With the widely application of the metagenomics, the relationship between microbiota and disease has become a hot research topic. Understanding the potential association between upper gastrointestinal cancer or precancerous lesions and microbiota may play an important role in the early detection, clinical diagnosis and treatment, and prognostic evaluation of upper gastrointestinal cancer. Therefore, a literature retrieval was conducted by using PubMed, Embase and wanfang databases to summarize the latest research progress in the microbiota of upper gastrointestinal cancer, including oral, esophageal, gastric cancer and precancerous lesions. Lower microbial diversity or richness in esophageal cancer and precancerous lesions and specific prognostic biomarkers for esophageal cancer were found. Lactobacillus richness showed an increase trend during the process from gastritis to gastric cancer. This paper summarizes the progress in the research of potential biological etiology of upper gastrointestinal cancer from the perspective of metagenomics in order to provide evidence on the, prevention and control of upper gastrointestinal cancer.
Esophageal Neoplasms/microbiology* ; Gastrointestinal Microbiome ; Gastrointestinal Neoplasms/microbiology* ; Gastrointestinal Tract/microbiology* ; Humans ; Lactobacillus ; Metagenomics/trends* ; Microbiota ; Precancerous Conditions/microbiology* ; Prognosis ; Research/trends* ; Risk Factors ; Stomach Neoplasms/microbiology*

Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
Anti-Bacterial Agents ; therapeutic use ; Gastrointestinal Microbiome ; drug effects ; Gastrointestinal Neoplasms ; microbiology ; prevention & control ; Gastrointestinal Tract ; microbiology ; Humans

Accumulating evidence suggests that intestinal bacteria play an important role in the pathogenesis of colorectal cancer (CRC). Due to the complexity of the intestinal microbiome, identification of the specific causative microbial agents in CRC remains challenging, and the search for the causative microbial agents is intense. However, whether bacteria or their products can induce inflammation that results in tumorigenesis or directly causes CRC in humans is still not clear. This review will mainly focus on the progress of bacterial infection and CRC, and introduce the microbial contribution to the hallmarks of cancer. This article uses Salmonella and its chronic infection as an example to investigate a single pathogen and its role in the development of CRC, based on laboratory and epidemiological evidence. The bacterial infection leads to an altered intestinal microbiome. The review also discusses the dysfunction of the microbiome and the mechanism of host-microbial interactions, for example, bacterial virulence factors, key signaling pathways in the host, and microbial post-translational modifications in the tumorigenesis. Colonic carcinogenesis involves a progressive accumulation of mutations in a genetically susceptible host leading to cellular autonomy. Moving forward, more human data are needed to confirm the direct roles of bacterial infection in CRC development. Insights into the inhibiting infection will help to prevent cancer and develop strategies to restore the balance between host and microorganisms.
Bacterial Infections/complications* ; Carcinogenesis ; Colorectal Neoplasms/microbiology* ; Gastrointestinal Microbiome ; Humans

Objective: To explore the correlation between age and diversity and microbial composition in saliva and feces microbiota in high-risk population of upper gastrointestinal cancer. Methods: Based on the national project on early diagnosis and early treatment of upper gastrointestinal cancer, 38 participants were enrolled in Linzhou in Henan province in August 2019. The participant information was collected by questionnaire. Saliva and feces specimens were collected from each participant for 16S rRNA sequencing and bioinformatics analysis. Spearman rank correlation was used to analyze the correlation between age and α diversity (Observed ASVs and Shannon index) and relative abundance of microbiota (phyla, genera, and species) in saliva and feces. Results: The median age (age range) of 38 participants was 54 (43-60) years old, and there were 16 males (42.1%). The Observed ASVs of saliva was negatively correlated with age (r_s=-0.35, P<0.05), but the observed ASVs of feces was not correlated with age. In saliva, the relative abundance of Treponema (r_s=‒0.44, P<0.05), Alloprevotella (r_s=‒0.42, P<0.05), and Porphyromonas (r_s=‒0.41,P<0.05) were significantly negatively correlated with age. At the species level, the relative abundance of Porphyromonas endodontalis, Alloprevotella tannerae, Haemophilus influenza, Moraxella bovoculi, Prevotella sp.oral clone ID019, and Prevotella sp.oral clone ASCG10 in saliva were significantly negatively correlated with age, and the r_s values were -0.50, -0.40, -0.38, -0.35, -0.33 and -0.33 (P<0.05), respectively. In feces, the relative abundance of Enterobacteria (r_s=-0.35, P<0.05), Escherichia (r_s=-0.33, P<0.05), and Bifidobacteria (r_s=0.33, P<0.05) were correlated with age. At the species level, the relative abundance of Romboutsia sedimentorum, Citrobacter murliniae, and bacteroides uniformis in feces were correlated with age, and the r_s values were -0.42, -0.37 and 0.36 (P<0.05), respectively. Conclusion: Age of the high-risk population of upper gastrointestinal cancer is correlated with the relative abundance of microbiota in saliva and feces.
Male ; Humans ; Adult ; Saliva/microbiology* ; RNA, Ribosomal, 16S/genetics* ; Feces/microbiology* ; Microbiota ; Gastrointestinal Neoplasms

