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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.
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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.
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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.
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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.
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OBJECTIVE@#To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects.@*METHODS@#Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*RESULTS@#In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05).@*CONCLUSION@#BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.
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Rats , Animals , Rats, Sprague-Dawley , Gastrointestinal Microbiome , Chromatography, Liquid , Claudin-1 , Occludin , RNA, Ribosomal, 16S , Tandem Mass Spectrometry , Drugs, Chinese Herbal/pharmacology , Heart FailureABSTRACT
As a complex and large microbial community colonized in the human body, the intestinal flora and its metabolites short-chain fatty acids (SCFAs) play an important role in participating in human metabolism, resisting pathogens, and regulating immune mechanisms. In recent years, many studies have found that the intestinal flora is closely related to bone metabolism. The intestinal flora is able to regulate bone metabolism and affect bone mass changes through various pathways such as absorption of nutrition, generation of SCFAs, regulation of immunity, and influence on body metabolism. The potential pathways and mechanisms by which intestinal flora affect bone mass changes were reviewed in this article in bone metabolism. The related study on Traditional Chinese Medicine that has effects in balancing intestinal flora for regulating bone metabolism was also introduced in order to provide new ideas for the prevention and treatment of osteoporosis, a disease related to bone metabolism.
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Objective:To explore the relationship between the neural development of preterm infants and gut microbiota.Methods:66 premature infants who were hospitalized in the Neonatology Department of Hunan Children′s Hospital from September 2018 to September 2019 were included in the study. Their fecal samples and clinical data from the first admission were collected. According to the neurodevelopment, the patients were divided into normal neurodevelopment group and neurodysplasia group. The bacterial DNA of fecal samples was extracted by 16S rDNA high-throughput sequencing technology and bioinformatics analysis was conducted to compare the composition and diversity of gut microbiota between the two groups.Results:(1) The Shannon index of gut microbiota in normal neurodevelopmental group and neurodysplastic group was 0.89(0.41, 1.51) and 1.01(0.47, 1.31), respectively. There was no significant difference in diversity index between the two groups ( P>0.05). (2) Bifidobacterium, veronica and negativites in the gut microbiota of the normal neurodevelopmental group were significantly higher (all P<0.05), and streptococcus in the gut microbiota of the dysplastic group were significantly higher ( P<0.05). The gut microbiota of the two groups were mainly enterococcus and escherichia shigella. Conclusions:At the genus level, enterococcus and escherichia are the dominant flora of early gut microbiota in preterm infants. Gut microbiota is related to the neural development of preterm infants. The increased abundance of streptococcus, and the decreased abundance of bifidobacterium, veronicus, and negativites may be risk factors for neurodysplasia of preterm infants. The diversity of gut microbiota in early preterm infants may not be significantly related to neural development.
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Osteoporosis (OP) is a systemic bone disease characterized by decreased bone density and damage to bone microstructure, leading to brittle fractures. It is a multifactorial disease that is more common in postmenopausal women, and its high incidence and serious complications are receiving increasing attention. Currently, clinical anti-osteoporosis drugs are mainly divided into two categories: inhibiting bone resorption and promoting bone formation, including bisphosphonates, calcitonin and estrogen, etc. But the side effects and high economic cost of drugs limit the scope of their use to some extent. In recent years, the effect of intestinal flora on bone health, especially on osteoporosis, has become a potential new target for regulating bone density. Probiotics belong to intestinal flora and are defined as living microorganisms. They have initially shown good efficacy in the treatment of some bone metabolic diseases, suggesting that intestinal flora can be used as a potential target for the prevention and treatment of osteoporosis and the application of probiotics as a new therapeutic method for osteoporosis. This paper mainly reviews the relevant studies on probiotics and osteoporosis, shows the latest research progress of probiotics intervention in OP, clarifies the relevant action mechanism of probiotics intervention in OP through intestinal tract, and analyzes the research status and prospect of probiotics treatment in OP.
