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

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

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

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

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

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

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

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

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

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

The relationship between enteral nutrition-related diarrhea and intestinal flora in critically ill patients and the effect of microflora transplantation / 中国医师进修杂志

Objective:To investigate the relationship between enteral nutrition-related diarrhea and intestinal flora in critically ill patients and the effect of microflora transplantation.Methods:A total of 60 critically ill patients with enteral nutrition-related diarrhea who were scheduled to undergo microflora transplantation in Taizhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2020 to August 2021 were prospectively and continuously selected as the research group, and 60 critically ill patients without enteral nutrition-related diarrhea were selected as the control group. The bacterial count of 4 kinds of intestinal flora in the feces including bifidobacterium, lactobacillus, enterococcus, and escherichia coli were detected and compared between the two groups, and the value of the fecal colony numbers of 4 kinds of intestinal flora in diagnosing non-enteral nutrition-related diarrhea in critically ill patients was analyzed by receiver operating characteristic (ROC) curve. All patients in the research group received microflora transplantation, and the diarrhea score, hematochezia score, partial Mayo score and European five-dimension health scale (EQ-5D) were detected and compared before treatment, 1 week after treatment and 1 month after treatment to evaluate the treatment effect. The Pearson linear correlation method was used to analyze the relationship between the colony count of 4 kinds of intestinal flora colonies in the feces of the research group at baseline and the therapeutic indexes for 1 week and 1 month after treatment.Results:The number of fecal bifidobacterium and lactobacillus colonies in the study group were lower than those in the control group: (7.12 ± 0.58) × 10 7 cfu/L vs. (11.85 ± 1.25) × 10 7 cfu/L, (8.78 ± 1.05) × 10 7 cfu/L vs. (11.25 ± 1.57) ×10 7 cfu/L. The colony number of enterococcus and Escherichia coli were higher than those of control group: (8.58 ± 0.88) × 10 7 cfu/L vs. (3.84 ± 0.72) ×10 7 cfu/L, (8.25 ± 0.97) ×10 7 cfu/L vs. (3.66 ± 0.63) ×10 7 cfu/L. The differences were statistically significant ( P<0.05). ROC curve analysis results showed that the area under the curve of fecal bifidobacterium, lactobacillus, enterococcus and escherichia coli colonies in diagnosing patients with enteral nutrition-related diarrhea were all >0.7, which had certain diagnostic value. The diarrhea scores, stool blood scores and some Mayo scores of the study group at 1 week and 1 month after treatment were lower than those before treatment: (1.52 ± 0.36) and (1.13 ± 0.24) points vs. (2.45 ± 0.51) points, (0.95 ± 0.28) and (0.77 ± 0.21) points vs. (2.39 ± 0.54) points, (4.17 ± 1.24) and (3.26 ± 0.85) points vs. (7.86 ± 1.82) points, and the EQ-5D score of patients 1 week and 1 month after treatment was higher than that before treatment: (0.66 ± 0.11) and (0.79 ± 0.13) points vs. (0.58 ± 0.08) points, the difference was statistically significant ( P<0.05). Conclusions:The intestinal flora of critically ill patients is closely related to enteral nutrition-related diarrhea, and can affect the therapeutic effect of bacterial flora transplantation and the health status of patients.

Effects of Bifidobacterium triple viable capsules combined with Berberine tablets on blood lipid and intestinal flora in patients with hyperlipidemia / 中国医师进修杂志

