The FUT2 gene is integral in gut health. FUT2 creates instructions for a process known as fucosylation. Fucosylation involves the addition of a fucose sugar molecule to the micro villi in the intestines. The FUT2 genotypes, termed “non-secretors”, do not secrete their blood type antigens into mucosal fluids, and lack terminal fucose on intestinal micro villi. Research between FUT2 genotype, microbiological associations and various health conditions have been established. Clinical and experimental investigations are underway to determine what may improve the gut health of FUT2 non-secretors.
Your gut flora plays a critical role in your immune system. In many respects, the 100 trillion microorganisms that line your gut, function as a second organism within an organism. Your gut flora regulates immune responses, inflammation, removal of toxins & heavy metals, roles in your digestion and in the synthesis of B-vitamins, fats and fat-soluble vitamins. These are some of its most important functions.
Our gut flora is influenced by a variety of factors related to: diet, environmental factors, body burden of toxicity, as well as our genetic predispositions.
The role of genetics and our health is a rapidly evolving field of study and interest, and researchers continue to produce breakthroughs in understanding this relationship. New developments continue to emerge regarding the role of our genetics and the functionality of our gut flora microbes.
Recent research has identified a key gene that influences gut bacteria in a major way. This gene is known as FUT2, or fucosyltransferase 2. Genetic mutations in FUT2 has shown to be a link towards decreases in bifidobacterium, a key, beneficial microbial colony that lines the gut. Additionally, research shows that FUT2 mutations are strongly associated with Crohn’s Disease, an inflammatory and autoimmune bowel condition.
Role Of FUT2 In the Gut
Approximately 20-30% of the U.S. population carry FUT2 variations known as “non-secretory” status. This is based on 1 one or 2 SNP’s located within the FUT2 gene. FUT2 is involved in the formation of an immune complex known as the H antigen. FUT2 forms a sugar-polymer known as oligosaccharide. Oligosaccharides become food for gut flora. FUT2 regulates the expression of certain “blood-group antigens”, via the secretion of the blood type antigen into mucosal fluids (including the gut). The FUT2 “non-secretors” lack sufficient fucose moieties, and have impaired formation of intestinal glycolipids and glycoproteins. FUT2 non-secretors have distinct interactions with microorganisms, including various perceived pathogens.
Health Conditions Associated with FUT2 Non-Secretors
- FUT2 non-secretors have been shown to have lower concentrations of gut keystone strains, bifidobacterium, and akkermansia (4)
- FUT2 non-secretors have shown a greater association to Crohn’s Disease (5)
- A Finish study found FUT2 non-secretory status is associated to Celiac Disease (2)
- FUT2 non-secretors have shown higher levels of serum lipase and increased risk of pancreatitis (1)
- Female FUT2 non-secretors have been shown to be associated with urinary tract infections (UTI’s) (6)
- Blood type antigen secretory status has been shown to affect post antibiotic bacterial expansion, and the complexity of antibiotic resistant bacteria (7)
- FUT2 non-secretors have shown to have an increased risk of duodenal ulcers
- A Japanese cohort was found to be associated with the development of type 1 diabetes in children (3)
- FUT2 non-secretors have been shown to be at higher risk of dominant stenosis and sclerosing cholangitis (9)
- Compared to FUT2 “secretors”, the “non-secretors” have reduced susceptibility to calciviruses, and respiratory viruses (15)
- Compared to FUT2 “secretors”, the “non-secretors” have increased susceptibility to: candida infections, streptococcus and Neisseria meningitis (15)
What Do I Do If I Have The FUT2 Gene Mutation?
The FUT2 “non-secretor” status is defined primarily by:
- The FUT2 gene, rs601338, “AA” genotype
If you are AA for the above FUT2 variant, you are considered a blood type antigen “non-secretor”.
NOTE: If you have genetic test results from 23andme or AncestryDNA, you can purchase a report to learn your FUT2 status.
Michael McEvoy’s Comments:
FUT2 non-secretor therapies may include: intensive probiotic therapies, individualized nutritional therapies, as well as the exclusion of factors which may further damage and weaken the gut ecology. These damaging factors may include:
- Increased exposure to toxic metals and chemicals. Research has shown that toxic metals damage gut flora. Mercury, for example has been shown to produce antibiotic-resistant forms of pathogenic bacteria (12, 13).
- Increased use of antibiotics. Antibiotics of all types are well established to damage the intestinal flora. A recent study has shown that only after 11 days of antibiotic treatment, gut flora protein production decreased significantly, and decreases of iron uptake and the digestion of certain foods was significantly diminished as well (14).
- Reduce exposure to glyphosate – Glyphosate is a pesticide chemical that is known to disrupt intestinal and urinary tract microbiomes, and has been identified as neurotoxic to maternal brain neuro-plasticity (10, 11).
It is significant to address that just because you have FUT2 gene mutations, there is no guarantee that you will develop Crohn’s disease or any disease. Genetic variants and SNP’s (singular nucleotide polymorphisms) should not confine one into thinking there is nothing that can be done to improve one’s health. On the contrary, SNP’s and genetic variants should serve as a “wake-up call” for you to become serious and more pro-active with your health and nutrition practices.
Fortunately, there are existing nutritional-related strategies available. Many researchers believe that these therapies are the future of medicine. Even though gene variants may not be correctable, in many cases, it is possible to “bypass” them, by providing nutrients which may otherwise be missing.
Because the FUT2 non-secretors tend to have abnormal gut flora concentrations, and a greater proclivity towards various complications, they need to be pro-active with their heath and paying closer attention should be warranted. Nutritional-related strategies that improve upon bowel flora concentrations can have powerful impacts upon the overall health of the individual. These therapies may in fact serve as the best preventative strategies to prevent the development of Crohn’s disease, and other autoimmune conditions. To date, there has yet to be the development of clinical trials to study therapeutics for FUT2 non-secretors. Here are a few suggestions for future clinical studies, based upon my research into FUT2 non-secretors:
- 2′ Fucosyllactose (2’FL) for FUT2 Non-Secretors- 2’FL is a fucose-based prebiotic sugar that theoretically could benefit FUT2 non-secretors. Future studies could be conducted to show if FUT2 non-secretors benefit from 2’FL prebiotic supplementation, and if there are measurable physiological changes that occur
- Intensive Probiotic Supplementation With Prebiotics for FUT2 Non-Secretors– The aim here would be straightforward. Since it is known that FUT2 non-secretors tend towards lower bifibobacterium and akkermansia, would intensive probiotic + prebiotic supplementation benefit non-secretors?
- Helminthic Therapy for FUT2 Non-Secretors – It was identified in 2008 by researchers that the FUT2 gene evolved due to to “pathogen richness” (15). Because of this, Evolutionary Mismatch may explain why modern day health conditions are associated to FUT2 non-secretor status. In this hypothesis, FUT2 non-secretors may be better adapted to thrive in pathogen-rich environments, specifically where helminths and parasites are more endemic. In the 1st world there is a lack of pathogen diversity, compared to that of our evolutionary past, and consequently Evolutionary Mismatches occur with certain genotypes in a mismatched environment. This scenario results in the development of modern day, disease phenotypes. One proposed solution to Evolutionary Mismatch is Helminthic Therapy, which is the ingestion or cutaneous inoculation with commensal worms or their ova. Will this work for FUT2? It hasn’t been studied, but is worthy of investigation because obviously FUT2 secretory status greatly affects microbial interactions with the host, and this fact implies an evolutionary dynamic with microorganisms, that likely was quite different prior to the industrial farming era.