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

Abstract

BACKGROUND

Anemia is a prevalent and challenging complication in patients with hematologic and solid malignancies, which stems from the direct effects of malignancy, treatment-induced toxicities, and systemic inflammation. It affects patients’ survival, functional status, and quality of life profoundly. Recent literature has highlighted the emerging role of the gut microbiome in the pathogenesis of cancer-associated anemia. The gut microbiota, through its intricate interplay with iron metabolism, inflammatory pathways, and immune modulation, may either exacerbate or ameliorate anemia depending on its composition, and functional integrity. Dysbiosis, characterized by disruption in the gut microbial ecosystem, is very common in cancer patients. This microbial imbalance is implicated in anemia causation through diminished iron absorption, persistent low-grade inflammation, and suppression of erythropoiesis.

AIM

To consolidate current evidence regarding the interplay between gut microbiome and anemia in the setting of malignancies. It aims to provide a detailed exploration of the mechanistic links between dysbiosis and anemia, identifies unique challenges associated with various cancer types, and evaluates the efficacy of microbiome-focused therapies. Through this integrative approach, the review seeks to establish a foundation for innovative clinical strategies aimed at mitigating anemia and improving patient outcomes in oncology.

METHODS

A literature search was performed using multiple databases, including Google Scholar, PubMed, Scopus, and Web of Science, using a combination of keywords and Boolean operators to refine results. Keywords included “cancer-associated anemia”, “gut microbiome”, “intestinal microbiota”, “iron metabolism”, “gut dysbiosis”, “short-chain fatty acids”, “hematopoiesis”, “probiotics”, “prebiotics”, and “fecal microbiota transplantation”. Articles published in English between 2000 and December 2024 were included, with a focus on contemporary and relevant findings.

RESULTS

Therapeutic strategies aimed at restoration of gut microbial homeostasis, such as probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation (FMT), can inhibit anemia-causing pathways by enhancing microbial diversity, suppressing detrimental flora, reducing systemic inflammation and optimizing nutrient absorption.

CONCLUSION

Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients. Microbiome-centered interventions, such as probiotics, prebiotics, dietary modifications, and FMT, have shown efficacy in restoring microbial balance, reducing inflammation, and enhancing nutrient bioavailability. Emerging approaches, including engineered probiotics and bacteriophage therapies, are promising precision-based, customizable solutions for various microbiome compositions and imbalances. Future research should focus on integrating microbiome-targeted strategies with established anemia therapies.

Key Words: Microbiome-targeted therapies; Systemic inflammation; Iron metabolism; Dysbiosis; Cancer-associated anemia; Gut microbiome

Core Tip: The gut microbiome is increasingly recognized as a pivotal factor in cancer-associated anemia, influencing its pathophysiology, clinical manifestations, and potential therapeutic strategies. Dysbiosis, or microbial imbalance, is common in cancer patients and exacerbates anemia through mechanisms such as impaired iron absorption, heightened systemic inflammation, and suppression of erythropoiesis. Emerging evidence highlights how gut microbiota modulates iron metabolism, inflammatory cytokine production, and immune responses, linking microbial health directly to anemia severity. Promising interventions, including probiotics, prebiotics, fecal microbiota transplantation, and dietary modifications, aim to restore microbial balance, optimize iron bioavailability, and reduce inflammation. As research advances, microbiome-targeted therapies could transform anemia management, integrating seamlessly with existing treatments and offering personalized solutions for oncology patients. Further studies are needed to refine these approaches and establish microbiome-based biomarkers for anemia prediction and therapeutic monitoring.

INTRODUCTION

Anemia is a common and debilitating complication in malignancy, affecting 30%-90% of patients depending on the cancer type, stage, and treatment regimen[1-3]. The etiology of anemia in cancer is multifactorial, encompassing systemic inflammation, bone marrow suppression, nutritional deficits, and direct tumor-mediated effects. Moreover, cancer therapies such as chemotherapy, radiation, and targeted treatments exacerbate anemia through their myelosuppressive effects[4-6]. Reduced hemoglobin levels compromises oxygen delivery to tissues, and results in fatigue, dyspnea, and an overall diminution in functional capacity and quality of life. While conventional interventions, such as erythropoiesis-stimulating agents, red blood cell transfusions, and iron supplementation remain mainstays of treatment, several limitations do exist, warranting development of alternative therapeutic strategies[7,8].

The gut microbiome has recently emerged as a significant contributor to optimal hematopoiesis and iron metabolism. The gastrointestinal tract houses trillions of microorganisms that produce bioactive metabolites, regulate nutrient absorption, and modulate immune and inflammatory pathways[9-11]. Cancer patients often experience gut dysbiosis, which is characterized by altered microbial diversity and abundance. Dysbiosis is frequently driven by chemotherapy, radiation, antibiotics, and dietary changes, and has profound implications on anemia[12,13]. Impaired iron absorption due to altered expression of critical gut-associated proteins, such as ferroportin and divalent metal transporter 1, promotes systemic inflammation through increased bacterial translocation and endotoxin production, and suppresses erythropoiesis through inflammatory cytokines[14,15].

Given the intricate relationship between the gut microbiome and cancer-associated anemia, microbiome-targeted interventions have garnered considerable attention. Strategies such as probiotics, prebiotics, and fecal microbiota transplantation (FMT) have demonstrated the potential to restore microbial diversity and mitigate systemic inflammation[16,17]. Emerging evidence further suggests that dietary modifications and microbiome-focused therapies may enhance iron bioavailability, reduce inflammation, and promote hematopoietic recovery in cancer patients[18,19]. This review integrates current evidence on the role of the gut microbiome in the pathophysiology of anemia associated with hematologic and solid malignancies, highlighting emerging therapeutic directions and laying the groundwork for innovative approaches to improve outcomes for patients with cancer.