Objective:To explore the effects of Bifidobacterium triple viable capsules combined with Berberine tablets on blood lipid and intestinal flora in patients with hyperlipidemia.Methods:A total of 420 hyperlipidemia patients admitted to the Second Medical Center of PLA General Hospital & National Clinical Research Center for Geriatric Diseases from January 2019 to December 2020 were selected and divided into the observation group and the control group according to the random number table method, with 210 cases in each group. Both groups were routinely given lipid-lowering drugs, the control group was also given Bifidobacterium triple viable capsules orally, and the observation group was combined with Berberine tablets orally on the basis of the control group. The levels of serum inflammatory factor, blood lipid, apolipoprotein and the number of intestinal flora before and after treatment were compared between the two groups. The incidence of adverse reactions was compared between the two groups during the treatment.Results:After treatment, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP) in the observation group were significantly lower than those in the control group: (26.78 ± 5.63) ng/L vs. (30.06 ± 5.79) ng/L, (12.88 ± 4.76) ng/L vs. (15.45 ± 5.32) ng/L, (8.22 ± 2.80) mg/L vs. (10.26 ± 3.71) mg/L, there were statistical differences ( P<0.05). After treatment, the levels of blood lipid in the observation group were improve better than those in the control group, the levels of apolipoprotein AⅠ in the observation group was higher than that in the control group: (2.00 ± 0.45) g/L vs. (1.72 ± 0.39) g/L; and the levels of apolipoprotein B and apolipoprotein E in the observation group were lower than those in the control group: (1.08 ± 0.18) g/L vs. (1.20 ± 0.22) g/L, (4.80 ± 0.68) g/L vs. (5.12 ± 0.62) g/L, there were statistical differences ( P<0.05). After treatment, the numbers of Bifidobacterium and Lactic acid bacteria in the observation group were higher than those in the control group: (8.80 ± 0.80) lg CFU/g vs. (8.30 ± 0.75) lg cfu/g, (8.85 ± 0.64) lg cfu/g vs. (8.45 ± 0.68) lg cfu/g; and the numbers of Colon bacillus and Enterococcus faecalis in the observation group were lower than those in the control group: (8.20 ± 0.55) lg cfu/g vs. (8.52 ± 0.50) lg cfu/g, (6.42 ± 0.60) lg cfu/g vs.(6.84 ± 0.65) lg cfu/g, there were statistical differences ( P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Bifidobacterium triple viable capsules combined with Berberine tablets in treatment of patients with hyperlipidemia can effectively reduce the level of blood lipid and regulate intestinal flora, with good safety.

Intestinal microecology and sepsis / 中国小儿急救医学

Sepsis is a common critical illness in PICU, with high morbidity and mortality.As the pathogenesis is still not well defined, the clinical management of sepsis can be tricky.The gastrointestinal tract is currently considered as one of the most susceptible organs in the early stages of sepsis, and intestinal microecology plays important roles in the development, progression and prognosis of this disease.There is a closely relationship between intestinal flora dysbiosis/translocation and sepsis.They interact with each other, and ultimately leading to multi-organ dysfunction.In this review, we provided a brief summary of intestinal microecological changes and its pathogenesis in sepsis, as well as the progress of treatment.

Regulation of Xuanbai Chengqi Decoction on lung-gut injury and intestinal microflora in sepsis mice / 中华急诊医学杂志

Objective:To investigate the effect of Xuanbai Chengqi Decoction (XBCQT) on lung-gut injury and intestinal function, and analyze its effect on intestinal flora in sepsis mice.Methods:C57 male mice were randomly divided into three groups with 12 mice in each group: control group, model group and treatment group. The sepsis model was prepared by intra-peritoneal injection of lipopolysaccharide (LPS) 5 mg/kg. XBCQT was administered by gavage 24 h before, 0.5 h after and 12 h after modeling. The lung, colon and blood samples were collected at 24 h after modeling. The pulmonary and intestinal inflammatory cytokine content of interleukin-1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α) and monocyte chemoattractant protein (MCP-1) was measured by real-time fluorescence quantitative PCR. HE staining was used to evaluate the structural damage and changes of lung and gut, and Western blot and Immunohistochemistry methods were used to analyze the expression of occludin and claudin-1 in intestinal epithelium. Finally, the plasma endotoxin content of each group was tested by Limulus test kit. Fecal DNA of mice was extracted and the changes of intestinal flora in sepsis mice were detected by 16S rDNA quantitative PCR. The measurement data among the three groups were compared by one-way analysis of variance.Results:(1) XBCQT significantly reduced the pulmonary inflammatory cytokine IL-1β, IL-6, TNF-α and MCP-1 expression (all P<0.05), and attenuated lung injury. (2) Compared to the model group, the treatment group exhibited a reduction in intestinal damage and a decrease in the intestinal inflammatory cytokines (all P<0.05). XBCQT increased the expression of epithelial tight junction and mucin of colon, and improved the intestinal epithelium barrier function. (3) XBCQT treatment decreased the content of endotoxin in plasma of sepsis mice ( P<0.05), promoted the growth of beneficial bacteria Akkermansia muciniphila and reduced the expression of Enterococcus in the intestine of sepsis mice (all P<0.05). Conclusions:XBCQT can significantly improve the intestinal inflammatory injury, regulate the intestine epithelium barrier and improve the intestinal function in sepsis mice.