OBJECTIVE: To investigate the changes in bacterial flora in fecal samples, at the tumor loci and in adjacent mucosa in patients with colorectal cancer (CRC). METHODS: We collected fecal samples from 13 patients with CRC and 20 healthy individuals and tumor and adjacent mucosa samples from 6 CRC patients. The differences in bacterial composition between the fecal and mucosa samples were analyzed with 16S rDNA sequencing and bioinformatics methods. We also detected the total number of bacteria in the feces using flow cytometry, isolated and identified the microorganisms in the fecal and mucosa samples using common bacterial culture media. We further tested the effects of 7 isolated bacterial strains on apoptosis of 3 CRC cell lines using lactate dehydrogenase detection kit. RESULTS: The bacterial α-diversity in the feces of healthy individuals and in adjacent mucosa of CRC patients was significantly higher than that in the feces and tumor mucosa in CRC patients (P < 0.05). Lactobacillaceae is a specific bacteria in the feces, while Escherichia, Enterococcus, and Fusobacterium are specific bacteria in tumor mucosa of CRC patients as compared with healthy individuals. Cell experiment with3 CRC cell lines showed that Bacteroides fragilis isolated from the tumor mucosa of CRC patients produced significant inhibitory effects on cell proliferation (P < 0.0001), while the isolated strain Fusobacterium nucleatum obviously promoted the proliferation of the cell lines (P < 0.001). CONCLUSION The bacterial flora in the feces, tumor mucosa and adjacent mucosa of CRC patients is significantly different from that in the feces of healthy individuals, and the fecal flora of CRC patients can not represent the specific flora of the tumor mucosa. Inhibition of F. nucleatum colonization in the tumor mucosa and promoting B. fragilis colonization may prove beneficial for CRC treatment.
Bacteria ; Colorectal Neoplasms/pathology* ; Feces/microbiology* ; Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa

Objective To evaluate the gastric microbiome in patients with chronic superficial gastritis (CSG) and intestinal metaplasia (IM) and investigate the influence of Helicobacter pylori (H. pylori) on the gastric microbiome. Methods Gastric mucosa tissue samples were collected from 54 patients with CSG and IM, and the patients were classified into the following four groups based on the state of H. pylori infection and histology: H. pylori-negative CSG (n=24), H. pylori-positive CSG (n=14), H. pylori-negative IM (n=11), and H. pylori-positive IM (n=5). The gastric microbiome was analyzed by 16S rRNA gene sequencing. Results H. pylori strongly influenced the bacterial abundance and diversity regardless of CSG and IM. In H. pylori-positive subjects, the bacterial abundance and diversity were significantly lower than in H. pylori-negative subjects. The H. pylori-negative groups had similar bacterial composition and bacterial abundance. The H. pylori-positive groups also had similar bacterial composition but different bacterial relative abundance. The relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella were richer in the I-HP group than in G-HP group, especially Neisseria (t=175.1, P<0.001). Conclusions The gastric microbial abundance and diversity are lower in H. pylori- infected patients regardless of CSG and IM. Compared to H. pylori-positive CSG group and H. pylori-positive IM, the relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella is higher in H. pylori-positive patients with IM than in H. pylori-positive patients with CSG, especially Neisseria.
Gastric Mucosa/microbiology* ; Gastritis, Atrophic/microbiology* ; Gastrointestinal Microbiome/genetics* ; Helicobacter Infections/microbiology* ; Helicobacter pylori/genetics* ; Humans ; Metaplasia ; RNA, Ribosomal, 16S/genetics* ; Stomach Neoplasms

