INTERNATIONAL JOURNAL OF LATEST TECHNOLOGY IN ENGINEERING,  
MANAGEMENT & APPLIED SCIENCE (IJLTEMAS)  
ISSN 2278-2540 | DOI: 10.51583/IJLTEMAS | Volume XIV, Issue XI, November 2025  
The Gut-Blood Axis: A Literature Review on the Role of Gut  
Microbes and Probiotics in the Management of Anaemia  
Alpana Sahaa, b  
aCSIR-National Institute of Science Communication and Policy Research, Dr KS Krishnan Marg, New  
Delhi-110012, India  
bAcademy of Scientific and Innovation Research (AcSIR), Ghaziabad-201002, India  
DOI: https://doi.org/10.51583/IJLTEMAS.2025.1411000039  
Received: 18 November 2025; Accepted: 27 November 2025; Published: 05 December 2025  
ABSTRACT  
Anaemia, a condition characterized by a deficiency in red blood cells or haemoglobin, remains a global public  
health challenge affecting nearly a third of the world's population. Traditional management strategies primarily  
focus on nutrient supplementation (e.g., iron, vitamin B12, folate) and treating underlying causes. However,  
variable efficacy and side effects of these approaches have prompted the exploration of novel adjuvants. The  
human gut microbiome, a complex ecosystem of trillions of microorganisms, is increasingly recognized as a  
critical regulator of host physiology, including nutrient absorption and immune function. This literature review  
synthesizes current evidence on the mechanisms by which gut microbes and their therapeutic derivatives,  
probiotics, influence the pathogenesis and management of anaemia. We explore the triad relationship between  
the gut microbiota, iron homeostasis, and inflammation, detailing how specific bacterial taxa can enhance or  
inhibit iron absorption. Furthermore, we examine the direct role of microbes in the synthesis of folate and vitamin  
B12, essential cofactors for erythropoiesis. Evidence from preclinical and clinical studies demonstrating the  
efficacy of various probiotic strains, particularly Lactobacillus and Bifidobacterium, in improving haemoglobin  
status is critically appraised. The review also discusses the potential of synbiotics and postbiotics as next-  
generation therapeutic tools. Finally, we identify key research gaps and future directions, concluding that  
targeted modulation of the gut microbiome represents a promising, multifaceted strategy for the prevention and  
management of various forms of anaemia, moving beyond conventional nutrient-replacement paradigms.  
Keywords: Anaemia, Microbiome, Probiotics, Iron, Inflammation, Folate, Vitamin B12, Gut-Blood  
Axis, Lactobacillus, Bifidobacterium  
INTRODUCTION  
Anaemia is a pervasive global health problem, with the World Health Organization (WHO) estimating that 1.8  
billion people were affected in 2021, representing 27% of the world's population, with the highest burden among  
preschool children and pregnant women (WHO, 2024). It is a condition defined by a reduced oxygen-carrying  
capacity of the blood, resulting from a decrease in the number of circulating red blood cells or a reduction in the  
concentration of haemoglobin within them (Chaparro & Suchdev, 2019). The functional consequences are  
profound, including fatigue, impaired cognitive development in children, reduced work capacity in adults, and  
increased risk of maternal and child mortality (Peyrin-Biroulet et al., 2015).  
The aetiologies of anaemia are multifactorial and often interconnected. Iron deficiency is the most common  
cause, accounting for approximately 50% of cases globally (Camaschella, 2019). Other significant causes  
include deficiencies in other micronutrients like vitamin B12 and folate, chronic inflammation (leading to  
anaemia of inflammation, AI), inherited haemoglobin disorders (e.g., thalassemia, sickle cell disease), and  
parasitic infections such as malaria and helminthiasis (Kassebaum et al., 2014). Conventional management has  
predominantly relied on oral or parenteral supplementation of the deficient nutrient, such as ferrous sulfate for  
iron deficiency anaemia (IDA). While effective, these approaches have limitations, including poor  
www.ijltemas.in  
Page 453  
INTERNATIONAL JOURNAL OF LATEST TECHNOLOGY IN ENGINEERING,  
MANAGEMENT & APPLIED SCIENCE (IJLTEMAS)  
ISSN 2278-2540 | DOI: 10.51583/IJLTEMAS | Volume XIV, Issue XI, November 2025  
gastrointestinal tolerance of iron supplements (e.g., constipation, nausea), low adherence, and limited efficacy  
in anaemia of inflammation where iron sequestration is the primary issue (Paganini & Zimmermann, 2017).  
