Table 2.

Summary findings of studies included in the systematic synthesis.

Author	Year	Country	Population	Sex	Type of Study	Bacteria species	Organ	Gastric cancer description	Outcome	Conclusion	Quality Of evidence
Zihan et al. (23)	2023	China	117 patients	Male:90 Female:27	Prospective cohort study	Lactobacillus, Bacillota, Bacteroidota and Actinobacteria, Proteobacteria outnumbered Actinobacteria	Gastric	Metastatic/unresectable HER2-negative gastric/gastroesophageal junction adenocarcinoma	The nature of the gut microbiota influences the efficacy of various therapies in patients with HER2-negative advanced gastric cancer. Increased levels of Lactobacillus are linked to improved outcomes with anti-PD-1/PD-L1 immunotherapy and extended progression-free survival (PFS). Patients with increased levels of Lactobacillus exhibited more variety in their gut microbiota and showed an increase in metabolic pathways associated with amino acid and energy metabolism. In the group receiving immunotherapy in addition to chemotherapy, a decreased presence of Streptococcus was linked to improved response and extended progression-free survival (PFS). The gut microbiota profiles associated with treatment response differ between chemotherapy, immunotherapy, and combination therapy groups, indicating an intricate interaction. Lactobacillus has the potential to enhance the effectiveness of immunotherapy in treating gastric cancer.	The study highlights the importance of gut microbiota in cancer treatment, with Lactobacillus potentially playing a crucial role. Focusing on these bacteria could potentially improve treatment outcomes and enhance patient outcomes.	High
Jones et al. (24)	2017	United States	It was tested on Drosophila melanogaster	-	Experimental study	Helicobacter pylori	Gastric	-	Expression of the H. pylori virulence factor In the Drosophila gut model, CagA stimulates abnormal growth of epithelial cells, a characteristic of gastric cancer in people with H. pylori infection. CagA expression results in dysbiosis of the gut microbial population. The altered microbiota caused by CagA expression leads to increased cell proliferation, indicating that dysbiosis may worsen stomach cancer development in H. pylori infection.	The gut microbiome composition influences treatment response in HER2-negative advanced gastric cancer patients. High Lactobacillus abundance leads to better response and longer progression-free survival. Lower Streptococcus abundance in immunotherapy plus chemotherapy group improves response and PFS. Lactobacillus may be a potential adjuvant agent for immunotherapy efficacy.	High
Miao et al. (21)	2022	China	51 patients	Female:51	Cross-sectional study		Gastric	Enterococcus Fusicatenibacter Faecalibacterium, RoseburiaLachnoclos Lachnoclostridium, Tyzzerella_3, Roseburia, Butyricicoccus, and Dorea	Reduced gut microbial alpha diversity (richness and diversity) and altered dissimilarity of the microbial community structure were found in the gastric mucosal atypical hyperplasia and gastric cancer groups compared to the superficial gastritis group. Several bacterial genera were enriched in different stages: (a) Superficial gastritis group: Dorea,Erysipelotrichaceae_unclassified, Ruminococcaceae_unclassified, Fusicatenibacter, Faecalibacterium, Roseburia, Lachnoclostridium, Butyricicoccus (b) Atrophic gastritis group: Tyzzerella_3, Actinomyces, Lachnospiraceae_unclassified (c) Gastric mucosal atypical hyperplasia group: Burkholderiales_unclassified, Peptoniphilus, Alloprevotella, Prevotella_7 (d) Gastric cancer group: Porphyromonas, Scardovia, Halomonas, Actinobacteria_unclassified, Bergeyella, Enterococcus The genera Scardovia and Halomonas were newly associated with gastric cancer. The metabolic pathways of Genetic Information Processing and Circulatory System were more abundant in the gastric cancer group compared to non-cancer groups.	The study explores the connection between gut microbiota and cancer treatment response. It found that certain microbial taxa, like L. mucosae and L. salivarius, are associated with better immunotherapy response. Lactobacillus abundance in responders is linked to immunotherapy effects, while higher alpha-diversity indicates a more diverse gut microenvironment. The combination of immunotherapy and chemotherapy has a distinct microbiome signature. Streptococcus abundance in responders correlates with shorter progression-free survival. These findings suggest gut microbiota could be a potential biomarker for cancer diagnosis and patient stratification.	Moderate
