BACKGROUND The gastric microbiota in patients with gastric cancer(GC)has received increasing attention,but the profiling of the gastric microbiome through the histological stages of gastric tumorigenesis remains poorl...BACKGROUND The gastric microbiota in patients with gastric cancer(GC)has received increasing attention,but the profiling of the gastric microbiome through the histological stages of gastric tumorigenesis remains poorly understood,especially for patients with Helicobacter pylori-negative GC(HPNGC).AIM To characterize microbial profiles of gastric mucosa and juice for HPNGC carcinogenesis and identify distinct taxa in precancerous lesions.METHODS The 16S rRNA gene analysis was performed on gastric mucosa from 134 Helicobacter pylori-negative cases,including 56 superficial gastritis(SG),9 atrophic gastritis(AG),27 intestinal metaplasia(IM),29 dysplasia(Dys),and 13 GC cases,to investigate differences in gastric microbial diversity and composition across the disease stages.In addition,paired gastric mucosa and juice samples from 18 SG,18 IM,and 18 Dys samples were analyzed.α-Diversity was measured by Shannon and Chao1 indexes,andβ-diversity was calculated using partial least squares discrimination analysis(PLS-DA).Differences in the microbial composition across disease stages in different sample types were assessed using the linear discriminant analysis effect size.RESULTS The diversity and composition of the bacterial microbiota in the gastric mucosa changed progressively across stages of gastric carcinogenesis.The diversity of the gastric mucosa microbiota was found to be significantly lower in the IM and Dys groups than in the SG group,and the patients with GC had the lowest bacterial community richness(P<0.05).Patients with IM and those with Dys had similar gastric mucosa microbiota profiles with Ralstonia and Rhodococcus as the predominant genera.Microbial network analysis showed that there was increasing correlation strength between IM and Dys(|correlation threshold|≥0.5,P<0.05).GC and its precancerous lesions have distinguishable bacterial taxa;our results identified HPNGC-associated bacteria Streptococcaceae and Lactobacillaceae(P<0.05).Additionally,across precancerous lesion stages from AG to Dys in Helicobacter pylori-negative patients,Burkholderiaceae abundance continuously increased,while Streptococcaceae and Prevotellaceae abundance presented a continuous downward trend.Furthermore,the microbial diversity was higher in gastric juice(P<0.001)than in the mucosa,while PLS-DA revealed a statistically significant difference between the two groups(ANOSIM,P=0.001).A significant difference in the microbial structure was identified,with Proteobacteria being more prevalent in the gastric mucosa and Firmicutes being more abundant in gastric juice.CONCLUSION Our results provide insights into potential taxonomic biomarkers for HPNGC and its precancerous stages and assist in predicting the prognosis of IM and Dys based on the mucosal microbiota profile.展开更多
AIM: To determine whether study on the carcinogenic potential of reflux juice from patients with remote gastrectomy could clarify the inherent relationship between duodenal reflux and gastric stump cancer. METHODS: A ...AIM: To determine whether study on the carcinogenic potential of reflux juice from patients with remote gastrectomy could clarify the inherent relationship between duodenal reflux and gastric stump cancer. METHODS: A total of 37 reflux juice samples (13 Billroth I, 24 Billroth II) were employed in the present study. A two-stage transformation assay using BALB/c 3T3 cells was carried out to test the initiating or promoting activity of these samples. RESULTS: Two of 18 (11.1%) reflux samples exerted initiating activities, whereas 9/19 (47.4%) samples enhanced the MNNG-initiating cell transformation, suggesting the duodenal reflux juice might more frequently possess the tumor-promoter activity (P = 0.029). In addition, there was no difference in initiating activities of the samples irrespective of surgical procedures (P = 0.488), while Billroth II samples exhibited stronger tumor-promoter activity than Billroth I samples (P = 0.027). Furthermore, the promoter activities were well correlated with the histological changes of the stomas (r(s) = 0.625, P = 0.004), but neither their cytotoxicities nor initiating activities had this correlation (Probabilities were 0.523 and 0.085, respectively). CONCLUSION: The duodenal reflux juice from patients with remote postgastrectomy did have carcinogenic potential, and suggested that tumor-promoting activity should principally account for the high incidence of gastric cancer in gastrectomy patients. In contrast, it is difficult to explain the high stump-cancer incidence with the N-nitroso compounds theory-a popular theory for the intact stomach carcinogenesis, and it seemed to be justified to focus chemo-prevention of this cancer on the tumor-promoting potential of reflux juice.展开更多
基金Supported by National Natural Science Foundation of China,No.81700496,and No.81870386Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation,No.BMU2021PY002and Key Laboratory for Helicobacter pylori Infection and Upper Gastrointestinal Diseases,Beijing Key Laboratory,No.BZ0371.
