Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly ...Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.展开更多
BACKGROUND Colorectal polyps,which are characterized by a high recurrence rate,represent preneoplastic conditions of the intestine.Due to unclear mechanisms of pathogenesis,first-line therapies for non-hereditary recu...BACKGROUND Colorectal polyps,which are characterized by a high recurrence rate,represent preneoplastic conditions of the intestine.Due to unclear mechanisms of pathogenesis,first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection.Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps,the exact compositions and roles of bacteria in the mucosa around the lesions,rather than feces,remain unsettled.AIM To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps.METHODS Mucosal samples were collected from four patients consistently with adenomatous polyps(Ade),seven consistently with non-Ade(Pol),ten with current Pol but previous Ade,and six healthy individuals,and bacterial patterns were evaluated by 16S rDNA sequencing.Linear discriminant analysis and Student’s t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes.Pearson’s correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators.RESULTS The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals.These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps,but also existed in histologically normal tissue 10 cm distal from the lesions.Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions,Pol,and Ade.Increased abundance of Gram-negative bacteria,including Klebsiella,Plesiomonas,and Cronobacter,was observed in Pol group and Ade group,suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment.Meanwhile,age and gender were linked to bacteria changes,indicating the potential involvement of sex hormones.CONCLUSION These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps,especially adenoma.Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.展开更多
Gut dysbiosis,a phenomenon in which the existing commensal microbiome cha-nges to an adverse microenvironment in the colon,is thought to lead to altered cellular signals.How this is involved in producing mucosal outgr...Gut dysbiosis,a phenomenon in which the existing commensal microbiome cha-nges to an adverse microenvironment in the colon,is thought to lead to altered cellular signals.How this is involved in producing mucosal outgrowths such as polyps in the colon is intriguing.Deciphering the various mechanisms involved provides an in-depth understanding of the link between gut dysbiosis and colonic polyps.展开更多
A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of...A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).A subgroup of NAFLD patients have a severely progressive form,namely nonalcoholic steatohepatitis(NASH),which is characterized by histological findings that include inflammatory cell infiltration and fibrosis.NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma.The oral microbiota may serve as an endogenous reservoir for gut microbiota,and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis.Gut dysbiosis increases the production of potential hepatotoxins,including lipopolysaccharide,ethanol,and other volatile organic compounds such as acetone,phenol and cyclopentane.Moreover,gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall,leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation.In particular,many animal studies support that oral administration of Porphyromonas gingivalis,a typical periodontopathic bacterium,induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis.NAFLD,also known as the hepatic phenotype of metabolic syndrome,is strongly associated with metabolic complications,such as obesity and diabetes.Periodontal disease also has a bidirectional relationship with metabolic syndrome,and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively.In this review,we will describe the link between periodontal disease and NAFLD with a focus on basic,epidemiological,and clinical studies,and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome.In conclusion,it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease,gut microbiota,and metabolic syndrome.Thus,the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics,prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.展开更多
Heat stress is one of the most challenging stressors for animal production due to high economic losses resulting from impaired animal’s productivity,health and welfare.Despite the fact that all farm animal species ar...Heat stress is one of the most challenging stressors for animal production due to high economic losses resulting from impaired animal’s productivity,health and welfare.Despite the fact that all farm animal species are susceptible to heat stress,birds and pigs are particularly sensitive to heat stress due to either lacking or non-functional sweat glands.Con-vincing evidence in the literature exists that gut dysbiosis,a term used to describe a perturbation of commensal gut microbiota,develops in broilers and pigs under heat stress.Owing to the protective role of commensal bacteria for the gut barrier,gut dysbiosis causes a disruption of the gut barrier leading to endotoxemia,which contributes to the typical characteristics of heat stressed broilers and growing and growing-finishing pigs,such as reduced feed intake,decreased growth and reduced lean carcass weight.A substantial number of studies have shown that feeding of probiotics,prebiotics and synbiotics is an efficacious strategy to protect broilers from heat stress-induced gut barrier disruption through altering the gut microbiota and promoting all decisive structural,biochemical,and immunologi-cal elements of the intestinal barrier.In most of the available studies in heat stressed broilers,the alterations of gut microbiota and improvements of gut barrier function induced by feeding of either probiotics,prebiotics or synbiot-ics were accompanied by an improved productivity,health and/or welfare when compared to non-supplemented broilers exposed to heat stress.These findings indicate that the restoration of gut homeostasis and function is a key target for dietary interventions aiming to provide at least partial protection of broilers from the detrimental impact of heat stress conditions.Despite the fact that the number of studies dealing with the same feeding strategy in heat stressed pigs is limited,the available few studies suggest that feeding of probiotics might also be a suitable approach to enhance productivity,health and welfare in pigs kept under heat stress conditions.展开更多
Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic disturbance.Trimethylamine N-oxide(TMAO),produced in the dietary choline metaboli...Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic disturbance.Trimethylamine N-oxide(TMAO),produced in the dietary choline metabolism,has been found to accelerate neurodegeneration in AD pathology.In this study,the cognitive function and gut microbiota of TgCRND8(Tg)mice of different ages were evaluated by Morris water maze task(MWMT)and 16S rRNA sequencing,respectively.Young pseudo germ-free(PGF)Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type(WT)mice were selected to determine the role of the gut microbiota in the process of neuropathology.Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions.Our results showed that gut dysbiosis,neuroinflammation response,Ab deposition,tau hyperphosphorylation,TMAO overproduction and cyclin-dependent kinase 5(CDK5)/transcription 3(STAT3)activation occurred in Tg mice age-dependently.Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice,with the activation of CDK5/STAT3 signaling in the brains.On the contrary,faecal microbiota transplantation from WT mice alleviated the cognitive deficits,attenuated neuroinflammation,Ab deposition,tau hyperphosphorylation,TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice.Moreover,excessive choline treatment was also shown to aggravate the cognitive deficits,Ab deposition,neuroinflammation and CDK5/STAT3 pathway activation.These findings provide a novel insight into the interaction between gut dysbiosis and AD progression,clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.展开更多