Oh et al. (25)	2015	South Korea	32		Randomized controlled trial	H. pylori, Streptococcus faecium Bacillus subtilis phyla, Bacillota, Bacteroidota, and Proteobacteria	Gastric	Chronic gastritis, gastric and duodenal ulcers as well as gastric cancer	probiotic supplementation during H. pylori eradication therapy helped reduce the disruption of gut microbiota caused by the antibiotics. Maintaining a healthy, balanced gut microbiota is important, as dysbiosis (imbalance) of gut microbiota has been linked to several diseases, including gastric cancer. While the study did not directly evaluate gastric cancer risk, maintaining gut microbiota balance by using probiotics during H. pylori eradication may help reduce risk factors associated with gastric cancer development.	Probiotic supplementation can reduce the antibiotic-induced alteration and imbalance of the gut microbiota composition. This effect may restrict the growth of antibiotic-resistant bacteria in the gut and improve the H. pylori eradication success rate.	Moderate
Park et al. (26)	2018	South Korea	138 patients	Male:63	Cross-sectional study	H. pylori Rhizobiales Cyanobacteria	Gastric	H. pylori-negative CSG, H. pylori-negative IM, H. pylori-negative cancer, H. pylori-positive CSG, H. pylori-positive IM, and H. pylori-positive cancer	The relative abundance of the bacterial taxa Rhizobiales was higher in patients with H. pylori-negative intestinal metaplasia compared to those with H. pylori-negative chronic superficial gastritis or H. pylori-negative gastric cancer. Genes encoding type IV secretion system (T4SS) proteins, which are essential for transferring the CagA virulence factor from H. pylori into human gastric epithelial cells, were highly prevalent in the metagenome of patients with intestinal metaplasia. The authors hypothesized that the abundance of T4SS genes in intestinal metaplasia, mainly contributed by bacteria like Rhizobiales and Neisseriaceae, may facilitate horizontal gene transfer of T4SS genes to H. pylori, promoting gastric carcinogenesis through enhanced CagA translocation. The gastric microbiome composition after successful H. pylori eradication therapy resembled that of the H. pylori-negative intestinal metaplasia group, which was regarded as a high-risk group for gastric cancer development.	A study found that patients with H. pylori-negative intestinal metaplasia (IM) had a higher abundance of Rhizobiales bacteria compared to those with chronic superficial gastritis (CSG) or cancer. The metagenome of IM patients also showed high T4SS protein genes, potentially promoting gastric carcinogenesis. The study suggests that horizontal gene transfer between H. pylori and other bacteria may contribute to gastric cancer development.	High
Park et al. (27)	2019	South Korea	83	Male:39 Female:44	Cross-sectional study	H. pylori Acidobacteriaceae, Burkholderiaceae, Neisseriaceae, Pasteurellaceae, Veillonellaceae, Bartonellaceae, Brucellaceae, unclassified Rhizobiales, Pseudomonadaceae, Sphingomonadaceae, Staphylococcaceae, and Xanthomonadaceae		Patients with gastric neoplasms including carcinoma, mucosa-associated lymphoid tissue lymphoma, or adenoma; and (c) patients who underwent gastrectomy	Through weighted correlation network analysis identified two microbial modules (pink and brown modules) that were positively correlated with an advanced stage of gastric carcinogenesis (intestinal metaplasia with or without H. pylori infection). The pink and brown modules included various bacteria such as nitrosating/nitrate-reducing bacteria (e.g., Neisseriaceae, Pasteurellaceae, Veillonellaceae, Pseudomonadaceae, Staphylococcaceae), type IV secretion system (T4SS) protein gene-contributing bacteria (e.g., Acidobacteriaceae, Burkholderiaceae, Neisseriaceae, Bartonellaceae, Brucellaceae, Rhizobiales, Pseudomonadaceae, Sphingomonadaceae, Xanthomonadaceae), and other bacterial families like Gordoniaceae, Tsukamurellaceae, Prevotellaceae, Cellulomonadaceae, Methylococcaceae, and Procabacteriaceae. The abundance of bacterial taxa in the pink and brown modules was higher in patients with intestinal metaplasia (precancerous lesion) compared to those without intestinal metaplasia. In contrast, the blue module, which included H. pylori, was negatively correlated with intestinal metaplasia. The findings suggest that diverse intragastric bacteria, beyond just H. pylori, are associated with an advanced stage of gastric carcinogenesis, and these bacteria can be clustered into specific microbial network modules through weighted correlation analysis.	The study identifies two bacterial modules associated with gastric carcinogenesis, including H. pylori and other taxa. It also reveals that the abundance of these taxa decreases in patients with intestinal metaplasia. This contributes to a better understanding of the gastric microbiome and its association with gastric carcinogenesis.	High
Zheng et al. (29)	2019	China	100	Male:84 Female:16	Randomized controlled trial	Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis and Bacillus cereus Streptococcus, Peptostreptococcus and Prevotella, Bifidobacterium Bacteroides, Faecalibacterium and Akkermansia	Gastric	Gastric cancer	The probiotic combination containing Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis and Bacillus cereus significantly reduced inflammation indexes (leukocytes) and enhanced immunity indexes (lymphocytes) and nutrition indexes (albumin and total protein) in gastric cancer patients after partial gastrectomy compared to the control group. Gastric cancer had a strong influence on the microbial diversity in the stomach, enhancing the abundance of pathogens like Streptococcus, Peptostreptococcus and Prevotella, while reducing the probiotic Bifidobacterium. The probiotic combination reduced the Bacillota /Bacteroidota ratio in the gut microbiota of gastric cancer patients after gastrectomy compared to the control group, which is associated with a healthier state. At the genus level, the probiotic combination enhanced beneficial bacteria like Bacteroides, Faecalibacterium and Akkermansia, while lowering the pathogen Streptococcus in the gut of gastric cancer patients after surgery. Overall, the probiotic combination enhanced immune response, reduced inflammation severity, and helped restore a healthier gut microbial balance in gastric cancer patients after partial gastrectomy surgery.	Gastrectomy, a common treatment for gastric cancer, can cause severe physiological and microbial disorders. A study suggests using a probiotic combination can reduce side effects, improve health, and restore a healthier balance in the stomach and intestinal microbiota. Further research is needed to understand the underlying mechanisms.	High
Yuan et al. (30)	2018	China	32 mice	Female:32	Experimental study	Escherichia shigella Enterobacter Bacillota Lachnospiracea_NK4 A136, Bacteroides, Odoribacter, Mucispirillum, and Blautia		Colorectal cancer	Antibiotics treatment that disrupted the gut microbiota reduced the anti-tumor efficacy of 5-FU in the mice with colorectal cancer. Administration of probiotics along with 5-FU did not significantly increase the anti-tumor efficacy compared to 5-FU alone, although it improved body weight in mice at day 33. 5-FU treatment altered the diversity and composition of the gut microbiota, with increased abundance of certain bacterial genera like Lachnospiraceae, Enterobacter, Escherichia-Shigella, Bacteroides, etc. Functional analysis showed genes involved in amino acid metabolism, replication/repair, translation, and nucleotide metabolism were expressed lower in the antibiotics +5-FU group compared to other groups. The results suggest that gut microbiota dysbiosis induced by antibiotics may contribute to reduced anti-tumor efficacy of 5-FU, highlighting the potential role of gut microbiota in modulating chemotherapeutic drug responses in colorectal cancer.	The study reveals that gut microbiota imbalance can reduce the effectiveness of 5-Fluorouracil (5-FU) treatment in reducing tumor growth in colorectal cancer. The imbalance alters the composition and function of the microbiota, leading to increased harmful bacteria and decreased beneficial ones. Probiotics do not significantly alter the gut microbiota diversity, but change the types of bacteria present.	High