MATERIALS AND METHODS

Literature search strategy

This review was conducted using a systematic and comprehensive approach to identify, evaluate, and synthesize current evidence on the relationship between the gut microbiome and cancer-associated anemia. A literature search was performed using multiple databases, including Google Scholar, PubMed, Scopus, and Web of Science, to ensure broad and inclusive coverage. The search strategy incorporated a combination of keywords and Boolean operators to refine results. Keywords included “cancer-associated anemia”, “gut microbiome”, “intestinal microbiota”, “iron metabolism”, “gut dysbiosis”, “short-chain fatty acids”, “hematopoiesis”, “probiotics”, “prebiotics”, and “fecal microbiota transplantation”. Articles published in English between 2000 and December 2024 were included, with a focus on contemporary and relevant findings. This review was not registered, and no protocol was prepared prior.

The search process was conducted iteratively, with manual review of search results to identify additional studies through references cited in key articles. This snowballing technique ensured that no major studies were omitted from the review. The literature search and study selection were performed independently by multiple authors to minimize bias and ensure the reliability of results.

Inclusion and exclusion criteria

To ensure relevance and rigor, predefined inclusion and exclusion criteria were applied. Studies were included if they addressed the interplay between the gut microbiome and anemia in cancer patients, particularly regarding iron metabolism, systemic inflammation, immune modulation, or erythropoiesis. Research focusing on microbiome-targeted interventions, such as probiotics, prebiotics, dietary modifications, and FMT, was also prioritized. Preclinical studies, clinical trials, observational studies, and systematic reviews or meta-analyses with mechanistic or therapeutic insights were included.

Studies were excluded if they focused exclusively on anemia in non-cancer populations, lacked original data, or were limited to non-peer-reviewed formats such as editorials, opinion pieces, or conference abstracts. The selection process ensured that only high-quality and relevant studies were included for analysis.

Data extraction and synthesis

A structured process was used to extract and synthesize data from the included studies. Titles and abstracts were screened first to assess relevance, followed by a full-text review of eligible articles. Data extraction focused on study characteristics, including study design, population characteristics, interventions, outcomes, and mechanistic insights into the gut microbiome’s role in anemia. Specific emphasis was placed on identifying how the gut microbiome influences key aspects of anemia pathophysiology, such as iron absorption, systemic inflammation, and immune regulation.

The extracted data were then synthesized to create a cohesive narrative. Studies were categorized thematically to explore mechanistic pathways, clinical challenges, and therapeutic interventions. For example, studies focusing on microbiome-induced changes in iron homeostasis or inflammation were grouped together, while research on interventions like probiotics and prebiotics was analyzed separately. Thematic synthesis enabled identification of common patterns and gaps in the literature, which were integrated into the discussion of findings.

Ethical considerations

This review relied solely on publicly available data from peer-reviewed studies and did not involve human or animal subjects. As a secondary research study, ethical approval was not required. The review adhered to the highest standards of scientific integrity, ensuring that all data sources were appropriately cited and credited.

Study framework

The review was designed to systematically analyze the role of the gut microbiome in cancer-associated anemia from multiple perspectives, including its pathophysiology, clinical impact, and therapeutic potential. This multi-faceted framework enabled the integration of basic, translational, and clinical research findings into a comprehensive and actionable analysis. This methodology provided a robust foundation for synthesizing current evidence and formulating conclusions about the gut microbiome’s role in cancer-associated anemia. The rigorous approach ensured the inclusion of relevant, high-quality studies to inform the findings and recommendations presented in this review.

RESULTS

Risk factors for anemia

Anemia in cancer patients is the result of a complex interplay between tumor biology, therapeutic interventions, systemic inflammation, and nutritional deficits. Tumor-related mechanisms are significant contributors to anemia, particularly in cases where hematologic malignancies, such as leukemia and lymphoma, or metastatic solid tumors infiltrate the bone marrow, thereby impairing hematopoiesis[1,6,20]. Additionally, malignancies affecting the gastrointestinal or genitourinary (GU) systems often cause chronic blood loss. For instance, occult bleeding associated with colorectal and gastric cancers is a common driver of iron deficiency and subsequent anemia[2,21]. Furthermore, many tumors secrete pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which disrupt normal erythropoiesis by altering the bone marrow microenvironment and inducing anemia of chronic disease (ACD)[5,22].

The impact of cancer therapies on anemia cannot be overstated. Chemotherapy, particularly platinum-based compounds and alkylating agents, directly damages hematopoietic progenitor cells, resulting in myelosuppression and reduced red blood cell production[23,24]. Similarly, radiation therapy targeted at regions such as the pelvis, spine, or chest often leads to bone marrow hypoplasia, further exacerbating anemia[25,26]. Emerging treatment modalities, including immune checkpoint inhibitors (ICI) and other targeted therapies, also contribute to anemia, albeit through less direct mechanisms, such as autoimmune hemolysis or bone marrow failure[27,28]. While these therapies are pivotal in improving cancer control, their cumulative effects on anemia necessitate vigilant monitoring and proactive management to safeguard patient quality of life and outcomes[3,29].

Nutritional deficiencies represent another critical but often underappreciated factor in the pathogenesis of anemia among cancer patients. Chemotherapy and antibiotic-induced dysbiosis disrupt the gastrointestinal microbiome, impairing the absorption of essential nutrients like iron, folate, and vitamin B12, all of which are indispensable for effective erythropoiesis[30,31]. Additionally, systemic inflammation associated with malignancy and its treatment elevates hepcidin levels, thereby blocking iron absorption from the gastrointestinal tract[32,33]. Malnutrition, frequently driven by cancer-associated anorexia, further exacerbates these deficiencies, creating a vicious cycle that perpetuates anemia (Figure 1). Comprehensive strategies incorporating dietary interventions and microbiome restoration are vital to addressing these underlying causes and optimizing erythropoietic function[34,35].

