How Lewis Blood Grouping System like ABO influence our gut microbiome?

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Abstract:
The Lewis blood grouping system, like the ABO system, plays a crucial role in shaping the human gut microbiome through genetically determined fucosylated glycans expressed on mucosal surfaces. These glycans act as microbial binding sites and nutrient sources, influencing the colonization and composition of gut bacteria. Secretor status, governed by FUT2 and FUT3 genes, determines the presence of Lewis antigens, which affects microbial diversity, immune interactions, and susceptibility to infections and inflammatory diseases. This abstract explores how host genetics, particularly the Lewis and ABO blood group systems, contribute to the dynamic and evolving relationship between humans and their gut microbiota.

First and foremost, what is Lewis Blood Grouping System?
The Lewis Blood Grouping System is a minor but clinically relevant blood group system based on the presence of Lewis antigens (Leᵃ and Leᵇ), which are carbohydrate molecules found in body fluids and on the surface of red blood cells.

Genes Involved in this blood grouping system:
• FUT2 (Secretor gene)
• FUT3 (Lewis gene)
These genes control the synthesis of Leᵃ and Leᵇ antigens.

The Lewis blood group system depends on two key genes: FUT3 and FUT2. These genes encode enzymes that modify precursor sugar chains by adding fucose molecules, forming Lewis antigens. If only FUT3 is active, Leᵃ is formed. If both FUT3 and FUT2 are active, Leᵇ is produced. These antigens, present in secretions and on cell surfaces, influence how certain microbes interact with our gut.

What are precursor chains? - Also called, precursor sugar chains, they are basic sugar structures found on cells. Think of them as a blank base that enzymes decorate by adding specific sugars, turning them into blood group antigens like Leᵃ or Leᵇ. The precursor sugar chains modified in the Lewis blood group system are found on epithelial cells, especially in the: GIT (Gastrointestinal Tract), respiratory tract, salivary glands and urogenital tract.

These epithelial cells secrete Lewis antigens into bodily fluids (like saliva, mucus, etc.), and the antigens can also attach to red blood cells secondarily (they’re not produced directly on RBCs like in the ABO system).

Precursor chains refer to basic sugar chains (oligosaccharides) found on the surfaces of cells or in body fluids. These chains act as starting templates that can be modified by enzymes to produce different blood group antigens, like Lewis, ABO, etc.

In the Lewis blood group, enzymes (fucosyltransferases) add fucose molecules to specific positions on these precursor chains to form Leᵃ and Leᵇ antigens.

Coming to the main aspect:

The Lewis blood group system—especially the Le^a and Le^b antigens—plays a fascinating and important role in shaping our gut microbiome.

🔹 Le(a− b+) → Secretors (FUT2 & FUT3 active)

  • Antigen present: Leᵇ

  • Microbiome impact:

    • Rich in beneficial bacteria (Bifidobacteria, Lactobacilli)

    • Stronger mucosal immunity

    • Better gut barrier & nutrient absorption

🔹 Le(a+ b−) → Non-secretors (FUT3 active, FUT2 inactive)

  • Antigen present: Leᵃ

  • Microbiome impact:

    • Less microbial diversity

    • Reduced Bifidobacteria

    • Higher risk of IBS, Crohn’s, infections

🔹 Le(a− b−) → Double non-secretors (FUT2 & FUT3 inactive)

  • Antigen present: None

  • Microbiome impact:

    • Lowest diversity

    • Poor mucosal defense

    • Gut more prone to dysbiosis & inflammation

ABO + Lewis Blood Type → Microbiome Influence:
Le(a− b−) individuals are not secretors (check the intentionally mentioned erroneous first row), as they lack functional FUT2 and FUT3 genes.
This phenotype means no ABO or Lewis antigens are secreted into body fluids.
It leads to low gut microbiome diversity and weaker mucosal immunity.
These individuals are more prone to infections, IBS, and inflammation.

Simple Summary:

  • Secretors (Leᵇ present) feed and support good gut microbes, especially in A/B/AB types.

  • Non-secretors or Le(a− b−) types have fewer antigens in the gut, which limits microbial growth and diversity.

  • ABO antigens + Lewis antigens in secretions = rich microbial environment that helps digestion, immunity, and disease prevention.


The story of host-microbe co-evolution:


Gut microbes spread over the globe along with humans.


The relationship between the gut microbiome and Lewis blood group factors is a clear example of host-microbe co-evolution. Lewis antigens—fucosylated carbohydrates produced by the FUT2 and FUT3 genes—are expressed on intestinal epithelial cells and in bodily secretions. These antigens act as attachment sites and energy sources for certain microbes. Beneficial bacteria like Bacteroides and Bifidobacterium have evolved to utilize these structures, supporting gut health by aiding digestion, producing short-chain fatty acids, and regulating the immune response. Individuals who express Lewis antigens, particularly secretors (Leᵇ+), tend to show greater microbial diversity and resilience against gut inflammation. However, this same mechanism can be exploited by harmful microbes. Pathogens such as Helicobacter pylori, Norovirus, and certain strains of E. coli can bind to Lewis antigens to initiate colonization, increasing the risk of gastrointestinal infections, ulcers, and inflammatory bowel disease. Non-secretors (Leᵃ+, Leᵇ− or Leᵃ−b−), on the other hand, often display reduced microbial diversity and are more susceptible to conditions like Crohn’s disease and celiac disease. Thus, Lewis antigens not only shape the microbial landscape of the gut but also influence susceptibility to both health and disease, making them a critical intersection point in the evolutionary dialogue between humans and their microbiota.

Lewis Blood Group and the Gut: A Relationship Still Unfolding

This complex interplay between Lewis blood group factors and the gut microbiome is not just a static trait, but an ongoing evolutionary conversation—one that continues to shape human health in subtle yet powerful ways. As research deepens, it becomes clear that these antigens do more than define blood types; they serve as molecular gatekeepers that influence microbial colonization, immune signaling, and disease susceptibility. Recognizing this dynamic relationship not only enhances our understanding of gut ecology but also raises important questions about how genetic variations like secretor status might inform future strategies in nutrition, medicine, and microbiome-based therapies.

CITE: Bandyopadhyay A. "How Lewis Blood Group influence our gut microbiome?" Fresh Science Trends (2025) https://freshsciencetrends.blogspot.com/2025/04/how-lewis-blood-grouping-system-like.html

Comments

  1. Abhishek10 April 2025 at 00:05

    In the gut, sugar structures talk—and microbes listen :))

    ReplyDelete

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