Exploring the gut microbiome’s influence on cancer-associated anemia: Mechanisms, clinical challenges, and innovative therapies

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

FMT: Fecal microbiota transplantation; SCFA: Short-chain fatty acid.

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

SCFA: Short-chain fatty acid.

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