In recent years, a paradigm shift has occurred with the recognition of the human gut microbiome as a virtual  
endocrine organ that profoundly influences host health. The gut microbiota, comprising bacteria, archaea,  
viruses, and eukaryotes, is integral to metabolic functions, immune modulation, and pathogen exclusion (Sender  
et al., 2016). The concept of the "gut-blood axis" has emerged, highlighting the bidirectional communication  
between gut microbial communities and systemic haematological parameters (Yan & Charles, 2018).  
This literature review aims to critically synthesize and evaluate the current scientific evidence on the importance  
of gut microbes and probiotics in managing anaemia. It will delineate the mechanisms by which the microbiota  
influences iron homeostasis, inflammation, and the synthesis of erythropoietic vitamins. Furthermore, it will  
review interventional studies using probiotics, synbiotics, and postbiotics, appraising their efficacy and potential  
as novel therapeutic or adjuvant strategies. By integrating findings from molecular, animal, and human studies,  
this review seeks to provide a comprehensive overview of this rapidly evolving field and to identify future  
research priorities.  
The Gut Microbiome: A Primer and Its Connection to Systemic Health  
The human colon harbors the densest microbial community on Earth, with estimates of 10^13 to 10^14  
microorganisms, the majority of which are bacteria from the phyla Firmicutes and Bacteroidetes (Lloyd-Price et  
al., 2016). The composition of this ecosystem is shaped by genetics, diet, age, geography, and medication use,  
and its stability is crucial for health. A state of dysbiosis, an imbalance in the microbial community, has been  
linked to a plethora of diseases, including inflammatory bowel disease (IBD), obesity, type 2 diabetes, and even  
neurological disorders (Lynch & Pedersen, 2016).  
The microbiota contributes to host health through several key functions:  
1. Metabolism of Dietary Components: Fermenting indigestible dietary fibers to produce short-chain fatty  
acids (SCFAs) like acetate, propionate, and butyrate, which serve as energy sources for colonocytes and  
have systemic anti-inflammatory effects (Parada Venegas et al., 2019).  
2. Synthesis of Vitamins: De novo synthesis of essential vitamins, including vitamin K and most B vitamins,  
such as folate (B9), riboflavin (B2), and cobalamin (B12) (Magnúsdóttir et al., 2015).  
3. Barrier Function and Immune Regulation: The microbiota helps maintain the integrity of the gut  
epithelial barrier and educates the host immune system, promoting a balanced inflammatory response  
(Belkaid & Harrison, 2017).  
The connection to anaemia becomes apparent when these functions are disrupted. For instance, gut inflammation  
can lead to dysbiosis, which in turn may impair iron absorption or increase systemic inflammation, creating a  
vicious cycle that perpetuates anaemia.  
Mechanisms of Microbial Influence on Anaemia  
The gut microbiota influences erythropoiesis and haemoglobin levels through three primary, interconnected  
mechanisms: modulation of iron absorption, regulation of systemic inflammation, and direct synthesis of  
haematopoietic vitamins.  
Modulation of Iron Homeostasis  
Iron absorption is a tightly regulated process occurring primarily in the duodenum and proximal jejunum. Dietary  
iron (Fe³⁺) is reduced to the more soluble ferrous form (Fe²⁺) by ferric reductases, then transported into  
enterocytes by the divalent metal transporter 1 (DMT1). It is either stored as ferritin or exported into the  
circulation via ferroportin, where it is oxidized and bound to transferrin (Ganz, 2013). The hormone hepcidin,  
produced by the liver, is the master regulator of iron homeostasis; it degrades ferroportin, thereby trapping iron  
in enterocytes and macrophages and reducing plasma iron availability (Ganz & Nemeth, 2012).  
www.ijltemas.in  
Page 454  
INTERNATIONAL JOURNAL OF LATEST TECHNOLOGY IN ENGINEERING,  
MANAGEMENT & APPLIED SCIENCE (IJLTEMAS)  
ISSN 2278-2540 | DOI: 10.51583/IJLTEMAS | Volume XIV, Issue XI, November 2025  
The gut microbiota competes with the host for dietary iron. This is particularly evident in situations of dietary  
iron restriction, where the growth of certain pathogenic bacteria (e.g., Salmonella spp., Escherichia coli) is  
suppressed, while commensals like Lactobacillus spp. are more resilient (Dostal et al., 2014). However, the  
relationship is bidirectional and complex. Specific microbial metabolites can directly influence host iron  
absorption:  
Short-Chain Fatty Acids (SCFAs): Produced by bacterial fermentation of fiber, SCFAs (particularly  
butyrate) have been shown to downregulate the expression of hepcidin in vitro and in vivo (Shah et al.,  
2021). Lower hepcidin levels increase ferroportin activity, enhancing iron export from enterocytes and  
macrophages into the circulation. Butyrate also stimulates the proliferation of intestinal epithelial cells,  
potentially increasing the absorptive surface area (Parada Venegas et al., 2019).  
