Did you know?
Anemia affects more than 2 billion people worldwide, about 30% of the global population. This makes it the most common blood disorder on the planet.
Anemia
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Karen Pendergrass
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Karen Pendergrass
Anemia is a reduction in red blood cells or hemoglobin, often influenced by the gut microbiome’s impact on nutrient absorption.
Research feed -
Karen Pendergrass
Researched by:
-
Karen Pendergrass
ID
Karen Pendergrass
Fact-checked by:
-
Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
Overview 
Research Feed Overview
Anemia, a condition characterized by a decrease in red blood cells (RBCs) or the amount of hemoglobin in the blood, affects millions worldwide and can lead to severe health problems if left untreated. It can stem from various causes, including nutritional deficiencies, genetic disorders, chronic diseases, and infections. The relationship between the gut microbiome and anemia is a promising field of study that could lead to novel therapeutic strategies and improve our understanding of how gut health affects systemic disease states.
What are the different types of anemia?
| Type of Anemia | Mechanism and Gut Microbiome Role |
|---|---|
| Iron-Deficiency Anemia | The most common type globally, primarily due to a lack of iron crucial for hemoglobin production. Iron absorption occurs mainly in the duodenum and is influenced by the gut microbiome. Certain gut bacteria enhance iron absorption by reducing it to a more absorbable form or competing with pathogenic bacteria. Dysbiosis can lead to decreased iron absorption. |
| Anemia of Chronic Disease | Commonly associated with chronic infections, autoimmune diseases, and other inflammatory conditions, characterized by impaired iron utilization and reduced erythropoiesis. Chronic diseases alter gut microbiota, potentially affecting the body’s inflammatory response and iron metabolism. Inflammatory cytokines can increase hepcidin levels, blocking iron absorption. |
| Megaloblastic Anemia | Caused by deficiencies in folate or vitamin B12 necessary for RBC maturation, leading to large and inefficient RBCs. The gut microbiota synthesizes and assists in the absorption of B vitamins. Changes in microbiota composition can affect vitamin availability, impacting anemia status. |
| Hemolytic Anemia | Characterized by the accelerated destruction of RBCs and a shortened lifespan in the bloodstream. Emerging evidence suggests that gut microbiota may influence hemolysis and RBC integrity indirectly by modulating bile acid metabolism and the immune response. |
Associated Conditions
Anemia can arise from or be exacerbated by various conditions, ranging from nutritional deficiencies to chronic diseases. The condition is often a symptom of underlying health issues that disrupt the body’s ability to produce or maintain healthy red blood cells.
What conditions are associated with anemia?
| Condition | Association with Anemia |
|---|---|
| Vitamin B12 or Folate Deficiency | Both vitamins are crucial for DNA synthesis in red blood cells. Deficiency leads to megaloblastic anemia, where red blood cells are abnormally large and inefficient. |
| Chronic Kidney Disease (CKD) | Impaired kidney function leads to decreased production of erythropoietin, a hormone essential for red blood cell production, resulting in anemia. |
| Chronic Inflammatory Diseases | Conditions like rheumatoid arthritis, endometriosis, or inflammatory bowel disease can lead to anemia of chronic disease, where iron is sequestered away from the bone marrow, inhibiting its availability for red blood cell production. |
| Hemolytic Anemia | Conditions that lead to premature destruction of red blood cells, such as autoimmune diseases, certain medications, or hereditary defects like sickle cell disease. |
Associated Pathogens
Anemia can be associated with various pathogens that directly affect red blood cell production or indirectly influence iron availability and erythropoiesis.