Figure 1 Schematic representation of the interplay between gut microbiome, iron metabolism, and systemic inflammation in anemia.

Pathophysiology of anemia and gut dysbiosis

Microcytic anemia: Microcytic anemia commonly arises from chronic blood loss or iron deficiency, both of which are prevalent in cancer patients due to tumor-associated bleeding or treatment-induced gastrointestinal toxicity[36-38]. Dysbiosis, a disruption of the gut microbiome, further exacerbates iron deficiency by impairing iron metabolism and absorption[38,39]. Beneficial gut microbes, such as Bifidobacterium and Lactobacillus, are integral in supporting intestinal iron uptake, producing short-chain fatty acids (SCFAs), and fostering an optimal gut environment for nutrient absorption[40,41]. When dysbiosis reduces these microbial populations, the delicate balance of iron homeostasis is disrupted, aggravating anemia[42,43]. Compounding this issue, inflammation-driven hepcidin overproduction—a process influenced by gut dysbiosis—blocks the release of iron from macrophages and suppresses intestinal iron absorption, creating a vicious cycle of iron depletion[44,45].

Normocytic anemia: Normocytic anemia, frequently encountered in cancer patients, is closely tied to ACD, which stems from systemic inflammation and immune dysregulation. Although often overlooked, the gut microbiome plays a significant role in this process. Dysbiosis can lead to a decrease in beneficial microbial metabolites, such as butyrate and other SCFAs, which are critical for regulating immune function[46,47]. This reduction contributes to an overproduction of inflammatory cytokines, including IL-6 and TNF-α, which suppress erythropoiesis and impair bone marrow function[48,49]. Moreover, gut barrier disruption due to dysbiosis allows endotoxins, such as lipopolysaccharides (LPS), to enter the systemic circulation, further amplifying inflammation and exacerbating ACD[50,51].

Macrocytic anemia: Macrocytic anemia results from deficiencies in folate or vitamin B12, both essential for DNA synthesis and red blood cell production. In cancer patients, these deficiencies can be attributed to chemotherapy-induced malabsorption, inadequate dietary intake, or gut microbiome imbalances[52,53]. Specific gut bacteria, including Bacteroides and Clostridium, play a critical role in synthesizing folate and vitamin B12[54,55]. Dysbiosis, by reducing the abundance of these microbial populations, diminishes the availability of these vital nutrients, thus worsening macrocytic anemia[56,57]. Chemotherapy further exacerbates this condition by damaging gut epithelial integrity, impairing the absorption of folate and vitamin B12, and contributing to anemia[58,59].

The role of the gut microbiome in anemia development

The gut microbiome is intricately involved in regulating iron metabolism, a key factor in the prevention and treatment of anemia. Specific bacterial species, such as Bacteroides, contribute to optimizing dietary iron absorption by creating a favorable gut environment and generating metabolites that enhance duodenal iron uptake[60,61]. However, a disruption in the balance of the gut microbiota, termed dysbiosis, compromises this process, leading to reduced iron bioavailability even when dietary intake is sufficient[62,63]. Furthermore, during dysbiosis, the competition between microbes for luminal iron exacerbates the host’s deficiency, amplifying the risk of microcytic anemia[64,65]. This disruption is particularly problematic in patients with malignancies, where cancer-associated inflammation and the gastrointestinal toxicity of chemotherapy further destabilize the gut microbiome, compounding iron malabsorption[66,67].

The gut microbiome also has significant influence over systemic inflammation, a central mechanism underlying anemia in malignancies. Dysbiosis increases levels of pro-inflammatory cytokines, including IL-6 and TNF-α, which suppress erythropoiesis by inhibiting erythropoietin production and inducing excessive hepcidin secretion[68-70]. Elevated hepcidin reduces iron release from macrophages and limits its absorption in the intestines, fueling anemia associated with chronic inflammation[71,72]. Compounding this issue, a weakened intestinal barrier during dysbiosis permits translocation of bacterial endotoxins, such as LPS, into systemic circulation. These endotoxins trigger immune activation and perpetuate the inflammatory cascade[71,72]. Cancer treatments, including chemotherapy, often intensify gut microbiome imbalances, creating a feedback loop of inflammation and anemia that is particularly challenging to interrupt[73,74].

Beyond iron metabolism and inflammation, the gut microbiome also plays a critical role in immune modulation, influencing hematopoiesis and anemia development. A healthy microbiome supports balanced T-cell differentiation and function, particularly through beneficial bacteria like Lactobacillus and Bifidobacterium, which promote the differentiation of regulatory T-cells that suppress inflammation and sustain hematopoietic stem cell (HSC) activity[75-78]. Dysbiosis, however, disrupts this equilibrium, pushing T-cell responses toward a pro-inflammatory phenotype that damages the bone marrow microenvironment and suppresses red blood cell production[79,80]. Additionally, microbial metabolites, such as butyrate, are essential for maintaining HSC quiescence and promoting erythropoiesis[81,82]. In states of dysbiosis, the depletion of these metabolites destabilizes hematopoiesis, further perpetuating anemia in cancer patients[83,84].

The multifaceted interplay between gut microbiota, iron metabolism, inflammation, and immune regulation highlights the importance of addressing dysbiosis in managing anemia, particularly in patients undergoing cancer treatment.

Anemia in solid malignancies

Head and neck cancers: Anemia frequently complicates head and neck cancers, driven by both the malignancy itself and its treatment regimens. Chronic blood loss and mucositis, particularly following chemoradiation, contribute to persistent anemia by impairing nutritional intake and promoting systemic inflammation[85,86]. Dysbiosis, characterized by an imbalance in the gut microbiota, further exacerbates this condition. Treatment-induced mucositis compromises the gut barrier, facilitating the translocation of microbial endotoxins into circulation and triggering heightened inflammatory responses[87,88]. Additionally, dysbiosis reduces the availability of essential nutrients, such as iron, folate, and vitamin B12, which are indispensable for erythropoiesis[89,90].