Objective To compare the differences in fecal flora among patients with esophageal cancer,gastric cancer,or colorectal cancer and between patients with gastrointestinal tumors and healthy people.Methods The 16S rRNA method was used to analyze the differences in fecal flora among 13 patients with esophageal squamous cell carcinoma,23 patients with gastric cancer,6 patients with colorectal cancer,and 49 healthy persons.Results Bifidobacterium,,and were less abundant in the fecal flora of cancer patients than in those of healthy controls(all <0.05).Some species of and were significantly reduced in the feces of patients with esophageal cancer or gastric cancer than in healthy people(<0.05),whereas others showed consistency with the intestinal cancer group.Anti-tumor treatment,antibiotics,and lactic acid could affect the fecal flora of cancer patients.Conclusion The gut microbiota compositions(mainly and )and some specific bacteria species in the feces of patients with esophageal cancer and gastric cancer are similar to those in the feces of patients with intestinal cancer,suggesting these bacteria may be involved in the development of upper gastrointestinal tumors.
Bacteria ; classification ; Case-Control Studies ; Esophageal Neoplasms ; microbiology ; Esophageal Squamous Cell Carcinoma ; microbiology ; Feces ; microbiology ; Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S ; genetics

Tuberculosis remains an important cause of morbidity and mortality, especially in underdeveloped and developing nations. Manifestations could be nonspecific and may mimic many other conditions, including malignancies. Oesophageal involvement is surprisingly rare despite the high prevalence of pulmonary tuberculosis and the close proximity of these two structures. We report two cases of oesophageal tuberculosis; a 73-year-old man with simultaneous oesophageal, stomach and duodenal involvement, and a 45-year-old man with isolated oesophageal involvement. Underlying malignancies were initially suspected in both cases, but they were eventually diagnosed as tuberculosis.
Abdominal Pain ; microbiology ; Aged ; Diagnosis, Differential ; Esophageal Diseases ; diagnosis ; microbiology ; Esophageal Neoplasms ; diagnosis ; Esophagoscopy ; Gastroesophageal Reflux ; microbiology ; Granuloma ; diagnosis ; microbiology ; Humans ; Malaysia ; Male ; Middle Aged ; Tomography, X-Ray Computed ; Tuberculosis, Gastrointestinal ; diagnosis

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear. METHODS: We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups. RESULTS: Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella , Hungatella , Peptostreptococcus , and Parvimonas , and decreased Butyricicoccus , Lactobacillus , and Paraprevotella . The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups ( P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group ( Parvimonas , Desulfurispora , Sebaldella , and Veillonellales , among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium , Thermococci , and Cellulophaga . CONCLUSIONS Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.
Humans ; Gastrointestinal Microbiome/genetics* ; Diabetes Mellitus, Type 2 ; Microbiota ; Bacteria/genetics* ; Fatty Acids, Volatile ; Colorectal Neoplasms/metabolism* ; Butyrates ; Feces/microbiology*

Despite a higher incidence and less favorable outcome of malignant tumors in obese patients, much less recognized is the link between obesity and cancer. The mechanism of the association of obesity with carcinogenesis remains incompletely understood. Postulated mechanisms include insulin resistance, insulin-like growth factor signaling, chronic inflammation, immunomodulation, hyperglycemia-induced oxidative stress, and changes of intestinal microbiome. Insulin resistance leads to direct mitogenic and antiapoptotic signaling by insulin and the insulin-like growth factor axis. Obesity can be considered to be a state of chronic low-grade inflammation. In obesity, numerous proinflammatory cytokines are released from adipose tissue which may involve in carcinogenesis. Hyperglycemia in susceptible cells results in the overproduction of superoxide and this process is the key to initiating all damaging pathways related to diabetes. This hyperglycemia-induced oxidative stress could be one possible link among obesity, diabetes, and cancer development. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention.
Adipokines/metabolism/physiology ; Gastrointestinal Neoplasms/*etiology/microbiology ; Humans ; Inflammation/etiology ; Insulin/metabolism/physiology ; Leptin/metabolism/physiology ; Obesity/*complications/immunology/metabolism ; Oxidative Stress ; Somatomedins/metabolism/physiology