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©The Author(s) 2025.
World J Gastrointest Pharmacol Ther. Jun 5, 2025; 16(2): 105375
Published online Jun 5, 2025. doi: 10.4292/wjgpt.v16.i2.105375
Published online Jun 5, 2025. doi: 10.4292/wjgpt.v16.i2.105375
Table 1 Mechanisms and interventions in microbiome-targeted anemia management
Aspect | Key points | Examples or details |
Mechanisms of dysbiosis-induced anemia | Impaired iron absorption | Decreased Lactobacillus and Faecalibacterium disrupt iron uptake mechanisms. Altered expression of ferroportin and divalent metal transporter 1 due to microbial imbalances |
Systemic inflammation | Elevated cytokines like interleukin-6 and tumor necrosis factor-alpha drive hepcidin overproduction, reducing iron availability. Bacterial endotoxins (e.g., lipopolysaccharides) trigger systemic inflammatory responses | |
Suppression of erythropoiesis | Inflammatory cytokines disrupt erythropoietin signaling and bone marrow microenvironment. Reduced SCFA production affects hematopoietic stem cell function | |
Key challenges | Variable patient responses | Differences in microbiota composition impact therapy outcomes. Variability in cancer type and stage complicates standardized approaches |
Lack of standardized protocols | Absence of uniform methodologies for microbiome-targeted interventions. Limited consensus on FMT donor screening and dietary recommendations | |
Limited long-term outcome data | Few clinical trials evaluating long-term efficacy of combined microbiome-focused and conventional therapies. Insufficient tracking of adverse effects or durability of response | |
Microbiome-targeted interventions | Probiotics and prebiotics | Lactobacillus and Bifidobacterium strains improve gut barrier function and support iron metabolism. Prebiotics like inulin and fructooligosaccharides promote SCFA production and microbial diversity |
FMT | Restores microbial diversity and enhances iron absorption in treatment-resistant anemia. Potential to regulate the gut-liver axis, influencing systemic iron homeostasis | |
Dietary modifications | High-fiber diets rich in whole grains and legumes promote SCFA-producing bacteria (e.g., Faecalibacterium). Diets tailored to individual microbiota profiles address specific nutrient deficiencies like iron and vitamin B12 | |
Emerging technologies | CRISPR-Cas9 | Precision editing of microbial genomes to correct dysbiosis-related pathways. Application in modifying gut bacteria to enhance SCFA production or suppress inflammation |
Machine learning models | Integrates microbiome and host genomic data for predictive modeling of therapy outcomes. Facilitates personalized treatment plans by identifying high-risk microbial patterns | |
Integrative approaches | Combined probiotics/prebiotics with iron supplementation | Reduces gastrointestinal side effects commonly associated with iron therapy. Enhances bioavailability and absorption of iron |
FMT with erythropoiesis-stimulating agents | Combines microbial diversity restoration with stimulation of red blood cell production for synergistic benefits. Effective in patients with refractory anemia | |
Immunotherapy combined with microbiome modulation | Enhances antitumor immune responses by improving gut microbial balance. Addresses anemia caused by cancer therapy-induced dysbiosis |
Table 2 List of microbiome-targeted therapies with their mechanisms of action and current evidence
Therapy | Mechanism of action | Clinical utility |
Probiotics (Lactobacillus, Bifidobacterium) | Restore gut microbial balance, enhance nutrient absorption, reduce inflammation | Improved iron absorption and downregulation of inflammatory cytokines in cancer patients |
Prebiotics (dietary fibers, inulin, fructooligosaccharide) | Foster growth of beneficial gut bacteria, increase SCFA production, improve gut barrier function | Superior gut microbiota composition and reduction in anemia severity |
Fecal microbiota transplantation | Replenishes beneficial gut microbiota, restores iron metabolism, and reduces inflammation | Improvement in hemoglobin levels and microbiota diversity in anemic patients |
Synbiotics (probiotics + prebiotics) | Synergistic effect enhancing microbiota diversity, iron absorption, and immune modulation | Reduction in chemotherapy-induced anemia and gut inflammation |
Postbiotics (SCFAs, microbial metabolites) | Modulate immune response, improve iron bioavailability, and suppress inflammation | Enhanced erythropoiesis and reduced systemic inflammation |
Dietary interventions (fermented foods, fiber-rich diets, iron and vitamin supplementation) | Support beneficial microbiota, optimize iron and vitamin B12 absorption, reduce gut permeability | Increased erythropoiesis, superior efficacy when combined with probiotics or prebiotics |
Table 3 Comparative analysis of anemia prevalence and severity across different cancer types with microbiome involvement
Cancer type | Prevalence | Microbiome involvement |
Hematologic | 50%-90% | Gut microbiome alteration causes inflammation and nutrient malabsorption |
Gastrointestinal | 40%-80% | Gut dysbiosis reduces iron absorption, increases iron sequestration by macrophages due to elevation in hepcidin levels |
Gynecological | 30%-70% | Microbiome disruption impacts estrogen metabolism, inciting a dysregulated immune response and increased gut permeability |
Genitourinary | 30%-60% | Chronic inflammation and immune activation affect erythropoiesis; renal dysfunction impacts erythropoietin production; altered microbiome composition influences systemic inflammation |
Lung cancer | 40%-70% | Systemic inflammation leads to anemia of chronic disease; chemotherapy and radiation induce gut microbiome changes, exacerbating inflammation and iron dysregulation |
Breast cancer | 25%-50% | Chemotherapy and hormonal therapy impact gut microbiota, leading to malabsorption of iron and vitamins; systemic inflammation contributes to anemia |
- Citation: Bangolo A, Amoozgar B, Habibi M, Simms E, Nagesh VK, Wadhwani S, Wadhwani N, Auda A, Elias D, Mansour C, Abbott R, Jebara N, Zhang L, Gill S, Ahmed K, Ip A, Goy A, Cho C. Exploring the gut microbiome’s influence on cancer-associated anemia: Mechanisms, clinical challenges, and innovative therapies. World J Gastrointest Pharmacol Ther 2025; 16(2): 105375
- URL: https://www.wjgnet.com/2150-5349/full/v16/i2/105375.htm
- DOI: https://dx.doi.org/10.4292/wjgpt.v16.i2.105375