The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with...The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal-luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in Eubacterium, which is a butyrate-producing genera of bacteria, and a significant increase in Devosia in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to Eubacterium and Devosia may serve as a promising biomarker for the early detection of CRC.展开更多
Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal conse-quences.Despite identifying i...Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal conse-quences.Despite identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is evident.In our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus barrier.This enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory response.Importantly,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy drugs.Mechanistically,E.copr up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet cells.An espe-cially significant finding is that E.copr activates the AhR pathway,thereby promoting the expression of AUF1.In summary,our results strongly indicate that E.copr enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.展开更多
AIM： To examine the effect of Eubacteriuro Iiroosuro （E.Iiroosuro） on colonic epithelial cell line in vitro, and to evaluate the effect of E.limosum on experimental colitis.METHODS： E.Iimosum was inoculated anaero...AIM： To examine the effect of Eubacteriuro Iiroosuro （E.Iiroosuro） on colonic epithelial cell line in vitro, and to evaluate the effect of E.limosum on experimental colitis.METHODS： E.Iimosum was inoculated anaerobically and its metabolites were obtained. The growth stimulatory effect of the E.limosum metabolites on T84 cells was evaluated by SUDH activity, and the anti-inflammatory effect by IL-6 production. The change in mRNA of toll like receptor 4 （TLR4） was evaluated by real time PCR. Colitis was induced by feeding BALB/C mice with 2.0% dextran sodium sulfate. These mice received either 5% lyophilized E.lirnosum （n=7） or control diet （n=7）. Seven days after colitis induction, clinical and histological scores, colon length, and cecal organic acid levels were determined.RESULTS： The E.Iimosum produced butyrate, acetate, propionate, and lactate at 0.25, 1.0, 0.025 and 0.07 retool/L, respectively in medium. At this concentration, each acid had no growth stimulating activity on T84 cells; however, when these acids were mixed together at the above levels, it showed significantly high activity than control. Except for lactate, these acids significantly attenuated IL-6 production at just 0.1 mmol/L. In addition, under TNF-α stimulation, butyrate attenuated the production of TLR4 mRNA. The treatment with E.limosum significantly attenuated clinical and histological scores of colitis with an increase of cecal butyrate levels, compared with the control group.CONCLUSION： E.limosum can ameliorate experimental colonic inflammation. In part, the metabolite of E.lirnosurn, butyrate, increases mucosal integrity and shows anti-inflammatory action modulation of mucosal defense system via TLR4.展开更多
Cell free supernatant containing short chain fatty acid (SCFA) resulted from fermentation of resistant starch type three (RS3) by Clostridium butyricum BCC B2571 or Eubacterium rectale DSM 17629 were investigated for ...Cell free supernatant containing short chain fatty acid (SCFA) resulted from fermentation of resistant starch type three (RS3) by Clostridium butyricum BCC B2571 or Eubacterium rectale DSM 17629 were investigated for their ability to inhibit proliferation and induce apoptosis of human colon cancer cell line HCT-116. HCT-116 was cultured in complete medium and after 50% confluent, incubation was continued for another 48 hours in the absence or presence cell free supernatant containing SCFA mixture at butyrate levels up to 10 mM. The study revealed that the proliferation inhibition effect was higher (>80%) on HCT-116 treated with supernatant of C. butyricum BCC B2571 than that (<70%) of HCT-116 treated with supernatant of E. rectale DSM 17629. The cells were induced to undergo apoptosis by both supernatant. The apoptosis occured through mitochondrial pathway by changing the expression of gene Bcl-2 and Bax, thus incresed the Bax/Bcl-2 ratio by more than 3.5 fold. The protein caspase-3 was increased by more than 250% in the presence of the cell free supernatant.展开更多
Resistant starch type 3 (RS3) produced from high amylose food sources through retrogradation or enzymatic process is known to have physiological function as dietary fiber. Fermentation of RS3 by colonic microorganisms...Resistant starch type 3 (RS3) produced from high amylose food sources through retrogradation or enzymatic process is known to have physiological function as dietary fiber. Fermentation of RS3 by colonic microorganisms produced SCFA (acetate, propionate, and butyrate), maintained the health of colon, balance of gut microbiota, preventing inflammatory bowel diseases (IBD) and colon cancer. RS3 in this study was produced from IR-42 and Inpari-16 broken rice by enzymatic treatment (combination of amylase-pullulanase). The Resistant Starch was fermented for 12 and 24 h by colonic microbiota (extracted from healthy human subject), Clostiridium butyricum BCC-B2571, or Eubacterium rectale DSM 17629. SCFA produced was analyzed by gas chromatography. Treatment by amylase-pullulanase combination was advantageous to increase their RS3 content. The result showed that after enzymatic process, the RS3 content of IR-42 (41.13%) was not significantly different (p 0.05) from that of Inpari-16 (37.70%). High concentration of acetate (82.5 mM) and propionate (7.5 mM) were produced by colonic microbiota after 12 h fermentation and best concentration of butyrate (6.8 mM) was produced by colonic microbiota after 24 h fermentation. It is clear that utilization of colonic microbiota rather than single strain was better in the production of SCFA.展开更多
