scholarly journals Gut Microbial Dysbiosis and Changes in Fecal Metabolic Phenotype in Precancerous Lesions of Gastric Cancer Induced With N-Methyl-N′-Nitro-N-Nitrosoguanidine, Sodium Salicylate, Ranitidine, and Irregular Diet

2021 ◽  
Vol 12 ◽  
Author(s):  
Fuhao Chu ◽  
Yicong Li ◽  
Xiangmei Meng ◽  
Yuan Li ◽  
Tao Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Mucosa ◽  
Gut Microbiota ◽  
Inflammatory Cytokines ◽  
Rat Model ◽  
Sodium Salicylate ◽  
Precancerous Lesions ◽  
Metabolic Phenotype ◽  
Multiple Factors ◽  
Microbial Dysbiosis

Background and Aims: Precancerous lesions of gastric cancer (PLGC) are the most important pathological phase with increased risk of gastric cancer (GC) and encompass the key stage in which the occurrence of GC can be prevented. In this study, we found that the gut microbiome changed significantly during the process of malignant transformation from chronic gastritis to GC in N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) multiple factors-induced rat model. Accumulating evidence has shown that alterations in gut microbiota and metabolism are potentially linked to chronic inflammation and cancer of the gastrointestinal tract. However, the correlation of gut microbiota and metabolites, inflammatory factors, and the potential mechanism in the formation of PLGC have not yet been revealed.Methods: In this study, multiple factors including MNNG, sodium salicylate drinking, ranitidine feed, and irregular diet were used to establish a PLGC rat model. The pathological state of the gastric mucosa of rats was identified through HE staining and the main inflammatory cytokine levels in the serum were detected by the Luminex liquid suspension chip (Wayen Biotechnologies, Shanghai, China). The microbial composition and metabolites in the stool samples were tested by using 16S ribosomal RNA (rRNA) gene sequencing and non-targeted metabolomics. The correlation analysis of gut microbiota and inflammatory cytokines in the serum and gut microbiota and differential metabolites in feces was performed to clarify their biological function.Results: The results showed that compared to the control group, the gastric mucosa of the model rats had obvious morphological and pathological malignant changes and the serum levels of inflammatory cytokines including interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and macrophage colony-stimulating factor (M-CSF) increased significantly, while the level of chemokine (C-X-C motif) ligand 1 (CXCL1) in serum reduced significantly. There were significant differences in the composition of the gut microbiota and fecal metabolic profiles between the model and control rats. Among them, Lactobacillus and Bifidobacterium increased significantly, while Turicibacter, Romboutsia, Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-005, and Ruminococcus_1 reduced significantly in the model rats compared to the control rats. The metabolites related to the lipid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathway have also undergone significant changes. In addition, there was a significant correlation between the changes of the differential inflammatory cytokines in the serum, fecal metabolic phenotypes, and gut microbial dysbiosis in model rats.Conclusion: The activation of the inflammatory response, disturbance of the gut microbiota, and changes in the fecal metabolic phenotype could be closely related to the occurrence of PLGC. This study provides a new idea to reveal the mechanism of risk factors of chronic gastritis and GC from the perspective of inflammation-immune homeostasis, gut microbiota, and metabolic function balance.

scholarly journals Integrative analysis of the gut microbiome and metabolome in a rat model with stress induced irritable bowel syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yue Hu ◽  
Fang Chen ◽  
Haiyong Ye ◽  
Bin Lu
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiota ◽  
Rat Model ◽  
Gut Microbiome ◽  
16S Rrna Gene Sequencing ◽  
Metabolic Phenotype ◽  
Control Group ◽  
Rrna Gene ◽  
Microbial Dysbiosis ◽  
Irritable Bowel

AbstractStress is one of the major causes of irritable bowel syndrome (IBS), which is well-known for perturbing the microbiome and exacerbating IBS-associated symptoms. However, changes in the gut microbiome and metabolome in response to colorectal distention (CRD), combined with restraint stress (RS) administration, remains unclear. In this study, CRD and RS stress were used to construct an IBS rat model. The 16S rRNA gene sequencing was used to characterize the microbiota in ileocecal contents. UHPLC-QTOF-MS/MS assay was used to characterize the metabolome of gut microbiota. As a result, significant gut microbial dysbiosis was observed in stress-induced IBS rats, with the obvious enrichment of three and depletion of 11 bacterial taxa in IBS rats, when compared with those in the control group (q < 0.05). Meanwhile, distinct changes in the fecal metabolic phenotype of stress-induced IBS rats were also found, including five increased and 19 decreased metabolites. Furthermore, phenylalanine, tyrosine and tryptophan biosynthesis were the main metabolic pathways induced by IBS stress. Moreover, the altered gut microbiota had a strong correlation with the changes in metabolism of stress-induced IBS rats. Prevotella bacteria are correlated with the metabolism of 1-Naphthol and Arg.Thr. In conclusion, the gut microbiome, metabolome and their interaction were altered. This may be critical for the development of stress-induced IBS.

