Gastric cancer (GC), once largely confined to older populations, is increasingly diagnosed in younger adults across developed nations. A comprehensive review led by researchers at The Chinese University of Hong Kong (CUHK) sheds new light on how dietary habits and the complex community of stomach microbes—collectively known as the gastric microbiome—interact to drive or suppress cancer risk. Their findings, published May 12 in the journal Research, map out a multifaceted strategy for GC prevention through personalized nutrition and microbiome-targeted therapies.
A Rising Threat in Younger Generations
Gastric cancer remains the world’s fifth most common malignancy and the third leading cause of cancer-related deaths, claiming more than 784,000 lives annually. Historically a disease of the elderly, emerging epidemiological data reveal an unsettling trend: incidence rates are climbing among individuals under 50 in many affluent countries. The reasons behind this demographic shift are not fully understood, but changing dietary patterns, widespread Helicobacter pylori infection, and alterations in the gastric microbiome are key suspects.
Helicobacter pylori: A Necessary but Insufficient Culprit
H. pylori, a spiral-shaped bacterium that colonizes the stomach lining, infects roughly half of the global population. It has long been recognized as a major risk factor for GC, but fewer than 3 percent of those infected ever develop the disease. This discrepancy suggests that H. pylori acts in concert with additional factors—particularly the broader gastric microbial community and environmental influences like diet—to tip the balance toward malignancy.
Diet as a Double-Edged Sword
The review led by Professor Jun Yu from CUHK’s State Key Laboratory of Digestive Disease explores how specific dietary components either promote or protect against GC. The researchers emphasize that what we eat directly shapes the stomach’s microbial ecosystem and its metabolic byproducts, thereby influencing cancer risk.
Dietary Patterns That Promote Gastric Carcinogenesis
- High-Salt Foods: Salt-preserved items—staples in many East Asian cuisines—damage the gastric mucosa and foster the proliferation of harmful bacteria. Chronic exposure to excess salt compromises the stomach’s defense mechanisms and accelerates inflammatory processes.
- Processed Meats: Consumption of meats cured or smoked at high temperatures generates carcinogenic compounds such as heterocyclic amines and polycyclic aromatic hydrocarbons. These chemicals can induce DNA damage in gastric epithelial cells.
- Heavy Alcohol Intake: Alcohol metabolism produces acetaldehyde, a toxic compound that disrupts cellular structures and promotes oxidative stress. Excessive drinking correlates with increased GC incidence.
- High-Fat Diets: Diets rich in saturated fats contribute to systemic inflammation and overproduction of bile acids—factors that can accelerate tumor growth and metastasis.
Protective Dietary Components
- Fruits and Vegetables: Diets abundant in fresh produce supply antioxidants, vitamins, and fiber. These components neutralize free radicals, enhance immune surveillance, and support a healthy microbial balance.
- Cruciferous Vegetables: Broccoli sprouts and related greens contain sulforaphane, a compound shown to inhibit H. pylori colonization and reduce gastric inflammation.
- Walnuts and Other Nuts: Rich in polyphenols and omega-3 fatty acids, walnuts exhibit anti-inflammatory and antiproliferative properties, supporting gastric mucosal health.
The Gastric Microbiome: More Than Just H. pylori
Recent advances in high-throughput sequencing have revealed a diverse community of non-H. pylori microbes inhabiting the stomach. Professor Yu and colleagues catalogued both harmful and beneficial bacterial species, uncovering their mechanistic roles in tumorigenesis.
Harmful Microbes Fueling Cancer Development
- Streptococcus anginosus: This species proliferates in GC patients and produces toxins that damage DNA. It also depletes specific amino acids needed for effective T-cell responses, undermining immune defenses.
- Fusobacterium nucleatum: Known for its role in colorectal cancer, F. nucleatum colonizes gastric tumors and secretes inflammatory mediators that promote cell proliferation and invasion.
Both species contribute to a pro-inflammatory microenvironment, amplifying the carcinogenic effects of dietary insults and H. pylori infection.
Beneficial Bacteria and Protective Metabolites
- Akkermansia muciniphila: A mucin-degrading bacterium that strengthens the gastric mucus layer, enhancing barrier function and reducing pathogen access to epithelial cells.
- Butyrate-Producing Species: Genera such as Roseburia and Faecalibacterium convert dietary fiber into butyrate, a short-chain fatty acid that supports healthy cell differentiation, regulates inflammation, and induces apoptosis in premalignant cells.
A diet rich in fiber, fruits, and vegetables supports these protective microbes, tipping the microbial balance away from cancer-promoting species.
Epigenetic Mechanisms: Vitamin C as a Model
The review also highlights how micronutrients influence gene regulation in gastric cells via epigenetic modifications. Professor Akihito Ishigami’s team at Tokyo Metropolitan Institute for Geriatrics and Gerontology recently demonstrated that vitamin C promotes DNA demethylation in skin cells, reigniting under-expressed genes. A similar mechanism may operate in the stomach: dietary compounds could modulate the activity of ten-eleven-translocation (TET) enzymes, restoring normal patterns of gene expression and inhibiting tumor-promoting pathways.
Toward Personalized Prevention and Treatment
Integrating dietary and microbial insights opens avenues for multifaceted prevention strategies tailored to individual risk profiles.
Precision Nutrition
- Microbiome Profiling: Sequencing a patient’s gastric microbiome can identify overrepresentation of harmful species or depletion of protective ones, guiding dietary recommendations.
- Nutrient Supplementation: Targeted use of sulforaphane-rich extracts, omega-3 supplements, or vitamin C could reinforce mucosal defenses and counteract epigenetic aberrations.
Microbiome-Based Therapies
- Probiotics and Engineered Bacteria: Next-generation probiotics designed to outcompete pathogens or deliver anticancer metabolites directly in the stomach.
- Prebiotics: Non-digestible fibers that selectively feed beneficial microbes, fostering a protective microbial community.
- Bacteriophage Therapy: Phages targeting H. pylori or other GC-promoting bacteria, reducing their abundance without broad antibiotic use.
Clinical Trials and Future Research
Ongoing trials are evaluating engineered probiotics for colorectal cancer prevention; analogous studies in GC are anticipated. Large-scale cohort studies will clarify the interplay between diet, microbiome, and genetic factors in diverse populations. Ultimately, a combination of lifestyle modification, microbial engineering, and conventional therapies may transform GC outcomes.
Public Health Implications
Gastric cancer prevention has traditionally focused on H. pylori eradication and endoscopic surveillance in high-risk individuals. While these remain vital, the CUHK‐led review argues for broader public health initiatives:
- Dietary Guidelines: Public campaigns promoting reduced salt and processed meat intake, increased consumption of fruits, vegetables, and whole grains.
- Microbiome Awareness: Educating clinicians and patients on the importance of gut health, encouraging dietary and lifestyle choices that support microbial balance.
- Screening Programs: Incorporating microbiome and dietary risk assessments into existing GC screening protocols to identify high-risk individuals earlier.
Conclusion
The convergence of nutritional science, microbiome research, and cancer biology offers a new paradigm in gastric cancer prevention and treatment. As GC incidence rises among younger adults, a personalized approach—addressing both dietary exposures and the gastric microbiome—will be essential to stemming this global health burden. The findings from Professor Jun Yu’s team and collaborators provide a roadmap for future research, clinical innovation, and public health policy, with the ultimate goal of reducing GC incidence and improving survival outcomes worldwide.
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