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Objective:To investigate the effect of Liangxue Huoxue decoction on intestinal flora, intestinal barrier and NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pyroptosis signaling pathway in mice model of sepsis-induced acute kidney injury (AKI).Methods:The model of AKI was established by cecal ligation and perforation (CLP). Thirty male C57BL/6 mice were randomly divided into sham operation group (Sham group), sepsis group (CLP group) and sepsis+Liangxue Huoxue decoction (CLP+LXHX group), with 10 mice in each group. Mice in Sham group only underwent laparotomy. Two hours before model establishment, mice in CLP+LXHX group were treated with Liangxue Huoxue decoction (6 g/kg) by gavage; mice in Sham group and CLP group were given equal volume of normal saline by gavages. After 24 hours of modeling, all mice were sacrificed under anesthesia, and the colon and kidney tissues and fresh feces in the colon were taken. The pathological changes of kidney and colon were observed by hematoxylin-eosin (HE) staining under light microscope. Real-time polymerase chain reaction (RT-PCR) was used to detect inflammatory factors (interleukins, IL-1β and IL-18) in renal tissue. The expressions of NLRP3, caspase-1 and GSDMD were detected by Western blotting. The changes of intestinal flora in mice were detected by 16S rDNA high-throughput sequencing.Results:Compared with the Sham group, the inflammatory cell infiltration of the kidney tissue was increased and the kidney became vacuolated in CLP group, the mRNA expressions of IL-1β, IL-18, and the protein expressions of NLRP3, caspase-1 and GSDMD were significantly increased in CLP group, the species richness of intestinal microflora decreased significantly, the relative abundance of Enterococcus and Escherichia-Shigella increased significantly, and the relative abundance of Ileibacterium, Alloprevotella, Lachnospiraceae, Klebsiella and Parasutterella increased significantly in CLP group. Compared with CLP group, Liangxue Huoxue decoction can significantly reduce the pathological changes of kidney and colon tissue, reduce the pathological score (1.75±0.43 vs. 3.50±0.50 for kidney tissue, 1.25±0.43 vs. 4.50±0.50 for colon tissue, both P < 0.05), improve the composition of intestinal flora, reduce the relative abundance of Enterococcus and Escherichia-Shigella, and significantly increase the relative abundance of Lactobacillus and Akkermansia. In addition, Liangxue Huoxue decoction can significantly reduce mRNA expressions of IL-1β and IL-18 in kidney tissue [IL-1β mRNA (2 -ΔΔCt): 1.59±0.05 vs. 4.61±0.88, IL-18 mRNA (2 -ΔΔCt): 1.69±0.17 vs. 2.86±0.63, both P < 0.05] and the protein expressions of NLRP3, caspase-1 and GSDMD (NLRP3/GAPDH: 0.71±0.04 vs. 0.89±0.01, caspase-1/GAPDH: 1.04±0.04 vs. 1.48±0.04, GSDMD/GAPDH: 0.90±0.01 vs. 1.41±0.02, all P < 0.05). Conclusions:Liangxue Huoxue decoction has obvious protective effect on AKI induced by sepsis. It can improve intestinal barrier by regulating intestinal flora, thereby inhibiting the activation of NLRP3/caspase-1/GSDMD signaling pathway in kidney tissue and reducing the expression of proptosis-related inflammatory factors.
