A Gene That Can Impact Gut Health (FUT2)

The FUT2 gene encodes an enzyme named galactoside 2-alpha-L-fucosyltransferase 2. This enzyme is involved in the production of ABO blood group antigens that are released (secreted) into saliva, mucus, and other fluids of the gut [R].

ABO blood group antigens are molecules found on the surfaces of red blood cells. The type of ABO antigen that is found on these red blood cells helps to characterize blood. For example, B antigen is found on the surface of red blood cells in individuals with type B blood [R].

Although ABO blood group antigens are more commonly associated with blood type, ABO antigens are also found in the gut, where they can play a major role in gut health [R]. 

Depending on their ability or inability to secrete ABO blood group antigens into gut fluids, carriers of FUT2 variants are categorized respectively as “secretors” or “non-secretors” (“secretor status”) [R].  

The FUT2 gene encodes an enzyme that is necessary for producing molecules that are released (secreted) into fluids of the gut. Carriers of FUT2 variants are known as “secretors” or “non-secretors,” depending on whether their encoded enzyme has the ability to release these molecules.

Gut Bacteria

The gut is home to trillions of microscopic organisms that help to maintain gut health. The majority of these microscopic organisms are bacteria [R]. 

Among other beneficial actions, gut bacteria can help to digest nutrients after eating food, as well as form a barrier in the gut that protects against some infections [R, R]. 

The gut contains trillions of beneficial bacteria that are essential to maintaining gut health. 

FUT2 & Gut Bacteria 

The composition of bacteria in the gut differs greatly when comparing non-secretors to secretors. These differences may impact the gut health of those carrying certain FUT2 polymorphisms, such as rs601338 and rs1047781. 

To study this, researchers analyzed the fecal bacteria of human secretors and non-secretors. Bacteria of non-secretors were found to be reduced in both number and diversity, in comparison to secretors. While this might suggest that secretors have “healthier guts," the researchers also found that certain strains of bacteria can digest nutrients more effectively in non-secretors than secretors [R, R]. 

Other studies have found similar, seemingly conflicting results. In comparison to secretors, non-secretors have been associated with a higher risk of developing celiac disease, but a lower risk of developing ulcerative colitis. Non-secretors have also been associated with higher vitamin B12 absorption, in comparison to secretors [R, R, R]. 

In addition, while rs601338-A confers protection against the development of Crohn’s disease, rs1047781-T confers a greater risk of Crohn’s disease development [R, R, R].

In an animal study, a diet high in sugar and low in starch was observed to eliminate the differences in gut bacteria that are usually observed in non-secretors and secretors. This suggests that the effect of FUT2 variants on gut bacteria is diet-dependent, although human studies are needed to support this claim [R]. 

FUT2 gene variants may result in an altered composition of gut bacteria. While some FUT2 variants may place carriers at greater risk of developing certain health issues and diseases related to the gut, these same variants may also provide protection against other gut issues and diseases. 

How This Works

The increased risk of celiac disease in non-secretors in comparison to secretors can, in part, be explained by their differing compositions of gut bacteria. 

A low amount and diversity of gut bacteria can increase susceptibility to infections of the gut. Gut infections have been suggested to alter the way that the immune system responds to future threats — a potential early step in the development of celiac disease [R, R].

Poor vitamin B12 absorption in secretors has been linked to infections specifically caused by Helicobacter pylori (H. pylori) bacteria. 

ABO antigens, found in mucus that lines the guts of secretors, can act as attachment sites for both harmful and beneficial bacteria to latch onto. The attachment of harmful bacteria, such as H. pylori, onto ABO antigens can cause complex inflammatory reactions in the gut lining. These inflammatory reactions can result in breakdown of the gut lining and the formation of stomach ulcers, which ultimately prevent the release of a compound required for vitamin B12 to be absorbed by the intestines [R, R].

Non-secretors are more susceptible to gut infections that can alter future immune system responses, due to their low amount and diversity of gut bacteria. This can place non-secretors at increased risk of developing celiac disease. Secretors are more likely to have gut infections specifically caused by H. pylori bacteria, which can break down the gut lining and ultimately reduce the absorption of vitamin B12.

SNP Summary and Table

FUT2 rs601338

• ‘AA’ = non-secretor
• ‘AG’ = secretor
• ‘GG’ = secretor

Most individuals (99.2%) of East Asian descent carry the ‘GG’ (secretor) genotype of this variant [R].

In Finnish populations, the minor ‘A’ allele has been associated with a greater risk of developing celiac disease, but may protect against the development of Crohn’s disease and ulcerative colitis [R].  

In European and West African populations, the ‘AA’ (non-secretor) genotype of this variant has been associated with higher vitamin B12 absorption in comparison to secretor genotypes [R].

FUT2 rs1047781

• ‘AA’ = secretor 
• ‘AT’ = secretor 
• ‘TT’ = non-secretor 

91% of individuals worldwide carry the major ‘A’ allele of rs1047781. rs1047781 is closely associated with rs601338 in all individuals but those of Japanese descent. In individuals of Japanese descent, only rs1047781 determines secretor status [R].

The minor ‘T’ allele has been associated with higher vitamin B12 absorption, but a greater risk of developing Crohn’s disease. This allele has also been associated with a reduced amount and diversity of gut bacteria [R, R, R].