What pathogens are associated with anemia?
| Pathogen | Association with Anemia |
|---|---|
| Plasmodium spp. | Malaria caused by Plasmodium leads to hemolytic anemia, where red blood cells are destroyed by the parasite. |
| Hookworms | These parasites cause chronic blood loss in the gastrointestinal tract, leading to iron-deficiency anemia. |
| Helicobacter pylori | Infection can cause gastric ulcers and chronic gastritis, leading to blood loss and iron-deficiency anemia. Additionally, H. pylori may sequester iron, exacerbating iron deficiency. |
| Human Immunodeficiency Virus (HIV) | HIV can cause anemia of chronic disease by affecting the bone marrow’s ability to produce red blood cells and by altering iron metabolism. |
| Schistosoma spp. | Parasitic infections, especially with Schistosoma, can cause chronic blood loss and malnutrition, leading to the condition. |
Mechanisms
The gut microbiota significantly impacts health, particularly in the development and management of anemia. It synthesizes B vitamins and enhances iron absorption by altering the gut environment. This process is crucial for the proper formation and function of red blood cells. Gut bacteria also affect systemic inflammation, influencing hepcidin production and iron metabolism. Additionally, a healthy gut microbiota prevents pathogenic bacteria from colonizing, which can lead to the condition. These roles highlight the critical influence of gut microbiota on nutrient availability and immune function, which is essential for preventing and managing the condition.
What are the implications of these mechanisms for the treatment and management of anemia?
Probiotics and Prebiotics: Modifying the gut microbiota through diet or supplements like probiotics and prebiotics could become a strategy to enhance nutrient absorption and reduce inflammation, potentially ameliorating the condition.
Dietary Modifications: Tailoring diets to modify the gut microbiome, thereby enhancing the bioavailability of critical nutrients like iron and B vitamins, could be an effective approach to managing or preventing anemia.
Personalized Medicine: Understanding individual microbiome configurations might help tailor interventions that prevent or treat the condition based on personal microbial profiles.
Interventions
Common interventions for anemia typically include iron supplementation. However, the relationship between iron supplementation, especially in the context of chronic infections, is complex and may even exacerbate infections. [x] This challenges current management practices for the condition, especially concerning iron supplementation. Further, and most paradoxically, iron chelators like lactoferrin improve the condition without the common side effects of iron supplementation. [x] Research into iron regulation mechanisms and chronic infections is vital for safer, more effective treatments.
Future Directions
To advance our understanding of how the gut microbiome impacts anemia, a concerted effort in research is imperative. Specifically, more robust clinical trials are essential to evaluate the effectiveness of microbiome-based interventions for treating various types of the condition. These studies will help determine the practical applications of modifying the gut microbiota to improve patient outcomes. Additionally, mechanistic studies are crucial as they provide deeper insights into how the gut microbiome influences iron metabolism. Understanding these interactions at a molecular level can enable us to harness these processes effectively in managing the condition, potentially leading to more targeted and effective therapeutic strategies. Together, these research initiatives are fundamental in moving from theoretical knowledge to practical applications in healthcare.
Research Feed
How Severe Anemia Might Influence the Risk of Invasive Bacterial Infections in African Children
September 22, 2020
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Anemia
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Anemia
Did you know?
Anemia affects more than 2 billion people worldwide, about 30% of the global population. This makes it the most common blood disorder on the planet.
The hypothesis presented in the study is that severe anemia may contribute to the risk of invasive bacterial infections in African children through dysregulation of iron homeostasis and/or iron-regulatory proteins, particularly by affecting the regulation of the hepatic hormone hepcidin and subsequent iron availability for bacterial growth. This hypothesis, therefore, not only opens new avenues for research into the pathophysiology of anemia and bacterial infections but also for developing better therapeutic interventions that could reduce morbidity and mortality in those affected by these conditions.
What Was Reviewed?
This review investigates the hypothesis that severe anemia contributes to the elevated risk of invasive bacterial infections in African children through dysregulation of iron homeostasis, including the disruption of hepcidin—a hepatic hormone that governs iron availability in the body. The authors synthesize evidence from epidemiological, mechanistic, and experimental studies, proposing that the interplay between anemia, haemolysis, immune dysfunction, and gut permeability collectively facilitates systemic infections. The paper places particular emphasis on how bacterial pathogens exploit iron and haem to thrive under conditions of anemia-induced iron dysregulation, especially in regions with high burdens of infectious disease and malnutrition.