Esophageal and gastric cancers

Chronic blood loss and iron deficiency are common in esophageal and gastric cancers, often resulting from tumor erosion of the gastrointestinal lining[91,92]. Reduced gastric acid production, either tumor-induced or following gastrectomy, disrupts gut microbiota composition, impairing dietary iron solubilization and absorption[93,94]. Dysbiosis worsens this imbalance, diminishing the microbiome's role in supporting iron metabolism. For instance, reductions in beneficial bacteria such as Bifidobacterium and Lactobacillus, which facilitate iron uptake, are frequently observed in gastric cancer patients, correlating with more severe anemia[95,96].

Pancreatic cancer

Anemia in pancreatic cancer arises from chronic inflammation, malnutrition, and systemic effects of the malignancy. Cachexia and exocrine insufficiency exacerbate deficiencies in nutrients critical for erythropoiesis, including iron, folate, and vitamin B12[97,98]. Dysbiosis amplifies this process, with microbial imbalances exacerbating systemic inflammation and impairing erythropoiesis[99,100]. Bangolo et al[101] highlight the role of inflammatory markers, including interleukins, in pancreatic cancer-associated anemia. These markers, modulated by the gut microbiota, represent potential therapeutic targets for alleviating anemia. Chemotherapy regimens, such as FOLFIRINOX, further complicate this scenario by inducing gastrointestinal toxicity and worsening dysbiosis[101,102].

Colorectal and anal cancers

Chronic bleeding and systemic inflammation are key drivers of anemia in colorectal and anal cancers[103,104]. The gut microbiota is profoundly affected, with significant reductions in beneficial bacteria such as Faecalibacterium prausnitzii and Blautia[105,106]. These microbial shifts promote a pro-inflammatory state, inhibiting erythropoiesis and exacerbating anemia[107,108]. Additionally, cancer therapies such as chemotherapy and radiation further aggravate gut dysbiosis, impairing nutrient absorption and intensifying anemia[109,110].

GU cancers

In GU cancers, encompassing bladder, kidney, and prostate malignancies, anemia arises from systemic inflammation, direct marrow suppression, and treatment-related toxicities[111,112]. Radiation targeting pelvic tumors frequently damages HSCs, while chemotherapy and ICI exacerbate myelosuppression. Dysbiosis in GU cancers further amplifies systemic inflammation, impairing erythropoiesis[113,114]. Reduced levels of anti-inflammatory bacteria, such as Akkermansia muciniphila, are associated with elevated inflammatory markers and worsened anemia in prostate cancer patients undergoing treatment[115].

Inflammation as a central mechanism

Inflammation serves as a unifying mechanism linking cancer, dysbiosis, and anemia across solid malignancies. Pro-inflammatory cytokines such as IL-6 and TNF-α suppress erythropoiesis by reducing erythropoietin production and increasing hepcidin levels[116]. Dysbiosis exacerbates this inflammatory state by allowing microbial endotoxins, including LPS, to enter systemic circulation[117]. This creates a feedback loop where inflammation perpetuates dysbiosis, further impairing red blood cell production[118].

Gut microbiota in nutritional deficiencies

Dysbiosis contributes to anemia by disrupting the absorption of key nutrients essential for erythropoiesis. Beneficial bacterial species such as Bifidobacterium and Lactobacillus play pivotal roles in iron metabolism, while Bacteroides species are involved in folate production[119,120]. The loss of these bacteria in cancer patients leads to deficiencies in iron, folate, and vitamin B12, exacerbating anemia severity[121,122].

Therapy-induced microbiome alterations

Cancer therapies, including chemotherapy, radiation, and ICI, significantly contribute to dysbiosis and its downstream effects. Damage to the gut epithelial barrier allows pathogenic bacteria to dominate the microbiome, intensifying systemic inflammation and anemia[74,123,124]. ICI, while effective in tumor control, further disrupt the microbiome, emphasizing the need for targeted interventions to manage therapy-induced anemia[125,126].

DISCUSSION

Microbiome-targeted therapeutics

Emerging evidence underscores the potential of microbiome-targeted therapies to alleviate anemia in solid malignancies (Figures 2, 3 and 4). Probiotic supplementation with Lactobacillus rhamnosus and Bifidobacterium longum has been shown to reduce inflammation and improve iron absorption in cancer patients[127,128]. Prebiotics, including inulin and resistant starch, support the growth of beneficial bacteria, enhancing nutrient absorption and mitigating anemia severity[129,130]. FMT also holds promise as a therapeutic avenue, restoring microbial balance and improving hematopoiesis in cancer patients[131,132]. Recent findings further suggest that microbiome modulation, through dietary interventions or pharmacologic agents targeting gut inflammation, could complement existing therapies[133,134]. Additionally, ongoing research into personalized microbiome-based approaches is anticipated to refine treatment efficacy[135,136]. These interventions highlight the transformative potential of microbiome strategies in addressing anemia across oncologic settings[137].

Figure 2 Diagram illustrating microbiome-targeted interventions, including probiotics, prebiotics, dietary interventions, and fecal microbiota transplantation. GOS: Galactooligosaccharide; FOS: Fructooligosaccharide; SCFA: Short-chain fatty acid.

Figure 3 Comparison of microbiota composition in healthy vs anemic cancer patients. IL: Interleukin; SCFA: Short-chain fatty acid; TNF: Tumor necrosis factor-alpha.

Figure 4 Role of dietary intervention in attaining a healthy gut microbiome. DASH: Dietary approaches to stop hypertension; MIND diet: Combines mediterranean and DASH diets.

Anemia in hematologic malignancies

Anemia represents a significant clinical challenge in hematologic malignancies, including leukemias, lymphomas, and multiple myeloma. The pathophysiology is multifaceted, involving a combination of direct tumor effects, treatment-induced myelosuppression, and systemic inflammation. Emerging research highlights the gut microbiome's critical role in influencing anemia through its regulation of iron metabolism, inflammation, and hematopoiesis (Figure 5).

