Blood type and the microbiome- untangling a complex relationship with lessons from pathogens

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Highlights

  • A historical perspective on associations between ABO blood type and bacteria.

  • Mechanisms that drive relationships between host blood type and commensal and pathogenic bacteria.

  • Review of conflicting evidence for an influence of host blood type on the intestinal microbiome.

  • How this knowledge may inform the development of microbiome-targeted intervention strategies.

The complex communities of microbes that constitute the human microbiome are influenced by host and environmental factors. Here, we address how a fundamental aspect of human biology, blood type, contributes to shaping this microscopic ecosystem. Although this question remains largely unexplored, we glean insights from decades of work describing relationships between pathogens and blood type. The bacterial strategies, molecular mechanisms, and host responses that shaped those relationships may parallel those that characterize how blood type and commensals interact. Understanding these nuanced interactions will expand our capacity to analyze and manipulate the human microbiome.

Section snippets

ABCs of ABO

At the beginning of the 20th century Dr. Karl Landsteiner discovered the ABO blood group, which not only informed safe blood transfusions but profoundly contributed to our understanding of the human immune system [1]. Over a century later there are 36 recognized blood groups but the ABO/H, secretor and Lewis systems remain the most clinically relevant and are known together as the histo-blood group antigens (HBGA) [2,3]. An individual’s blood type can be defined by two factors: 1) specific

Attachment and adherence

For many microbes, success in the host begins with the ability to adhere, and host glycans are ideal receptors. The diversity of blood glycan structures likely arose as a means to inhibit the binding of pathogens to host cells, but these molecules also present a scaffold for commensals [21,22,6]. It has been proposed that the secretion of these glycans also evolved as a strategy to bind up pathogens before they encounter infectable cells [23]. These evolutionary skirmishes have resulted in

Masquerading and mimicry

Once anchored in the host, a microbe needs to avoid detection and clearance. An effective tactic to evade host immune responses is directly co-opting or mimicking host antigens [30]. A particularly nefarious strategy employed by Group A Streptococcus is to lyse host red blood cells and then cloak themselves in the erythrocyte membrane to evade detection by circulating immune cells [31••]. A more refined strategy is to express molecules that mimic host glycans [32]. For instance, E. coli O86

Farmers and foragers

Bacteria not only target HBGAs as receptors but can utilize them as a nutrient source. Some bacteria even have the capacity to induce host expression of these glycans. The infant gut is dominated by sialylated glycans and the mature gut is defined by fucosylated glycans including the ABO blood antigens. This shift to fucosylated glycans, like the induction of anti-ABO antibodies, is dependent on colonization of the gut by microbes [47]. The induction of glycan expression is of direct benefit to

Quandaries and questions

The relationships between bacteria and host blood glycans are abundant and complex. The very existence of different blood types is likely the result of millennia of evolutionary arms races and peace treaties between microbes and mammals. While these relationships and the mechanisms driving them have been well explored in culturable strains of bacteria, they remain relatively unexamined with our commensal bacteria.

Although multiple studies have found that secretor status is significantly

Funding sources

This work was supported by the National Institutes of Health NIAID training grant (Training Program in Immunology; T32-AI07405) award to Kathleen L Arnolds.

Conflict of interest statement

Nothing declared.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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