Lactic  
Acid  
and  
Other  
Microbial  
Products: Probiotic  
bacteria  
like Lactobacillus and Bifidobacterium produce lactic acid, which can lower the local pH in the gut lumen.  
This acidic environment helps maintain iron in its more bioavailable ferrous (Fe²⁺) state and may stimulate  
DMT1 activity (Rusu et al., 2020).  
Bacterial Iron Metabolism: Bacteria have their own sophisticated systems for iron acquisition  
(siderophores) and storage. Some commensals possess high-affinity iron transporters that can sequester  
luminal iron, theoretically reducing host absorption. However, the overall impact of the community is likely  
a net positive, as SCFA-producing bacteria seem to promote host iron availability (Das et al., 2020).  
Table 1: Microbial Mechanisms Influencing Iron Homeostasis  
Mechanism  
Key Microbial Players / Metabolites  
Effect on Host Iron Absorption  
Faecalibacterium  
prausnitzii, Roseburia spp., Eubacterium spp.  
(Butyrate); Bacteroides spp.  
Acetate)  
↓ Hepcidin expression → ↑  
Ferroportin activity → Enhanced iron  
export into circulation.  
SCFA  
Production  
(Propionate,  
Lactobacillus spp., Bifidobacterium spp. (Lactic  
acid)  
Maintains iron in soluble Fe²⁺ form;  
may upregulate DMT1.  
Luminal  
Acidification  
Can sequester luminal iron via  
siderophores, potentially limiting host  
access.  
Competition  
for Iron  
Pathobionts (e.g., Salmonella, E. coli)  
Enhances intestinal integrity, reducing  
Modulation  
inflammation-driven  
malabsorption.  
iron  
of  
Barrier  
Gut  
SCFAs, Lactobacillus spp., Bifidobacterium spp.  
Regulation of Inflammation in Anaemia of Inflammation (AI)  
Anaemia of Inflammation (AI), also known as anaemia of chronic disease, is the second most prevalent anaemia  
worldwide. It is characterized by a functional iron deficiency: despite adequate iron stores, iron is sequestered  
in macrophages and the liver, making it unavailable for erythropoiesis (Weiss & Goodnough, 2005). This is  
primarily mediated by hepcidin, whose expression is strongly induced by inflammatory cytokines, particularly  
interleukin-6 (IL-6) (Nemeth et al., 2004).  
www.ijltemas.in  
Page 455  
INTERNATIONAL JOURNAL OF LATEST TECHNOLOGY IN ENGINEERING,  
MANAGEMENT & APPLIED SCIENCE (IJLTEMAS)  
ISSN 2278-2540 | DOI: 10.51583/IJLTEMAS | Volume XIV, Issue XI, November 2025  
The gut microbiome is a pivotal regulator of systemic immunity. A healthy, diverse microbiota promotes a state  
of immunological tolerance and maintains gut barrier integrity, preventing the translocation of bacterial  
lipopolysaccharides (LPS) into the portal circulation. LPS is a potent trigger of systemic inflammation, leading  
to the production of IL-6 and other cytokines that stimulate hepcidin production (Sebastian & Mostoslavsky,  
2021).  
In conditions of dysbiosis, such as in IBD, obesity, or chronic kidney disease, this barrier is compromised.  
Increased gut permeability ("leaky gut") allows for LPS translocation, fueling chronic, low-grade inflammation.  
This sustained inflammatory state leads to persistent hepcidin elevation, blocking iron absorption and recycling,  
there by driving AI (Deschemin & Vaulont, 2013). Probiotics and prebiotics can counter this process by:  
1. Restoring Microbial Balance: Increasing the abundance of SCFA-producing bacteria, which have anti-  
inflammatory properties and strengthen the gut barrier.  
2. Reducing Pro-inflammatory Cytokines: Certain probiotic strains can directly modulate immune cell  
responses, reducing the production of IL-6, TNF-α, and other hepcidin-inducing cytokines (Yan & Charles,  
2018).  
