Progress of research on gut flora and inflammatory bowel disease accompanied with spondyloarthritis / 胃肠病学

Inflammatory bowel disease (IBD) is a chronic non ‑ specific intestinal inflammatory disease. Spondyloarthritis (SpA) is a chronic inflammatory disease that occurs in the axial skeleton and surrounding joints, and is one of the most common extraintestinal manifestations of IBD. The main pathophysiologic mechanism of IBD accompanied with SpA involves the "gut‑joint axis" hypothesis, and dysbiosis of gut flora plays a key role in explaining the pathologic connection of the "gut‑joint axis" in patients with IBD accompanied with SpA. This article reviewed the progress of research on gut flora and IBD accompanied with SpA.

Research progress on the regulatory mechanism of intestinal flora metabolites on mitochondria of intestinal epithelial cells and the traditional Chinese medicine intervention / 药学学报

It was found that intestinal flora could directly regulate mitochondria of intestinal epithelial cells or indirectly through the nucleus. This effect is associated with the flora metabolites such as short-chain fatty acids (SCFAs), hydrogen sulfide (H2S) and nitric oxide (NO). These metabolites are involved in mitochondria-related energy metabolic processes and the production of mitochondrial reactive oxygen species (mtROS), and even in the immune response of the whole organism. Numerous studies have also shown that intestinal flora metabolites and mitochondria have become a hot spot for research on the mechanism of action of traditional Chinese medicine, but the research on the mechanism of association between them is not yet in-depth. In this review, we summarize the mechanism of mitochondrial regulation of intestinal epithelial cells by intestinal flora metabolites and herbal interventions to provide a theoretical basis for targeting intestinal microbes and mitochondria to regulate body metabolism and health.

Quantitative Analysis of Relationship Between Gut Flora Dysbiosis and Severity of Liver Cirrhosis / 胃肠病学

Background: The incidence of liver cirrhosis is increasing year by year in China. Decompensated liver cirrhosis and its related complications seriously threaten people's health. Aims: To investigate the changes of gut flora in cirrhotic patients and its correlation with the severity and prognosis of the disease. Methods: One hundred patients with liver cirrhosis admitted from Dec. 2010 to Jul. 2011 at the Nanfang Hospital, Southern Medical University were enrolled. Fifty healthy subjects were served as controls. Using genus-specific primers and genomic DNA extracted from the fecal samples, a quantitative analysis of the gut flora was conducted by real-time PCR. Relationships between the changes of gut flora and grade of liver function, prognostic score, inflammatory indicator and complications of cirrhosis were analyzed. Results: Compared with healthy subjects, fecal Enterobacterium was significantly enriched, while fecal Lactobacillus, Bacteroides and Clostridium were significantly reduced in cirrhotic patients (all P<0.05). Enterobacterium was positively correlated with the grade of liver function, Child-Turcotte-Pugh (CTP) score, model for end-stage liver disease (MELD) score, C-reactive protein (CRP), and the occurrence of spontaneous peritonitis, respectively (all P<0.05), while Clostridium was negatively correlated with the above mentioned indices (all P<0.05). Conclusions: Gut flora dysbiosis, including increase in Enterobacterium and decrease in Clostridium, is correlated with the severity and prognosis of patients with liver cirrhosis. It may aggravate liver cirrhosis by promoting an inflammatory response.

Research Progress of Polysaccharide Utilization Loci and Its Application in Pharmacological Research of Chinese Medicinal Herb / 中国实验方剂学杂志