Yu et al. (31)	2023	China			Experimental study	H. pylori			The nanogenerators (Fe-HMME@DHA@MPN) can generate ROS like singlet oxygen and hydroxyl radicals under ultrasonication and acidic conditions mimicking the H. pylori infection microenvironment in the stomach. The ROS produced by these nanogenerators were effective in killing multidrug-resistant H. pylori strains and removing H. pylori biofilms in vitro. In a mouse model of H. pylori infection, treatment with these nanogenerators showed high therapeutic efficacy in eliminating the H. pylori infection without disrupting the normal gut microbiota.	A gastric acid-responsive ROS nanogenerator made from biocompatible DHA, tannic acid, HMME, and Fe (II, III) has been used to treat H. pylori infection in mice through sonodynamic and chemodynamic processes. The nanogenerator catalyzes H2O2 and produces ROS in an acidic environment, effectively eliminating drug-susceptible and drug-resistant H. pylori and biofilm without harming bacteria or cells.	Moderate
Watanabe et al. (32)	2020	Japan	29 H. pylori-infected patients	Male:24 Female:5	Case control study	H. pylori	Gastric Cancer	Early GC	H. pylori infection was associated with reduced richness and evenness of gastric bacteria compared to H. pylori-negative patients. Several genera like Blautia, Ralstonia, Faecalibacterium, Methylobacterium, and Megamonas were depleted in H. pylori-positive patients. H. pylori eradication only partially restored microbial diversity, and those 5 genera remained depleted compared to H. pylori-negative patients. The gastric microbiota composition clustered into three distinct groups based on H. pylori status: negative, pre-eradication, and post-eradication.	Helicobacter pylori, a major cause of gastric cancer, affects over half of the global population. Drug resistance is affecting antibiotic-based triple therapy efficacy. Other gastric microbiomes also contribute to GC tumorigenesis. Early GC patients risk metachronous GC, and dysbiosis may persist post-eradication.	High
Wang et al. (33)	2016	China	315	Male:190	Case–control study	H. pylori	Gastric	Chronic gastritis Gastric Cancer	There was an increased bacterial load (overgrowth) in the gastric mucosa of patients with gastric cancer compared to chronic gastritis. The structure of the microbial communities was more diversified in gastric cancer patients. Five bacterial genera (Lactobacillus, Escherichia-Shigella, Nitrospirae, Burkholderia fungorum, and Lachnospiraceae uncultured) were enriched in gastric cancer patients. The presence of Helicobacter pylori infection was associated with increased bacterial load but did not significantly alter the relative abundance of other bacteria. The altered microbiota in gastric cancer, with increased bacterial quantity, diversified communities, and enrichment of bacteria with potential cancer-promoting activities, could contribute to gastric carcinogenesis.	The study aimed to characterize gastric microbiota in cancer, finding an increased number of diverse bacteria. The altered microbiota may have cancer-promoting activities, but mechanisms and pathways remain unclear.	Moderate