Differential expression of human telomerase reverse transcriptase β-site remaining alternative splicing variants (hTERT β+ ASV) in gastric carcinogenesis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15641-e15641
Author(s):  
X. Geng
Keyword(s):  
Gastric Cancer ◽  
Enzyme Activity ◽  
Alternative Splicing ◽  
Gastric Mucosa ◽  
Precancerous Lesions ◽  
Normal Mucosa ◽  
Gastric Carcinogenesis ◽  
Normal Gastric Mucosa ◽  
Rt Pcr ◽  
Splicing Variants

e15641 Background: To investigate the changes of hTERT alternative splicing variants pattern in gastric cancer, precancerous lesions and normal gastric mucosa tissue. Methods: Three alternative splicing sites (α, β, γ) were selected and designed PCR primer. The expression of 8 hTERT alternative splicing variants (ASVs) in gastric cancer, precancerous lesions and normal gastric mucosa were detected by Semi-nested RT-PCR. The expression of β-site remaining ASV (β+ASV) in specimens of gastric cancer and specimens of precancerous lesions was detected by SYBER Green real-time PCR. Telomerase enzyme activity was evaluated associated with the different hTERT ASVs. Results: The positive rate of active full-length (α+β+γ+ ) ASV was significantly higher in gastric cancer than in precancerous lesions and normal mucosa (94.7% vs. 40.0% and 0, P<0.05). The positive rates of other ASVs were not different among the 3 groups(P>0.05). The positive rates of β+ ASVs (including α+β+γ+ASV, α-deletion ASV, γ-deletion ASV, αγ-deletion ASV) were 11.1% in normal mucosa,40.0% in precancerous lesions and 94.7% in gastric cancer (P<0.05). SYBR Green real-time RT-PCR showed that the expression level of β+ASV was 6.99 times higher in gastric cancer than in precancerous lesions. Further, increased telomerase enzyme activity was only associated with expression of the full-length hTERT isoform. Conclusions: hTERT alternative splicing pattern is different during gastric carcinogenesis. β+ASV was widely expressed in gastric carcinogenesis and may provide some information for diagnosis of gastric cancer or precancerous lesions. The gene expression patterns of hTERT alternative splicing variants may provide some useful information for diagnosis of gastric cancer and precancerous lesions. No significant financial relationships to disclose.

scholarly journals Onset and Progression of Precancerous Lesions on Gastric Mucosa of Patients Treated for Gastric Lymphoma

2020 ◽  
Vol 29 (1) ◽  
pp. 27-31
Author(s):  
Angelo Zullo ◽  
Angela Rago ◽  
Stefano Felici ◽  
Stefano Licci ◽  
Lerenzo Ridola ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Mucosa ◽  
Malt Lymphoma ◽  
Precancerous Lesions ◽  
Gastric Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Primary Gastric Lymphoma ◽  
Low Grade Dysplasia

Background and Aims: Patients with primary gastric lymphoma are at an increased risk of developing gastric cancer. Data on gastric precancerous lesions development in these patients are scanty. We assessed gastric precancerous lesions in a cohort of patients with primary lymphoma. Methods: Data of patients with primary gastric lymphoma [mucosa-associated lymphoid tissue (MALT)- lymphoma or diffuse large B-cell lymphoma (DLBCL)] were analysed. Multiple (>10) biopsies were performed on gastric mucosa at each endoscopic control, beyond macroscopic lesions. Presence and distribution of intestinal metaplasia (IM) at baseline, the onset at follow-up, and progression through the stomach or transformation in the incomplete IM type were assessed. The onset of neoplastic lesions was recorded. Results: Data of 50 patients (mean age of 63.6 ± 10.7 years; M/F: 25/25), including 40 with MALT-lymphoma and 10 with DLBCL, with median follow-up of 30.5 months (range: 9-108) and a median of 6 endoscopic controls (range: 3-14) were evaluated. At entry, IM was present in 12 (24%), and it developed in other 22 (57.9%) patients at a median follow-up of 6 (range: 3-40) months. Overall, progression of IM was observed in 7 (21.2%) cases, including extension in the stomach (n=5) or transformation into the incomplete type (n=2). Low-grade dysplasia was detected in 4, and indefinite dysplasia in other 7 patients. In one patient, low-grade dysplasia had progressed to high-grade and gastric adenocarcinoma of the fundus. Conclusions: Our data found a frequent onset and rapid progression of precancerous lesions on gastric mucosa of lymphoma patients. This observation could explain the increased incidence of metachronous gastric cancer in these patients.

