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.