Microbiome and metabolome dysbiosis analysis in impaired glucose tolerance for the prediction of progression to diabetes mellitus

Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders;however,comprehensive studies on impaired glucose tolerance(IGT),a diabetes mellitus(DM)precursor,are lacking.Here,we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance(NGT);patients with IGT are followed up after 4 years for progression to DM.Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT,DM,and NGT groups.In addition,13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM,including higher levels of Eggerthella unclassified,Coprobacillus unclassified,Clostridium ramosum,L-valine,L-norleucine,and L-isoleucine,and lower levels of Eubacterium eligens,Bacteroides faecis,Lachnospiraceae bacterium 3_1_46FAA,Alistipes senegalensis,Megaspaera elsdenii,Clostridium perfringens,α-linolenic acid,10E,12Z-octadecadienoic acid,and dodecanoic acid.A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM(AUC=0.87).These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.

评价散寒化湿颗粒与奈玛特韦-利托那韦对照治疗轻型/中型新型冠状病毒感染有效性和安全性的随机、开放、多中心临床研究

Sanhan Huashi granules(SHG)demonstrated therapeutic effects against coronavirus disease 2019(COVID-19)in observational studies.In order to compare the effectiveness and safety of SHG and nirmatrelvir–ritonavir in treating adults with mild-to-moderate COVID-19,we conducted a randomized,activecontrolled,open-label,multi-center trial conducted between February and July in 2023.The patients were randomized in a 1:1 ratio to the SHG group and the nirmatrelvir–ritonavir group.A total of 400participants were randomized,among which 200 participants ultimately received SHG and 198 received nirmatrelvir–ritonavir.The primary outcome was time to sustained clinical recovery through day 28.SHG significantly shortened the median time to sustained clinical recovery compared to nirmatrelvir–ritonavir(6.0(95%CI,5.0 to 6.0)vs.8.0(95%CI,6.0 to 9.0)d;P=0.001),particularly for individual symptoms including fever,sore throat,cough and fatigue.No participants in either group died and incidence of severe COVID-19 showed no difference between two groups.Participants who received nirmatrelvir–ritonavir demonstrated a higher rate of virus clearance on day 5 compared to those received SHG(46.4%(95%CI,39.1 to 53.7)vs.65.6%(95%CI,58.3 to 72.4);P<0.001).Most adverse events were mild in both groups.In summary,SHG was superior to nirmatrelvir–ritonavir in shortening the time to sustained clinical recovery in participants with mild-to-moderate COVID-19,despite a lower virus clearance rate observed after 5 d of treatment(Chinese Clinical Trial Registry Identifier:Chi CTR2300067872).

Double-blinded,randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia

Background:Accumulating evidence suggests that metabolic disorders,including type 2 diabetes mellitus(T2DM),can be treated with traditional Chinese medicine formulas,such as the Gegen Qinlian decoction(GQD).This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD.Methods:We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM.During the 12-week intervention,anthropometric measurements and diabetic traits were recorded every 4 weeks.Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing,liquid chromatography-mass spectrometry,and Bio-Plex panels.Results:Anti-diabetic effects were observed in the GQD group in the human trial.Specifically,glycated hemoglobin,fasting plasma glucose,and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group.Additionally,Faecalibacterium was significantly enriched in the GQD group,and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group.Moreover,Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin,fasting plasma glucose,and pro-inflammatory cytokines.Finally,the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzi(DSMZ 17677)in T2DMmousemodel.Conclusions:GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota,alleviating metabolic disorders and the inflammatory state.

脏腑风湿理论在自身免疫性疾病中的应用

自身免疫性疾病具有“发作期—缓解期”反复交替的病程特点,病原体感染、温度等环境因素是导致其发生与加重的重要因素。脏腑风湿理论是基于传统中医“痹证”“伏邪”理论所创立的新学说,涵盖了以外感风寒湿等外邪为始动因素的多种疾病,强调外邪伏留致病的重要作用,可为自身免疫性疾病的认识和治疗提供重要思路。本文基于中医学理论、基础研究和流行病学证据,系统论述了脏腑风湿理论在自身免疫性疾病中的应用,为其提供中医药有效治疗方法。并提出未来应进一步加强有效方药临床研究,补充高等级循证医学证据;通过表型组学等手段,揭示“新感”与“伏邪”等中医宏观概念的免疫学本质;通过现代中药药理及多组学技术,探究有效中药复方的内在机制,筛选有效药物成分及治疗靶标,从而切实提升自身免疫性疾病临床疗效,促进本领域中西医融合发展。

Practice and principle of traditional Chinese medicine for the prevention and treatment of COVID-19

Traditional Chinese medicine(TCM)has played an important role in the prevention and treatment of Coronavirus disease 2019(COVID-19)epidemic in China.The integration of Chinese and Western medicine is an important feature of Chinese COVID-19 prevention and treatment.According to a series of evidence-based studies,TCM can reduce the infection rate of severe acute respiratory syndrome coronavirus 2 in high-risk groups.For patients with mild and moderate forms of COVID-19,TCM can relieve the related signs and symptoms,shorten the period of nucleic-acid negative conversion,and reduce conversion rate to the severe form of the disease.For COVID-19 patients with severe and critical illnesses,TCM can improve inflammatory indicators and blood oxygen saturation,shorten the hospital stay,and reduce the mortality rate.During recovery,TCM can improve patients’symptoms,promote organ function recovery,boost the quality of patients’life,and reduce the nucleic-acid repositive conversion rate.A series of mechanism research studies revealed that capability of TCM to treat COVID-19 through antiviral and anti-inflammatory effects,immune regulation,and protection of organ function via a multicomponent,multitarget,and multipathway approach.