scholarly journals Is There an Optimal Age Threshold for Searching for Intestinal Metaplasia on Gastric Mucosa in Western Populations?

2021 ◽  
pp. 1-5
Author(s):  
Angelo Zullo ◽  
Edith Lahner ◽  
Cesare Hassan ◽  
Bruno Annibale ◽  
Gianluca Esposito
Keyword(s):  
Gastric Cancer ◽  
Gastric Mucosa ◽  
Intestinal Metaplasia ◽  
Early Stage ◽  
Precancerous Lesions ◽  
Smoking Habit ◽  
Gastric Body ◽  
Screening Programs ◽  
Gastric Cancer Screening

<b><i>Introduction:</i></b> Since screening programs for gastric cancer are not applicable in Western countries, identification and follow-up of gastric precancerous lesions, such as extensive intestinal metaplasia (IM), are worthwhile to increase the diagnosis of cancer at an early stage. We investigated whether an optimal age threshold to detect extensive IM in a European country exists. <b><i>Methods:</i></b> This was a post hoc analysis of prospectively collected data in a nationwide study involving consecutive patients aged between 50 and 65 years who underwent an upper endoscopy with the standard 5 gastric biopsies. The presence of extensive (antral and gastric body) IM on gastric mucosa was considered. <b><i>Results:</i></b> Data found that the prevalence of extensive IM was distinctly higher in patients aged 60–65 years, with a 2.28-fold increased probability compared to younger patients. None of the other considered factors (sex, BMI, smoking habit, first-degree family history, and symptoms) emerged as an independent predictor of extensive IM in the stomach. <b><i>Conclusion:</i></b> When deciding for an occasional gastric cancer screening in Western populations, the choice of an age range of 60–65 years might be appropriate, allowing detection of a distinctly high prevalence of extensive IM deserving scheduled follow-up.

scholarly journals Carcinoembryonic Antigen Related Cell Adhesion Molecule 6 Promotes Carcinogenesis of Gastric Cancer and Anti-CEACAM6 Fluorescent Probe Can Diagnose the Precancerous Lesions

2021 ◽  
Vol 11 ◽  
Author(s):  
Fangmei An ◽  
Chuwei Zheng ◽  
Guoqiang Zhang ◽  
Liangyun Zhou ◽  
Yuqing Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Adhesion ◽  
Molecular Imaging ◽  
Gastric Mucosa ◽  
Cell Adhesion Molecule ◽  
Precancerous Lesions ◽  
Mice Model ◽  
Related Cell

The diagnosis of precancerous lesions or early gastric cancer (EGC) is very important for patient survival. Molecular imaging is a visualized method that can easily and precisely diagnose tumors. However, there are currently few studies about molecular imaging diagnosis of EGC. Here, we studied the expression of carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6) in the progression of GC. Then, the regulatory roles of CEACAM6 in GC cells were investigated. Furthermore, both the fluorescent-labeled and near infrared molecular-labeled probes were synthesized, and the diagnostic value of anti-CEACAM6 probes in GC was evaluated in vivo using a GC mice model as well as in vitro using fresh dysplastic gastric mucosa obtained from endoscopic submucosal dissection (ESD) operations. Our study showed that CEACAM6 was over expressed in GC tissues compared to adjacent tissues, and the patients with higher CEACAM6 expression had lower survival time. Moreover, the CEACAM6 expression was higher in the dysplastic gastric mucosa than in the adjacent normal mucosa. CEACAM6 accelerated the growth, proliferation, and invasion of GC cells in the in vitro and in vivo studies. Moreover, up regulated CEACAM6 can induce the expression of proteins related to GC progression. Furthermore, the anti-CEACAM6 probes exhibited good affinity with GC cell lines. The probes can track tumors as well as metastases in the mice model in vivo, and can precisely identify the area of dysplastic gastric mucosa using specimens obtained from ESD operations by wide field fluorescent endoscopy. The surface micro features of the mucosa can also be observed using fluorescent micro endoscopy, and the degree of atypia can be distinguished by both the signal intensity and surface micro morphology. CEACAM6 is a key molecular marker in GC progression, and the anti-CEACAM6 probe-assisted fluorescent endoscopy may be a potential option for the diagnosis of precancerous lesions.