Who Was Reviewed?
The review draws on research concerning sub-Saharan African children who commonly experience severe anemia due to malaria, nutritional deficiencies, sickle cell disease, and HIV. It includes human observational data, animal model findings, and in vitro studies related to bacterial infections, immune response, and iron regulation pathways.
What Were the Most Important Findings?
Severe anemia in African children correlates strongly with an increased risk of invasive bacterial infections, particularly with Gram-negative organisms such as non-typhoidal Salmonella (NTS), E. coli, and Haemophilus influenzae, as well as Gram-positive organisms including Staphylococcus aureus and Streptococcus pneumoniae. This elevated susceptibility is mechanistically linked to increased erythropoietic drive and haemolysis, both of which suppress hepcidin via the erythroid hormone erythroferrone (ERFE). Reduced hepcidin enhances plasma iron levels and promotes the release of iron from macrophage stores, thereby removing the “nutritional immunity” that would otherwise limit iron availability to pathogens. Simultaneously, haemolysis releases non-transferrin-bound iron (NTBI) and free haem, which are more readily exploited by pathogens through siderophore-mediated and haem-binding iron acquisition systems.
Of particular relevance to microbiome researchers, the review notes that severe anemia can disrupt gut barrier integrity and provoke dysbiosis. The increased gut permeability facilitates the translocation of enteric pathogens, notably NTS and E. coli, into systemic circulation. This breach is exacerbated by inflammation, destabilization of tight junction proteins like ZO-1, and macrophage-mediated changes to mucosal immunity. The review references mouse models where anemia-induced epithelial dysfunction was dependent on macrophage-driven cytokine signaling, especially IFN-γ, as well as bacterial studies showing enhanced virulence and iron uptake capacity in haem-rich or iron-rich conditions. Importantly, these microbial strategies overlap with the exact niches disrupted in severe anemia, such as haem overload, NTBI availability, and compromised mucosal defenses.
Major microbial associations (MMAs) include:
| Pathogen | Key Iron Acquisition Strategies |
|---|---|
| Non-typhoidal Salmonella | Siderophores (salmochelin, enterobactin), Fe2+ uptake via ferroportin Strong association with anemia. |
| E. coli | Enterobactin, salmochelin, aerobactin, haem receptors. Strong association with anemia. |
| Haemophilus influenzae | Haem- and haemoglobin-binding proteins (HgpA/B/C, HxuA). Moderate association with anemia. |
| Staphylococcus aureus | Isd system, staphyloferrin siderophores, transferrin binding. Moderate association with anemia. |
| Streptococcus pneumoniae | ABC transporters (piu, pia, pit), haemoglobin-binding proteins. Moderate association with anemia. |
What Are the Greatest Implications of This Review?
The review suggests that treating severe anemia in high-infection-burden areas like sub-Saharan Africa should involve caution, particularly regarding iron supplementation. While iron repletion is essential, excessive or unregulated iron can exacerbate infection risk, especially in the presence of low hepcidin levels. This carries profound public health implications, as many iron supplementation programs do not account for concurrent infectious burdens or the child's hepcidin status. Clinically, these insights demand a reevaluation of iron therapy protocols, particularly in settings where malaria, HIV, or bacterial sepsis are endemic. The review also encourages further exploration of therapies that modulate iron availability (e.g., hepcidin agonists or iron chelators) and highlights the need for comprehensive microbiome assessments in anaemic populations. The tight interconnection between gut microbiota, intestinal permeability, and systemic iron overload represents a mechanistic intersection worth pursuing in microbiome-targeted interventions.
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
Lactoferrin
Lactoferrin (LF) is a naturally occurring iron-binding glycoprotein classified as a postbiotic with immunomodulatory, antimicrobial, and prebiotic-like properties.