Figure 5 Dysbiosis-induced immune dysregulation.

Leukemias

Anemia is a common complication in acute leukemias such as acute myeloid leukemia and acute lymphoblastic leukemia, primarily resulting from bone marrow infiltration by malignant cells and treatment-associated myelosuppression[138,139]. Chemotherapeutic agents like cytarabine and anthracyclines impair hematopoietic progenitor cell function, leading to disruptions in erythropoiesis[140,141]. Moreover, gut microbiome imbalances exacerbate hematologic deficiencies. Patients with reduced microbial diversity, particularly lower levels of commensal bacteria such as Faecalibacterium, exhibit delayed recovery of hematologic parameters, including prolonged neutropenia and anemia, post-induction chemotherapy[142,143]. Dysbiosis further affects the production of key metabolites, including butyrate, which plays a vital role in maintaining HSC function[144,145].

Lymphomas

In lymphomas, anemia is often mediated by systemic inflammation, which suppresses erythropoiesis through the overproduction of inflammatory cytokines[146,147]. Cytokines such as IL-6 and TNF-α interfere with erythropoietin signaling and promote iron sequestration through increased hepcidin levels[148,149]. Dysbiosis contributes to this inflammatory cascade by enabling gut barrier dysfunction and systemic translocation of microbial endotoxins, including LPS[150,151]. Elevated circulating LPS levels further stimulate cytokine production, compounding anemia[152,153]. Notably, patients with greater microbial diversity in the gut microbiome have demonstrated better responses to lymphoma therapies and improved hematologic profiles[154,155].

Multiple myeloma

In multiple myeloma, anemia arises due to bone marrow infiltration by malignant plasma cells, impaired erythropoietin production, and resistance to erythropoietin signaling[156,157]. Dysbiosis in these patients is marked by disruptions in SCFAs, particularly butyrate and propionate, which are essential for immune and hematopoietic regulation[158,159]. Decreased SCFA levels are linked to heightened inflammation and reduced erythropoiesis[160]. Microbiota-derived metabolites also influence myeloma progression by modulating cytokine activity and T-cell differentiation[161]. Emerging preclinical studies suggest that restoring microbial balance using probiotics or FMT may improve anemia and potentially slow disease progression[162].

Microbiome-targeted interventions

Targeting the gut microbiome represents a promising strategy for alleviating anemia in hematologic malignancies. Probiotic strains, including Lactobacillus and Bifidobacterium, have shown potential in restoring microbial diversity and enhancing hematologic recovery[163]. Prebiotics and dietary interventions aimed at supporting the growth of beneficial bacteria have demonstrated efficacy in reducing systemic inflammation and improving nutrient absorption (Figure 2). In more refractory cases, FMT is being investigated as a method to re-establish a healthy gut microbiome and support erythropoiesis. Although promising, these approaches require further clinical validation to optimize their application in managing anemia in this patient population[163,165].

Challenges in clinical application

FMT is categorized as a drug and a biologic by the Food and Drug Administration. Standardized protocols, involving rigorous donor screening, are followed to prevent transmission of infections, deleterious microbial metabolites, or antibiotic resistant pathogens to prospective recipients. Unlike synthetic microbial consortium, FMT inoculates varied microbial ecosystems into the recipients. Furthermore, there is limited, longitudinal data on its long-term safety, especially pertaining to inadvertent immune and metabolic sequelae. Systemic inflammation can drive instability in the recipient’s gut microbiome and may give rise to metabolic disorders which can take months to years to manifest. Undiagnosed disorders of iron metabolism or dysbiotic microbiome in the donor can be transmitted to the recipient through FMT. Lack of standardization in composition and efficacy of FMT inocula makes it harder to deduce anticipated benefits. Moreover, variability in patients’ microbiomes leads to heterogeneous treatment responses. Standard microbiome profiling techniques need to be developed. Additionally, data on the effect of gut microbiome on anemia in cancer patients is unclear (Figure 6). Well-powered randomised controlled trials need to be conducted to establish standardized evidence-based treatment guidelines. Microbiome-based diagnostics need to be explored in order to identify the subset of patients who can potentially benefit from this modality. Use of FMT in treatment of cancer-related anemia is largely experimental or off-label due to the absence of a fixed molecular composition, and unpredictable therapeutic effect. Therefore, regulatory bodies continue to scrutinize the efficacy of FMT in the realm of cancer-related anemia.

Figure 6 Gut microbiome in colon cancer.

Microbiome variability has been shown to impact responsiveness to certain cancer therapeutics. For example, presence of Akkermansia muciniphila, Bifidobacterium, and Faecalibacterium prausnitzii correlates with increased responsiveness to ICI. Intuitively, dysbiotic microbiome often results in a suboptimal immunotherapy response. Identification of specific gut microbial signatures can help stratify patients prior to initiation of a particular therapy. For instance, low levels of Akkermansia muciniphila are predictive of suboptimal response to immunotherapy. Microbial modulation is recommended in these patients Studies have demonstrated that FMT from ICI responders to non-responders improves response to ICIs in the latter group. Gammaproteobacteria has been shown to reduce responsiveness to gemcitabine in pancreatic cancer patients. Also, SCFA-producing organisms have been shown to ameliorate chemotherapy-induced adverse effects, namely mucositis and diarrhea, in cancer patients. Symbiotic microbiome confers protection against radiation enteritis by maintaining epithelial integrity and curtailing systemic inflammation. Studies utilizing synthetic/engineered microbial consortia tailored to improve response to therapies are underway. Selective modulation of gut microbiota using CRISPR technology is being explored to enhance drug metabolism and efficacy. Nonetheless, several regulatory hurdles need to be addressed for approval of microbiome based interventions as adjunct therapies. Longitudinal data to ascertain the trajectory of gut microbiome and resultant treatment durability needs to be procured.

