osteonecrosis of the femoral head based on 16S rDNA sequencing technique. METHODS:The model of osteonecrosis of the femoral head was established in Wistar rats by intragastric administration of retinoic acid.The therapeutic effect of Luzhongjiangu decoction was evaluated by serum hormone,bone histopathology and serum hormone levels.16s rDNA sequencing technique was used to detect the intestinal flora of rats in the blank control group,model group and middle-dose Luzhongjiangu decoction group.The corresponding library was constructed and OTU clustering and microbial community diversity and abundance analysis were carried out to determine the composition of intestinal flora and the changes of species and diversity among groups. RESULTS AND CONCLUSION:Luzhongjiangu decoction could significantly increase the expression of osteocalcin,osteopontin and other osteogenic related factors,alleviate the destruction of bone trabeculae,increase bone mineral density,and had a significant therapeutic effect on osteonecrosis of the femoral head,of which the middle dose group showed the most significant effect.The results of intestinal flora sequencing showed that Luzhongjiangu decoction improved the flora disorder of rats with osteonecrosis of the femoral head to some extent,and screened out different colonies such as Bacillus,Desulfurizans,Desulfurization,Isobacteria,Bifidobacterium and so on;it could up-regulate the abundance of beneficial bacteria such as Bifidobacterium,down-regulate the abundance of harmful bacteria such as Desulfovibrio,and improve the structure of intestinal flora.Functional prediction analysis indicated that Luzhongjiangu decoction could mainly affect amino acid metabolism and energy metabolism.Correlation analysis showed that the differential bacteria of Bifidobacterium and Intestinimonas in the middle dose group of Luzhongjiangu decoction were positively correlated with vitamin D3,estradiol and calcitonin,and negatively correlated with prostaglandin E2.In the model group,Escherichia-Shigella,Desulfovibrio,Globicatella and Streptococcus were positively correlated with prostaglandin E2 and negatively correlated with vitamin D3,estradiol and calcitonin.To conclude,Luzhongjiangu decoction may play a role in the treatment of osteonecrosis of the femoral head by regulating the structure of intestinal flora,up-regulating the abundance of beneficial bacteria and affecting the secretion of vitamin D3,estradiol,calcitonin and prostaglandin E2.
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AIM:To investigate the therapeutic effect of menstrual blood-derived endometrial stem cells(MenSCs)on chemotherapy-induced intestinal mucositis and flora disorders in mice,and to explore the potential mecha-nism.METHODS:The mice were randomly divided into 3 groups including normal treatment,cisplatin(Cis)treatment and Cis+MenSC treatment,with 10 mice in each group.To induce intestinal mucositis,the mice were treated with Cis(2 mg·kg-1·d-1)by intraperitoneal injection for 5 consecutive days.Control mice for normal group were received equal vol-umes of normal saline.For Cis+MenSC treatment,MenSCs(1×106)was transplanted into the mice of Cis treated mice through tail vein.The performances and weight changes of mice were examined during the experiment.After the treat-ment,the small intestine and colon were isolated for subsequent HE staining,the ratio of F4/80 and IL-6 positive cells in small intestine were detected by immunohistochemical staining,and the expression of tight junction,inflammation and apoptosis related proteins was detected by Western blot.16S rDNA amplicon sequencing was performed to detect the diver-sity and richness of intestinal flora in mice.RESULTS:Compared to the Cis group,the MenSCs-treated mice showed sig-nificantly increased body weight,relieved intestinal lymphocytes infiltration,alleviated intestinal villous edema,and or-derly arranged glands in intestinal tissues.Further analysis indicated that MenSCs transplantation significantly up-regulat-ed the expression of intestinal tight junction related proteins ZO-1 and occludin in Cis-treated mice(P＜0.05).Subse-quently,MenSCs transplantation significantly inhibited the macrophages infiltration in intestinal tissues(P＜0.01),down-regulated the expression of pro-inflammatory factors IL-1 and IL-6 and pro-apoptotic protein Bax(P＜0.01),while up-regu-lated anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2(P＜0.01).Additionally,further microflora sequenc-ing indicated that MenSCs transplantation prevented mice from Cis-induced intestinal flora disorder,and significantly re-duced the abundance of harmful bacteria such as isenbergiella tayi and Anaerotruncus colihominis(P＜0.01).At the same time,the abundance of beneficial bacteria Lactobacillus apodemi was increased(P＜0.05),thereby restoring the composi-tion and function of healthy intestinal flora.CONCLUSION:MenSCs transplantation alleviates the chemotherapy-in-duced damage of intestinal structure,relieves the symptoms of chemotherapy-induced mucositis and restores the homeosta-sis of intestinal flora in mice.
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@#The treatment of patients with advanced lung cancer has been revolutionized with the advent of immunotherapy. However, not all patients can benefit equally from immunotherapy. In recent years, the relationship between intestinal flora and the efficacy of immunotherapy has gradually attracted scholars' attention. During the treatment of immune checkpoint inhibitors, the use of antibiotics, proton pump inhibitors and other drugs will affect the patient's intestinal flora, thus affecting the efficacy of immune checkpoint inhibitors, leading to poor prognosis of patients. This review will discuss that antibiotics and proton pump inhibitors reduce the efficacy of immunotherapy by affecting the diversity of intestinal flora, in order to facilitate the rational use of related drugs in clinical practice and improve the patient's outcomes.
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With the increasing prevalence of diabetes, the prevention and treatment of diabetes nephropathy have become a worldwide problem. The molecular mechanism of the occurrence and development of diabetes nephropathy is still unclear, but many studies in recent years have shown that gut microbiota plays an important role in the progress on diabetes nephropathy. The research progress on the mechanism of gut microbiota participating in diabetes nephropathy was reviewed in this article.