Background: Intestinal microbial dysbiosis is involved in liver disease pathogenesis. However, its role in primary liver cancer(PLC), particularly in hepatocarcinogenesis remains unclear. The present study aimed to st...Background: Intestinal microbial dysbiosis is involved in liver disease pathogenesis. However, its role in primary liver cancer(PLC), particularly in hepatocarcinogenesis remains unclear. The present study aimed to study the changes in intestinal flora at various stages of PLC and clarify the relationship between intestinal microbes and PLC. Methods: Twenty-four patients with PLC(PLC group), 24 patients with liver cirrhosis(LC group), and 23 healthy control individuals(HC group) were enrolled from October 2016 to October 2017. Stool specimens of the participants were collected and the genomic DNA of fecal bacteria was isolated. High-throughput pyrosequencing of 16 S r DNA was used to identify differences in gut bacterial diversity among HC, LC, and PLC groups. We also analyzed the relationship between clinical factors and intestinal microorganisms in LC and PLC groups. Results: Diversity of Firmicutes tended to decrease from the HC to LC and PLC groups at the phylum level. Among species, Enterobacter ludwigii displayed an increasing trend in the PLC group, wherein the relative abundance of Enterobacter ludwigii in the PLC group was 100 times greater than that in the HC and LC groups. The ratio of Firmicutes/Bacteroidetes was significantly decreased with the disease progression. In addition, the linear discriminant analysis effect size method indicated that Clostridia were predominant in the gut microbiota of the HC group, whereas Enterococcaceae, Lactobacillales, Bacilli and Gammaproteobacteria may be used as diagnostic markers of PLC. Redundancy analysis showed a correlation between intestinal microbial diversity and clinical factors AST, ALT, and AFP. Veillonella showed a significant positive correlation with AFP in the PLC group, whereas Subdoligranulum showed a negative correlation with AFP. Conclusions: This study indicates that dysbiosis of the gut microbiota might be involved in PLC development and progression.展开更多
Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastri...Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (i.e., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.展开更多
Genomic sequencing,bioinformatics,and initial speciation(e.g.,relative abundance)of the commensal microbiome have revolutionized the way we think about the“human”body in health and disease.The interactions between t...Genomic sequencing,bioinformatics,and initial speciation(e.g.,relative abundance)of the commensal microbiome have revolutionized the way we think about the“human”body in health and disease.The interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases,including those impacting the esophagus.Although relatively stable,there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome(EM)and the host.These changes are thought to be a product of age,diet,antibiotic and other medication use,oral hygiene,smoking,and/or expression of antibiotic products(bacteriocins)by other flora.These effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation,systemic inflammation,and ultimately disease progression.Research has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is,therefore,not merely the result of esophageal mucosal exposure to corrosives(i.e.,acid).Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory cascade.Here,we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief(i.e.,acid suppression).展开更多
AIM To investigate alterations in the fecal microbiome using 16 S r RNA amplicon sequencing in couples in the same cohabitation environment.METHODS Fecal samples were collected from eight ulcerative colitis(UC) patien...AIM To investigate alterations in the fecal microbiome using 16 S r RNA amplicon sequencing in couples in the same cohabitation environment.METHODS Fecal samples were collected from eight ulcerative colitis(UC) patients and their healthy partners at Lishui People's Hospital, Zhejiang Province, China. DNA was extracted and the variable regions V3 and V4 of the 16 S r RNA genes were PCR amplified using a two-step protocol. Clear reads were clustered into operational taxonomic units(OTUs) at the 97% sequence similarity level using UCLUST v1.2.22. The Wilcoxon rank-sumtest(R v3.1.2) was used to compare inter-individual differences. Differences with a P value < 0.05 were considered statistically significant.RESULTS Fecal microbial communities were more similar among UC patients than their healthy partners(P = 0.024). UC individuals had a lower relative abundance of bacteria belonging to the Firmicutes, especially Blautia, Clostridium, Coprococcus and Roseburia(P < 0.05). Microbiota dysbiosis was detected in UC patients and their healthy partners. Relevant genera included Akkermansiam, Bacteroides, Escherichia, Lactobacillales, Klebsiella and Parabacteroides. The enriched pathways in fecal samples of UC patients were related to lipid and nucleotide metabolism. Additionally, the pathways involved in membrane transport and metabolism of cofactors and vitamins were more abundant in the healthy partners.CONCLUSION Our results suggested that the microbial composition might be affected in healthy partners cohabiting with UC patients, especially in terms of microbiota dysbiosis.展开更多
AIM To analyze the alterations of fecal microbiota in Chinese patients with inflammatory bowel disease(IBD).METHODS Fecal samples from 15 patients with Crohn's disease(CD)(11 active CD, 4 inactive CD), 14 patients...AIM To analyze the alterations of fecal microbiota in Chinese patients with inflammatory bowel disease(IBD).METHODS Fecal samples from 15 patients with Crohn's disease(CD)(11 active CD, 4 inactive CD), 14 patients with active ulcerative colitis(UC) and 13 healthy individuals were collected and subjected to 16 S ribosomal DNA(rDNA) gene sequencing. The V4 hypervariable regions of 16 S rDNA gene were amplified from all samples and sequenced by the Illumina Mi Seq platform. Quality control and operational taxonomic units classification of reads were calculated with QIIME software. Alpha diversity and beta diversity were displayed with R software.RESULTS Community richness(chao) and microbial structure in both CD and UC were significantly different from those in normal controls. At the phyla level, analysis of the microbial compositions revealed a significantly greater abundance of Proteobacteria in IBD as compared to that in controls. At the genera level, 8 genera in CD and 23 genera in UC(in particular, the Escherichia genus) showed significantly greater abundance as compared to that in normal controls. The relative abundance of Bacteroidetes in the active CD group was markedly lower than that in the inactive CD group. The abundance of Proteobacteria in patients with active CD was nominally higher than that in patients with inactive CD; however, the difference was not statistically significant after correction. Furthermore, the relative abundance of Bacteroidetes showed a negative correlation with the CD activity index scores.CONCLUSION Our study profiles specific characteristics and microbial dysbiosis in the gut of Chinese patients with IBD. Bacteroidetes may have a negative impact on inflammatory development.展开更多
BACKGROUND Gut dysbiosis and small intestinal bacterial overgrowth(SIBO)are commonly observed in patients with cirrhosis.Despite the substantial number of articles describing the relations between disorders of gut mic...BACKGROUND Gut dysbiosis and small intestinal bacterial overgrowth(SIBO)are commonly observed in patients with cirrhosis.Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis,dysbiosis and SIBO were always studied separately.AIM To study the relationship of gut dysbiosis and SIBO in cirrhosis.METHODS This observational study included 47 in-patients with cirrhosis.Stool microbiome was assessed using 16 S r RNA gene sequencing.SIBO was assessed using the lactulose hydrogen breath test.RESULTS SIBO was found in 24/47(51.1%)patients.Patients with SIBO had a higher abundance of Firmicutes(P=0.017)and Fusobacteria(P=0.011),and a lower abundance of Bacteroidetes(P=0.013)than patients without SIBO.This increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia(P=0.020)of the Lachnospiraceae family(P=0.047),while the abundance of other major families of this phylum[Ruminococcaceae(P=0.856),Peptostreptococcaceae(P=0.066),Clostridiaceae(P=0.463),Eubacteriaceae(P=0.463),Lactobacillaceae(P=0.413),and Veillonellaceae(P=0.632)]did not differ significantly between the patients with and without SIBO.Reduced level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum[Bacteroidaceae(P=0.014),Porphyromonadaceae(P=0.002),and Rikenellaceae(P=0.047)],with the exception of Prevotellaceae(P=0.941).There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis[Proteobacteria(P=0.790),Bacilli(P=0.573),Enterobacteriaceae(P=0.632),Streptococcaceae(P=0.170),Staphylococcaceae(P=0.450),and Enterococcaceae(P=0.873)]between patients with and without SIBO.CONCLUSION Despite the differences observed in the gut microbiome between patients with and without SIBO,gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.展开更多