Polysaccharide utilization loci (PULs) are a group of gene clusters related to polysaccharides catabolism and located in specific areas, including starch utilization system(SusC), SusD, encoding outer membrane glycoprotein binding proteins, and carbohydrate active enzymes. The wide existence of PULs in Bacteroides, and the extraordinary ability of utilizing polysaccharide is its survival strategy to adapt to the intestinal tract. On one hand, Bacteroides feature a high abundance and variety, making it the most important bacterial target group regulated by traditional Chinese medicine(TCM). On the other hand, polysaccharide is an important effective constituent among TCM chemicals, with a high content, and can also be used as a competitive carbon source for intestinal bacteria. Therefore, what is the mechanism of regulating the intestinal flora based on the carbon source of polysaccharide is an important part of the pharmacological research of TCM. According to the latest literatures, this paper introduces the gene and protein composition of PULs, reviews the latest developments in PULs research, and analyzes the structure of PULs in the genomes of Bacteroides fragilis and Bacteroides thetaiotaomicron. Furthermore, we also put forward a prospect for the pharmacological micro-ecological mechanism of TCM based on PULs based on our carbon source experiments, which focuses the effects of Bacteroides by TCM polysaccharides in vitro. This research is not only the new content of bacterial PULs researches, but also the important part of researches of "human-drug-bacteria" holistic view and TCM spleen-tonifying concept.

Update on the theory of intestinal origin of Parkinson's disease / 中华神经科杂志

Parkinson's disease (PD) is a progressive degenerative disease of the central nervous system,which is characterized by the aggregation of alpha-synuclein.Accumulating evidence suggests that PD may arise in the gut.Aggregation of alpha-synuclein was found in the enteric nervous system of patients with prodromal stage of PD,alpha-synuclein might spread from the enteric nervous system to the centralnervous system through vagus nerve based on animal model.The increased permeability and oxidative stress of gut may also be associated with the aggregation of alpha-synuclein and its propagation from gut to the central nerve system.

Clinical effect of Yiqiwenyang Huoxuelishui prescription on patients with cardiorenal syndrome and its influence on gut flora / 中国中西医结合急救杂志

Objective To observe the clinical therapeutic effect of Yiqiwenyang Huoxuelishui [a traditional Chinese medicine (TCM) prescription] on patients with cardiorenal syndrome (CRS) and its influence on gut flora. Methods Sixty-nine patients with definite diagnosis of CRS accompanied by heart-kidney yang deficiency admitted to Department of Geriatrics of the Third People's Hospital of Hangzhou from January 2015 to December 2016 were enrolled, and the patients were divided into two groups according to whether they received traditional Chinese medicine (TCM) or not. The control group (33 cases) was treated with only western medicine; the combination group (32 cases) was treated with conventional western medicine in addition of 100 mL of Yiqiwenyang Huoxuelishui decoction oral administration, twice a day, and the therapeutic course of both groups was 8 weeks. Before and after treatment, the level changes of left ventricular ejection fraction (LVEF), plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), carbohydrate antigen-125 (CA-125), growth differentiation factor-15 (GDF-15), growth differentiation factor-11 (GDF-11), blood creatinine (SCr), blood urea nitrogen (BUN), gut flora changes and the incidence of adverse reactions were observed in the two groups; after treatment, the clinical therapeutic effect of the two groups were compared. Results After treatment, the levels of LVEF and bifidobacteria, lactobacilli in intestinal tract of the two groups were significantly higher than those before treatment; while the levels of NT-proBNP, DGF-15, GDF-11, CA-125, SCr, BUN and enterococcus and enterobacter in the two groups were significantly lower than those before treatment, and the changes of the above indicators in combination group were more obvious than those in the control group [LVEF: 0.51±0.10 vs. 0.46±0.08, NT-proBNP (ng/L): 658±45 vs. 814±57, GDF-15 (ng/L): 604±32 vs. 708±36, CA-125 (U/L): 4.50±0.33 vs. 5.10±0.37, GDF-11 (ng/L): 491±19 vs. 594±23, SCr (μmol/L): 105±11 vs. 125±13, BUN (mmol/L): 8.1±3.5 vs. 9.7±4.2, bifidobacteria (cfu/g): 8.23±0.46 vs. 7.54±0.33, lactobacilli (cfu/g): 7.96±0.31 vs. 7.09±0.23, enterococcus (cfu/g): 6.32±0.19 vs. 7.15±0.28, enterobacter (cfu/g): 6.13±0.33 vs. 7.18±0.37, all P < 0.05]. In the combination group, there were 2 cases with mild abdominal distension and nausea at the initial stage, and 1 case with mild diarrhea, and because the manifestations were so mild, it was not necessary to stop the treatment. No hypotension occurred in both groups, and no liver or kidney function damage was observed. The rate of total therapeutic effect in the combination group was higher than that of the control group [87.5% (28/32) vs. 60.6% (20/33), P < 0.05]. Conclusion Yiqiwenyang Huoxuelishui prescription for treatment of patients with CRS accompanied by heart-kidney yang deficiency was safe and effective, it can elevate the clinical therapeutic effect, quality of life and improve the gut flora.

