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

Abstract

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.

Figure 1.. ABO blood antigens:

• The A and B antigens are determined by which terminal sugar is expressed on a precursor oligosaccharide chain, the H antigen. • The FUT1 gene encodes a fucosyltransferase responsible for the assembly of the H-antigen on RBC. • The expression of A or B or both is determined by the ABO gene, which has three alleles that encode the glycosyltransferases responsible for the assembly of the A or B antigen and leaves the H precursor unmodified. • These antigens are expressed throughout the body and can be anchored in cell membranes by proteins or lipids or can be secreted.

Figure 2.. Antibodies against foreign blood antigens

• Individuals carry circulating serum antibodies against the blood antigens they don’t express. These are mainly IgG and IgM and exposure can induce pro-hemolytic complement cascades. • These are referred to as “natural antibodies” because they are present despite the absence of exposure to RBC expressing these antigens. • Although there is some controversy, it has been hypothesized that natural antibodies are generated by environmental exposures to compounds structurally similar to blood antigens, some of which may be microbial in origin.

Figure 3.. Secretor status

• ~80% of humans are secretors, meaning their H antigens are released from the originating cell. FUT2, the causal locus for secretion, encodes a fucosyltransferase that produces soluble H antigen which is decorated by ABO oligosaccharides. • Secretor status is autosomal dominant and non-secretors are homozygous for nonsense mutations at the FUT2 locus. • These soluble antigens can be found in bodily fluids beyond the circulatory system such as saliva, tears, urine, and mucus.