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Objective:To explore the therapeutic effect and mechanism of Dachengqi decoction on patients with mild acute pancreatitis (MAP).Methods:A parallel randomized controlled trial was conducted. Sixty-eight patients with acute pancreatitis (AP) admitted to Shanghai Traditional Chinese Medicine (TCM)-Integrated Hospital from March 2018 to February 2021 were enrolled. Referring to the condition on admission of the patients and whether they agreed to receive the Dachengqi decoction or not, they were divided into conventional treatment group and Dachengqi decoction group according to the principle of 1∶1 equal randomness. Meanwhile, 20 healthy volunteers were recruited as controls. Both groups of patients were treated with octreotide, fasting, gastrointestinal decompression, antipyretic and analgesic, anti-inflammatory, inhibition of gastric acid and pancreatic juice secretion, maintenance of electrolyte balance and other western conventional medicine. The patients in the Dachengqi decoction group received Dachengqi decoction orally on the basis of routine treatment, 100 mL each time, twice a day, for seven consecutive days. The inflammation parameters [white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6)] before and after treatment and the recovery time of gastrointestinal function (first exhaust time, time to recover bowel sounds, first defecation time) of patients were recorded. 16S rRNA gene sequencing of stool samples was recorded, and normalized data were obtained after quality control and other related processing. The data were subjected to diversity analysis (Alpha diversity and Beta diversity) and linear discriminant analysis effect size analysis (LEfSe analysis) to observe changes in the gut microbiota of MAP patients. Spearman rank correlation coefficient was used to analyze the correlation between inflammatory indexes and microorganisms at the intestinal genus level. Blood, urine, stool samples, renal function, and electrocardiogram (ECG) during treatment of MAP patients were detected to assess the safety of the treatment.Results:Of the 68 patients with AP, 16 were excluded from moderate-severe AP, 4 were not collected or voluntarily abandoned treatment. Finally, 48 patients with MAP were enrolled, 24 in the conventional treatment group and 24 in the Dachengqi decoction group. The inflammation parameters levels at 7 days of treatment in both groups were significantly lower than those before treatment. CRP, PCT and IL-6 levels in the Dachengqi decoction group were significantly lower than those in the conventional treatment group [CRP (mg/L): 8.50 (3.50, 13.00) vs. 16.00 (9.25, 29.75), PCT (μg/L): 0.06 (0.03, 0.08) vs. 0.09 (0.05, 0.11), IL-6 (ng/L): 6.36 (3.96, 10.79) vs. 13.24 (6.69, 18.87), all P < 0.05]. The first exhaust time, time to recover bowel sounds and first defecation time in the Dachengqi decoction group were significantly shorter than those in the conventional treatment group [first exhaust time (days): 1.62±0.65 vs. 2.80±0.65, time to recover bowel sounds (days): 1.13±0.58 vs. 2.31±0.76, first defecation time (days): 3.12±0.75 vs. 4.39±0.76, all P < 0.05]. The analysis of intestinal microflora diversity showed that both the diversity and abundance of microbial communities were the highest in the healthy control group and the lowest in the conventional treatment group. In addition, the coincidence degree of microbial communities in healthy controls and MAP patients was small, while the coincidence degree of MAP patients among different treatment methods was relatively large. LEfSe analysis showed that Dachengqi decoction reduced the relative abundance of Escherichia coli-Shigella and Clostridium erysipelae, and increased the relative abundance of three beneficial bacteria, namely Lactobacillus, Rombutzia and Brutella. In the intestines of MAP patients, Lactobacillus mucilaginus and Lactobacillus conjunctus were significantly enriched. Correlation analysis showed that positive correlations between Escherichia coli- Shigella and the four inflammatory indicators including WBC, CRP, PCT, IL-6 were statistically significant ( r value was 0.31, 0.41, 0.57, 0.43, respectively, all P < 0.05). There was no significant correlation between other bacteria and inflammatory indicators. During the treatment, there was no obvious abnormality in blood, urine and feces, renal function and ECG of MAP patients. Conclusions:Dachengqi decoction could reduce inflammatory responses and promote recovery of intestinal microecological balance and gastrointestinal function in patients with MAP by regulating the composition of intestinal flora. No significant adverse effects were observed during the treatment period.