Microbiome overgrowth can also result in small intestinal bowel overgrowth, causing distressing gastrointestinal side effects. Microbiome based interventions, namely FMT, probiotics and live bacterial therapeutics must be utilized with caution in immunosuppressed patients. Probiotic sepsis, bacteremia, endotoxemia, and infections with multidrug resistant organisms can occur in immunocompromised recipients. Dysregulated immune responses with microbiome-based interventions can manifest in several ways. Probiotics can worsen graft-versus-host disease in transplant patients by T helper type 1 (TH1)/TH17 upregulation. FMT can seldom exacerbate the side effects of chemo/immunotherapy and/or cause a cytokine storm from excessive immune activation, worsening cancer-related inflammation. Owing to absence of regulatory oversight and quality control while utilizing live-bacterial therapies, postbiotics (SCFAs) and microbiome-derived compounds are deemed safer immuno-modulatory alternatives that do not pose serious infectious risks.

Gaps in literature and future directions

The evolving understanding of the interplay between the gut microbiome and anemia in hematologic malignancies provides a foundation for innovative therapeutic approaches. Future research should focus on integrating gut microbiome profiling into routine clinical practice to identify dysbiosis patterns unique to specific malignancies. Large-scale microbiome biomarker studies and prospective trials to assess the efficacy of microbiome-based therapies in anemia management need to be conducted. Current literature on this topic is extremely limited. Moreover, the data on dose-response relationship between prebiotic/probiotic supplementation and degree of anemia amelioration lacks granularity, and needs to be explored further. Development of machine learning (ML) algorithms can assist with analysis of complex microbiome-based data and subsequent creation of anemia risk prediction tools based on distinct microbial signatures. Supervised learning models can utilize microbial composition for anemia classification in cancer patients. Deep learning models can longitudinally analyze vast amounts of complex microbiome-anemia interactions, and scrutinize dynamic changes in treatment response and composition of iron regulating bacteria within the hosts. ML based models can combine data on microbiome sequencing, hosts’ dietary, laboratory and genomic markers to predict anemia severity, treatment response, and develop personalized dietary and microbiome-based approaches to address anemia. Personalized microbiome-based interventions, combined with standard oncologic therapies, could enhance hematologic outcomes, improve quality of life, and address the multifactorial nature of anemia in patients with hematologic cancers.

Complications of anemia in malignancies

Anemia introduces significant challenges in the management of malignancies, amplifying the physical, psychological, and therapeutic burden of cancer care. Its impact extends beyond mere laboratory findings, affecting patient outcomes and complicating treatment strategies.

Fatigue and quality of life

One of the most debilitating effects of anemia in cancer patients is its contribution to cancer-related fatigue, a condition that profoundly diminishes quality of life. Fatigue limits patients' ability to engage in daily activities, often leading to physical deconditioning and emotional distress[166]. Research underscores a direct correlation between hemoglobin levels and fatigue severity, illustrating how anemia exacerbates both physical and emotional challenges[167]. Moreover, the pervasive fatigue caused by anemia extends its impact beyond the patient, increasing caregiver strain and elevating healthcare resource demands[166-169].

Impaired treatment efficacy

The presence of anemia compromises the effectiveness and tolerability of cornerstone cancer therapies, including chemotherapy and radiotherapy. These treatments frequently worsen anemia through mechanisms such as myelosuppression and erythrocyte destruction[170]. In turn, anemia can necessitate dose reductions or delays in therapy, which may compromise oncologic outcomes[171]. Additionally, anemia-induced tumor hypoxia is a critical concern. Hypoxic conditions enhance tumor aggressiveness by promoting angiogenesis and invasion while diminishing the efficacy of therapies, particularly radiotherapy[172]. Tumor hypoxia decreases reactive oxygen species generation, thereby reducing radiation-induced cytotoxicity. This phenomenon is notably observed in malignancies like cervical and head-and-neck cancers, where anemia correlates with poor treatment responses and survival outcomes[170-175].

Prognostic implications

Anemia is increasingly recognized as an independent prognostic factor in oncology, with significant associations identified across various cancer types. Lower hemoglobin levels are linked to reduced overall survival and progression-free survival in both hematologic and solid malignancies[176,177]. Beyond cancer-specific outcomes, anemia exacerbates preexisting comorbid conditions, such as cardiovascular disease, by worsening tissue hypoxia. This contributes to elevated morbidity and mortality risks in affected patients[176-178].

Systemic inflammation and erythropoietin resistance

The interplay between anemia and systemic inflammation perpetuates a complex cycle of fatigue, immune dysfunction, and resistance to erythropoietin-based therapies. Chronic inflammation, driven by cancer itself or its treatments, exacerbates erythropoietic suppression and disrupts iron homeostasis[179,180]. This emphasizes the need for comprehensive management strategies that address underlying mechanisms. Therapies aimed at modulating dysregulated iron metabolism and correcting gut microbiome imbalances have shown promise in mitigating anemia's multifactorial effects[181].

Treatment of anemia: Focus on gut microbiome modulation

Probiotics and prebiotics: The potential of probiotics and prebiotics in addressing anemia lies in their ability to enhance gut microbial diversity, support SCFA production, and modulate systemic inflammation[182]. Probiotic strains such as Lactobacillus and Bifidobacterium are critical in maintaining gut barrier function and promoting iron absorption at the level of the duodenum. Clinical trials involving cancer patients undergoing chemotherapy have demonstrated the effectiveness of Lactobacillus rhamnosus GG in reducing gastrointestinal toxicity, indirectly supporting erythropoiesis and nutrient absorption[182-184]. Complementing this, prebiotics such as inulin and fructooligosaccharides serve as substrates for beneficial gut bacteria, fostering microbial activity and metabolite synthesis[185]. These effects are especially relevant in mitigating chemotherapy-induced dysbiosis, as prebiotics improve the microenvironment required for red blood cell production by reducing systemic inflammation[186].

