Nonsecretor status is a common genetic variation affecting approximately 20% of individuals, primarily those of European descent. People with this status cannot express specific carbohydrate structures, known as histo-blood group antigens (HBGAs), in their bodily fluids and mucosal linings. This lack of secretion, determined by a single gene, creates a distinct internal environment. This difference has profound implications for health, particularly concerning susceptibility to infections and chronic diseases.
The Genetic Basis of Secretor Status
The ability to secrete histo-blood group antigens is controlled by the Fucosyltransferase 2 (\(FUT2\)) gene, often called the “Secretor gene.” This gene instructs the creation of the \(\alpha(1,2)\) fucosyltransferase enzyme, which places a specific sugar molecule onto precursor chains. This final step creates the ABH antigens, allowing them to be shed into secretions and expressed on mucosal surfaces.
Secretor status follows Mendelian inheritance; having even one functional copy of \(FUT2\) (\(Se/Se\) or \(Se/se\)) makes a person a secretor. Nonsecretor status is a recessive trait, requiring the inheritance of two non-functional copies (\(se/se\)).
The nonsecretor phenotype is usually caused by the \(rs601338\) variant, a nonsense mutation in \(FUT2\). This mutation introduces a premature stop codon, halting the protein-building process early. This prevents the production of the necessary, fully functional enzyme. Without the active enzyme, ABH antigens cannot be synthesized in a soluble form, classifying the person as a nonsecretor, regardless of their ABO blood type.
The Function of ABH Antigens
Histo-blood group antigens (HBGAs) are complex carbohydrate structures, or glycans, found anchored to cell surfaces and floating freely in bodily fluids. In secretors, the \(\alpha(1,2)\) fucosyltransferase enzyme ensures these antigens are present in secretions like saliva, breast milk, tears, and the mucus lining the digestive and respiratory tracts.
The presence of ABH antigens in mucosal layers serves two primary biological roles related to the host-microbe relationship. These glycans act as attachment sites, or receptors, that certain pathogens bind to for cell entry. They also represent a readily available source of nutrient-rich carbohydrates for commensal bacteria living on mucosal surfaces.
In secretors, this decoration provides a complex, nutrient-dense environment supporting local microbial communities. Nonsecretors lack the functional \(FUT2\) enzyme, meaning this mucosal decoration is missing, leading to a fundamentally different chemical landscape in the gut.
How Nonsecretor Status Shapes the Gut Microbiome
The difference in ABH antigen secretion profoundly affects the gut microbiome because these glycans serve as a prebiotic food source. In secretors, the readily available fucosylated antigens promote the growth and diversity of microbial species specializing in consuming these complex sugars, leading to a distinct ecosystem.
Nonsecretors lack these fucosylated structures in their intestinal mucus, removing a major food source for certain microbes. This absence results in a different overall composition of gut flora, forcing the microbial community to adapt to a differently provisioned environment. Consequently, the entire metabolic capacity of the microbial community shifts.
Infant secretor status is strongly associated with the early colonization of the gut. For example, nonsecretor infants may show a different profile of Bifidobacteria species, such as an enrichment of Bifidobacterium breve. Since Bifidobacteria utilize glycans, they are sensitive to the presence or absence of secreted antigens.
This compositional shift also affects the gut’s metabolic output; nonsecretor microbiota tend to show higher levels of genes involved in sucrose degradation. The \(FUT2\) gene is recognized as one of the few single host genetic factors that significantly drives variation in the human gut microbiome.
Specific Disease Links and Susceptibilities
Nonsecretor status confers a unique set of susceptibilities and resistances to specific diseases, particularly those involving pathogens that interact with mucosal surfaces.
Infectious Disease Resistance and Susceptibility
A significant benefit for nonsecretors is near-complete resistance to infection by the Norovirus GII.4 strain, the most common cause of acute gastroenteritis. This occurs because the virus relies on binding to secreted ABH antigens to infect host cells; without the antigens, the virus cannot attach effectively.
However, nonsecretors demonstrate greater susceptibility to certain bacterial infections. They are at increased risk for recurrent urinary tract infections and infections caused by bacteria such as Streptococcus pneumoniae and Haemophilus influenzae. Conversely, secretors are more susceptible to the stomach bacterium Helicobacter pylori, which uses the secreted antigens as an adhesion point.
Chronic and Autoimmune Conditions
Beyond infectious agents, nonsecretor status is correlated with an increased risk for several chronic autoimmune and inflammatory conditions. Nonsecretors have a higher susceptibility to Crohn’s disease, an inflammatory bowel disease, likely linked to the altered mucus layer and changes in the gut microbiome.
The \(FUT2\) nonsecretor genotype is also associated with an elevated risk of developing Type 1 Diabetes, with studies indicating an odds ratio of approximately 1.29. This complex pattern of resistance and susceptibility highlights how genetic differences in carbohydrate expression shape an individual’s overall health profile.