3. Competitive Exclusion: Preventing the overgrowth of pro-inflammatory pathobionts.  
Microbial Synthesis of Haematopoietic Vitamins  
Beyond iron, adequate levels of vitamin B12 and folate are non-negotiable for DNA synthesis and erythrocyte  
maturation. Deficiencies in either lead to megaloblastic anaemia. While humans must obtain most of their  
vitamin B12 from animal-derived foods, the gut microbiota is a significant source of folate (B9) and, to a lesser  
extent, B12 (Magnúsdóttir et al., 2015).  
Folate  
Synthesis: Numerous  
gut  
bacteria,  
including Lactobacillus spp., Bifidobacterium spp.,  
and Streptococcus thermophilus, are prolific producers of folate (Rossi et al., 2011). This microbial folate  
can be absorbed across the colonic epithelium, contributing to the host's folate status. Studies have shown  
that probiotic supplementation can increase serum and erythrocyte folate concentrations in humans (Strozzi  
& Mogna, 2008).  
Vitamin B12 Synthesis: Although several gut bacteria synthesize B12, this occurs predominantly in the  
colon, a site where absorption of the vitamin is minimal, as the intrinsic factor-mediated absorption  
mechanism is active only in the ileum (Degnan et al., 2014). Therefore, the contribution of microbial B12  
to host status is likely limited. However, a healthy microbiota may still play an indirect role by preventing  
the overgrowth of bacteria that compete with the host for dietary B12.  
Table 2: Probiotic Strains with Documented Effects on Haematopoietic Nutrients  
Probiotic Strain  
Documented Effects  
Proposed Mechanism  
Increased iron absorption;  
reduced hepcidin; improved Hb  
in IDA (Søndergaard et al.,  
2021).  
Acidification, SCFA production, reduction of luminal iron-binding  
phytates.  
Lactobacillus  
plantarum 299v  
Improved iron status in animal  
Lactobacillus  
acidophilus  
models;  
increased  
folate  
Folate synthesis; luminal acidification; immune modulation.  
production (Rusu et al., 2020).  
Bifidobacterium  
longum  
Reduced  
inflammation; improved iron  
bioavailability in weaning  
systemic  
Anti-inflammatory cytokine profile; enhanced gut barrier function.  
www.ijltemas.in  
Page 456  
INTERNATIONAL JOURNAL OF LATEST TECHNOLOGY IN ENGINEERING,  
MANAGEMENT & APPLIED SCIENCE (IJLTEMAS)  
ISSN 2278-2540 | DOI: 10.51583/IJLTEMAS | Volume XIV, Issue XI, November 2025  
Probiotic Strain  
Documented Effects  
Proposed Mechanism  
infants (Mitsuyoshi et al.,  
2021).  
High in situ production of folate  
in the gut (Rossi et al., 2011).  
Streptococcus  
thermophilus  
De novo folate synthesis.  
Improved vitamin B12 status in  
deficient  
combination  
interventions) (Degnan et al.,  
2014).  
individuals  
with  
(in  
other  
Lactobacillus  
reuteri  
Potential reduction of competing microbes; local synthesis.  
Evidence from Interventional Studies with Probiotics and Synbiotics  
The mechanistic insights have been translated into numerous interventional studies investigating the efficacy of  
probiotics, often in combination with prebiotics (synbiotics), in managing anaemia.  
Preclinical (Animal) Studies  
Animal models have been instrumental in establishing proof-of-concept. For example, a study in iron-deficient  
piglets showed that supplementation with L. plantarum 299v significantly improved iron absorption and  
haemoglobin regeneration efficiency compared to controls (Kullen et al., 2019). Similarly, in a rat model of  
anaemia, a synbiotic containing L. acidophilus and fructo-oligosaccharides (FOS) led to a greater increase in  
haemoglobin and serum iron than iron supplementation alone (Hoppe et al., 2017). These studies consistently  
highlight the role of probiotics in modulating DMT1 and ferroportin expression and reducing systemic  
inflammation.  
Human Clinical Trials  
Human trials, though more variable in design and outcome, show promising results.  
Iron Deficiency Anaemia (IDA): A randomized controlled trial (RCT) in pregnant women with IDA  
found that co-administration of a probiotic mixture (L. acidophilus, B. bifidum, L. casei, L. fermentum)  
with iron supplements resulted in a significantly greater increase in haemoglobin and serum ferritin  
compared to iron supplements alone, with fewer gastrointestinal side effects (Rezaei et al., 2019). Another  
RCT in iron-deficient women showed that L. plantarum 299v, when combined with iron, was more  
effective at restoring iron status than iron with a placebo (Søndergaard et al., 2021).  