Antidiabetic Effects of Gegen Qinlian Decoction via the Gut Microbiota Are Attributable to Its Key Ingredient Berberine

Gegen Qinlian Decoction(GQD),a traditional Chinese medicine(TCM)formula,has long been used for the treatment of common metabolic diseases,including type 2 diabetes mellitus.However,the main limitation of its wider application is ingredient complexity of this formula.Thus,it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action.Here,we compared the effects of GQD and berberine,a hypothetical key active pharmaceutical ingredient of GQD,on a diabetic rat model by comprehensive analyses of gut microbiota,short-chain fatty acids,proinflammatory cytokines,and ileum transcriptomics.Our results show that berberine and GQD had similar effects on lowering blood glucose levels,modulating gut microbiota,inducing ileal gene expression,as well as relieving systemic and local inflammation.As expected,both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria,including Faecalibacterium and Roseburia,thereby attenuating intestinal inflammation and lowering glucose.Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD.Moreover,concentration of serum proinflammatory cytokines and expression of immune-related genes,including Nfkb1,Stat1,and Ifnrg1,in pancreatic islets were significantly reduced after treatment.Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota.The strategy employed would facilitate further standardization and widespread application of TCM in many diseases.

The role played by traditional Chinese medicine in preventing and treating COVID-19 in China

Traditional Chinese medicine(TCM),an ancient system of alternative medicine,played an active role in the prevention and control of COVID-19 in China.It improved the clinical symptoms of patients,reduced the mortality rate,improved the recovery rate,and effectively relieved the operating pressure on the national medical system during critical conditions.In light of the current global pandemic,TCM-related measures might open up a new channel in the control of COVID-19 in other countries and regions.Here,we summarize the TCM-related measures that were widely used in China,including TCM guidelines,the Wuchang pattern,mobile cabin hospitals,integrated treatment of TCM and modern medicine for critical patients,and non-medicine therapy for convalescent patients,and describe how TCM effectively treated patients afflicted with the COVID-19.Effective TCM therapies could,therefore,be recommended and practiced based on the existing medical evidence from increased scientific studies.

Essential factors of Sui Zheng Shi Liang strategy in Type 2 diabetes treatment assessed by questionnaire

OBJECTIVE: Sui Zheng Shi Liang strategy (regulating prescription dosage with different syndromes) is an important part of syndrome differentiation and treatment in Traditional Chinese Medicine (TCM). Questionnaires were given to doctors and patients to study the essential factors (indicators and timing) of Sui Zheng Shi Liang strategy in the treatment process of type 2 diabetes (T2DM). METHODS: Two questionnaires were designed for diabetes patients and their doctors. The questionnaires included the most important indicators for determining the patient's condition, the ability of TCM in treating T2DM, the length of time it takes for TCM to be effective, and when to adjust the prescription dosage.The frequency of answers was calculated, summarized, and analyzed after the survey. RESULTS: Twenty questionnaires from doctors and 90 questionnaires from patients were included in the analysis. Doctors and patients recognized thatTCM could decrease blood glucose, improve syndromes, and delay complications. Doctors were mainly concerned about glycosylated hemoglobin, while the patients were concerned about fasting plasma glucose for determining whether treatment was effective. Doctors also paid attention to changes in blood sugar and syndromes 2 weeks after medication was given as the indication to adjust the prescription dosage, while patients were concerned about these factors in 4 weeks.The prescription should be regulated when there are side effects or the medication is ineffective. CONCLUSION: The essential factor in the treatment process of T2DM in Sui Zheng Shi Liang strategy is that if fasting blood glucose level did not decrease after 4 weeks of treatment, the Chinese medicine prescription should be adjusted.

Distinct gut microbiota and health outcomes in asymptomatic infection,viral nucleic acid test re-positive,and convalescent COVID-19 cases

Gut microbiota composition is suggested to associate with coronavirus disease 2019(COVID-19)severity,but the impact of gut microbiota on health outcomes is largely unclear.We recruited 81 individuals from Wuhan,China,including 13 asymptomatic infection cases(Group A),24 COVID-19 convalescents with adverse outcomes(Group C),31 severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)re-positive cases(Group D),and 13 non-COVID-19 healthy controls(Group H).The microbial features of Groups A and D were similar and exhibited higher gut microbial diversity and more abundant short-chain fatty acid(SCFA)-producing species than Group C.Group C was enriched with opportunistic pathogens and virulence factors related to adhesion and toxin production.The abundance of SCFA-producing species was negatively correlated,while Escherichia coli was positively correlated with adverse outcomes.All three groups(A,C,and D)were enriched with the mucusdegrading species Akkermansia muciniphila,but decreased with Bacteroides-encoded carbohydrate-active enzymes.The pathways of vitamin B6 metabolic and folate biosynthesis were decreased,while selenocompound metabolism was increased in the three groups.Specifically,the secondary bile acid(BA)metabolic pathway was enriched in Group A.Antibiotic resistance genes were common among the three groups.Conclusively,the gut microbiota was related to the health outcomes of COVID-19.Dietary supplementations(SCFAs,BA,selenium,folate,vitamin B6)may be beneficial to COVID-19 patients.