Background:Anorexia nervosa(AN)is a psychological disorder,which is characterized by the misunderstanding of body image,food restriction,and low body weight.An increasing number of studies have reported that the patho...Background:Anorexia nervosa(AN)is a psychological disorder,which is characterized by the misunderstanding of body image,food restriction,and low body weight.An increasing number of studies have reported that the pathophysiological mechanism of AN might be associated with the dysbiosis of gut microbiota.The purpose of our study was to explore the features of gut microbiota in patients with AN,hoping to provide valuable information on its pathogenesis and treatment.Methods:In this cross-sectional study,from August 2020 to June 2021,patients with AN who were admitted into Peking University Third Hospital and Peking University Sixth Hospital(n=30)were recruited as the AN group,and healthy controls(HC)were recruited from a middle school and a university in Beijing(n=30).Demographic data,Hamilton Depression Scale(HAMD)scores of the two groups,and length of stay of the AN group were recorded.Microbial diversity analysis of gut microbiota in stool samples from the two groups was analyzed by 16S ribosomal RNA(rRNA)gene sequencing.Results:The weight(AN vs.HC,[39.31±7.90]kg vs.[56.47±8.88]kg,P<0.001)and body mass index(BMI,AN vs.HC,[14.92±2.54]kg/m^(2)vs.[20.89±2.14]kg/m^(2),P<0.001)of patients with AN were statistically significantly lower than those of HC,and HAMD scores in AN group were statistically significantly higher than those of HC.For alpha diversity,there were no statistically significant differences between the two groups;for beta diversity,the two groups differed obviously regarding community composition.Compared to HC,the proportion of Lachnospiraceae in patients with AN was statistically significantly higher(AN vs.HC,40.50%vs.31.21%,Z=-1.981,P=0.048),while that of Ruminococcaceae was lower(AN vs.HC,12.17%vs.19.15%,Z=-2.728,P=0.007);the proportion of Faecalibacterium(AN vs.HC,3.97%vs.9.40%,Z=-3.638,P<0.001)and Subdoligranulum(AN vs.HC,4.60%vs.7.02%,Z=-2.369,P=0.018)were statistically significantly lower,while that of Eubacterium_halli_group was significantly higher(AN vs.HC,7.63%vs.3.43%,Z=-2.115,P=0.035).展开更多
基金This current study was supported by the Shanghai Sixth People's Hospital Grant (No. YNLC201725)the National Natural Science Foundation of China (No. 81800708)Outstanding Academic Leaders of Shanghai Health System (No. 2017BR008) and Yangtze River Scholar.
文摘The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal-luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in Eubacterium, which is a butyrate-producing genera of bacteria, and a significant increase in Devosia in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to Eubacterium and Devosia may serve as a promising biomarker for the early detection of CRC.
基金This work was supported by the National Natural Science Foundation of China(No.82373910,82204409)The“Double First-Class”University Project(CPU2022QZ20,China)。
文摘Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal conse-quences.Despite identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is evident.In our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus barrier.This enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory response.Importantly,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy drugs.Mechanistically,E.copr up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet cells.An espe-cially significant finding is that E.copr activates the AhR pathway,thereby promoting the expression of AUF1.In summary,our results strongly indicate that E.copr enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.
文摘AIM： To examine the effect of Eubacteriuro Iiroosuro （E.Iiroosuro） on colonic epithelial cell line in vitro, and to evaluate the effect of E.limosum on experimental colitis.METHODS： E.Iimosum was inoculated anaerobically and its metabolites were obtained. The growth stimulatory effect of the E.limosum metabolites on T84 cells was evaluated by SUDH activity, and the anti-inflammatory effect by IL-6 production. The change in mRNA of toll like receptor 4 （TLR4） was evaluated by real time PCR. Colitis was induced by feeding BALB/C mice with 2.0% dextran sodium sulfate. These mice received either 5% lyophilized E.lirnosum （n=7） or control diet （n=7）. Seven days after colitis induction, clinical and histological scores, colon length, and cecal organic acid levels were determined.RESULTS： The E.Iimosum produced butyrate, acetate, propionate, and lactate at 0.25, 1.0, 0.025 and 0.07 retool/L, respectively in medium. At this concentration, each acid had no growth stimulating activity on T84 cells; however, when these acids were mixed together at the above levels, it showed significantly high activity than control. Except for lactate, these acids significantly attenuated IL-6 production at just 0.1 mmol/L. In addition, under TNF-α stimulation, butyrate attenuated the production of TLR4 mRNA. The treatment with E.limosum significantly attenuated clinical and histological scores of colitis with an increase of cecal butyrate levels, compared with the control group.CONCLUSION： E.limosum can ameliorate experimental colonic inflammation. In part, the metabolite of E.lirnosurn, butyrate, increases mucosal integrity and shows anti-inflammatory action modulation of mucosal defense system via TLR4.