Anaemia of Inflammation: In patients with chronic kidney disease (CKD), who frequently suffer from  
AI, probiotic supplementation has been shown to reduce markers of inflammation (e.g., CRP, IL-6) and  
increase haemoglobin levels, allowing for a reduced dose of erythropoiesis-stimulating agents (ESAs) in  
some cases (Mirzaei et al., 2022). Similar anti-inflammatory and haemoglobin-boosting effects have been  
observed in studies on obese individuals and the elderly (Mitsuyoshi et al., 2021).  
Other Forms of Anaemia: Preliminary evidence suggests that probiotics may also benefit individuals  
with sickle cell disease or thalassemia by reducing inflammation and oxidative stress, though research in  
this area is still nascent (Yan & Charles, 2018).  
Figure 1: Conceptual Framework of Probiotic Mechanisms in Managing Anaemia  
+------------------------+  
+----------------------+  
www.ijltemas.in  
Page 457  
INTERNATIONAL JOURNAL OF LATEST TECHNOLOGY IN ENGINEERING,  
MANAGEMENT & APPLIED SCIENCE (IJLTEMAS)  
ISSN 2278-2540 | DOI: 10.51583/IJLTEMAS | Volume XIV, Issue XI, November 2025  
| Probiotic / Symbiotic |  
| Healthy Gut Microbiome |  
|----->| (Eubiosis)  
+----------------------+  
| Supplementation  
+------------------------+  
| (SCFAs, Barrier Integrity)  
v
+---------------------------------------------------+  
|
Multimodal Mechanisms  
|
+---------------------------------------------------+  
| ↓ Systemic Inflammation | ↑ Iron Absorption | ↑ Vitamin Synthesis |  
| ↓ Hepcidin  
| ↑ DMT1/Ferroportin| (Folate, B2)  
| Acidic pH  
| Phytate degradation|  
|
| ↓ Pro-inflammatory  
| cytokines (IL-6)  
|
|
|
+---------------------------------------------------+  
|
v
+---------------------------------------------------+  
|
Improved Haematological Outcomes  
|
+---------------------------------------------------+  
| ↑ Haemoglobin (Hb) | ↑ Serum Ferritin  
|
| ↑ Erythrocyte Count | ↓ Reticulocyte Production|  
| Resolution of Anaemia | Time  
+---------------------------------------------------+  
|
Table 3: Summary of Select Clinical Trials on Probiotics/Synbiotics in Anaemia Management  
Study  
Population  
Intervention  
Duration  
Key Findings  
Reference  
Significantly greater  
increase in Hb and  
ferritin in probiotic  
group. Fewer GI side  
effects.  
Ferrous  
Probiotic  
acidophilus, B.  
bifidum, L.  
Sulfate  
mix  
+
(L.  
(Rezaei et al.,  
2019)  
Pregnant women  
with IDA (n=80)  
12 weeks  
casei, L.  
www.ijltemas.in  
Page 458  
INTERNATIONAL JOURNAL OF LATEST TECHNOLOGY IN ENGINEERING,  
MANAGEMENT & APPLIED SCIENCE (IJLTEMAS)  
ISSN 2278-2540 | DOI: 10.51583/IJLTEMAS | Volume XIV, Issue XI, November 2025  
Study  
Population  
Intervention  
Duration  
Key Findings  
Reference  
fermentum) vs. Ferrous  
Sulfate + Placebo  
Probiotic group had  
significantly higher  
iron absorption and  
Hb levels.  
Ferrous  
plantarum 299v  
Ferrous Sulfate + Placebo  
Sulfate  
+ L.  
vs.  
(Søndergaard  
et al., 2021)  
Iron-deficient  
women (n=60)  
12 weeks  
8 weeks  
6 months  
Probiotic group had  
significant reduction  
in hs-CRP and IL-6,  
and increase in Hb.  
Synbiotic (various strains  
+ FOS) vs. Placebo  
(Mirzaei et al.,  
2022)  
Patients  
with  
CKD (n=60)  
Probiotic group had  
better iron status and  
lower inflammation  
markers.  
Iron-fortified cereal + B.  
lactis vs.  
cereal alone  
(Mitsuyoshi et  
al., 2021)  
Weaning  
infants (n=120)  
Iron-fortified  
Beyond Probiotics: Synbiotics, Postbiotics, and Fecal Microbiota Transplantation  
The therapeutic landscape is expanding beyond traditional probiotics.  
