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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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Objective:To study the changes of intestinal flora before and after dietary intervention in pregnant women with gestational diabetes mellitus (GDM) and explore its correlation with the results of oral glucose tolerance test (OGTT), using third generation high-throughput sequencing of full-length 16S rDNA.Methods:Thirty pregnant women who received regular antenatal care in the First Affiliated Hospital of Xinjiang Medical University between July 2022 and March 2023 were selected. Demographic data and laboratory examination results of these pregnant women were collected. The pregnant women with GDM (the GDM group) were given individualized dietary intervention, while the control group were given routine dietary guidance, for a total of 2 weeks. The stool was collected before and after the intervention in both groups, and a total of 60 stool samples were collected. Through the PacBio Sequencing platform, the third generation sequencing of full-length 16S rDNA was utilized to investigate the intestinal microbiome diversity. The composition, abundance and diversity of intestinal flora were compared between groups, both before and after the intervention.Results:There were 74 species showing significant differences in abundance between the two groups of pregnant women, 54 of which were enriched in the GDM group. The correlation analysis of blood glucose levels tested by OGTT as an environmental factor showed that Lachnospirales ( P=0.002) and unclassified Bacteria ( P=0.035) were positively correlated with OGTT-0h blood glucose ( P<0.05), while Christensenellales ( P=0.018)and Oscillospirales ( P=0.045) negatively. Lachnospirales ( P=0.027)and unclassified Bacteria ( P=0.028) were positively correlated with OGTT-1 h blood glucose ( P<0.05), while Oscillospirales ( P=0.025) negatively. There was a positive correlation between Lachnospirales ( P=0.027) and OGTT-2h blood glucose ( P<0.05). Conclusions:After the individualized diet intervention, the dominant bacteria of the intestinal flora changed and the fasting blood glucose of declined in pregnant women with GDM. It's a reasonable presumption that individualized diet intervention can contribute to the regulation of the disordered intestinal flora in pregnant women with GDM, which implies a role of dietary intervention in the treatment of GDM.
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Objective To optimize the method of combining azomethane oxide(AOM)and dextran sodium sulfate(DSS)to create a colitis-associated colon cancer(CAC)model,and to explore the pathogenesis of the intestinal flora in CAC.Methods Model groups A and B were established by one and two injections of AOM,respectively,combined with free drinking of DSS,and a normal control group was injected intraperitoneally with normal saline combined with purified water(n=10 mice per group).The better modeling scheme was selected by comprehensive evaluation of the disease activity index score,colon length,tumor rate,and mortality.Serum levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and tumor markers CA199,CEA,and CA724 were detected by enzyme-linked immunosorbent assay.Colon lesions were evaluated by hematoxylin and eosin(HE)staining.Changes in the intestinal microbiota in CAC mice were detected by 16S rDNA high-throughput gene sequencing analysis of mouse feces.Results Both single and enhanced AOM injections combined with DSS induced CAC mice;however,colon growths were larger,more closely arranged,and their morphological size was more consistent in group B compared with group A,with a tumor-formation rate of 100％.IL-6 levels were increased in the model group compared with the normal group(P＜0.05).TNF-α levels were increased in the model group compared with the normal group(P＞0.05).The CA199 and CEA levels were also significantly increased(P＜0.05),but CA724 levels were not.Infiltration of inflammatory cells in the colon detected by HE pathology was accompanied by high-grade intraepithelial tumor-like changes on the surface of the lumen.The diversity and abundance of intestinal bacteria were decreased in CAC mice compared with normal mice:phyla Verrucomicrobiota and Actinobacteriota were significantly increased(P＜0.05),Bacteroidota and Campilobacterota were significantly decreased(P＜0.05).Akkermansia,Prevotellaceae,Ruminococcus,and Bifidobacterium were significantly increased(P＜0.05),and Roseburia,Rikenellaceae_RC9_gut_group,Anaeroplasma,and Muribaculaceae were significantly decreased(P＜0.05).Conclusions Two injections of AOM combined with 1.5％(1.5 g/100 mL)DSS induced CAC model mice with a high colon-tumorigenesis rate,uniform tumor morphology,and low mortality,and may thus be the preferred modeling scheme for pharmacodynamic experiments.Disorders or dysfunction of the intestinal flora may lead to increased permeability,loss of intestinal mucosal barrier function,and the release of enterogenic endotoxins,Resultsing in a sustained inflammatory response,as an indirect or direct cause of CAC pathogenesis.