BACKGROUND Gut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus(T1DM).However,the alterations in the gut microbiota and their correlation with fasting blood ...BACKGROUND Gut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus(T1DM).However,the alterations in the gut microbiota and their correlation with fasting blood glucose(FBG)in Chinese children with T1DM remain unclear.AIM To investigate alterations in the gut microbiota in Chinese children with T1DM and their associations with clinical indicators.METHODS Samples from 51 children with T1DM and 47 age-matched and gender-matched healthy controls were obtained,to explore the structural and functional alterations in the fecal microbiota.The V3-V4 regions of the 16S rRNA gene were sequenced on a MiSeq instrument,and the association with FBG were analyzed.RESULTS We found that the bacterial diversity was significantly increased in the T1DMassociated fecal microbiota,and changes in the microbial composition were observed at different taxonomic levels.The T1DM-reduced differential taxa,such as Bacteroides vulgatus ATCC8482,Bacteroides ovatus,Bacteroides xylanisolvens,and Flavonifractor plautii,were negatively correlated with FBG,while the T1DMenriched taxa,such as Blautia,Eubacterium hallii group,Anaerostipes hadrus,and Dorea longicatena,were positively correlated with FBG.Bacteroides vulgatus ATCC8482,Bacteroides ovatus,the Eubacterium hallii group,and Anaerostipes hadrus,either alone or in combination,could be used as noninvasive diagnostic biomarkers to discriminate children with T1DM from healthy controls.In addition,the functional changes in the T1DM-associated fecal microbiota also suggest that these fecal microbes were associated with altered functions and metabolic activities,such as glycan biosynthesis and metabolism and lipid metabolism,which might play vital roles in the pathogenesis and development of T1DM.CONCLUSION Our present comprehensive investigation of the T1DM-associated fecal microbiota provides novel insights into the pathogenesis of the disease and sheds light on the diagnosis and treatment of T1DM.展开更多
BACKGROUND Gut dysbiosis is common in cirrhosis.AIM To study the influence of gut dysbiosis on prognosis in cirrhosis.METHODS The case-control study included 48 in-patients with cirrhosis and 21 healthy controls.Stool...BACKGROUND Gut dysbiosis is common in cirrhosis.AIM To study the influence of gut dysbiosis on prognosis in cirrhosis.METHODS The case-control study included 48 in-patients with cirrhosis and 21 healthy controls.Stool microbiome was assessed using 16S ribosomal ribonucleic acid gene sequencing.We used modified dysbiosis ratio(MDR):[Bacilli(%)+Proteobacteria(%)]/[Clostridia(%)+Bacteroidetes(%)].Patients with MDR more the median made up the group with severe dysbiosis,others did the group with nonsevere dysbiosis.The follow-up period was 4 years.RESULTS The mortality rate of patients with severe dysbiosis was significantly higher than that of patients with non-severe dysbiosis(54.2%vs 12.5%;P=0.001).The presence of severe dysbiosis was independent risk factors for death[hazard ratio=8.6×(1.9-38.0);P=0.005].The abundance of Enterobacteriaceae(P=0.002),Proteobacteria(P=0.002),and Lactobacillaceae(P=0.025)was increased and the abundance of Firmicutes(P=0.025)and Clostridia(P=0.045)was decreased in the deceased patients compared with the survivors.The deceased patients had a higher MDR value than the survivors[0.131×(0.069-0.234)vs 0.034×(0.009-0.096);P=0.004].If we applied an MDR value of 0.14 as the cutoff point,then it predicted patient death within the next year with a sensitivity of 71.4%and a specificity of 82.9%[area under the curve=0.767×(0.559-0.974)].MDR was higher in patients with cirrhosis than in health controls[0.064×(0.017-0.131)vs 0.005×(0.002-0.007);P<0.001],and in patients with decompensated cirrhosis than in patients with compensated cirrhosis[0.106×(0.023-0.211)vs 0.033×(0.012-0.074);P=0.031].MDR correlated negatively with prothrombin(r=-0.295;P=0.042),cholinesterase(r=-0.466;P=0.014)and serum albumin(r=-0.449;P=0.001)level and positively with Child–Turcotte–Pugh scale value(r=0.360;P=0.012).CONCLUSION Gut dysbiosis is associated with a poorer long-term prognosis in cirrhosis.展开更多
Objective:Coronavirus disease 2019(COVTD-19)is often accompanied by gastrointestinal symptoms,which are related to gut microbiota dysbiosis(GMD).Whether washed microbiota transplantation(WMT)is an effective treatment ...Objective:Coronavirus disease 2019(COVTD-19)is often accompanied by gastrointestinal symptoms,which are related to gut microbiota dysbiosis(GMD).Whether washed microbiota transplantation(WMT)is an effective treatment for COV1D-19 patients suspected of having GMD by restoring the gut microbiota is unknown.This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD.Methods:This is a randomized,multicenter,single-blind prospective study.COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT.The frequency of WMT will be once a day for three consecutive days.Laboratory and imaging examinations will be performed at admission,1 and 2 weeks after treatment,and on the day of discharge.Then a telephone follow-up will be conducted at 1st week,2nd week,and 6th month after discharge.The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function,homeostasis,inflammatory response,intestinal mucosal barrier function,and immunity of the patients will be evaluated.Results:By following the proposed protocol,WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD,and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function,inflammatory response,and immunity.Conclusion:The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD.展开更多
The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes.First,faecal and salivary samples were collected from periodontally healthy participants(P...The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes.First,faecal and salivary samples were collected from periodontally healthy participants(PH group,n=16)and patients with severe periodontitis(SP group,n=21)and analysed by 16S ribosomal RNA sequencing.Significant differences were observed in both the faecal and salivary microbiota between the PH and SP groups.Notably,more saliva-sourced microbes were observed in the faecal samples of the SP group.Then,the remaining salivary microbes were transplanted into C57BL6/J mice(the C-PH group and the C-SP group),and it was found that the composition of the gut microbiota of the C-SP group was significantly different from that of the C-PH group,with Porphyromonadaceae and Fusobacterium being significantly enriched in the C-SP group.In the colon,the C-SP group showed significantly reduced crypt depth and zonula occludens-1 expression.The m RNA expression levels of pro-inflammatory cytokines,chemokines and tight junction proteins were significantly higher in the C-SP group.To further investigate whether salivary bacteria could persist in the intestine,the salivary microbiota was stained with carboxyfluorescein diacetate succinimidyl ester and transplanted into mice.We found that salivary microbes from both the PH group and the SP group could persist in the gut for at least 24 h.Thus,our data demonstrate that periodontitis may induce gut microbiota dysbiosis through the influx of salivary microbes.展开更多