Synbiotics: These are combinations of probiotics and prebiotics designed to improve the survival and  
implantation of live microbial supplements. The prebiotic component (e.g., inulin, FOS) selectively  
stimulates the growth of endogenous beneficial bacteria as well as the administered probiotics, creating a  
synergistic effect. Studies using synbiotics often report superior outcomes in improving iron status and  
reducing inflammation compared to probiotics alone (Hoppe et al., 2017).  
Postbiotics: Defined as preparations of inanimate microorganisms and/or their components that confer a  
health benefit. This includes bacterial lysates, cell-free supernatants, and metabolites like SCFAs.  
Postbiotics offer advantages in terms of safety (no risk of bacterial translocation or antibiotic resistance  
gene transfer), stability, and shelf-life. Butyrate-producing postbiotic preparations are being explored for  
their potential to directly target hepcidin expression (Shah et al., 2021).  
Fecal Microbiota Transplantation (FMT): While primarily used for recurrent Clostridioides  
difficile infection, FMT represents the ultimate "microbial reset." Its application in anaemia management  
is purely speculative but intriguing. In theory, transferring a healthy, diverse microbiota from a donor with  
robust iron status could potentially correct dysbiosis-driven AI in a recipient, though significant safety  
and ethical hurdles exist.  
Challenges, Limitations, and Future Directions  
Despite the promising evidence, several challenges remain. The probiotic field suffers from a lack of strain-  
specificity; effects are not generalizable across different bacterial strains. The optimal dosage, duration, and  
formulation (single strain vs. consortium) for different types of anaemia are yet to be standardized. Many human  
studies have small sample sizes and are of short duration, limiting the strength of the conclusions.  
www.ijltemas.in  
Page 459  
INTERNATIONAL JOURNAL OF LATEST TECHNOLOGY IN ENGINEERING,  
MANAGEMENT & APPLIED SCIENCE (IJLTEMAS)  
ISSN 2278-2540 | DOI: 10.51583/IJLTEMAS | Volume XIV, Issue XI, November 2025  
Future research should focus on:  
1. Large-scale, long-term, well-designed RCTs in diverse populations and specific disease states (e.g.,  
IBD, CKD).  
2. Mechanistic Elucidation: Using gnotobiotic (germ-free) animal models and multi-omics approaches  
(metagenomics, metabolomics) to precisely delineate causal pathways.  
3. Personalized Nutrition: Developing strategies based on an individual's baseline microbiome  
composition to predict and optimize response to probiotic intervention.  
4. Exploration of Postbiotics: Rigorously testing defined postbiotic formulations as stable and safe  
alternatives to live bacteria.  
5. Investigating the Virome and Mycobiome: Expanding research beyond bacteria to include the roles of  
gut viruses and fungi in haematological health.  
CONCLUSION  
The burgeoning field of microbiome research has unequivocally established that gut microbes are critical players  
in host nutrient homeostasis and immune function. This review has synthesized compelling evidence that the gut  
microbiota exerts a profound influence on the pathogenesis and management of anaemia through three core  
mechanisms: enhancing iron bioavailability via SCFA-mediated hepcidin suppression and luminal acidification,  
mitigating the chronic inflammation that underlies AI, and directly supplying essential haematopoietic vitamins  
like folate.  
While oral nutrient supplementation remains the cornerstone of anaemia treatment, its limitations are clear. The  
adjunctive use of specific probiotic strains, synbiotics, and potentially postbiotics, offers a novel, safe, and  
multifaceted strategy to improve therapeutic outcomes. By targeting the gut-blood axis, these interventions can  
enhance the efficacy of iron therapy, reduce its side effects, and address the root inflammatory causes in AI.  
Future research must move from correlation to causation and towards personalized, microbiome-based  
therapeutics. Ultimately, harnessing the power of our microbial inhabitants promises to revolutionize our  
approach to combating this ancient and widespread malady.  