scholarly journals Dietary supplementation with carbonate increases expression of ornithine decarboxylase and proliferation in gastric mucosa in a rat model of gastric cancer

2007 ◽  
Vol 122 (4) ◽  
pp. 727-733 ◽  
Author(s):  
Roy A. Ehrnström ◽  
Lars Magnus Bjursten ◽  
Otto Ljungberg ◽  
Béla Veress ◽  
Monica E. Haglund ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Mucosa ◽  
Ornithine Decarboxylase ◽  
Rat Model ◽  
Dietary Supplementation

scholarly journals Helicobacter pylori-Induced Inflammation: Possible Factors Modulating the Risk of Gastric Cancer

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1099
Author(s):  
Sushil Kumar ◽  
Girijesh Kumar Patel ◽  
Uday C. Ghoshal
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Gut Microbiota ◽  
Dietary Habits ◽  
Tissue Injury ◽  
Precancerous Lesions ◽  
Gastric Carcinogenesis ◽  
Future Research ◽  
Intestinal Helminths ◽  
H Pylori

Chronic inflammation and long-term tissue injury are related to many malignancies, including gastric cancer (GC). Helicobacter pylori (H. pylori), classified as a class I carcinogen, induces chronic superficial gastritis followed by gastric carcinogenesis. Despite a high prevalence of H. pylori infection, only about 1–3% of people infected with this bacterium develop GC worldwide. Furthermore, the development of chronic gastritis in some, but not all, H. pylori-infected subjects remains unexplained. These conflicting findings indicate that clinical outcomes of aggressive inflammation (atrophic gastritis) to gastric carcinogenesis are influenced by several other factors (in addition to H. pylori infection), such as gut microbiota, co-existence of intestinal helminths, dietary habits, and host genetic factors. This review has five goals: (1) to assess our current understanding of the process of H. pylori-triggered inflammation and gastric precursor lesions; (2) to present a hypothesis on risk modulation by the gut microbiota and infestation with intestinal helminths; (3) to identify the dietary behavior of the people at risk of GC; (4) to check the inflammation-related genetic polymorphisms and role of exosomes together with other factors as initiators of precancerous lesions and gastric carcinoma; and (5) finally, to conclude and suggest a new direction for future research.

scholarly journals Green Tea and Its Relation to Human Gut Microbiome

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3907
Author(s):  
Sergio Pérez-Burillo ◽  
Beatriz Navajas-Porras ◽  
Alicia López-Maldonado ◽  
Daniel Hinojosa-Nogueira ◽  
Silvia Pastoriza ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Green Tea ◽  
Bacterial Species ◽  
Bioactive Molecules ◽  
Bioactive Metabolites ◽  
Microbial Dysbiosis ◽  
Inflammatory Processes ◽  
Health Promoting ◽  
Middle Man ◽  
Specific Species

Green tea can influence the gut microbiota by either stimulating the growth of specific species or by hindering the development of detrimental ones. At the same time, gut bacteria can metabolize green tea compounds and produce smaller bioactive molecules. Accordingly, green tea benefits could be due to beneficial bacteria or to microbial bioactive metabolites. Therefore, the gut microbiota is likely to act as middle man for, at least, some of the green tea benefits on health. Many health promoting effects of green tea seems to be related to the inter-relation between green tea and gut microbiota. Green tea has proven to be able to correct the microbial dysbiosis that appears during several conditions such as obesity or cancer. On the other hand, tea compounds influence the growth of bacterial species involved in inflammatory processes such as the release of LPS or the modulation of IL production; thus, influencing the development of different chronic diseases. There are many studies trying to link either green tea or green tea phenolic compounds to health benefits via gut microbiota. In this review, we tried to summarize the most recent research in the area.

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