BACKGROUND Obesity and comorbidities onset encompass gut dysbiosis,altered intestinal permeability,and endotoxemia.Treatments that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease(NAFLD)...BACKGROUND Obesity and comorbidities onset encompass gut dysbiosis,altered intestinal permeability,and endotoxemia.Treatments that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease(NAFLD)management.Peroxisome proliferator-activated receptor(PPAR)-alpha activation and dipeptidyl-peptidase-4(DPP-4)inhibition alleviate NAFLD,but the mechanism may involve gut microbiota modulation and merits further investigation.AIM To address the effects of PPAR-alpha activation and DPP-4 inhibition(isolated or combined)upon the gut-liver axis,emphasizing inflammatory pathways in NAFLD management in high-fat-fed C57BL/6J mice.METHODS Male C57BL/6J mice were fed a control diet(C,10%of energy as lipids)or a highfat diet(HFD,50%of energy as lipids)for 12 wk,when treatments started,forming the groups:C,HF,HFA(HFD+PPAR-alpha agonist WY14643,2.5 mg/kg body mass),HFL(HFD+DPP-4 inhibitor linagliptin,15 mg/kg body mass),and HFC(HFD+the combination of WY14643 and linagliptin).RESULTS The HFD was obesogenic compared to the C diet.All treatments elicited significant body mass loss,and the HFC group showed similar body mass to the C group.All treatments tackled oral glucose intolerance and raised plasma glucagon-like peptide-1 concentrations.These metabolic benefits restored Bacteroidetes/Firmicutes ratio,resulting in increased goblet cells per area of the large intestine and reduced lipopolysaccharides concentrations in treated groups.At the gene level,treated groups showed higher intestinal Mucin 2,Occludin,and Zo-1 expression than the HFD group.The reduced endotoxemia suppressed inflammasome and macrophage gene expression in the liver of treated animals.These observations complied with the mitigation of liver steatosis and reduced hepatic triacylglycerol,reassuring the role of the proposed treatments on NAFLD mitigation.CONCLUSION PPAR alpha activation and DPP-4 inhibition(isolated or combined)tackled NAFLD in dietinduced obese mice by restoration of gut-liver axis.The reestablishment of the intestinal barrier and the rescued phylogenetic gut bacteria distribution mitigated liver steatosis through antiinflammatory signals.These results can cope with NAFLD management by providing pre-clinical evidence that drugs used to treat obesity comorbidities can help to alleviate this silent and harmful liver disease.展开更多
Exercise-induced changes of the microbiome in inflammatory bowel diseases(IBD)is a promising field of research with the potential for personalized exercise regimes as a promising therapeutic adjunct for restoring gut ...Exercise-induced changes of the microbiome in inflammatory bowel diseases(IBD)is a promising field of research with the potential for personalized exercise regimes as a promising therapeutic adjunct for restoring gut dysbiosis and additionally for regulating immunometabolic pathways in the management of IBD patients.Structured exercise programmes in IBD patients of at least of 12 wk duration are more likely to result in disease-altering changes in the gut microbiome and to harness potential anti-inflammatory effects through these changes along with immunometabolic pathways.展开更多
AIM: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice. METHODS: Two sets of experiments were designed. In the first set, recently weaned mice were eith...AIM: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice. METHODS: Two sets of experiments were designed. In the first set, recently weaned mice were either orally administered ferrous (Fe2+) iron salt or ferric (Fe3+) microencapsulated iron for 6 wk. The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced. In the second set, juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments. In both sets of experiments, animals were sacrificed 7 d after TNBS instillation. Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (MPO) activity. Alteration of the microflora profile was estimated usingquantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora, Bacteroidetes, Firmicutes and enterobacteria. RESULTS: Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain. Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27 MPO U/mg proteinvs 2.47 ± 0.22 MPO U/mg protein in colitic mice). In contrast, ferric iron significantly prevented the increase of MPO activity (1.64 ± 0.14 MPO U/mg protein) in TNBS-induced colitis. Moreover, this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po - 6 wk). In the study we also compared, in both rats and mice, the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po - 6 wk) on TNBS-induced colitis and its related dysbiosis. We confirmed that ferric iron limited the TNBS-induced increase of MPO activity in both the rodent species. Furthermore, we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis. At first, we needed to optimize the isolation and quantify DNA copy numbers using standard curves to perform by qPCR this interspecies comparison. Using this approach, we determined that total microflora was similar in control rats and mice and was mainly composed of Firmicutes and Bacteroidetes at a ratio of 10/1. Ferric juvenile administration did not modify the microflora profile in control animals. Total microflora numbers remained unchanged whichever experimental conditions studied. Following TNBS-induced colitis, the Firmicutes/Bacteroidetes ratio was altered resulting in a decrease of the Firmicutes numbers and an increase of the Bacteroidetes numbers typical of a gut inflammatory reaction. In parallel, the subdominant population, the enterobacteria was also increased. However, ferric iron supplementation for the juvenile period prevented the increase of Bacteroidetes and of enterobacteria numbers consecutive to the colitis in both the studied species at adulthood.CONCLUSION: Rats and mice juvenile chronic ferric iron ingestion prevents colitis and dysbiosis at adulthood as assessed by the first interspecies comparison.展开更多
BACKGROUND Gut dysbiosis and changes in body composition(i.e.,a decrease in the proportion of muscle mass and an increase in extracellular fluid)are common in cirrhosis.AIM To study the relationship between the gut mi...BACKGROUND Gut dysbiosis and changes in body composition(i.e.,a decrease in the proportion of muscle mass and an increase in extracellular fluid)are common in cirrhosis.AIM To study the relationship between the gut microbiota and body composition in cirrhosis.METHODS This observational study included 46 patients with cirrhosis.Stool microbiome was assessed using 16S rRNA gene sequencing.Multifrequency bioelectrical impedance analysis was performed to assess body composition in these patients.RESULTS An increase in fat mass and a decrease in body cell mass were noted in 23/46(50.0%)and 15/46(32.6%)patients,respectively.Changes in the gut microbiome were not independently associated with the fat mass percentage in cirrhosis.The abundance of Bacteroidaceae(P=0.041)and Eggerthella(P=0.001)increased,whereas that of Erysipelatoclostridiaceae(P=0.006),Catenibacterium(P=0.021),Coprococcus(P=0.033),Desulfovibrio(P=0.043),Intestinimonas(P=0.028),and Senegalimassilia(P=0.015)decreased in the gut microbiome of patients with body cell mass deficiency.The amount of extracellular fluid increased in 22/46(47.6%)patients.Proteobacteria abundance(P<0.001)increased,whereas Firmicutes(P=0.023),Actinobacteria(P=0.026),Bacilli(P=0.008),Anaerovoraceceae(P=0.027),Christensenellaceae(P=0.038),Eggerthellaceae(P=0.047),Erysipelatoclostridiaceae(P=0.015),Erysipelotrichaceae(P=0.003),Oscillospiraceae(P=0.024),Rikenellaceae(P=0.002),Collinsella(P=0.030),Hungatella(P=0.040),Peptococcaceae(P=0.023),Slackia(P=0.008),and Senegalimassilia(P=0.024)abundance decreased in these patients.Patients with clinically significant ascites(n=9)had a higher abundance of Proteobacteria(P=0.031)and a lower abundance of Actinobacteria(P=0.019)and Bacteroidetes(P=0.046)than patients without clinically significant ascites(n=37).CONCLUSION Changes in the amount of body cell mass and extracellular fluid are associated with changes in the gut microbiome in cirrhosis patients.展开更多
文摘Hyperuricemia(HUA)is a condition associated with a high concentration of uric acid(UA)in the bloodstream and can cause gout and chronic kidney disease.The gut microbiota of patients with gout and HUA is significantly altered compared to that of healthy people.This article focused on the complex interconnection between alterations in the gut microbiota and the development of this disorder.Some studies have suggested that changes in the composition,diversity,and activity of microbes play a key role in establishing and progressing HUA and gout pathogenesis.Therefore,we discussed how the gut microbiota contributes to HUA through purine metabolism,UA excretion,and intestinal inflammatory responses.We examined specific changes in the composition of the gut microbiota associated with gout and HUA,highlighting key bacterial taxa and the metabolic pathways involved.Additionally,we discussed the effect of conventional gout treatments on the gut microbiota composition,along with emerging therapeutic approaches that target the gut microbiome,such as the use of probiotics and prebiotics.We also provided insights into a study regarding the gut microbiota as a possible novel therapeutic intervention for gout treatment and dysbiosis-related diagnosis.