Wang et al. (34)	2019	China	313	Male:165 Female:148	Cohort Study	H. pylori		Gastric ulcer, gastric cancer, and many nongastrointestinal disorders	alterations in the gut microbiome composition and functions in H. pylori positive individuals compared to H. pylori negative individuals. Specific microbial species like Prevotella copri, linked to inflammatory conditions like rheumatoid arthritis, were enriched in H. pylori positive individuals. Microbial genes/pathways related to vitamin B12 biosynthesis were diminished in H. pylori positive individuals, who also had lower blood vitamin B12 levels. Overall, the study suggests H. pylori infection leads to dysbiosis of the gut microbiome, which may contribute to the downstream effects and disease risks associated with H. pylori, including gastric cancer, though this was not directly studied.	The study shows that Helicobacter pylori infection impacts the microbial makeup and function of the human intestines in the Chinese population. The study also shows variations in the prevalence of immunologically associated bacteria P. copri. Dysbiosis of gut microbiota connected to HPI can elevate the likelihood of VB12 insufficiency, offering fresh perspectives on the relationship between H. pylori and the microecology of the host’s gastrointestinal system.	High
Turati et al. (35)	2023		1,600		Case report????? (case control)		stomach	There were 946 cases of oral cavity/pharynx cancer, 198 cases of nasopharynx cancer, 304 cases of esophageal cancer, and 230 cases of stomach cancer. Over 4,000 individuals treated to the same hospitals for acute nonneoplastic and non-diet-related diseases were chosen as control subjects.	No association was observed between intake of most prebiotic fibers (inulin-type fructans, fructooligosaccharides like kestose, nystose, 1F-β-fructofuranosylnystose, and galactooligosaccharide stachyose) and risk of stomach cancer. high intake of the galactooligosaccharide raffinose was associated with a reduced risk of stomach cancer. Specifically, the odds ratio for stomach cancer in the highest vs. lowest tertile of raffinose intake was 0.6 (95% CI: 0.3–0.9).	Fiber intake may lower digestive tract cancer risk by modifying gut microbiota. However, no data exists on specific fiber fractions with prebiotic activity. No association was found between prebiotic intake and oral cavity, pharynx, nasopharynx, and esophagus cancers.	High
Song et al. (36)	2017	China	35	Male:35	Experimental study	Desulfovibrio, Mucispirillum, Odoribacter, Lactobacillus			Pretreatment with the probiotic cocktail Bifico ameliorated colitis and reduced tumor formation in the CAC mouse model. Bifico treatment alleviated weight loss, reduced tumor multiplicity and size, and lowered expression of pro-inflammatory genes like Tnfa, Il1b, Il6, and Ptgs1. Bifico altered the composition of the gut microbiota, decreasing abundance of genera like Desulfovibrio, Mucispirillum, Odoribacter and increasing Lactobacillus. The changes in gut microbiota induced by Bifico correlated with reduced expression of CXCR2 ligand chemokines like CXCL1, CXCL2, CXCL3, CXCL5 which promote tumor progression.	Individuals with inflammatory bowel disease are at high risk of developing colitis-associated cancer (CAC). Probiotic mixture Bifico has shown efficacy in chemopreventive effects on CAC. However, causal relationship between changes in transcriptome and microbial community and attenuated tumorigenesis is unclear. Further studies are needed.	Moderate
Qi et al. (37)	2022	China	124 patients		Cohort study		Colorectal cancer	Colorectal cancer	There were no significant differences in gut bacterial alpha diversity between moderately and poorly differentiated CRC groups. At the genus level, 9 bacterial genera were more abundant in the poorly differentiated CRC group, including Bifidobacterium, Oscillospiraceae, and Eisenbergiella. 6 bacterial genera were more abundant in the moderately differentiated CRC group, including Megamonas, Erysipelotrichaceae_UCG-003, and Actinomyces. A random forest model using differential gut bacteria could predict poorly differentiated CRC with 100% accuracy, with Pseudoramibacter, Megamonas and Bifidobacterium being the most important bacterial predictors. The study suggests that gut bacterial composition is related to the degree of pathological differentiation in CRC, and specific bacteria may serve as biomarkers for predicting poorly differentiated CRC.	Colorectal cancer mortality is high, malignant malignancy is high, and prognosis poor. Gut flora affects pathological differentiation, with different bacterial flora used as biomarkers for poorly differentiated colorectal cancer.	High