Systematic Reviews
Copyright ©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
Table 1 Mechanisms and interventions in microbiome-targeted anemia management
Aspect
Key points
Examples or details
Mechanisms of dysbiosis-induced anemiaImpaired iron absorptionDecreased Lactobacillus and Faecalibacterium disrupt iron uptake mechanisms. Altered expression of ferroportin and divalent metal transporter 1 due to microbial imbalances
Systemic inflammationElevated 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 erythropoiesisInflammatory cytokines disrupt erythropoietin signaling and bone marrow microenvironment. Reduced SCFA production affects hematopoietic stem cell function
Key challengesVariable patient responsesDifferences in microbiota composition impact therapy outcomes. Variability in cancer type and stage complicates standardized approaches
Lack of standardized protocolsAbsence of uniform methodologies for microbiome-targeted interventions. Limited consensus on FMT donor screening and dietary recommendations
Limited long-term outcome dataFew clinical trials evaluating long-term efficacy of combined microbiome-focused and conventional therapies. Insufficient tracking of adverse effects or durability of response
Microbiome-targeted interventionsProbiotics and prebioticsLactobacillus and Bifidobacterium strains improve gut barrier function and support iron metabolism. Prebiotics like inulin and fructooligosaccharides promote SCFA production and microbial diversity
FMTRestores microbial diversity and enhances iron absorption in treatment-resistant anemia. Potential to regulate the gut-liver axis, influencing systemic iron homeostasis
Dietary modificationsHigh-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 technologiesCRISPR-Cas9Precision editing of microbial genomes to correct dysbiosis-related pathways. Application in modifying gut bacteria to enhance SCFA production or suppress inflammation
Machine learning modelsIntegrates microbiome and host genomic data for predictive modeling of therapy outcomes. Facilitates personalized treatment plans by identifying high-risk microbial patterns
Integrative approachesCombined probiotics/prebiotics with iron supplementationReduces gastrointestinal side effects commonly associated with iron therapy. Enhances bioavailability and absorption of iron
FMT with erythropoiesis-stimulating agentsCombines microbial diversity restoration with stimulation of red blood cell production for synergistic benefits. Effective in patients with refractory anemia
Immunotherapy combined with microbiome modulationEnhances 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 inflammationImproved 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 functionSuperior gut microbiota composition and reduction in anemia severity
Fecal microbiota transplantationReplenishes beneficial gut microbiota, restores iron metabolism, and reduces inflammationImprovement in hemoglobin levels and microbiota diversity in anemic patients
Synbiotics (probiotics + prebiotics)Synergistic effect enhancing microbiota diversity, iron absorption, and immune modulationReduction in chemotherapy-induced anemia and gut inflammation
Postbiotics (SCFAs, microbial metabolites)Modulate immune response, improve iron bioavailability, and suppress inflammationEnhanced 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 permeabilityIncreased 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
Hematologic50%-90%Gut microbiome alteration causes inflammation and nutrient malabsorption
Gastrointestinal40%-80%Gut dysbiosis reduces iron absorption, increases iron sequestration by macrophages due to elevation in hepcidin levels
Gynecological30%-70%Microbiome disruption impacts estrogen metabolism, inciting a dysregulated immune response and increased gut permeability
Genitourinary30%-60%Chronic inflammation and immune activation affect erythropoiesis; renal dysfunction impacts erythropoietin production; altered microbiome composition influences systemic inflammation
Lung cancer40%-70%Systemic inflammation leads to anemia of chronic disease; chemotherapy and radiation induce gut microbiome changes, exacerbating inflammation and iron dysregulation
Breast cancer25%-50%Chemotherapy and hormonal therapy impact gut microbiota, leading to malabsorption of iron and vitamins; systemic inflammation contributes to anemia