基金Supported by National Science Foundation of China,No.82160546the Science Foundation of Jiangxi Province,No.20202BBG73027+1 种基金the Foundation of Jiangxi Province for Distinguished Scholars,No.jxsq2023201020the Science and Technology Project of Jiangxi Administration of Traditional Chinese Medicine,No.2022B789.
文摘BACKGROUND Colorectal polyps,which are characterized by a high recurrence rate,represent preneoplastic conditions of the intestine.Due to unclear mechanisms of pathogenesis,first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection.Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps,the exact compositions and roles of bacteria in the mucosa around the lesions,rather than feces,remain unsettled.AIM To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps.METHODS Mucosal samples were collected from four patients consistently with adenomatous polyps(Ade),seven consistently with non-Ade(Pol),ten with current Pol but previous Ade,and six healthy individuals,and bacterial patterns were evaluated by 16S rDNA sequencing.Linear discriminant analysis and Student’s t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes.Pearson’s correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators.RESULTS The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals.These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps,but also existed in histologically normal tissue 10 cm distal from the lesions.Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions,Pol,and Ade.Increased abundance of Gram-negative bacteria,including Klebsiella,Plesiomonas,and Cronobacter,was observed in Pol group and Ade group,suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment.Meanwhile,age and gender were linked to bacteria changes,indicating the potential involvement of sex hormones.CONCLUSION These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps,especially adenoma.Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.
文摘Gut dysbiosis,a phenomenon in which the existing commensal microbiome cha-nges to an adverse microenvironment in the colon,is thought to lead to altered cellular signals.How this is involved in producing mucosal outgrowths such as polyps in the colon is intriguing.Deciphering the various mechanisms involved provides an in-depth understanding of the link between gut dysbiosis and colonic polyps.
文摘A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).A subgroup of NAFLD patients have a severely progressive form,namely nonalcoholic steatohepatitis(NASH),which is characterized by histological findings that include inflammatory cell infiltration and fibrosis.NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma.The oral microbiota may serve as an endogenous reservoir for gut microbiota,and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis.Gut dysbiosis increases the production of potential hepatotoxins,including lipopolysaccharide,ethanol,and other volatile organic compounds such as acetone,phenol and cyclopentane.Moreover,gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall,leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation.In particular,many animal studies support that oral administration of Porphyromonas gingivalis,a typical periodontopathic bacterium,induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis.NAFLD,also known as the hepatic phenotype of metabolic syndrome,is strongly associated with metabolic complications,such as obesity and diabetes.Periodontal disease also has a bidirectional relationship with metabolic syndrome,and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively.In this review,we will describe the link between periodontal disease and NAFLD with a focus on basic,epidemiological,and clinical studies,and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome.In conclusion,it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease,gut microbiota,and metabolic syndrome.Thus,the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics,prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.
基金Open Access funding enabled and organized by Projekt DEAL.No funding was used to write this manuscript.
文摘Heat stress is one of the most challenging stressors for animal production due to high economic losses resulting from impaired animal’s productivity,health and welfare.Despite the fact that all farm animal species are susceptible to heat stress,birds and pigs are particularly sensitive to heat stress due to either lacking or non-functional sweat glands.Con-vincing evidence in the literature exists that gut dysbiosis,a term used to describe a perturbation of commensal gut microbiota,develops in broilers and pigs under heat stress.Owing to the protective role of commensal bacteria for the gut barrier,gut dysbiosis causes a disruption of the gut barrier leading to endotoxemia,which contributes to the typical characteristics of heat stressed broilers and growing and growing-finishing pigs,such as reduced feed intake,decreased growth and reduced lean carcass weight.A substantial number of studies have shown that feeding of probiotics,prebiotics and synbiotics is an efficacious strategy to protect broilers from heat stress-induced gut barrier disruption through altering the gut microbiota and promoting all decisive structural,biochemical,and immunologi-cal elements of the intestinal barrier.In most of the available studies in heat stressed broilers,the alterations of gut microbiota and improvements of gut barrier function induced by feeding of either probiotics,prebiotics or synbiot-ics were accompanied by an improved productivity,health and/or welfare when compared to non-supplemented broilers exposed to heat stress.These findings indicate that the restoration of gut homeostasis and function is a key target for dietary interventions aiming to provide at least partial protection of broilers from the detrimental impact of heat stress conditions.Despite the fact that the number of studies dealing with the same feeding strategy in heat stressed pigs is limited,the available few studies suggest that feeding of probiotics might also be a suitable approach to enhance productivity,health and welfare in pigs kept under heat stress conditions.
基金This work was partially supported by National Natural Science Foundation of China(Project No.:82104414)Natural Science Foundation of Guangdong Province of China(Project No.:2022A1515011682)a direct grant from The Chinese University of Hong Kong(Project No.:2021.071).
文摘Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic disturbance.Trimethylamine N-oxide(TMAO),produced in the dietary choline metabolism,has been found to accelerate neurodegeneration in AD pathology.In this study,the cognitive function and gut microbiota of TgCRND8(Tg)mice of different ages were evaluated by Morris water maze task(MWMT)and 16S rRNA sequencing,respectively.Young pseudo germ-free(PGF)Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type(WT)mice were selected to determine the role of the gut microbiota in the process of neuropathology.Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions.Our results showed that gut dysbiosis,neuroinflammation response,Ab deposition,tau hyperphosphorylation,TMAO overproduction and cyclin-dependent kinase 5(CDK5)/transcription 3(STAT3)activation occurred in Tg mice age-dependently.Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice,with the activation of CDK5/STAT3 signaling in the brains.On the contrary,faecal microbiota transplantation from WT mice alleviated the cognitive deficits,attenuated neuroinflammation,Ab deposition,tau hyperphosphorylation,TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice.Moreover,excessive choline treatment was also shown to aggravate the cognitive deficits,Ab deposition,neuroinflammation and CDK5/STAT3 pathway activation.These findings provide a novel insight into the interaction between gut dysbiosis and AD progression,clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.
基金supported by grants from National Natural Science Foundation of China(31570509 and 31770536)
文摘Background: Intestinal microbial dysbiosis is involved in liver disease pathogenesis. However, its role in primary liver cancer(PLC), particularly in hepatocarcinogenesis remains unclear. The present study aimed to study the changes in intestinal flora at various stages of PLC and clarify the relationship between intestinal microbes and PLC. Methods: Twenty-four patients with PLC(PLC group), 24 patients with liver cirrhosis(LC group), and 23 healthy control individuals(HC group) were enrolled from October 2016 to October 2017. Stool specimens of the participants were collected and the genomic DNA of fecal bacteria was isolated. High-throughput pyrosequencing of 16 S r DNA was used to identify differences in gut bacterial diversity among HC, LC, and PLC groups. We also analyzed the relationship between clinical factors and intestinal microorganisms in LC and PLC groups. Results: Diversity of Firmicutes tended to decrease from the HC to LC and PLC groups at the phylum level. Among species, Enterobacter ludwigii displayed an increasing trend in the PLC group, wherein the relative abundance of Enterobacter ludwigii in the PLC group was 100 times greater than that in the HC and LC groups. The ratio of Firmicutes/Bacteroidetes was significantly decreased with the disease progression. In addition, the linear discriminant analysis effect size method indicated that Clostridia were predominant in the gut microbiota of the HC group, whereas Enterococcaceae, Lactobacillales, Bacilli and Gammaproteobacteria may be used as diagnostic markers of PLC. Redundancy analysis showed a correlation between intestinal microbial diversity and clinical factors AST, ALT, and AFP. Veillonella showed a significant positive correlation with AFP in the PLC group, whereas Subdoligranulum showed a negative correlation with AFP. Conclusions: This study indicates that dysbiosis of the gut microbiota might be involved in PLC development and progression.