Effect of tacrolimus on short chain fatty acids in rats / 器官移植

Objective To investigate the changes of short chain fatty acids (SCFA) induced by tacrolimus (FK506) in rats and evaluate its effect on blood glucose levels. Methods Ten SD rats were divided into the FK506 group and control group (n=5 in each group). In the FK506 group, the rats were received a subcutaneous injection of FK506 (3 mg/kg) +sunflower oil solution containing 10% ethanol daily for consecutive 4 weeks. In the control group, the rats were received a subcutaneous injection of an equivalent amount of sunflower oil solution containing 10% ethanol for consecutive 4 weeks. During the drug injection period, the body mass of rats was measured every week in two groups. After the drug injection period, blood glucose level, SCFA content in the blood and feces samples were measured in two groups. Results Compared with the control group, the relative body mass of rats in the FK506 group was significantly lower at the 2nd, 3rd and 4thweeks (all P<0.01). Compared with the control group, the blood glucose levels of rats in the FK506 group were significantly increased at 0, 30, and 60 min after giving glucose (P<0.01-0.05). Compared with the control group, the contents of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid and valeric acid in the feces sample were significantly lower in the FK506 group (P<0.01-0.05). Conclusions FK506 can upregulate the blood glucose level in rats, which is probably induced by the decrease of SCFA content in rat feces.

Macleaya cordata helps improve the growth-promoting effect of chlortetracycline on broiler chickens / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Chlortetracycline (CTC), one kind of common antibiotic for prevention and treatment of various diseases, also exhibits good performance in accelerating the growth of livestock. Macleaya cordata, a traditional Chinese medicine, is usually used as a natural additive in livestock because of its anti-microbial, anti-fungal, anti-inflammatory, and pesticidal activity. In this work, we studied whether M. cordata helps regulate the growth-promoting effect of CTC on broiler chickens. It is demonstrated that M. cordata improves the growth-promoting effect of CTC on growth performance indices of broiler chickens, such as survival rate, daily weight, and feed to weight rate. M. cordata also delays the maximum of CTC residues in plasma. It may depend on the higher values of operational taxonomic unit (OTU) and the indices of α diversity driven by simultaneous use of CTC and M. cordata.

Effects of lactobacillus on cholesterolemia and gut flora in hyperlipidemia mice / 中国康复医学杂志

Objective:To test the effects of natural lactobacillus bio-products on lipid metabolism and intestinal microflora.Method:A hyperlipidemia mouse model system was developed.30 hyperlipidemia mice were randomly divided into three equal groups,i.e,saline water (control treatment),lactobacillus cocktail,and simvastatin.Mice were injected daily with saline water,lactobacillus (L.plantarum,L.acidophilus and L.casei,mixture in equal volume),and simvastatin solution,respectively.Result:Significant lower total cholesterol (TC),triglyceride (TG),and low-density lipoprotein cholesterol (LDL-C) were found in the blood serum from mice treated with lactobacillus and pharmaceutical simvastatin.CFUs (colony forming unity) of lactobacillus were much higher (P ＜ 0.05),whereas CFUs of Escherichia coli and Enterococcus faecalis were much lower (P＜ 0.05 and P＜ 0.05,respectively) in mice feces of treated by lactobacillus compared to pharmaceutical simvastatin.Conclusion:Lactobacillus probiotics reduced levels of cholesterolemia,increased CFUs of lactobacillus and reduced CFUs of E.coli and E.faecalis in gut.