Relationship between intestinal flora and location and nature of diarrheal irritable bowel syndrome in Traditional Chinese Medicine / 国际中医中药杂志

Irritable bowel syndrome is a common functional gastrointestinal disorder, among which diarrhea-type irritable bowel syndrome (IBS-D) is the main type in China, which is seriously affecting the quality of life for patients. The pathogenesis of IBS-D is still unclear. It has been found that Intestinal flora disorder is an important pathogenesis of IBS-D. There is a close relationship between intestinal flora and IBS-D TCM syndrome types, and there are differences in intestinal flora of different TCM syndrome types of IBS-D. However, TCM syndrome types are a complex and multi-factor combination. Therefore, based on the TCM theory of nature and location of disease, this article proposed the following conclusions through analyzing previous studies on intestinal flora of different TCM syndromes of IBS-D, including that the intestinal flora of different TCM syndromes have different characteristics and there are differences in the functions of flora, deficiency and excess of disease are associated with the diversity and abundance of intestinal flora, cold and heat of disease are related to the proportion of beneficial bacteria and opportunistic pathogens, and the characteristics of intestinal flora are the microcosmic manifestation of the disease position of TCM. In addition, this article also proposed the application of fecal bacteria transplantation based on the theory of nature and location of disease. Based on this theory, the study on intestinal flora of IBS-D can provide help for objectification of TCM syndrome types, and also provide TCM research ideas for revealing the pathogenesis of IBS-D.

Discussion on the pathogenesis of "spleen deficiency and dampness accumulation" of colorectal polyps based on intestinal flora and glucose and lipid metabolism / 国际中医中药杂志

Intestinal flora imbalance and abnormal glucose and lipid metabolism are important risk factors and pathological mechanisms of colorectal polyps. "Spleen deficiency and dampness accumulation" is the core pathogenesis of colorectal polyps. The imbalance of intestinal flora is related to spleen deficiency, and the application of Chinese herbs for invigorating spleen is helpful to the recovery of intestinal flora balance. Abnormal glucose and lipid metabolism is related to dampness accumulation, and it is effective to treat it with bitter and spicy herbs or spleen-invigorating and dampness-eliminating herbs. The interaction between intestinal flora imbalance and abnormal glucose and lipid metabolism changes intestinal microenvironment, damages intestinal epithelial cells, causes abnormal proliferation of intestinal stem cells and leads to colorectal polyps, which is consistent with the pathogenesis of spleen deficiency and dampness accumulation in Traditional Chinese Medicine. Thus, we tried to explore the biological connotation of the pathogenesis of "spleen deficiency and dampness accumulation" of colorectal polyps from the perspective of the interaction of intestinal flora and glucose and lipid metabolism, in order to provide reference for identifying high-risk population and analyzing the therapeutic mechanism of compound prescription for invigorating spleen and removing dampness.

Acupuncture point selection for prevention and treatment of generalized anxiety disorder from the perspective of Microbiota-Gut-Brain Axis / 国际中医中药杂志

Disorders of the gut flora (GF) affect the level of 5-hydroxytryptamine (5-HT) in the brain of patients with generalized anxiety disorder (GAD) and influence the development of the disease. Most of the acupuncture points selected for GAD are based on the principles of local acupuncture points and acupuncture points following the distant channels of the meridians, regarding Baihui (DU 20), Fengchi (GB 20), and Yintang (GV 29) as the main acupuncture points, and the acupuncture points selected for the regulation of GF are Zhongwan (CV 12), Tianshu (ST 25), and Guanyuan (RN 4) and Zusanli (ST 36). Recently, many studies have been conducted on the mechanism of action of acupuncture in the treatment of GAD from the perspective of GF, but few have investigated the theoretical of acupuncture points used to prevent and treat GAD. This paper discusses the theoretical basis of acupuncture to regulate the "microbiota-gut-brain axis" (MGBA) for the prevention and treatment of GAD, and proposes the method of "regulating the internal organs and calming the mind and relieving anxiety" through analyzing the researches on the regulation of GF and GAD.