文摘BACKGROUND The gastric microbiota in patients with gastric cancer(GC)has received increasing attention,but the profiling of the gastric microbiome through the histological stages of gastric tumorigenesis remains poorly understood,especially for patients with Helicobacter pylori-negative GC(HPNGC).AIM To characterize microbial profiles of gastric mucosa and juice for HPNGC carcinogenesis and identify distinct taxa in precancerous lesions.METHODS The 16S rRNA gene analysis was performed on gastric mucosa from 134 Helicobacter pylori-negative cases,including 56 superficial gastritis(SG),9 atrophic gastritis(AG),27 intestinal metaplasia(IM),29 dysplasia(Dys),and 13 GC cases,to investigate differences in gastric microbial diversity and composition across the disease stages.In addition,paired gastric mucosa and juice samples from 18 SG,18 IM,and 18 Dys samples were analyzed.α-Diversity was measured by Shannon and Chao1 indexes,andβ-diversity was calculated using partial least squares discrimination analysis(PLS-DA).Differences in the microbial composition across disease stages in different sample types were assessed using the linear discriminant analysis effect size.RESULTS The diversity and composition of the bacterial microbiota in the gastric mucosa changed progressively across stages of gastric carcinogenesis.The diversity of the gastric mucosa microbiota was found to be significantly lower in the IM and Dys groups than in the SG group,and the patients with GC had the lowest bacterial community richness(P<0.05).Patients with IM and those with Dys had similar gastric mucosa microbiota profiles with Ralstonia and Rhodococcus as the predominant genera.Microbial network analysis showed that there was increasing correlation strength between IM and Dys(|correlation threshold|≥0.5,P<0.05).GC and its precancerous lesions have distinguishable bacterial taxa;our results identified HPNGC-associated bacteria Streptococcaceae and Lactobacillaceae(P<0.05).Additionally,across precancerous lesion stages from AG to Dys in Helicobacter pylori-negative patients,Burkholderiaceae abundance continuously increased,while Streptococcaceae and Prevotellaceae abundance presented a continuous downward trend.Furthermore,the microbial diversity was higher in gastric juice(P<0.001)than in the mucosa,while PLS-DA revealed a statistically significant difference between the two groups(ANOSIM,P=0.001).A significant difference in the microbial structure was identified,with Proteobacteria being more prevalent in the gastric mucosa and Firmicutes being more abundant in gastric juice.CONCLUSION Our results provide insights into potential taxonomic biomarkers for HPNGC and its precancerous stages and assist in predicting the prognosis of IM and Dys based on the mucosal microbiota profile.
文摘AIM: To determine whether study on the carcinogenic potential of reflux juice from patients with remote gastrectomy could clarify the inherent relationship between duodenal reflux and gastric stump cancer. METHODS: A total of 37 reflux juice samples (13 Billroth I, 24 Billroth II) were employed in the present study. A two-stage transformation assay using BALB/c 3T3 cells was carried out to test the initiating or promoting activity of these samples. RESULTS: Two of 18 (11.1%) reflux samples exerted initiating activities, whereas 9/19 (47.4%) samples enhanced the MNNG-initiating cell transformation, suggesting the duodenal reflux juice might more frequently possess the tumor-promoter activity (P = 0.029). In addition, there was no difference in initiating activities of the samples irrespective of surgical procedures (P = 0.488), while Billroth II samples exhibited stronger tumor-promoter activity than Billroth I samples (P = 0.027). Furthermore, the promoter activities were well correlated with the histological changes of the stomas (r(s) = 0.625, P = 0.004), but neither their cytotoxicities nor initiating activities had this correlation (Probabilities were 0.523 and 0.085, respectively). CONCLUSION: The duodenal reflux juice from patients with remote postgastrectomy did have carcinogenic potential, and suggested that tumor-promoting activity should principally account for the high incidence of gastric cancer in gastrectomy patients. In contrast, it is difficult to explain the high stump-cancer incidence with the N-nitroso compounds theory-a popular theory for the intact stomach carcinogenesis, and it seemed to be justified to focus chemo-prevention of this cancer on the tumor-promoting potential of reflux juice.