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Objective To investigate the effect of vitamin D(VD)on intestinal flora in spontaneously diabetic rats.Methods Zucker diabetic fatty rats(ZDF rats)were randomised to control(Con)group,VD control(VD)group,model(T2DM)group,and VD intervention(VD+T2DM)group.Fasting blood glucose profiles and oral glucose tolerance levels were determined in rats of each group.16S rDNA sequencing was used to assess changes in rat intestinal flora.OTU analysis(Venn diagram),α diversity analysis(chao1,observed species,PD whole tree,and shannon and simpson),βdiversity analysis(principal coordinate analysis(PCoA)),flora structure,and colony species variability analysis(linear discriminant analysis and influence factor(LEfSe)analysis)were also performed.Results VD intervention significantly improved fasting blood glucose levels and insulin resistance in T2DM rats(P＜0.05).α diversity showed no significant differences in chao1,observed species,PD whole tree,and shannon and simpson indices between T2DM and VD+T2DM groups(P＞0.05).β diversity analysis showed that the VD+T2DM group had more species similarity to the Con group than the T2DM group.The dominant bacteria of rat intestinal flora in each group were significantly different.In comparison to the T2DM group,the VD+T2DM group showed a decrease in abundance of Bacteroidetes and increases in abundances of Firmicutes and Clostridium XIVa.Conclusions VD improves fasting glucose elevation and insulin resistance in T2DM rats.VD improves the structure of intestinal flora,decreases Bacteroidetes,and elevates Firmicutes and Clostridium XIVa abundances in T2DM rats.
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Objective To compare the differences in the composition and diversity of intestinal flora between knee osteoarthritis(KOA)patients with dampness-heat obstruction syndrome,cold-dampness blockage syndrome and healthy people;To explore the characteristics of intestinal flora of KOA patients with the above two TCM syndrome types.Methods According to the inclusion and exclusion criteria,dampness-heat obstruction syndrome group,cold-dampness blockage syndrome group,and healthy control group were screened,with 10 cases for each group,and then their fecal samples were collected.16S rDNA sequencing technology was used to compare the differences of intestinal flora among groups by Alpha and Beta diversity analysis.Results There was no significant difference in species richness of intestinal flora among the three groups,but there was statistical significance in species diversity between cold-dampness blockage syndrome group and dampness-heat obstruction syndrome group,and healthy control group(P<0.05).There were statistical significance among the three groups in intestinal flora composition(P= 0.001).At the phylum level,Bacteroidota and Firmicutes were significantly dominant,and at genus level,the abundance of Prevotella in dampness-heat obstruction syndrome group and cold-dampness blockage syndrome group increased.The abundance of Enterobacteriaceae,Lachnospira and Klebsiella was relatively large in dampness-heat obstruction syndrome group.The abundance of Prevotella and Pseudomonas in cold-dampness blockage syndrome group was large.Conclusion There are differences in the intestinal flora structure between KOA patients with dampness-heat obstruction syndrome and cold-dampness blockage syndrome.
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There is a bidirectional relationship between intestinal flora and bile acids,and the imbalance of intestinal flora-bile acid axis metabolism is closely related to hypertension.Based on classical TCM literature and clinical practice,this article found that"earth deficiency"is the important pathological basis of hypertension,"wood depression"is the initiating factor of hypertension,and"earth deficiency and wood depression"is the key pathogenesis of hypertension.Combined with the research results of modern medicine and molecular biology,it is considered that the imbalance of intestinal flora and abnormal bile acid metabolism are closely related to the"earth deficiency"and"wood depression"of TCM respectively,and the imbalance of intestinal flora-bile acid axis coincides with the"earth deficiency and wood depression"of TCM in the process of hypertension.It is of great theoretical and practical significance to explore the biological connotation of hypertension"earth deficiency and wood depression"from the perspective of intestinal flora-bile acid axis for guiding TCM to prevent and treat hypertension.
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Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.
