Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice

Kwon, Soon-Kyeong; Park, Jun Chul; Kim, Kwang H.; Yoon, Jaekyung; Cho, Yejin; Lee, Buhyun; Lee, Jin-Jae; Jeong, Haengdueng; Oh, Yang-Hyo; Kim, Sunghee; Lee, So Dam; Hwang, Bo Ram; Chung, Yusook; Kim, Jihyun F.; Nam, Ki Taek; Lee, Yong Chan

doi:10.1136/gutjnl-2021-324489

Cited by 45 publications

(33 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an oral and respiratory pathogen, P. melaninogenica can colonize and overgrow in the stomach of the BRG group, which may be due to a large amount of bile acids reflux into the stomach, changing the intragastric environment, such as the increase of pH value. Recently published study on Gut, 2021 [49] showed that gastric microbiota from patients with intestinal metaplasia and gastric cancer induced premalignant lesions in the gastric mucosa of recipient germ-free mice after one-year post inoculation, providing the causality of associations of human gastric microbiome in the onset of gastric cancer. The germ-free mice model will be applied in future studies to investigate the role of the microbiota in the onset of gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis

et al. 2022

View full text Add to dashboard Cite

Bile reflux gastritis (BRG) is associated with the development of gastric cancer (GC), but the specific mechanism remains elusive. Here, a comprehensive study is conducted to explore the roles of refluxed bile acids (BAs) and microbiome in gastric carcinogenesis. The results show that conjugated BAs, interleukin 6 (IL‐6), lipopolysaccharide (LPS), and the relative abundance of LPS‐producing bacteria are increased significantly in the gastric juice of both BRG and GC patients. A secondary BA, taurodeoxycholic acid (TDCA), is significantly and positively correlated with the LPS‐producing bacteria in the gastric juice of these patients. TDCA promotes the proliferation of normal gastric epithelial cells (GES‐1) through activation of the IL‐6/JAK1/STAT3 pathway. These results are further verified in two mouse models, one by gavage of TDCA, LPS, and LPS‐producing bacteria (Prevotella melaninogenica), respectively, and the other by bile reflux (BR) surgery, mimicking clinical bile refluxing. Moreover, the bile reflux induced gastric precancerous lesions observed in the post BR surgery mice can be prevented by treatment with cryptotanshinone, a plant‐derived STAT3 inhibitor. These results reveal an important underlying mechanism by which bile reflux promotes gastric carcinogenesis and provide an alternative strategy for the prevention of GC associated with BRG.

show abstract

Section: Discussionmentioning

confidence: 99%

Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Initially, the alterations of gastric microbiota across stages of GC have been observed in cohort studies 11,12 . Subsequently, gastric microbiota transplantation experiment demonstrated that the phenotype of gastric malignance could be transferred from human to germ‐free mice, which suggests the causality between gastric microbes and GC 13 . Thus, the reconstruction of microbial homeostasis might be a potential strategy for GC prevention.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence suggest that the stomach harbors a complex microbial community and its composition changes across the stages of GC 11,12 . Furthermore, gastric microbiota transplantation from patients to germ‐free mice presented the causality of gastric microbial members other than H. pylori in instigating GC 13 . It is, therefore, pivotal to maintain the homeostasis of gastric microbiota, so as to stem GC development.…”

Section: Introductionmentioning

confidence: 99%

“…11,12 Furthermore, gastric microbiota transplantation from patients to germ-free mice presented the causality of gastric microbial members other than H. pylori in instigating GC. 13 It is, therefore, pivotal to maintain the homeostasis of gastric microbiota, so as to stem GC development. Herein, we found that supplemented with two Lactobacillus strains substantially inhibited H. pylori-induced premalignant lesions in INS-GAS mice.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Probiotics mitigate Helicobacter pylori‐induced gastric inflammation and premalignant lesions in INS‐GAS mice with the modulation of gastrointestinal microbiota