REFERENCES  
1. Belkaid, Y., & Harrison, O. J. (2017). Homeostatic immunity and the microbiota. Immunity, *46*(4),  
562–576. https://doi.org/10.1016/j.immuni.2017.04.008  
2. Camaschella, C. (2019). Iron deficiency. Blood, *133*(1), 30–39. https://doi.org/10.1182/blood-2018-  
05-815944  
3. Chaparro, C. M., & Suchdev, P. S. (2019). Anemia epidemiology, pathophysiology, and etiology in low-  
and middle-income countries. Annals of the New York Academy of Sciences, *1450*(1), 15–  
31. https://doi.org/10.1111/nyas.14092  
4. Das, N. K., Schwartz, A. J., Barthel, G., Inohara, N., Liu, Q., Sankar, A., ... & Ganesh, B. P. (2020).  
Microbial metabolite signaling is required for systemic iron homeostasis. Cell Metabolism, *31*(1), 115–  
130.e6. https://doi.org/10.1016/j.cmet.2019.10.005  
5. Degnan, P. H., Taga, M. E., & Goodman, A. L. (2014). Vitamin B12 as a modulator of gut microbial  
ecology. Cell Metabolism, *20*(5), 769–778. https://doi.org/10.1016/j.cmet.2014.10.002  
6. Deschemin, J. C., & Vaulont, S. (2013). Role of hepcidin in the setting of hypoferremia during acute  
inflammation. PLoS One, *8*(4), e61050. https://doi.org/10.1371/journal.pone.0061050  
7. Dostal, A., Lacroix, C., Bircher, L., Pham, V. T., Follador, R., Zimmermann, M. B., & Chassard, C. (2014).  
Iron modulates butyrate production by a child gut microbiota in vitro. mBio, *5*(6), e01492-  
14. https://doi.org/10.1128/mBio.01492-14  
8. Ganz, T. (2013). Systemic iron homeostasis. Physiological Reviews, *93*(4), 1721–  
1741. https://doi.org/10.1152/physrev.00008.2013  
www.ijltemas.in  
Page 460  
INTERNATIONAL JOURNAL OF LATEST TECHNOLOGY IN ENGINEERING,  
MANAGEMENT & APPLIED SCIENCE (IJLTEMAS)  
ISSN 2278-2540 | DOI: 10.51583/IJLTEMAS | Volume XIV, Issue XI, November 2025  
9. Ganz, T., & Nemeth, E. (2012). Hepcidin and iron homeostasis. Biochimica et Biophysica Acta (BBA) -  
Molecular Cell Research, *1823*(9), 1434–1443. https://doi.org/10.1016/j.bbamcr.2012.01.014  
10. Hoppe, M., Önning, G., Berggren, A., & Hulthén, L. (2017). Probiotic strain Lactobacillus plantarum 299v  
increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind  
study in women of reproductive age. British Journal of Nutrition, *118*(10), 782–  
791. https://doi.org/10.1017/S0007114517002830  
11. Kassebaum, N. J., GBD 2013 Anemia Collaborators. (2014). The global burden of  
anemia. Hematology/Oncology  
Clinics  
of  
North  
America, *28*(2),  
247–  
308. https://doi.org/10.1016/j.hoc.2013.11.002  
12. Kullen, M. J., Leemon, D. T., & O'Connor, H. T. (2019). Lactobacillus plantarum 299v improves iron  
status in piglets fed a high-phytate diet. British Journal of Nutrition, *122*(10), 1102–  
1109. https://doi.org/10.1017/S0007114519002000  
13. Lloyd-Price, J., Abu-Ali, G., & Huttenhower, C. (2016). The healthy human microbiome. Genome  
Medicine, *8*(1), 51. https://doi.org/10.1186/s13073-016-0307-y  
14. Lynch, S. V., & Pedersen, O. (2016). The human intestinal microbiome in health and disease. New  
England Journal of Medicine, *375*(24), 2369–2379. https://doi.org/10.1056/NEJMra1600266  
15. Magnúsdóttir, S., Ravcheev, D., de Crécy-Lagard, V., & Thiele, I. (2015). Systematic genome assessment  
of B-vitamin biosynthesis suggests co-operation among gut microbes. Frontiers in Genetics, *6*,  
148. https://doi.org/10.3389/fgene.2015.00148  
16. Mirzaei, M., Faghfoori, Z., & Khosroushahi, A. Y. (2022). The effects of synbiotic supplementation on  
inflammatory markers and hemoglobin in end-stage renal disease patients on hemodialysis: A randomized  