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Colorectal cancer is a common clinical malignant tumor. As the main therapeutic method of colorectal cancer, radiotherapy has a good inhibitory effect on tumor progression. In recent years, because of its good physical and biological advantages, carbon ion has shown better clinical efficacy than traditional radiotherapy in the treatment of local recurrence or distant metastasis of colorectal cancer. In this article, basic and clinical studies related to the efficacy of carbon ion therapy for the recurrence of colorectal cancer in recent years were reviewed, aiming to provide theoretical basis for preventing and reducing adverse reactions after radiotherapy and prolonging the survival of colorectal cancer patients.
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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.
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ObjectiveTo clarify the relationship between intestinal flora and intestinal motility in rats with slow transit constipation （STC） and qi stagnation syndrome by conducting a pseudo-sterile experiment and fecal microbiota transplantation （FMT） technology. MethodsTwenty-four Wistar rats were randomly divided into normal group （n=6）， STC with qi stagnation pattern group （n=6） and pseudo-sterile group （n=12）. In the STC group with qi stagnation pattern， 3 mg/kg of loperamide suspension by intragastric administration combined with tail clamping stimulation were performed to establish the rat model of STC with qi stagnation pattern. After successful modeling， fresh feces from the rats in the STC with qi stagnation pattern group and the normal group were collected to prepare 100 mg/ml of fecal bacterial suspension. In the pseudo-sterile group， the antibiotic cocktail method was used （a mixed antibiotic suspension containing bacitracin， streptomycin sulfate， and neomycin sulfate at 20 mg/ml each was administered intragastrically） to establish pseudo-sterile rats model. After successful modeling， the rats were randomly divided into normal fecal bacterial liquid group and STC with qi stagnation pattern fecal bacterial liquid group， with six rats in each group， and then were given 10 ml/kg of the prepared corresponding rat fecal bacterial suspension by gavage. Rats in STC with qi stagnation pattern group were given an equal volume of sterile water by gavage. All groups were administered once a day for 7 consecutive days. The small intestinal propulsion rate of the STC with qi stagnation pattern group， the normal fecal bacterial liquid group， and STC with qi stagnation pattern fecal bacterial liquid group were compared. ELISA method was used to detect serum 5-hydroxytryptamine （5-HT） levels. Immunohistochemistry was used to detect the positive expression levels of 5-hydroxytryptamine 3 receptor （5-HT3R） and 5-hydroxytryptamine 4 receptor （5-HT4R） in colon tissue. Western blot method was used to detect the protein expression levels of tryptophan hydroxylase 1 （TPH1）， tryptophan hydroxylase 2 （TPH2）， serotonin transporter （SERT）， and monoamine oxidase A （MAO-A） in colon tissue. ResultsCompared to those in the normal fecal bacterial liquid group， the small intestinal propulsion rate， serum 5-HT level， positive expression of 5-HT3R and 5-HT4R in colon tissue， and protein expression of TPH1， TPH2， SERT and MAO-A significantly decreased in the STC with qi stagnation pattern group and STC with qi stagnation pattern fecal bacterial liquid group （P＜0.05）. There was no statistically significant difference in the indicators between the STC with qi stagnation pattern group and STC with qi stagnation pattern fecal bacterial liquid group （P＞0.05）. ConclusionThe intestinal flora in STC rats with qi stagnation pattern can lead to a slowdown in intestinal transmission function， whose mechanism may be related to intestinal motility disorders affected by the synthesis， transport， metabolism and other pathways of 5-HT.