Peng

et al. 2022

Helicobacter

View full text Add to dashboard Cite

Background: Dysbiosis of gastric microbiota including Helicobacter pylori (H. pylori) infection is associated with the development of stomach cancer. Probiotics have been shown to attenuate H. pylori-induced gastritis, although their role in cancer prevention remains unclear. Thus, we aimed to explore the effects of probiotics on H. pyloriinduced carcinogenesis and the alterations of gastrointestinal microbiota.Methods: Male INS-GAS mice were randomly allocated to H. pylori-infected and noninfected groups. After 4 weeks, probiotic combination (containing Lactobacillus salivarius and Lactobacillus rhamnosus) was administered in drinking water for 12 weeks.Stomachs were collected for RNA-Sequencing and the differentially expressed genes were validated using RT profiler PCR array. 16S rRNA gene sequencing was performed to assess the alterations of gastrointestinal microbiota.Results: Probiotics significantly alleviate H. pylori-induced gastric pathology, including reduced infiltration of inflammation and lower incidence of precancerous lesions.RNA-Sequencing results showed that probiotics treatment decreased expressions of genes involved in pro-inflammatory pathways, such as NF-κB, IL-17, and TNF signaling pathway. Of note, probiotics did not suppress the growth of H. pylori, but dramatically reshaped the structure of both gastric and gut microbiota. The microbial diversity was increased in H. pylori-infected group after probiotics treatment. While gastric cancerassociated genera Lactobacillus and Staphylococcus were enriched in the stomach of H. pylori-infected group, the beneficial short-chain fatty acids-producing bacteria, including Bacteroides, Alloprevotella, and Oscellibacter, were more abundant in mice treated with probiotics. Additionally, probiotics restored the H. pylori-induced reduction of anti-inflammatory bacterium Faecalibaculum in the gut. Conclusions:Probiotics therapy can protect against H. pylori-associated carcinogenesis probably through remodeling gastrointestinal microbiota, which in turn prevent host cells from malignant transformation.

show abstract

“…The genera related to the AG and IM were not consistent in our research and previous studies. However, a study further explored the relationship between gastric microbiota and the occurrence of GC in a mouse model, and found that the bacteria of patients with IM or GC could selectively colonize the stomach of germ-free mice and induce gastric precancerous lesions [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of gastric microbiome reveals three distinctive microbial communities associated with the occurrence of gastric cancer

et al. 2022

View full text Add to dashboard Cite

Background Gastric microbial dysbiosis were reported to be associated with gastric cancer (GC). This study aimed to explore the variation, diversity, and composition patterns of gastric bacteria in stages of gastric carcinogenesis based on the published datasets. Methods We conducted a gastric microbial analysis using 10 public datasets based on 16S rRNA sequencing, including 1270 gastric biopsies of 109 health control, 183 superficial gastritis (SG), 135 atrophic gastritis (AG), 124 intestinal metaplasia (IM), 94 intraepithelial neoplasia (IN), 344 GC, and 281 adjacent normal tissues. And QIIME2-pipeline, DESeq2, NetMoss2, vegan, igraph, and RandomForest were used for the data processing and analysis. Results We identified three gastric microbial communities among all the gastric tissues. The first community (designate as GT-H) was featured by the high abundance of Helicobacter. The other two microbial communities, namely GT-F, and GT-P, were featured by the enrichment of phylum Firmicutes and Proteobacteria, respectively. The distribution of GC-associated bacteria, such as Fusobacterium, Peptostreptococcus, Streptococcus, and Veillonella were enriched in tumor tissues, and mainly distributed in GT-F type microbial communities. Compared with SG, AG, and IM, the bacterial diversity in GC was significantly reduced. And the strength of microbial interaction networks was initially increased in IM but gradually decreased from IN to GC. In addition, Randomforest models constructed in in GT-H and GT-F microbial communities showed excellent performance in distinguishing GC from SG and precancerous stages, with varied donated bacteria. Conclusions This study identified three types of gastric microbiome with different patterns of composition which helps to clarify the potential key bacteria in the development of gastric carcinogenesis.

show abstract

Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice

Cited by 45 publications

References 53 publications

Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis

Bile Acid–Microbiome Interaction Promotes Gastric Carcinogenesis

Probiotics mitigate Helicobacter pylori‐induced gastric inflammation and premalignant lesions in INS‐GAS mice with the modulation of gastrointestinal microbiota

Analysis of gastric microbiome reveals three distinctive microbial communities associated with the occurrence of gastric cancer

Contact Info

Product

Resources

About