文摘Proton pump inhibitors (PPIs) are common medications within the practice of gastroenterology. These drugs, which act through the irreversible inhibition of the hydrogen/potassium pump (H+/K+-ATPase pump) in the gastric parietal cells, are used in the treatment of several acid-related disorders. PPIs are generally well tolerated but, through the long-term reduction of gastric acid secretion, can increase the risk of an imbalance in gut microbiota composition (i.e., dysbiosis). The gut microbiota is a complex ecosystem in which microbes coexist and interact with the human host. Indeed, the resident gut bacteria are needed for multiple vital functions, such as nutrient and drug metabolism, the production of energy, defense against pathogens, the modulation of the immune system and support of the integrity of the gut mucosal barrier. The bacteria are collected in communities that vary in density and composition within each segment of the gastrointestinal (GI) tract. Therefore, every change in the gut ecosystem has been connected to an increased susceptibility or exacerbation of various GI disorders. The aim of this review is to summarize the recently available data on PPI-related microbiota alterations in each segment of the GI tract and to analyze the possible involvement of PPIs in the pathogenesis of several specific GI diseases.
文摘Genomic sequencing,bioinformatics,and initial speciation(e.g.,relative abundance)of the commensal microbiome have revolutionized the way we think about the“human”body in health and disease.The interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases,including those impacting the esophagus.Although relatively stable,there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome(EM)and the host.These changes are thought to be a product of age,diet,antibiotic and other medication use,oral hygiene,smoking,and/or expression of antibiotic products(bacteriocins)by other flora.These effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation,systemic inflammation,and ultimately disease progression.Research has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is,therefore,not merely the result of esophageal mucosal exposure to corrosives(i.e.,acid).Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory cascade.Here,we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief(i.e.,acid suppression).
基金Supported by Lishui Science and Technology Bureau Research Fund,No.2013JYZB43Medical and Health Science and Technology Plan Project of Zhejiang Province,No.2015KYB371
文摘AIM To investigate alterations in the fecal microbiome using 16 S r RNA amplicon sequencing in couples in the same cohabitation environment.METHODS Fecal samples were collected from eight ulcerative colitis(UC) patients and their healthy partners at Lishui People's Hospital, Zhejiang Province, China. DNA was extracted and the variable regions V3 and V4 of the 16 S r RNA genes were PCR amplified using a two-step protocol. Clear reads were clustered into operational taxonomic units(OTUs) at the 97% sequence similarity level using UCLUST v1.2.22. The Wilcoxon rank-sumtest(R v3.1.2) was used to compare inter-individual differences. Differences with a P value < 0.05 were considered statistically significant.RESULTS Fecal microbial communities were more similar among UC patients than their healthy partners(P = 0.024). UC individuals had a lower relative abundance of bacteria belonging to the Firmicutes, especially Blautia, Clostridium, Coprococcus and Roseburia(P < 0.05). Microbiota dysbiosis was detected in UC patients and their healthy partners. Relevant genera included Akkermansiam, Bacteroides, Escherichia, Lactobacillales, Klebsiella and Parabacteroides. The enriched pathways in fecal samples of UC patients were related to lipid and nucleotide metabolism. Additionally, the pathways involved in membrane transport and metabolism of cofactors and vitamins were more abundant in the healthy partners.CONCLUSION Our results suggested that the microbial composition might be affected in healthy partners cohabiting with UC patients, especially in terms of microbiota dysbiosis.
基金Supported by the National Natural Science Foundation of China,No.81470827
文摘AIM To analyze the alterations of fecal microbiota in Chinese patients with inflammatory bowel disease(IBD).METHODS Fecal samples from 15 patients with Crohn's disease(CD)(11 active CD, 4 inactive CD), 14 patients with active ulcerative colitis(UC) and 13 healthy individuals were collected and subjected to 16 S ribosomal DNA(rDNA) gene sequencing. The V4 hypervariable regions of 16 S rDNA gene were amplified from all samples and sequenced by the Illumina Mi Seq platform. Quality control and operational taxonomic units classification of reads were calculated with QIIME software. Alpha diversity and beta diversity were displayed with R software.RESULTS Community richness(chao) and microbial structure in both CD and UC were significantly different from those in normal controls. At the phyla level, analysis of the microbial compositions revealed a significantly greater abundance of Proteobacteria in IBD as compared to that in controls. At the genera level, 8 genera in CD and 23 genera in UC(in particular, the Escherichia genus) showed significantly greater abundance as compared to that in normal controls. The relative abundance of Bacteroidetes in the active CD group was markedly lower than that in the inactive CD group. The abundance of Proteobacteria in patients with active CD was nominally higher than that in patients with inactive CD; however, the difference was not statistically significant after correction. Furthermore, the relative abundance of Bacteroidetes showed a negative correlation with the CD activity index scores.CONCLUSION Our study profiles specific characteristics and microbial dysbiosis in the gut of Chinese patients with IBD. Bacteroidetes may have a negative impact on inflammatory development.
基金Supported by Biocodex Microbiota Foundation:National Research Grant Russia 2019.
文摘BACKGROUND Gut dysbiosis and small intestinal bacterial overgrowth(SIBO)are commonly observed in patients with cirrhosis.Despite the substantial number of articles describing the relations between disorders of gut microbiota and various manifestations of cirrhosis,dysbiosis and SIBO were always studied separately.AIM To study the relationship of gut dysbiosis and SIBO in cirrhosis.METHODS This observational study included 47 in-patients with cirrhosis.Stool microbiome was assessed using 16 S r RNA gene sequencing.SIBO was assessed using the lactulose hydrogen breath test.RESULTS SIBO was found in 24/47(51.1%)patients.Patients with SIBO had a higher abundance of Firmicutes(P=0.017)and Fusobacteria(P=0.011),and a lower abundance of Bacteroidetes(P=0.013)than patients without SIBO.This increase in the abundance of Firmicutes occurred mainly due to an increase in the abundance of bacteria from the genus Blautia(P=0.020)of the Lachnospiraceae family(P=0.047),while the abundance of other major families of this phylum[Ruminococcaceae(P=0.856),Peptostreptococcaceae(P=0.066),Clostridiaceae(P=0.463),Eubacteriaceae(P=0.463),Lactobacillaceae(P=0.413),and Veillonellaceae(P=0.632)]did not differ significantly between the patients with and without SIBO.Reduced level of Bacteroidetes in samples from patients with SIBO was a result of the decrease in bacterial numbers from all the major families of this phylum[Bacteroidaceae(P=0.014),Porphyromonadaceae(P=0.002),and Rikenellaceae(P=0.047)],with the exception of Prevotellaceae(P=0.941).There were no significant differences in the abundance of taxa that were the main biomarkers of cirrhosis-associated gut dysbiosis[Proteobacteria(P=0.790),Bacilli(P=0.573),Enterobacteriaceae(P=0.632),Streptococcaceae(P=0.170),Staphylococcaceae(P=0.450),and Enterococcaceae(P=0.873)]between patients with and without SIBO.CONCLUSION Despite the differences observed in the gut microbiome between patients with and without SIBO,gut dysbiosis and SIBO are most likely independent disorders of gut microbiota in cirrhosis.