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Objective:To investigate the effects of probiotics on intestinal flora, intestinal function, and T lymphocyte level in patients with cervical cancer after radiotherapy.Methods:A total of 92 patients with cervical cancer who underwent pelvic radiotherapy in The Second Affiliated Hospital of Zhengzhou University from September 2020 to February 2022 were included in this study. They were randomly divided into control and experimental groups ( n = 46/group). The patients in the experimental group took probiotics during radiotherapy, while the patients in the control group did not take probiotics during radiotherapy. The amount of intestinal flora, D-lactic acid, diamine oxidase, and T lymphocyte subset levels pre- and post-radiotherapy were compared between the two groups. Urinary lactulose (L) and mannitol (M) concentrations were determined in each group. Urinary excretion ratios of L to M were calculated. Results:After 10, 15, and 20 times of radiotherapy and after all radiotherapies, the amount of Escherichia coli and Enterococcus in the experimental group was significantly lower than that in the control group ( F = 128.60, 224.99, all P < 0.05). The amount of Bifidobacteria and Lactobacilli in the experimental group was significantly higher than that in the control group ( F = 2 065.46, 948.23, both P < 0.05). After 10, 15, and 20 times of radiotherapy and after all radiotherapies, plasma D-lactic acid level in the experimental group was (9.34 ± 1.63) μg/L, (9.15 ± 1.36) μg/L, (8.68 ± 1.06) μg/L, and (8.05 ± 0.82) μg/L, respectively. After 10, 15, and 20 times of radiotherapy and after all radiotherapies, plasma diamine oxidase level in the experimental group was (86.34 ± 20.25) μg/L, (84.28 ± 17.45) μg/L, (80.40 ± 13.35) μg/L, and (76.85 ± 10.87) μg/L, respectively, and urinary excretion ratio of L to M in the experimental group was (1.84 ± 0.16), (1.55 ± 0.12), (1.26 ± 0.09), (0.98 ± 0.06), respectively, all of which were significantly lower than those in the control group ( F = 121.60, 31.73, 417.84, all P < 0.05). After 10, 15, and 20 times of radiotherapy and after all radiotherapies, CD4 + level in the experimental group was (39.80 ± 4.90)%, (40.92 ± 5.30)%, (42.52 ± 6.14)%, (43.83 ± 6.55)%, respectively, CD4 +/CD8 + was (1.52 ± 0.25), (1.63 ± 0.22), (1.71 ± 0.39), (1.83 ± 0.22), respectively, all of which were significantly higher than those in the control group ( F = 58.69, 31.07, all P < 0.05). Conclusion:Probiotics can improve the status of intestinal flora and intestinal barrier function in patients with cervical cancer after radiotherapy, and simultaneously improve the cellular immune function of patients.
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Objective:To investigate the effects of modified Buzhong Yiqi Decoction on intestinal microflora in a rat model of chronic obstructive pulmonary disease. Methods:From April to June 2021, 60 specific pathogen-free Wistar rats were selected for this study. They were randomly divided into blank control, model, traditional Chinese medicine, and western medicine groups with 15 rats per group. Rat models of chronic obstructive pulmonary disease with lung and spleen deficiency were established in all groups except the blank control group. Rat models in the traditional Chinese medicine and western medicine groups were administered modified Buzhong Yiqi Decoction and synbiotics. Rat models in the model and blank control groups were identically administered 0.9% sodium chloride injection. After 7 days, the feces of rats in each group were collected for 16S rRNA sequencing of intestinal flora. Effective sequences were clustered to obtain operational taxonomic units for principal coordinate analysis, species composition analysis, and alpha diversity analysis. The effects of modified Buzhong Yiqi Decoction on the structure, diversity, and abundance changes of intestinal flora were analyzed. Results:The dominant bacteria in the traditional Chinese medicine and western medicine groups were Firmicutes, while the dominant bacteria in the blank control and model groups were Bacteroides. The dominant bacterial groups in each group were mainly Lactobacillus and Bacteroides. Alpha diversity analysis showed that the Shannon index in the community diversity indices of traditional Chinese medicine, western medicine, and blank control groups was (3.65 ± 0.35), (3.65 ± 0.36), and (3.59 ± 0.20), respectively, which were significantly higher than (3.37 ± 0.26) in the model group ( t = 2.49, 2.44, 2.60, all P < 0.05). There was no significant difference in the Shannon index among traditional Chinese medicine, western medicine, and blank control groups (all P > 0.05). The Sobs index of the traditional Chinese medicine, western medicine, and blank control group was (458.67 ± 73.11), (454.80 ± 95.13), and (525.93 ± 101.88), respectively, which were significantly higher than (337.40 ± 37.49) in the model group ( t = 5.72, 4.45, 6.73, all P < 0.05). The Sobs index in the blank control group was higher than that in the western medicine group. There was no significant difference in the Sobs index between blank control and traditional Chinese medicine groups and between western medicine and traditional Chinese medicine groups (both P > 0.05). Principal coordinate analysis revealed that compared with the blank control group, Actinomycetes decreased and Proteobacteria and Desulfurization bacteria increased at the phylum level in the model group, while compared with the blank control group, Bacteroides, Rombutzia,Trichospirillus, and Parabacteroides increased, and Prevotella, Clostridium, Brucella, and Ruminococcus decreased at the genus level. Compared with the western medicine group, Bacillus, Prevotella, Brucella, and Prevotellidae in the traditional Chinese medicine group increased, while Clostridium, Pectinobacter, Christensen, and Trichospirillus decreased in the traditional Chinese medicine group. There was a statistically significant difference in the composition of the bacterial population between groups (all P < 0.05). Conclusion:There is an imbalance in intestinal microecology in a rat model of chronic obstructive pulmonary disease. Modified Buzhong Yiqi Decoction can regulate the intestinal microecology environment, improve the structure of intestinal flora, and increase the diversity and abundance of intestinal flora.