controlled  
102813. https://doi.org/10.1016/j.ctim.2022.102813  
17. Mitsuyoshi, M., Nakamura, T., & Kimura, T. (2021). Bifidobacterium longum BB536 and iron status in  
weaning infants: randomized controlled trial. Nutrients, *13*(5),  
1508. https://doi.org/10.3390/nu13051508  
trial. Complementary  
Therapies  
in  
Medicine, *65*,  
A
18. Nemeth, E., Tuttle, M. S., Powelson, J., Vaughn, M. B., Donovan, A., Ward, D. M., ... & Kaplan, J. (2004).  
Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its  
internalization. Science, *306*(5704), 2090–2093. https://doi.org/10.1126/science.1104742  
19. Paganini, D., & Zimmermann, M. B. (2017). The effects of iron fortification and supplementation on the  
gut microbiome and diarrhea in infants and children: a review. The American Journal of Clinical  
Nutrition, *106*(Suppl 6), 1688S–1693S. https://doi.org/10.3945/ajcn.117.156067  
20. Parada Venegas, D., De la Fuente, M. K., Landskron, G., González, M. J., Quera, R., Dijkstra, G., ... &  
Hermoso, M. A. (2019). Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation  
and its relevance for inflammatory bowel diseases. Frontiers in Immunology, *10*,  
277. https://doi.org/10.3389/fimmu.2019.00277  
21. Peyrin-Biroulet, L., Williet, N., & Cacoub, P. (2015). Guidelines on the diagnosis and treatment of iron  
deficiency across indications: a systematic review. The American Journal of Clinical Nutrition, *102*(6),  
1585–1594. https://doi.org/10.3945/ajcn.114.103366  
22. Rezaei, M., Sanagoo, S., Jouybari, L., & Beedresh, M. (2019). The effect of probiotic supplementation on  
iron status and anemia in pregnant women: A randomized controlled trial. Journal of Maternal-Fetal &  
Neonatal Medicine, *32*(17), 2887–2892. https://doi.org/10.1080/14767058.2018.1450384  
23. Rossi, M., Amaretti, A., & Raimondi, S. (2011). Folate production by probiotic bacteria. Nutrients, *3*(1),  
118–134. https://doi.org/10.3390/nu3010118  
24. Rusu, I. G., Suharoschi, R., Vodnar, D. C., Pop, C. R., Socaci, S. A., Vulturar, R., ... & Muresan, C. I.  
(2020). Iron supplementation influence on the gut microbiota and probiotic intake effect in iron  
deficiency—A literature-based review. Nutrients, *12*(7), 1993. https://doi.org/10.3390/nu12071993  
25. Sebastian, S., & Mostoslavsky, R. (2021). The gut microbiome and systemic inflammation in  
aging. Nature Reviews Immunology, *21*(11), 705–706. https://doi.org/10.1038/s41577-021-00625-7  
www.ijltemas.in  
Page 461  
INTERNATIONAL JOURNAL OF LATEST TECHNOLOGY IN ENGINEERING,  
MANAGEMENT & APPLIED SCIENCE (IJLTEMAS)  
ISSN 2278-2540 | DOI: 10.51583/IJLTEMAS | Volume XIV, Issue XI, November 2025  
26. Sender, R., Fuchs, S., & Milo, R. (2016). Revised estimates for the number of human and bacteria cells in  
the body. PLoS Biology, *14*(8), e1002533. https://doi.org/10.1371/journal.pbio.1002533  
27. Shah, Y. M., Ferrand, A., & Aoi, Y. (2021). The role of gut microbiota and derived metabolites in  
inflammation  
and  
anemia. Current  
Opinion  
in  
Physiology, *21*,  
100428. https://doi.org/10.1016/j.cophys.2021.100428  
28. Søndergaard, M. J., Jørgensen, M. S., & Poulsen, M. W. (2021). Lactobacillus plantarum 299v  
(LP299V®) and its effect on iron status in healthy women of reproductive age: A randomized, double-  
blind, placebo-controlled study. Nutrients, *13*(11), 4027. https://doi.org/10.3390/nu13114027  
29. Strozzi, G. P., & Mogna, L. (2008). Quantification of folic acid in human feces after administration of  
Bifidobacterium probiotic strains. Journal of Clinical Gastroenterology, *42*(Suppl 3 Pt 2), S179–  
S184. https://doi.org/10.1097/MCG.0b013e31818087d8  
30. Weiss, G., & Goodnough, L. T. (2005). Anemia of chronic disease. New England Journal of  
Medicine, *352*(10), 1011–1023. https://doi.org/10.1056/NEJMra041809  
31. World Health Organization (WHO). (2024). Anaemia. Retrieved from https://www.who.int/health-  
topics/anaemia  
32. Yan, Q., & Charles, J. F. (2018). Gut microbiome and bone: to build, destroy, or both? Current  
Osteoporosis Reports, *16*(4), 376–384.  
www.ijltemas.in  
Page 462