基金National Natural Science Foundation of China,No.31700800,No.81771724,and No.81790631National S&T Major Project of China,No.2018YFC2000500.
文摘BACKGROUND Gut microbiota dysbiosis is reportedly actively involved in autoimmune diseases such as type 1 diabetes mellitus(T1DM).However,the alterations in the gut microbiota and their correlation with fasting blood glucose(FBG)in Chinese children with T1DM remain unclear.AIM To investigate alterations in the gut microbiota in Chinese children with T1DM and their associations with clinical indicators.METHODS Samples from 51 children with T1DM and 47 age-matched and gender-matched healthy controls were obtained,to explore the structural and functional alterations in the fecal microbiota.The V3-V4 regions of the 16S rRNA gene were sequenced on a MiSeq instrument,and the association with FBG were analyzed.RESULTS We found that the bacterial diversity was significantly increased in the T1DMassociated fecal microbiota,and changes in the microbial composition were observed at different taxonomic levels.The T1DM-reduced differential taxa,such as Bacteroides vulgatus ATCC8482,Bacteroides ovatus,Bacteroides xylanisolvens,and Flavonifractor plautii,were negatively correlated with FBG,while the T1DMenriched taxa,such as Blautia,Eubacterium hallii group,Anaerostipes hadrus,and Dorea longicatena,were positively correlated with FBG.Bacteroides vulgatus ATCC8482,Bacteroides ovatus,the Eubacterium hallii group,and Anaerostipes hadrus,either alone or in combination,could be used as noninvasive diagnostic biomarkers to discriminate children with T1DM from healthy controls.In addition,the functional changes in the T1DM-associated fecal microbiota also suggest that these fecal microbes were associated with altered functions and metabolic activities,such as glycan biosynthesis and metabolism and lipid metabolism,which might play vital roles in the pathogenesis and development of T1DM.CONCLUSION Our present comprehensive investigation of the T1DM-associated fecal microbiota provides novel insights into the pathogenesis of the disease and sheds light on the diagnosis and treatment of T1DM.
基金Supported by Biocodex Microbiota Foundation-National Research Grant Russia 2019.
文摘BACKGROUND Gut dysbiosis is common in cirrhosis.AIM To study the influence of gut dysbiosis on prognosis in cirrhosis.METHODS The case-control study included 48 in-patients with cirrhosis and 21 healthy controls.Stool microbiome was assessed using 16S ribosomal ribonucleic acid gene sequencing.We used modified dysbiosis ratio(MDR):[Bacilli(%)+Proteobacteria(%)]/[Clostridia(%)+Bacteroidetes(%)].Patients with MDR more the median made up the group with severe dysbiosis,others did the group with nonsevere dysbiosis.The follow-up period was 4 years.RESULTS The mortality rate of patients with severe dysbiosis was significantly higher than that of patients with non-severe dysbiosis(54.2%vs 12.5%;P=0.001).The presence of severe dysbiosis was independent risk factors for death[hazard ratio=8.6×(1.9-38.0);P=0.005].The abundance of Enterobacteriaceae(P=0.002),Proteobacteria(P=0.002),and Lactobacillaceae(P=0.025)was increased and the abundance of Firmicutes(P=0.025)and Clostridia(P=0.045)was decreased in the deceased patients compared with the survivors.The deceased patients had a higher MDR value than the survivors[0.131×(0.069-0.234)vs 0.034×(0.009-0.096);P=0.004].If we applied an MDR value of 0.14 as the cutoff point,then it predicted patient death within the next year with a sensitivity of 71.4%and a specificity of 82.9%[area under the curve=0.767×(0.559-0.974)].MDR was higher in patients with cirrhosis than in health controls[0.064×(0.017-0.131)vs 0.005×(0.002-0.007);P<0.001],and in patients with decompensated cirrhosis than in patients with compensated cirrhosis[0.106×(0.023-0.211)vs 0.033×(0.012-0.074);P=0.031].MDR correlated negatively with prothrombin(r=-0.295;P=0.042),cholinesterase(r=-0.466;P=0.014)and serum albumin(r=-0.449;P=0.001)level and positively with Child–Turcotte–Pugh scale value(r=0.360;P=0.012).CONCLUSION Gut dysbiosis is associated with a poorer long-term prognosis in cirrhosis.
基金supported by the Special Research Project on Prevention and Control of COVID-19 in Universities of the Guangdong Provincial Education Department(No.2020KZDZX1132).
文摘Objective:Coronavirus disease 2019(COVTD-19)is often accompanied by gastrointestinal symptoms,which are related to gut microbiota dysbiosis(GMD).Whether washed microbiota transplantation(WMT)is an effective treatment for COV1D-19 patients suspected of having GMD by restoring the gut microbiota is unknown.This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD.Methods:This is a randomized,multicenter,single-blind prospective study.COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT.The frequency of WMT will be once a day for three consecutive days.Laboratory and imaging examinations will be performed at admission,1 and 2 weeks after treatment,and on the day of discharge.Then a telephone follow-up will be conducted at 1st week,2nd week,and 6th month after discharge.The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function,homeostasis,inflammatory response,intestinal mucosal barrier function,and immunity of the patients will be evaluated.Results:By following the proposed protocol,WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD,and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function,inflammatory response,and immunity.Conclusion:The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD.
基金supported by the National Science Foundation of China(No.81970939)the Nanjing Clinical Research Center for Oral Diseases(No.2019060009)。
文摘The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes.First,faecal and salivary samples were collected from periodontally healthy participants(PH group,n=16)and patients with severe periodontitis(SP group,n=21)and analysed by 16S ribosomal RNA sequencing.Significant differences were observed in both the faecal and salivary microbiota between the PH and SP groups.Notably,more saliva-sourced microbes were observed in the faecal samples of the SP group.Then,the remaining salivary microbes were transplanted into C57BL6/J mice(the C-PH group and the C-SP group),and it was found that the composition of the gut microbiota of the C-SP group was significantly different from that of the C-PH group,with Porphyromonadaceae and Fusobacterium being significantly enriched in the C-SP group.In the colon,the C-SP group showed significantly reduced crypt depth and zonula occludens-1 expression.The m RNA expression levels of pro-inflammatory cytokines,chemokines and tight junction proteins were significantly higher in the C-SP group.To further investigate whether salivary bacteria could persist in the intestine,the salivary microbiota was stained with carboxyfluorescein diacetate succinimidyl ester and transplanted into mice.We found that salivary microbes from both the PH group and the SP group could persist in the gut for at least 24 h.Thus,our data demonstrate that periodontitis may induce gut microbiota dysbiosis through the influx of salivary microbes.