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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.
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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.
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ObjectiveTo explore the relationship between the intestinal flora and the impairment of liver and kidney in HIV-infected men who have heterosexual sex with healthy women. MethodsFecal samples from 41 HIV-infected heterosexual men who have sex with women （PMSW） and 43 age- and BMI-matched healthy heterosexual men who have sex with women （NMSW） were collected and subjected to 16S rDNA sequencing. The blood levels of AST， ALT， TBIL， UREA， Cr， UA， β2-MG and other liver and kidney function indicators were measured. Bioinformatics methods were used to analyze the characteristics of the intestinal flora of the patients in these two groups， to compare the differential bacteria strains， and to analyze their correlation with liver and kidney function indicators. ResultsIn comparison with NMSW， the alpha diversity of intestinal flora was decreased in PMSW， and the beta diversity analysis showed significant differences in flora characteristics between the two groups （P<0.05）. The abundance of Clostridium， Phylum thick-walled， Trichosporon， and Clostridium tumefaciens decreased but Fusobacteriota increased （LDA score >4）. The comparison of liver and kidney function indexes revealed that AST， β2-MG levels were higher in PMSW than in NMSW， while TBIL was lower in PMSW than in NMSW. The number of patients with abnormal β2-MG was much higher in PMSW than in NMSW， and the difference was statistically significant （P<0.001）. It was also found that AST was negatively correlated with Clostridium （P<0.05）； TBIL was negatively correlated with Clostridium and positively correlated with Phylum thick-walled and Trichosporon （P<0.05）. β2-MG was negatively correlated with Phylum thick-walled， Clostridium， Trichosporon and Rumenococcus （P<0.05） and positively correlated with Clostridium （P<0.05）. ConclusionIn PMSW group， the alpha diversity of the flora is decreased. AST and β2-MG levels are increased， and TBIL level is decreased. These changes were significantly correlated with different strains of bacteria in the intestinal flora.
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Bladder cancer is one of the most common urinary tumors, and human urinary tract has been proved to be non-sterile. The significance of urinary tract flora in pathophysiology and treatment of urothelial carcinoma remains to be studied. Meanwhile, intestinal flora has also become an important clinical factor, which has been proved to play a variety of roles in body metabolism, local and systemic inflammation and immunity. Microorganisms can affect the clinical course of cancer, efficacy of chemotherapy and immunotherapy drugs, bioavailability and side effects. This review will explore the relationship between bladder cancer and urinary tract and intestinal microbiome, and explore reliable disease predictors, prognostic indicators and therapeutic targets through a better understanding of the interaction between the microbiome and tumor cells.
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【Objective】 To investigate the effects of neuropathic pain induced by selective nerve injury (SNI) on intestinal microflora diversity in C57 mice. 【Methods】 36 C57 mice were randomly divided into SNI model group (n=18), sham-operation group (n=8), and control group (n=10). At day 0,1, 3, 7, and 14 after modeling, mechanical pain threshold and thermal pain sensitivity tests were carried out. At day 14 after modeling, colon content (fresh feces) from all the mice were collected for intestinal microflora diversity analysis. 【Results】 One day after modeling, the mechanical pain threshold in SNI group decreased significantly (more than 70%) due to nerve injury, and the thermal pain threshold decreased by 40%, while sham group and control group had no significant decrease. SNI group showed foot hyperalgesia, and the difference was statistically significant compared with sham group and control group (P<0.001). Compared with control group, sham-operation group had a transient decrease in thermal pain threshold on the first day after modeling (P=0.006), but there was no difference in pain threshold between the two groups on the third day after modeling. The α-diversity analysis showed that the abundance of Observed, Chao1, ACE and Simpson in SNI group was significantly lower than that in control group (P<0.05). That is, SNI group had flora disorder due to pain stimulation. Observed, Chao1, ACE, and Simpson were less abundant in sham group than in control group (P<0.05) and the change was between SNI group and control group. 【Conclusion】 Neuropathic pain induced by SNI model resulted in the decrease of mechanical pain threshold and thermal pain threshold, which leads to the reduction of intestinal flora diversity in C57 mice.