Probiotics and prebiotics also show promise in countering the inflammatory pathways that impair erythropoiesis. Research has demonstrated that these agents can downregulate pro-inflammatory cytokines, particularly IL-6 and TNF-α, which are major contributors to iron metabolism dysregulation and erythropoietin resistance[187,188]. Specific strains, such as Bifidobacterium animalis subsp. lactis, have been linked to improved iron uptake and increased hemoglobin levels in anemic patients, offering a targeted therapeutic avenue[189-192].

FMT

FMT represents a novel therapeutic strategy for anemia, particularly in cases associated with gut dysbiosis. By transferring a healthy microbiome, FMT restores microbial diversity, enhances nutrient absorption, and modulates inflammatory responses that contribute to anemia[193,194]. This approach has shown promise in hematologic malignancies, where dysbiosis exacerbates systemic inflammation and suppresses erythropoiesis[193,194]. A case report involving refractory ACD illustrated the potential of FMT to normalize hemoglobin levels and reduce dependence on erythropoiesis-stimulating agents[195].

Emerging research suggests that the benefits of FMT extend to regulating the gut-liver axis, a critical pathway in iron metabolism and red blood cell production[196,197]. Preclinical studies have highlighted FMT's ability to enhance populations of iron-assimilating bacteria such as Bacteroides and Faecalibacterium, further supporting its role in addressing cancer-related anemia[198,199]. These findings underscore the potential of FMT as a therapeutic option, particularly for patients with treatment-resistant anemia.

Dietary interventions

Dietary modifications aimed at promoting gut health have gained traction as adjuncts in anemia management. High-fiber diets rich in whole grains, legumes, and vegetables stimulate the growth of beneficial bacteria, thereby increasing SCFA production and improving iron absorption[200,201]. The fermentation of fiber by gut microbiota generates butyrate, a key SCFA that enhances intestinal epithelial integrity and reduces systemic inflammation—factors essential for erythropoiesis[202,203]. Studies in cancer patients have demonstrated that incorporating fiber-rich foods into their diets improves gut health and alleviates anemia-related complications.

Iron-fortified foods and supplements are commonly used in dietary interventions; however, their efficacy is contingent on the composition of the gut microbiome. Certain bacterial species facilitate iron metabolism, highlighting the importance of microbiome health in optimizing iron bioavailability[204,205]. Notably, combining iron supplementation with prebiotics such as galactooligosaccharides has been shown to enhance iron absorption and effectively address anemia[206,207]. These findings suggest that dietary strategies tailored to balance nutrient intake and promote microbial diversity offer a comprehensive approach to anemia management[208].

Combination therapies

Integrated therapeutic strategies combining probiotics, prebiotics, FMT, and dietary interventions may yield superior outcomes in anemia management. For instance, the co-administration of probiotics and prebiotics alongside dietary modifications has been shown to improve hemoglobin levels and attenuate systemic inflammation more effectively than standalone interventions[208,209]. Similarly, pairing FMT with targeted dietary changes can restore microbial diversity while addressing specific nutritional deficiencies[210]. These combination therapies are particularly valuable in the context of chemotherapy-induced anemia, as they alleviate gastrointestinal toxicity and enhance systemic nutrient availability[211,212].

Addressing challenges and limitations

Despite the promise of microbiome-targeted interventions, several challenges remain. Patient responses to these therapies are highly variable, necessitating personalized approaches to maximize efficacy[213-216]. The lack of standardized protocols and limited data on long-term outcomes further complicates their implementation in clinical practice. Additionally, the interplay between cancer therapies and gut microbiota must be carefully monitored to avoid potential adverse interactions, such as exacerbation of dysbiosis[217,218].

Future directions

To refine microbiome-targeted strategies for anemia management, future research should prioritize the identification of dysbiosis patterns specific to cancer patients. Advances in sequencing technologies can enable personalized interventions tailored to individual microbiome profiles[219,220]. Clinical trials evaluating the combined efficacy of probiotics, prebiotics, FMT, and dietary changes in conjunction with conventional treatments will be instrumental in establishing evidence-based guidelines[221-223]. Finally, elucidating the molecular pathways through which the gut microbiome influences erythropoiesis and systemic inflammation may uncover new therapeutic targets, paving the way for innovative approaches in oncology[224].

Future directions for gut microbiome and anemia

The advancing understanding of the gut microbiome’s role in anemia management has set the stage for innovative, patient-specific therapeutic strategies. By targeting dysbiosis and addressing its impacts on iron metabolism, inflammation, and immune regulation, future interventions may significantly enhance outcomes for cancer patients facing anemia.

Personalized microbiome therapies

Developments in microbiome research have enabled the customization of therapeutic approaches to address unique microbial imbalances in individual patients. Engineered probiotics capable of delivering essential metabolites, such as butyrate and folate, are under investigation for their ability to improve erythropoiesis and mitigate inflammation[225,226]. Another promising area involves bacteriophage-based therapies that specifically target pathogenic strains linked to dysbiosis. For example, bacteriophages designed for Escherichia coli strains associated with inflammation may effectively reduce cytokine activity, thereby improving iron absorption and erythropoiesis[227,229]. These personalized approaches are particularly relevant for patients undergoing chemotherapy, where gut microbial disruptions are widespread and poorly addressed by generalized treatments[230,231].

In addition, synthetic microbial consortia (SMC) designed to mimic the functions of a healthy microbiota offer a forward-looking strategy. These consortia could be customized based on the patient’s microbiota profile to encourage the growth of beneficial bacteria such as Bacteroides and Faecalibacterium, both of which are critical for efficient iron metabolism and inflammation control[232,233]. Tables 1 and 2 summarize the mechanisms and interventions in microbiome-targeted anemia management. Table 3 presents a comparative analysis of anemia prevalence and severity across different cancer types with microbiome involvement.