Effects of lactobacillus on cholesterolemia and gut flora in hyperlipidemia mice / 中国康复医学杂志

Objective:To test the effects of natural lactobacillus bio-products on lipid metabolism and intestinal microflora.Method:A hyperlipidemia mouse model system was developed.30 hyperlipidemia mice were randomly divided into three equal groups,i.e,saline water (control treatment),lactobacillus cocktail,and simvastatin.Mice were injected daily with saline water,lactobacillus (L.plantarum,L.acidophilus and L.casei,mixture in equal volume),and simvastatin solution,respectively.Result:Significant lower total cholesterol (TC),triglyceride (TG),and low-density lipoprotein cholesterol (LDL-C) were found in the blood serum from mice treated with lactobacillus and pharmaceutical simvastatin.CFUs (colony forming unity) of lactobacillus were much higher (P ＜ 0.05),whereas CFUs of Escherichia coli and Enterococcus faecalis were much lower (P＜ 0.05 and P＜ 0.05,respectively) in mice feces of treated by lactobacillus compared to pharmaceutical simvastatin.Conclusion:Lactobacillus probiotics reduced levels of cholesterolemia,increased CFUs of lactobacillus and reduced CFUs of E.coli and E.faecalis in gut.

Human microecology, especially gut microflora provides unprecedented opportunities and challenges for new drug research and development / 中国药理学与毒理学杂志

Since entering the 21st century,the trend of high incidence of chronic diseases in the in?ternational community has not been effectively controlled and the pharmaceutical and medical fields are put forward new challenges. Both the development and evaluation of chemical drugs,biological drugs or traditional Chinese medicine are facing with how to significantly improve the efficacy and reduce the side effect of the drugs. With the coming of the accurate medical treatment as well as the big data era,new opportunities and challenges are needed either in the development of new drugs or new use of old drugs. However,as known that the human body consists of the symbiotic microbial groups of human microecological system especially the gut microecology system is more and more important in human health and disease,and even part diseases such as obesity and diabetes have a certain degree of causality with the gut microflora,so we need to reanalyze the core ideas about drug development or even the current medical theory system. Therefore,it is possible to step out of the old way of current drug development in the new period,to make new contributions on the real effective implementation of prevention and control of chronic diseases. According to international human body microecological especially the research progress of gut microecological field,systematic analysis of the problems existing in the current research and development of new drugs,will not only focus on the human body itself,but also the human microecology as well as the balance between human and micro?ecological,which will promote rapid development of research and development of new drugs and prevention and control of chronic disease in order to improve the physical and mental health services in our country.

Quantitative analysis of intestinal bacteria in Caenorhabditis elegans using qPCR / 军事医学

Objective To establish a method for detecting intestinal bacteria in Caenorhabditis elegans.Methods The gut flora number of 1, 20 or, 50 C.elegans was quantified and compared using real-time quantitative PCR (qPCR). Results The gut flora of a single C.elegans could be detected using qPCR method , which could also reflect the difference in the number of gut bacteria between different samples .Conclusion The qPCR method can be uased to accurately quantify intestinal bacteria even in only one C.elegans and has the advantages of low-cost, high-sensitivity and good-specificity.

Translational research into gut microbiota: new horizons on obesity treatment: updated 2014

Obesity is currently a pandemic of worldwide proportions affecting millions of people. Recent studies have proposed the hypothesis that mechanisms not directly related to the human genome could be involved in the genesis of obesity, due to the fact that, when a population undergoes the same nutritional stress, not all individuals present weight gain related to the diet or become hyperglycemic. The human intestine is colonized by millions of bacteria which form the intestinal flora, known as gut flora. Studies show that lean and overweight human may present a difference in the composition of their intestinal flora; these studies suggest that the intestinal flora could be involved in the development of obesity. Several mechanisms explain the correlation between intestinal flora and obesity. The intestinal flora would increase the energetic extraction of non-digestible polysaccharides. In addition, the lipopolysaccharide from intestinal flora bacteria could trigger a chronic sub-clinical inflammatory process, leading to obesity and diabetes. Another mechanism through which the intestinal flora could lead to obesity would be through the regulation of genes of the host involved in energy storage and expenditure. In the past five years data coming from different sources established causal effects between intestinal microbiota and obesity/insulin resistance, and it is clear that this area will open new avenues of therapeutic to obesity, insulin resistance and DM2.