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ObjectiveTo observe the possible mechanism of Xixin Decoction （洗心汤， XXD） in the prevention and treatment of Alzheimer 's disease（AD）. MethodsFifty rapid aging model mice （SAMP8） were randomly divided into model group， probiotic group， high-， moderate- and low-dose group of XXD， with 10 mice in each group. Another 10 homologous anti-rapid aging mice （SAMR1） were set as control group. After 10 weeks of feeding， the control group and the model group were given 10 ml·kg-1·d-1 of distilled water by gavage， while the probiotic group （0.39 g·kg-1·d-1）， the high-dose group of XXD （5.08 g·kg-1·d-1）， the moderate-dose group of XXD （2.54 g·kg-1·d-1）， and the low-dose group of XXD （1.27 g·kg-1·d-1） were given corresponding drugs or decoctions by gavage， once a day in all groups. After 10 weeks of intragastric administration， Morris water maze was used to detect the spatial learning and memory ability of mice in each group. HE staining was used to observe the pathological changes of hippocampal CA3 region and colon. The levels of β-amyloid 1-42 （Aβ1-42）， lipopolysaccharide （LPS）， serum amyloid A （SAA） and acetylcholine （ACH） in hippocampus and colon were detected by ELISA.The diversity of intestinal flora in mouse feces was detected by 16S rRNA sequencing. ResultsCompared to those in the control group， the levels of Aβ1-42，LPS， SAA increased， while the level of ACH decreased in the model group （P＜0.05 or P＜0.01）. Compared to those in the model group， the escape latency period of the probiotic group was significantly shortened on the 2nd and 5th days， while the escape latency period was shortened， and the residence time in the target platform quadrant increased in the high-dose XXD group during the 2nd to 5th days； the escape latency period was shortened significantly in the moderate-dose XXD group on the 5th day （P＜0.05 or P＜0.01）. Compared to those in the model group， the hippocampal neuron cells in the high- and moderate-dose XXD groups were arranged more closely， with decreased levels of SAA， Aβ1-42 and LPS， increased ACH level， Simpson and Shannon index （P＜0.05 or P＜0.01）； the arrangement of hippocampal neuron cells in the probiotic group and the low-dose XXD group was relatively loose； the proportions of Bacteroidetes and Prevotella were significantly reduced in the probiotic group and the high-dose XXD group， while that of Firmicutes and Lactobacillus significantly increased （P＜0.05 or P＜0.01）. Compared to those in the probiotic group and the high-dose XXD group， the number of goblet cells in the moderate-dose XXD group decreased， and the number of glands in the low-dose XXD group decreased with atrophy. The high-dose XXD group had decreased Aβ1-42 level in the hippocampus， increased ACH level in thehippocampus and colon tissue， and decreased SAA in the colon tissue than the moderate- and low-dose XXD groups （P＜0.05 or P＜0.01）； moreover， the SAA level in the hippocampus was significantly higher in the low-dose XXD group than the high- and moderate-dose groups （P＜0.01）. ConclusionXXD can improve the spatial learning and memory ability of SAMP8， reduce the production and deposition of LPS， SAA and Aβ1-42 in brain and intestine， and increase the content of ACH. The mechanism of its prevention and treatment of AD maybe related to regulating intestinal microecology， affecting flora diversity and improving inflammatory response.