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

Biomarker development

The identification of microbiome-derived biomarkers that predict anemia severity and therapeutic response is a crucial next step. Studies have pointed to specific microbial patterns, such as reductions in Lactobacillus and Faecalibacterium, that correlate with heightened anemia risk in cancer patients[234-236]. Leveraging advanced sequencing technologies and ML tools, researchers are developing predictive models based on microbiota profiles[237-239]. Notably, SCFA profiles have been associated with enhanced iron absorption and hemoglobin improvement, providing a measurable endpoint for microbiome-focused interventions[240,241].

Beyond diagnostics, microbial metabolites like butyrate, propionate and acetate are being explored as therapeutic targets. These metabolites regulate both immune activity and iron homeostasis, offering potential for use as markers of intervention efficacy[242,243]. Incorporating such biomarkers into clinical practice could lead to earlier detection and precision-targeted management of anemia in oncology.

Postbiotics are bioactive compounds produced by beneficial bacteria during fermentation. These include SCFAs, peptides, enzymes, and bacterial cell wall components that exert health benefits without the need for live bacteria[209]. SCFAs maintain the integrity of gut barrier, enhance expression of iron transporters on enterocytes, and downregulate hepcidin, thereby increasing bioavailability of iron. They also exert an antioxidant effect, reduce the levels of pro-inflammatory cytokines, and promote a favorable milieu for iron-regulating bacteria[244-248].

Bacteriophage therapy has emerged as a promising supplemental treatment for certain malignancies. Phaga-mediate alteration of gut microbiota can negate dysbiosis, and influence cancer progression and treatment outcomes. Using viruses equipped to selectively destroy detrimental strains (Escherichia coli, Enterococcus faecalis, or antibiotic-resistant strains), while preserving beneficial microbes, allows for restoration of a healthy gut microbiome. Phage cocktails can be tailored to attain specific bacterial profiles in order to enhance response to cancer therapy. Phage therapy remains in its infancy and has yet to surpass regulatory hurdles before becoming mainstream. Additionally, issues with bacteriophage delivery mechanisms and treatment resistance also need to be addressed, and this remains an ongoing area of research[61,170].

SMC essentially comprises several beneficial bacterial strains, and are administered either as multi-strain probiotics/microbial cocktails (Faecalibacterium prausnitzii, Akkermansia muciniphila), genetically engineered microbes (SCFA producing strains), or prebiotic-supported consortia. SMC offers a promising approach to modulate gut microbiome for correction of dysbiosis, improvement of treatment response, development of personalized therapies and enhance overall patient outcomes. Nevertheless, they need to be rigorously tested and validated in clinical trials prior to use in clinical settings[246].

Integrative approaches

Future strategies in anemia management will rely on combining microbiome-targeted therapies with established interventions. Probiotics and prebiotics, for instance, can enhance the absorption of iron supplements while minimizing gastrointestinal side effects[249,250]. Similarly, integrating FMT with erythropoiesis-stimulating agents may provide synergistic benefits for patients with severe anemia[251-253].

Dietary modifications tailored to the patient’s unique microbiota composition represent another promising avenue. Diets rich in fibers, whole grains, and legumes promote beneficial bacterial populations and address specific nutrient deficiencies such as iron and vitamin B12[254,255]. Figure 2 illustrates some dietary patterns that positively impact the gut microbiome. Emerging research also highlights the potential of combining microbiome modulation with immunotherapy to bolster immune responses and address anemia comprehensively in cancer patients[256,257].

Technological innovations

Future therapies will benefit from advancements in microbiome engineering and computational technologies. CRISPR-Cas9 is being explored for its ability to edit microbial genomes, targeting pathways implicated in dysbiosis and anemia progression. Computational models that integrate microbiome and host genomic data could guide individualized treatment plans, optimizing therapeutic efficacy based on patient-specific factors. By incorporating these cutting-edge approaches, the field can move closer to delivering personalized, effective solutions for managing anemia in oncology[258-260].

CONCLUSION

The gut microbiome is an indispensable yet underappreciated factor in the pathogenesis and management of cancer-associated anemia. This review highlights the intricate interplay between dysbiosis and the mechanisms driving anemia, including disruptions in iron metabolism, immune regulation, systemic inflammation, and nutrient absorption. Gut dysbiosis causes anemia and impairs response to chemotherapy in cancer patients. It exacerbates chemotherapy-induced myelosuppression and systemic inflammation, further impairing erythropoiesis in hematologic malignancies. Similarly, in solid malignancies, chronic tumor-associated bleeding, treatment-induced gastrointestinal toxicity, and malabsorption of essential nutrients are compounded by microbiota imbalances. Microbiome-centered interventions, such as probiotics, prebiotics, dietary modifications, and FMT, have shown efficacy in restoring microbial balance, reducing inflammation, and enhancing nutrient bioavailability. Emerging approaches, including engineered probiotics and bacteriophage therapies, are promising precision-based, customizable solutions for various microbiome compositions and imbalances. Future research should focus on integrating microbiome-targeted strategies with established anemia therapies. Incorporating microbiome-based biomarkers into clinical practice could refine diagnostic precision, predict therapeutic outcomes, and enable tailored interventions. Additionally, advancing clinical trials to evaluate the efficacy of microbiome-based therapies is critical for establishing their role in standard oncology care. Understanding the intricate role of microbial metabolites in erythropoiesis and systemic inflammation will further refine our approach to anemia management. Bridging the gap between cutting-edge microbiome science and clinical oncology can provide transformative improvements in anemia management, enhancing quality of life, treatment tolerability, and overall outcomes for patients with malignancies. Continued research and innovation are imperative to fully unlock the therapeutic potential of microbiome interventions in oncology.