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ObjectiveTo explore the interaction between bruceoside B and gut microbiota and the inhibitory activity of its metabolites on human lung cancer A549 cells， and to explore the value of bruceoside B in the treatment of non-small cell lung cancer（NSCLC）. MethodBruceoside B was co-incubated with the human gut microbiota under anoxic conditions in vitro， and ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to analyze the metabolic transformation products. Cell counting kit-8（CCK-8） assay was performed to determine the effects of bruceoside B and its metabolites on the proliferation of human lung cancer A549 cells and the half inhibitory concentration（IC50） was calculated. Five healthy male rats were gavaged with bruceoside B（2 mg·kg-1） for 7 days after adaptive feeding. The feces of rats were collected before and after administration. 16S rRNA sequencing was used to assess gut microbiota. ResultBruceoside B was mainly metabolized to brusatol by human gut microbiota， the IC50 of bruceoside B and the conversion product to A549 cells were 1 755.50， 19.57 μmol·L-1， respectively， and the conversion product had a better activity at inhibiting A549 cells proliferation than bruceoside B. Additionally， The results of intestinal flora analysis showed no significant differences in α diversity and β diversity of gut microbiota after administration. In terms of species abundance， at the phylum level， bruceoside B decreased the relative abundance of Actinobacteriota and Proteobacteria， increased the relative abundance of Firmicutes， Patescibacteria and Cyanobacteria. At the genus level， bruceoside B decreased the relative abundance of Staphylococcus， Aerococcus and Psychrobacter， increased the relative abundance of Romboutsia， Lactobacillus， Clostridium sensu stricto 1， Norank-f-norank-o-Clostridia-UCG-014， Turicibacter， Allobaculum and Candidatus Saccharimonas. The results of functional prediction showed that the gut microbiota functional compositions were relatively stable. ConclusionBruceoside B can be deglycosylated by intestinal flora and converted into brusatol， with a significant increase in antitumor activity. The administration of bruceoside B will not cause significant changes in the structure and function of the intestinal flora， resulting in intestinal microecological balance disorders， and the administration appears to be beneficial to the intestinal flora of NSCLC patients.
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ObjectiveTo explore the possible mechanism of Bushen Huoxue Formula （补肾活血方， BHF） in the treatment of Parkinson's disease （PD） from the the perspective of intestinal flora. MethodsSeventy-two male C57/BL6J mice were randomly divided into blank group， model group， Madopar group and low-， medium- and high-dose BHF groups， with 12 mice in each group. The mice in the blank group were intraperitoneally injected with 10 ml/kg of normal saline， and those in the other groups were intraperitoneally injected with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 3 mg/ml to induce PD mice model， both once a day for 7 consecutive days. After successful modeling， the low-， medium-， and high-dose BHF groups were given 7.5， 15， and 30 g/（kg·d） of BHF by gavage， respectively， while the Madopar group was given 112.5 mg/（kg ·d） of Domedopar tablets by gavage， and the blank group and the model group were given 15 ml/（kg·d） of distilled water， all once a day for 14 consecutive days. The rod climbing test， rotating rod test， grip strength test and weight-bearing swimming test were used to evaluate the behavioral indicators of mice. Western blotting was used to measure the protein expression levels of Toll-like receptor （TLR）/nuclear factor kappa B （NF-κB） pathway inflammatory factors in the mouse ileum， including Toll-like receptor 2 （TLR2）， Toll-like receptor 4 （TLR4）， NF-κB， tumor necrosis factor α （TNF-α）， interleukin 6 （IL-6）， and interleukin 17 （IL- 17）. 16S rRNA high-throughput sequencing was used to analyze changes in mouse intestinal flora. ResultsCompared to those in the blank group， the mice in the model group had longer bottoming time when climbing the pole， reduced grip strength， shortened rotary pole duration and swimming duration， and increased protein expression levels of TLR2， TLR4， NF-κB， TNF-α， and IL-6 in the ileal tissue （P＜0.01）. Compared to the model group， the Madopar group and the low-， medium- and high-dose BHF groups had shortened bottoming time of the climbing pole and increased grip strength； the Madopar group and the high-dose BHF group had prolonged rotary pole duration， and reduced protein expressions of TLR2， TLR4， NF-κB， TNF-α， IL-6， and IL-17 levels； and only the high-dose BHF group had prolonged swimming duration （P＜0.05 or P＜0.01）. Compared to those in the low-dose BHF group， the bottoming time of the climbing pole were shorter in the moderate- and high-dose groups （P＜0.05 or P＜0.01）， and the grip strength increased while the protein expression levels of TLR2， TLR4 and IL-17 decreased in the high-dose group （P＜0.05 or P＜0.01）. The intestinal flora results showed significant differences between the blank group and the model group in the Dominance index， Pielou_e index， Shannon index， and Simpson index （P＜0.05 or P＜0.01）. Compared to those of the model group， the Shannon index， Chao1 index， and Observed_otus index of the Madopar group， as well as the Chao1 index， Observed_otus index， Dominance index， Pielou_e index， Shannon index， and Simpson index of the high-dose BHF group all showed significantly statistical differences （P＜0.05 or P＜0.01）. At the phylum level， the relative abundance categories of bacterial phyla with statistically significant differences in each group included Proteobacteria， Bacteroidetes， and Firmicutes （P＜0.05 or P＜0.01）. At the genus level， the relative abundance categories of bacterial genera with statistically significant diffe-rences among each group included Muribaculaceae， Akkermansia， and Helicobacter pylori （P＜0.05 or P＜0.01）. ConclusionThe possible mechanism of BHF in treating PD may be to reconstruct the disordered intestinal flora structure and improve the inflammatory response.