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ObjectiveTo study the possible mechanism of Chaihu Shugan Powder （柴胡疏肝散， CSP） in the treatment of functional dyspepsia （FD）. MethodsTwenty-four SD rats were randomly divided into a normal group， a model group， a CSP group and a probiotic group， with six rats in each group.The tail-clamping provocation method was used in all groups except for the normal group to replicate the FD rat model. Simultaneously， the normal group and the model group were given 10 ml/（kg·d） of saline by gavage， while the CSP group and the probiotic group were given 9.6 g/（kg·d） of CSP aqueous decoction and 0.945 g/（kg·d） of probiotic aqueous solution by gavage， respectively， twice daily for four weeks. After four weeks， the gastric emptying and small intestinal propulsion rates were detected in each group of rats. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the gastric sinusoids and duodenum of the rats. The changes in the intestinal flora were analyzed by 16s rDNA high-throughput gene sequencing， and the expressions of the duodenal zona occludin 1 （ZO-1） and Occludin were detected by immunohistochemistry and western blotting. Pearson correlation analysis was performed on intestinal flora and ZO-1 and Occludin protein expression. ResultsThe gastric antrum tissue structure was clear in all groups， and the gland structure was regular， with smooth gastric tissue mucosa and no pathological changes such as erosion and ulcer. Compared to those in the normal group， the intestinal villi in the duodenal tissue in the model group were significantly reduced or atrophied， and the goblet cells were arranged in disorder， with eosinophilic infiltration； the gastric emptying rate and small intestinal propulsion rate， as well as ZO-1 and Occludin protein expression in duodenal tissue significantly decreased （P＜0.01）. Compared to those in the model group， the duodenal tissue structure was clear， and the length intestinal villi was longer， with goblet cells neatly arranged in the CSP group and the probiotic group； no obvious eosinophil infiltration was found， and the gastric emptying rate and small intestinal propulsion rate as well as ZO-1 and Occludin protein expression significantly increased in the CSP group； a small amount of eosinophil infiltration was found， and the gastric emptying rate and Occludin protein expression significantly increased in the probiotic group （P＜0.05 or P＜0.01）. Beta diversity analysis of intestinal flora showed that the overall structure of intestinal flora in the model group changed significantly compared to that in the normal group （P＜0.01）. The overall structure of the intestinal flora in the CSP group and the probiotic group was closer to the normal group than the model group. Species composition analysis showed that the relative abundance of the Firmicutes decreased， while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae increased， and the Bacteroidetes/Firmicutes value increased in the model group than those in the normal group （P＜0.05 or P＜0.01）. Compared to those in the model group， the relative abundance of the Firmicutes increased， while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae， as well as the Bacteroidetes/Firmicutes value decreased in the CSP group and the probiotic group （P＜0.05 or P＜0.01）. There was no statistically significant difference in each indicator between the probiotic group and the CSP group （P＞0.05）. Pearson correlation analysis showed that at the phylum level， Firmicutes was positively correlated with ZO-1 （r=0.610， P=0.016） and Occludin （r=0.694， P=0.004） protein expression. Bacteroidetes was negatively correlated with ZO-1 （r=-0.557， P=0.031） and Occludin （r=-0.662， P=0.007） protein expression. At the genus level， norank_f_Muribaculaceae was negatively correlated with ZO-1 （r=-0.727， P=0.002） and Occludin （r=-0.760，P=0.001） protein expression. ConclusionCSP can restore the structure of intestinal flora， regulate the abundance levels of Firmicutes， Bacteroidetes and norank_f_Muribaculaceae， up-regulate ZO-1 and Occludin proteins， and thus repairing the duodenal mucosal barrier， and playing a therapeutic role in FD rats.
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Due to factors such as low pressure, low oxygen and cold in the plateau environment, people who enter the plateau rapidly are susceptible to digestive system diseases, such as upper abdominal pain, loss of appetite, nausea and vomiting and other gastrointestinal dysfunction, which seriously affect the health and work ability of people who enter the plateau rapidly. The gastrointestinal dysfunction caused by the rapid advance to the plateau is mainly reflected in three aspects: gastrointestinal motility dysfunction, impaired mucosal barrier function, and intestinal flora imbalance. At present, the pathogenesis of gastrointestinal dysfunction is still not very clear, and there are fewer drugs for targeted prevention and treatment. Gastrointestinal hormones, oxygen free radicals, inflammatory factors, intestinal flora and other factors, as well as the protective effects of related drugs were reviewed in this paper to provide treatment options and theoretical basis for the prevention and treatment of the gastrointestinal emergency response caused by entering the plateau.