Caenorhabditis elegans:an model organism for gut flora-host interactions research / 军事医学

Gut microbes play an important role in human health and are believed to be closely related to obesity , diabetes and some other metabolic diseases .Recently, intestinal flora has become a research hotspot and new target for disease prevention.The problems facing intestinal flora research included variability between individuals ,huge amounts and varieties of gut microbes .Caenorhabditis elegans, with the advantages of living on E.coli, short growth periods , easy observation,applicability to high throughput screening of drugs , is an ideal model organism for research of microbe-host interactions .It has been used in probiotics screening and interaction mechanism research of multifold bacteria .This review summarizes some new researches and applications in this area .

Advances in study on gut flora metabolism of chlorogenic acid / 中草药

Most of the Chinese materia medica (CMM) come into the digestive tract in the form of oral administration. Chemical constituents of being difficult in intestinal absorption or having long retention time in the gastrointestinal tract are more easier to be affected by gut flora. Many microbes in the intestinal tract play an important role in the metabolism of CMM. As one of the main active ingredients in many CMM, chlorogenic acid is getting a growing attention, especially its metabolism. In the stomach and small intestine, only about a third of chlorogenic acid is absorbed; Large intestine, especially colon with rich flora is the main metabolic absorption site of chlorogenic acid. This article mainly reviews in vivo and in vitro studies on the gut flora metabolism of chlorogenic acid and summarizes corresponding metabolic products, in order to provide the reference for further study of in vivo activities of chlorogenic acid.

Translational research into gut microbiota: new horizons in obesity treatment / Pesquisa translacional em microbiota intestinal: novos horizontes no tratamento da obesidade

Obesity is a pandemic which has been rapidly developing for three decades. When a population is submitted to the same nutritional stress, some individuals are less susceptible to diet-induced weight gain and hyperglycemia. This observation suggests that other mechanisms are involved which are not directly related to the human genome. The human gut contains an immense number of microorganisms, collectively known as the microbiota. Evidence that gut microbiota composition can differ between obese and lean humans has led to the speculation that gut microbiota can participate in the pathophysiology of obesity. Different mechanisms have been proposed to explain the link between gut flora and obesity. The first mechanism consists in the role of the gut microbiota to increase energy extraction from indigestible dietary polysaccharides. The second, consists in the role of gut flora to modulate plasma lipopolysaccharide levels which triggers chronic low-grade inflammation leading to obesity and diabetes. A third mechanism proposes that gut microbiota may induce regulation of host genes that modulate how energy is expended and stored. However, further studies are needed to clarify a number of issues related to the relationship between the gut microbiota and obesity.

A obesidade é uma pandemia que afeta milhões de pessoas em todo o mundo. Quando uma população é submetida ao mesmo estresse nutricional, alguns indivíduos são menos suscetíveis ao ganho de peso induzido pela dieta e à hiperglicemia. Essa observação sugere que outros mecanismos não diretamente relacionados ao genoma humano estejam envolvidos. O intestino humano é colonizado por milhões de bactérias, que coletivamente constituem a flora comensal normal. A evidência de que a composição da flora intestinal pode ser diferente em humanos magros e obesos levou à especulação de que a flora intestinal pode participar na fisiopatologia da obesidade. Diferentes mecanismos foram propostos para tentar explicar a correlação entre flora intestinal e obesidade. O primeiro mecanismo consiste no papel da flora intestinal na extração de energia de polissacarídeos não digeríveis. O segundo mecanismo envolve a modulação dos níveis de lipopolissacarídeo pela flora intestinal, o que desencadeia uma inflamação crônica subclínica que acarreta obesidade e diabetes. Um terceiro mecanismo propõe que a flora intestinal pode induzir a regulação de genes do hospedeiro que modulam como a energia é gasta e armazenada. Entretanto, estudos adicionais são necessários para estabelecer o papel da flora intestinal no desenvolvimento da obesidade.