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ObjectiveTo investigate the effect of Fuhe Decoction （敷和汤） with different doses of Suanzaoren （Ziziphus jujuba） for atopic dermatitis （AD）. MethodsForty-eight female BALB/c mice were randomly divided into normal group， model group， loratadine group， and Fuhe Decoction groups with high， medium， and low doses of Fuhe Decoction （Fuhe Decoction high-， medium-， and low-dose groups）， with eight mice in each group. The AD model was prepared by continuous stimulation with 2，4-dinitrofluorobenzene （DNFB） in all groups but the normal group. After modelling， the Fuhe Decoction high-， medium- and low-dose groups were given 24， 18 and 15 g/（kg·d） of Fuhe Decoction， the loratadine group was given 0.001 g/（kg·d） of loratadine dry suspension， and the normal group and the model group were given 10 ml/（kg·d） of normal saline by gavage. All groups were gavaged for 14 days. The number of scratches within 10 min and the score of skin lesions were observed on the 7th and 14th days of modelling and on the 7th and 14th days of drug administration， respectively； serum immunoglobulin E （IgE） was detected by ELISA； the histopathological and morphological changes of the skin were observed by HE staining； and the diversity and abundance of intestinal flora were detected by 16S rRNA sequencing of fecal matter from the colon of the mice. ResultsCompared with the normal group， mice in the model group on the 7th day and the 14th day of modelling and the 7th day， the 14th day of gavage showed increased scratching within 10 min and higher skin lesion scores （P＜0.05）， with hyperkeratotic or incomplete epidermis， marked thickening of spiny cells， and a large number of inflammatory cells infiltrated in the mice after gavage； serum levels of IgE elevated （P＜0.05）， and the abundance of Bacillota decreased， that of the Bacteroidota and bacteria elevated， and relative abundance of Lactobacillus spp. and Prevotella spp. decreased， and relative abundance of Anaplasma spp. and Treponema spp. increased （P＜0.05）. Compared with the model group， the number of scratches within 10 min and the skin lesion scores of mice in the loratadine group and the Fuhe Decoction medium- and high-dose groups decreased on the 7th day and the 14th day of gavage （P＜0.05）， serum IgE reduced， and the bacteria reduced in the loratadine group， the abundance of Bacteroidesmus spp. increased and Bacteriodesmus spp. decreased in the medium-dose group of Fuhe Decoction， the abundance of Bacteriodesmus spp. decreased in the loratadine group， the abundance of Bacteriodesmus spp. decreased， and that of both Lactobacillus spp. and Prevotella spp. increased in Fuhe Decoction medium-dose group （P＜0.05）. Compared with the loratadine group， the skin lesion scores increased in Fuhe Decoction low-dose group， and the number of scratching increased in the Fuhe Decoction low- and high-dose groups on the 7th day and the 14th day of gavage； the IgE content increased in Fuhe Decoction low-dose group， the Bacillota increased and the Bacteroidota decreased， the Lactobacillus spp. and Prevotella spp. increased in Fuhe Decoction middle-dose group， and Anopheles spp. increased in Fuhe Decoction high-dose group after gavage （P＜0.05）. ConclusionFuhe Decoction can improve the clinical symptoms of AD， regulate the relative abundance of intestinal flora to correct the disorders of the bacterial flora， among which the effect of Fuhe Decoction medium-dose group is optimal and comparable to that of the loratadine group， and the reduction of serum IgE inflammatory response may be one of its mechanisms of action.
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ObjectiveTo investigate the effects of probiotics combined with bismuth quadruple therapy （BQT） on clinical efficacy、gastrointestinal adverse reactions and intestinal flora in Helicobacter pylori （HP） positive patients. MethodsThe patients who were positive for HP from May 2023 to July 2023 in the department of gastroenterology of Shanghai first people's hospital were randomly divided into2 groups with 40 people in each group. The probiotic group was given 2 weeks of quadruple therapy with probiotics and standard BQT， followed by 4 weeks of oral probiotics after quadruple discontinuation. The placebo group was given 2 weeks of probiotic placebo and standard BQT， followed by 4 weeks of oral probiotic placebo. 13C urea breath test was used to evaluate the clinical efficacy， gastrointestinal symptoms rating Scale was used to evaluate the gastrointestinal adverse reactions of patients before and after the intervention， and microbial diversity 16S rDNA sequencing technology was used to detect the level of intestinal flora of patients before and after the intervention. ResultsThere was no significant difference in the eradication rate between the two groups （P>0.05）. Before the intervention， there was no significant difference in the scores of the gastrointestinal symptom rating scale between the probiotic group and the placebo group. After the intervention， patients in the probiotic group had significantly lower pain scores on acid reflux （1.10±0.30 vs 1.35±0.53， P<0.05） and stomach or abdominal hunger than in the placebo group （1.07±0.26 vs 1.30±0.52， P<0.05）. Through the before-and-after comparison of the probiotic group， the scores of abdominal pain （1.24±0.44 vs 1.58±0.71， P<0.05）， stomach or abdominal hunger （1.07±0.26 vs 1.27±0.45， P<0.05） and dry and hard stool （1.24±0.49 vs 1.48±0.75，P<0.05） were significantly lower in the probiotic group than before the intervention in the probiotic group. ConclusionProbiotics combined with BQT can improve the gastrointestinal adverse reactions and intestinal flora disorders in the process of quadruple drug therapy， but it does not improve the eradication rate of HP.
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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.