基金Supported by Coordena??o de Aperfei?oamento de Pessoal de Nível Superior–Brasil,No. CAPES–Finance Code 001Funda??o Carlos Chagas Filho de Amparo à Pesquisa do Rio de Janeiro (FAPERJ) to Souza-Mello V,No. E-26/202.657/2018 and No. E-26/010.002136/2019supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq),No. 303785/2020-9
文摘BACKGROUND Obesity and comorbidities onset encompass gut dysbiosis,altered intestinal permeability,and endotoxemia.Treatments that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease(NAFLD)management.Peroxisome proliferator-activated receptor(PPAR)-alpha activation and dipeptidyl-peptidase-4(DPP-4)inhibition alleviate NAFLD,but the mechanism may involve gut microbiota modulation and merits further investigation.AIM To address the effects of PPAR-alpha activation and DPP-4 inhibition(isolated or combined)upon the gut-liver axis,emphasizing inflammatory pathways in NAFLD management in high-fat-fed C57BL/6J mice.METHODS Male C57BL/6J mice were fed a control diet(C,10%of energy as lipids)or a highfat diet(HFD,50%of energy as lipids)for 12 wk,when treatments started,forming the groups:C,HF,HFA(HFD+PPAR-alpha agonist WY14643,2.5 mg/kg body mass),HFL(HFD+DPP-4 inhibitor linagliptin,15 mg/kg body mass),and HFC(HFD+the combination of WY14643 and linagliptin).RESULTS The HFD was obesogenic compared to the C diet.All treatments elicited significant body mass loss,and the HFC group showed similar body mass to the C group.All treatments tackled oral glucose intolerance and raised plasma glucagon-like peptide-1 concentrations.These metabolic benefits restored Bacteroidetes/Firmicutes ratio,resulting in increased goblet cells per area of the large intestine and reduced lipopolysaccharides concentrations in treated groups.At the gene level,treated groups showed higher intestinal Mucin 2,Occludin,and Zo-1 expression than the HFD group.The reduced endotoxemia suppressed inflammasome and macrophage gene expression in the liver of treated animals.These observations complied with the mitigation of liver steatosis and reduced hepatic triacylglycerol,reassuring the role of the proposed treatments on NAFLD mitigation.CONCLUSION PPAR alpha activation and DPP-4 inhibition(isolated or combined)tackled NAFLD in dietinduced obese mice by restoration of gut-liver axis.The reestablishment of the intestinal barrier and the rescued phylogenetic gut bacteria distribution mitigated liver steatosis through antiinflammatory signals.These results can cope with NAFLD management by providing pre-clinical evidence that drugs used to treat obesity comorbidities can help to alleviate this silent and harmful liver disease.
文摘Exercise-induced changes of the microbiome in inflammatory bowel diseases(IBD)is a promising field of research with the potential for personalized exercise regimes as a promising therapeutic adjunct for restoring gut dysbiosis and additionally for regulating immunometabolic pathways in the management of IBD patients.Structured exercise programmes in IBD patients of at least of 12 wk duration are more likely to result in disease-altering changes in the gut microbiome and to harness potential anti-inflammatory effects through these changes along with immunometabolic pathways.
基金Supported by Institut Polytechnique LaSalle Beauvais
文摘AIM: To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice. METHODS: Two sets of experiments were designed. In the first set, recently weaned mice were either orally administered ferrous (Fe2+) iron salt or ferric (Fe3+) microencapsulated iron for 6 wk. The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced. In the second set, juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments. In both sets of experiments, animals were sacrificed 7 d after TNBS instillation. Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (MPO) activity. Alteration of the microflora profile was estimated usingquantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora, Bacteroidetes, Firmicutes and enterobacteria. RESULTS: Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain. Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27 MPO U/mg proteinvs 2.47 ± 0.22 MPO U/mg protein in colitic mice). In contrast, ferric iron significantly prevented the increase of MPO activity (1.64 ± 0.14 MPO U/mg protein) in TNBS-induced colitis. Moreover, this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po - 6 wk). In the study we also compared, in both rats and mice, the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po - 6 wk) on TNBS-induced colitis and its related dysbiosis. We confirmed that ferric iron limited the TNBS-induced increase of MPO activity in both the rodent species. Furthermore, we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis. At first, we needed to optimize the isolation and quantify DNA copy numbers using standard curves to perform by qPCR this interspecies comparison. Using this approach, we determined that total microflora was similar in control rats and mice and was mainly composed of Firmicutes and Bacteroidetes at a ratio of 10/1. Ferric juvenile administration did not modify the microflora profile in control animals. Total microflora numbers remained unchanged whichever experimental conditions studied. Following TNBS-induced colitis, the Firmicutes/Bacteroidetes ratio was altered resulting in a decrease of the Firmicutes numbers and an increase of the Bacteroidetes numbers typical of a gut inflammatory reaction. In parallel, the subdominant population, the enterobacteria was also increased. However, ferric iron supplementation for the juvenile period prevented the increase of Bacteroidetes and of enterobacteria numbers consecutive to the colitis in both the studied species at adulthood.CONCLUSION: Rats and mice juvenile chronic ferric iron ingestion prevents colitis and dysbiosis at adulthood as assessed by the first interspecies comparison.
基金Supported by Biocodex Microbiota Foundation:National Research Grant Russia 2019.
文摘BACKGROUND Gut dysbiosis and changes in body composition(i.e.,a decrease in the proportion of muscle mass and an increase in extracellular fluid)are common in cirrhosis.AIM To study the relationship between the gut microbiota and body composition in cirrhosis.METHODS This observational study included 46 patients with cirrhosis.Stool microbiome was assessed using 16S rRNA gene sequencing.Multifrequency bioelectrical impedance analysis was performed to assess body composition in these patients.RESULTS An increase in fat mass and a decrease in body cell mass were noted in 23/46(50.0%)and 15/46(32.6%)patients,respectively.Changes in the gut microbiome were not independently associated with the fat mass percentage in cirrhosis.The abundance of Bacteroidaceae(P=0.041)and Eggerthella(P=0.001)increased,whereas that of Erysipelatoclostridiaceae(P=0.006),Catenibacterium(P=0.021),Coprococcus(P=0.033),Desulfovibrio(P=0.043),Intestinimonas(P=0.028),and Senegalimassilia(P=0.015)decreased in the gut microbiome of patients with body cell mass deficiency.The amount of extracellular fluid increased in 22/46(47.6%)patients.Proteobacteria abundance(P<0.001)increased,whereas Firmicutes(P=0.023),Actinobacteria(P=0.026),Bacilli(P=0.008),Anaerovoraceceae(P=0.027),Christensenellaceae(P=0.038),Eggerthellaceae(P=0.047),Erysipelatoclostridiaceae(P=0.015),Erysipelotrichaceae(P=0.003),Oscillospiraceae(P=0.024),Rikenellaceae(P=0.002),Collinsella(P=0.030),Hungatella(P=0.040),Peptococcaceae(P=0.023),Slackia(P=0.008),and Senegalimassilia(P=0.024)abundance decreased in these patients.Patients with clinically significant ascites(n=9)had a higher abundance of Proteobacteria(P=0.031)and a lower abundance of Actinobacteria(P=0.019)and Bacteroidetes(P=0.046)than patients without clinically significant ascites(n=37).CONCLUSION Changes in the amount of body cell mass and extracellular fluid are associated with changes in the gut microbiome in cirrhosis patients.