Optimization of Separating Conditions of Mouse Gut Flora by High Performance Ion Exchange Chromatography Analysis / 中国生物工程杂志

The influence of separating effect of different chromatographic conditions of mouse gut flora by high performance ion exchange chromatography analysis was studied. The optimum chromatographic conditions for separating gut bacteria were determined. The sample was applied to the chromatography column packed with Toyopearl SuperQ-650c anion resin, equilibrated with 0.02mol/L piperazin-hydrochloric acid buffer (pH 8.0), and elution salt 1mol/L NaCl, eluted with the gradient of 0-50% NaCl/ 80 min, then 50%~75% NaCl/ 25 min at the flow rate 1ml/min, and injecting volume was 1ml.Under these conditions, intestinal flora were separated into several fractions. The establishment of HPLC analysis method will lay a foundation of further research on the components of mouse gut flora and their dynamic changes.

Effects of probiotics on the gut flora and mucosal tumor necrosis factor?expression in rats with experimental colitis / 中华消化杂志

Objective To evaluate the effects of probioties on inflammation,intestinal flora and mucosal tumor necrosis factor alpha(TNF-?)expression in experimental colitis rats.Methods Thirty Wistar rats were randomly divided into normal control group(NC),model control group(UC),and pro- biotics treatment group(PC).The experimental colitis were induced by trinitrobenzene sulfonie acid (TNBS)/ethanol enema.Rats in PC group were fed with Bifico[live probiotics of combined bifidobacte- rium(Bif),lactobacillus (Lac) and enterococcus]by 2.2?10~9 colony-forming unit (CFU)/d for 4 weeks.Inflammatory scores and mucosal morphological changes under light microscopy were studied. Plasma endotoxin levels,expressions of TNF-?and interleukin-6 (IL-6) in mueosa were measured. Enteric microorganisms in cecum were fostered with standard methods.Results Inflammatory scores in PC group decreased compared with those in UC group(7.94?0.85 vs 10.25?1.36,P＜0.05),but still higher than those in NC group(7.94?0.85 vs 4.35?0.88,P＜0.01).There was a significant alteration in the enteric microbial flora,Bif and Lac were decreased significantly in UC group,Bifico supplement ameliorated this imbalance.Plasma endotoxin and mucosal TNF-?levels in PC were lower than those in UC group[endotoxin:(93.33?21.22)pg/ml vs (121.25?39.07)pg/ml;TNF-?:67.51?14.63 vs 85.99?18.17,P＜0.05],but higher than those in NC group[endotoxin:(93.33?21.22) pg/ml vs(35.20?15.12)pg/ml;TNF+?:67.51?14.63 vs 43.28 4?19.98,P＜0.01].There was no statistically significant difference in mucosal IL-6 levels between PC group and UC group,though its level in PC group was lower than that in UC group(155.22?34.01 vs 184.09?29.11,P＞0.05),but higher than that in NC group(155.22?34.01 vs 108.73?37.35,P＜0.01).Conclusions Probiotics can attenuate inflammation of experimental colitis of rats through reinstituting gut flora bal- anee.Improving gut flora imbalance,reducing endotoxin and pro-inflammatory cytokines may be the effects of probiotics.

Influences of enteral and parenteral nutrition on the gut microecology of the rats with abdominal infection / 肠外与肠内营养

Objective: To investigate the influences of enteral and parenteral nutrition suppled by gut on the gut microecology of the rats with abdominal infection. Methods: 14 Sprague-Dawley(SD)rats with abdominal infection models made with cecal ligation and perforation method were divided into two groups: parenteral nutrition (PN group, n=7) and PN+enteral nutrition (EN group, n=7) . The components of nutrition solutions in the two groups were isonitrogen and isocaloric. The rats were killed in the sixth day. The feces in cecum were cultured for anaerobic bacterial growth and analysed by bacterial group DNA fingerprint spectrum with random amplified polymorphic DNA . Results: ①The total death rate of the rats was 69.6%. Abdominal cavity abscess, liver abscess, and pulmonary infection commonly appeared in the model rats. ②The number of germs cultured in EN group was higher than in the PN group, but the quantity of Cl Perfrigens was higher , too. The gene stripe of probiotics group in EN group was similar to that in normal rats showed in the DNA fingerprint spectrum, but was significantly different in PN group with strange stripes. Conclusion: Application of early EN may correct the intestinal flora disturbance resulted from PN and increase the quantity of intestinal flora, but it can't control the species and may increase some conditional pathogenic bacteria .