Advances in intestinal flora metabolites deoxycholic acid and digestive diseases in children / 国际儿科学杂志

It is the hotspot that studying the interplay and mechanism between intestinal flora metabolites and diseases.Deoxycholic acid, one of the intestinal flora metabolites, is one of the most abundant secondary bile acids in human intestinal tract, which is corelated with many diseases, while the mechanisms remain unclear.The imbalance of deoxycholic acid is connected with the intestinal flora disorder and high fat diet, which could result in several immunoreaction and inflammatory reaction.In this review, the interaction between deoxycholic acid and digestive diseases in children, such as non-alcoholic fatty liver disease, inflammatory bowel disease and irritable bowel syndrome, is discussed to explore their related mechanism, so as to clarify the direction of further study on the influence of intestinal microbiota metabolites deoxycholic acid on the human body.

Advances in intestinal flora and attention deficit hyperactivity disorder / 国际儿科学杂志

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children, which can be characterized by hyperactivity and(or)impulsivity, inattention, or a combination.The etiology and pathophysiological mechanism of ADHD have not been clarified yet.More and more studies have shown ADHD has intestinal flora disorder, which may affect the occurrence and development of ADHD through microbiome-gut-brain axis (MGBA). Treatment strategies targeting gut microbiota, including probiotics and dietary therapies, are considered to be a novel and effective method for the prevention or treatment of ADHD.This article reviews the changes of intestinal flora and the progress of diet and probiotics in ADHD children, in order to provide new ideas for treatment of ADHD children.

Influences of intestinal flora metabolites on neonatal diseases / 国际儿科学杂志

The intestinal tract is an essential digestive organ of the human body, which is known as the "second brain". The intestinal flora disorder is closely related to the occurrence of host diseases.It has been found that the dysbiosis of intestinal flora plays an important role in the development of neonatal diseases.Gut microflora metabolites are bioactive, and the key metabolites can regulate or affect the host′s metabolic changes through different metabolic pathways.The metabolites of the neonatal intestine participate in and affect the progression and outcome of the diseases, and determine their short- and long-term quality of life.This review summarizes the effects of gut flora metabolites on neonatal diseases.

Difference in Intestinal Flora Among Patients with Esophageal Squamous Cell Carcinoma and Normal Population / 肿瘤防治研究

Objective To investigate the difference in intestinal flora among patients with esophageal squamous cell carcinoma and normal population and to provide a basis for the early diagnosis of esophageal squamous cell carcinoma as a marker. Methods DNA was extracted from biopsy tissue samples of 30 patients with esophageal squamous cell carcinoma (observation group) and 25 healthy people (control group) by microbial amplification sequencing. The integrity and quality of DNA were detected. The composition and abundance of intestinal flora in the samples of the two groups were determined. Results A great similarity in beta diversity was found between the two groups, but some differences were also observed. The relative abundance of Proteobacteria and Verrucomicrobia in the observation group was higher than that in the control group (P<0.05). The relative abundance of Megamonas in the observation group was lower than that in the control group (P=0.025). Conclusion Strengthening the study on the changes in intestinal flora among patients with esophageal squamous cell carcinoma may be of great significance for its prevention and treatment.

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

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

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

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

Effects of Akkermansia on AOM/DSS Inflammatory-associated Colorectal Cancer / 肿瘤防治研究

Objective To investigate the effects of Akkermansia muciniphila (AKK) on azomethane-oxide (AOM)/glucan sodium sulfate (DSS)-induced inflammatory colorectal cancer mouse model and intestinal stem cells. Methods AOM/DSS-induced mouse models of inflammatory-associated colorectal cancer were randomly divided into three groups, namely, model, AKK and aspirin groups, based on different administration of drugs by gavage. The tumor number, size, distribution, and burden were observed 10 weeks after intervention. Immunohistochemical method was used to analyze the expressions of Ki67 and Lgr5 proteins, which are utilized to characterize tumor malignancy and stem cells. The mRNA expressions of Lgr5, CD133, Nanog, and ALDH1 were detected by qRT-PCR. Results Compared with those of the model group, the tumor number, size, and burden of the AKK group were significantly reduced (P < 0.01). The expressions of Ki67 and Lgr5 in the AKK group of tumor tissues were significantly decreased (P < 0.05), and the mRNA expressions of CD133, Nanog and ALDH1 were significantly down-regulated. Conclusion AKK is effective against AOM/DSS-induced colitis-associated colorectal cancer in mice, and its mechanism of action may be closely related to colorectal stem cell activity.

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

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