文摘Cell free supernatant containing short chain fatty acid (SCFA) resulted from fermentation of resistant starch type three (RS3) by Clostridium butyricum BCC B2571 or Eubacterium rectale DSM 17629 were investigated for their ability to inhibit proliferation and induce apoptosis of human colon cancer cell line HCT-116. HCT-116 was cultured in complete medium and after 50% confluent, incubation was continued for another 48 hours in the absence or presence cell free supernatant containing SCFA mixture at butyrate levels up to 10 mM. The study revealed that the proliferation inhibition effect was higher (>80%) on HCT-116 treated with supernatant of C. butyricum BCC B2571 than that (<70%) of HCT-116 treated with supernatant of E. rectale DSM 17629. The cells were induced to undergo apoptosis by both supernatant. The apoptosis occured through mitochondrial pathway by changing the expression of gene Bcl-2 and Bax, thus incresed the Bax/Bcl-2 ratio by more than 3.5 fold. The protein caspase-3 was increased by more than 250% in the presence of the cell free supernatant.
文摘Resistant starch type 3 (RS3) produced from high amylose food sources through retrogradation or enzymatic process is known to have physiological function as dietary fiber. Fermentation of RS3 by colonic microorganisms produced SCFA (acetate, propionate, and butyrate), maintained the health of colon, balance of gut microbiota, preventing inflammatory bowel diseases (IBD) and colon cancer. RS3 in this study was produced from IR-42 and Inpari-16 broken rice by enzymatic treatment (combination of amylase-pullulanase). The Resistant Starch was fermented for 12 and 24 h by colonic microbiota (extracted from healthy human subject), Clostiridium butyricum BCC-B2571, or Eubacterium rectale DSM 17629. SCFA produced was analyzed by gas chromatography. Treatment by amylase-pullulanase combination was advantageous to increase their RS3 content. The result showed that after enzymatic process, the RS3 content of IR-42 (41.13%) was not significantly different (p 0.05) from that of Inpari-16 (37.70%). High concentration of acetate (82.5 mM) and propionate (7.5 mM) were produced by colonic microbiota after 12 h fermentation and best concentration of butyrate (6.8 mM) was produced by colonic microbiota after 24 h fermentation. It is clear that utilization of colonic microbiota rather than single strain was better in the production of SCFA.
基金funded by the Cross Seed Fund of Peking University(No.A74479-01).
文摘Background:Anorexia nervosa(AN)is a psychological disorder,which is characterized by the misunderstanding of body image,food restriction,and low body weight.An increasing number of studies have reported that the pathophysiological mechanism of AN might be associated with the dysbiosis of gut microbiota.The purpose of our study was to explore the features of gut microbiota in patients with AN,hoping to provide valuable information on its pathogenesis and treatment.Methods:In this cross-sectional study,from August 2020 to June 2021,patients with AN who were admitted into Peking University Third Hospital and Peking University Sixth Hospital(n=30)were recruited as the AN group,and healthy controls(HC)were recruited from a middle school and a university in Beijing(n=30).Demographic data,Hamilton Depression Scale(HAMD)scores of the two groups,and length of stay of the AN group were recorded.Microbial diversity analysis of gut microbiota in stool samples from the two groups was analyzed by 16S ribosomal RNA(rRNA)gene sequencing.Results:The weight(AN vs.HC,[39.31±7.90]kg vs.[56.47±8.88]kg,P<0.001)and body mass index(BMI,AN vs.HC,[14.92±2.54]kg/m^(2)vs.[20.89±2.14]kg/m^(2),P<0.001)of patients with AN were statistically significantly lower than those of HC,and HAMD scores in AN group were statistically significantly higher than those of HC.For alpha diversity,there were no statistically significant differences between the two groups;for beta diversity,the two groups differed obviously regarding community composition.Compared to HC,the proportion of Lachnospiraceae in patients with AN was statistically significantly higher(AN vs.HC,40.50%vs.31.21%,Z=-1.981,P=0.048),while that of Ruminococcaceae was lower(AN vs.HC,12.17%vs.19.15%,Z=-2.728,P=0.007);the proportion of Faecalibacterium(AN vs.HC,3.97%vs.9.40%,Z=-3.638,P<0.001)and Subdoligranulum(AN vs.HC,4.60%vs.7.02%,Z=-2.369,P=0.018)were statistically significantly lower,while that of Eubacterium_halli_group was significantly higher(AN vs.HC,7.63%vs.3.43%,Z=-2.115,P=0.035).
