Galactoside 2-alpha-L-fucosyltransferase 2 is an enzyme that in humans is encoded by the FUT2 (fucosyltransferase 2) gene.[5][6]
FUT2 is a key enzyme that catalyzes the transfer of L-fucose from guanosine diphosphate-beta-L-fucose to the terminal galactose on both O- and N-linked glycans of cell surface glycoproteins and glycolipids. This enzymatic activity is essential for the synthesis of the H antigen, a precursor required for the formation of ABO blood group antigens,[7] and determines "secretor status"—the presence of blood group antigens in bodily fluids such as saliva. Beyond its role in blood group antigen synthesis, FUT2 influences cell-cell interactions, modulates the composition of the gut microbiome, and impacts susceptibility to infections and autoimmune diseases, highlighting its broad significance in human health and disease.
Approximately 20% of Caucasians are non-secretors due to the G428A (rs601338) and C571T (rs492602?) nonsense mutations in FUT2 and therefore have strong although not absolute protection from the norovirus GII.4.[citation needed]\
Role in secretor status
The FUT2 gene determines an individual's secretor status by encoding an enzyme responsible for the expression of histo-blood group antigens in bodily secretions. Approximately 70–80% of people are secretors, meaning they possess at least one functional FUT2 allele.[8] Those who are homozygous for a nonfunctional allele are termed non-secretors, which has important health implications.
Clinical significance
Non-secretors display altered susceptibility to both infectious and autoimmune diseases. While they exhibit increased resistance to certain viral pathogens like norovirus,[8] they are more prone to developing chronic inflammatory conditions such as Crohn’s disease[9][10] and type 1 diabetes.[11]
Impact on the gut microbiome
Loss-of-function mutations in FUT2 dramatically alter the composition of the gut microbiome. Non-secretors have distinct microbial profiles compared to secretors, with studies reporting a reduction in Escherichia species and a rise in pro-inflammatory taxa.[12] Notably, non-secretors also exhibit increased levels of butyrate-producing bacteria, which are generally considered beneficial.
Consequences for microbial metabolism
Although FUT2 does not directly regulate microbial metabolism, its influence on microbial community structure can indirectly affect metabolite production. The enrichment of butyrate producers in non-secretors may represent a compensatory mechanism, but this benefit may be insufficient to counterbalance the elevated inflammatory potential of the overall microbiome. Thus, FUT2 loss-of-function variants may skew the microbiome toward a pro-inflammatory state, potentially exacerbating conditions such as inflammatory bowel disease (IBD) and masking the protective effects of beneficial metabolites like butyrate.
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Ball SP, Tongue N, Gibaud A, Le Pendu J, Mollicone R, Gerard G, et al. (Feb 1992). "The human chromosome 19 linkage group FUT1 (H), FUT2 (SE), LE, LU, PEPD, C3, APOC2, D19S7 and D19S9". Ann Hum Genet. 55 (Pt 3): 225–33. doi:10.1111/j.1469-1809.1991.tb00417.x. PMID1763885. S2CID30777695.
^Cheng S, Hu J, Wu X, Pan JA, Jiao N, Li Y, et al. (September 2021). "Altered gut microbiome in FUT2 loss-of-function mutants in support of personalized medicine for inflammatory bowel diseases". Journal of Genetics and Genomics = Yi Chuan Xue Bao. Special issue on Microbiome. 48 (9): 771–780. doi:10.1016/j.jgg.2021.08.003. PMID34419617.
Further reading
Reguigne-Arnould I, Couillin P, Mollicone R, Fauré S, Fletcher A, Kelly RJ, et al. (1995). "Relative positions of two clusters of human alpha-L-fucosyltransferases in 19q (FUT1-FUT2) and 19p (FUT6-FUT3-FUT5) within the microsatellite genetic map of chromosome 19". Cytogenetics and Cell Genetics. 71 (2): 158–162. doi:10.1159/000134098. PMID7656588.
Koda Y, Soejima M, Johnson PH, Smart E, Kimura H (September 1997). "Missense mutation of FUT1 and deletion of FUT2 are responsible for Indian Bombay phenotype of ABO blood group system". Biochemical and Biophysical Research Communications. 238 (1): 21–25. doi:10.1006/bbrc.1997.7232. PMID9299444.
Liu Y, Koda Y, Soejima M, Pang H, Schlaphoff T, du Toit ED, et al. (August 1998). "Extensive polymorphism of the FUT2 gene in an African (Xhosa) population of South Africa". Human Genetics. 103 (2): 204–210. doi:10.1007/s004390050808. PMID9760207. S2CID25253767.
Lindesmith L, Moe C, Marionneau S, Ruvoen N, Jiang X, Lindblad L, et al. (May 2003). "Human susceptibility and resistance to Norwalk virus infection". Nature Medicine. 9 (5): 548–553. doi:10.1038/nm860. PMID12692541. S2CID28663420.
Guo ZH, Xiang D, Zhu ZY, Wang JL, Zhang JM, Liu X, et al. (October 2004). "[Analysis on FUT1 and FUT2 gene of 10 para-Bombay individuals in China]". Zhonghua Yi Xue Yi Chuan Xue Za Zhi = Zhonghua Yixue Yichuanxue Zazhi = Chinese Journal of Medical Genetics. 21 (5): 417–421. PMID15476160.
Chen DP, Tseng CP, Wang WT, Peng CT, Tsao KC, Wu TL, et al. (2005). "Two prevalent h alleles in para-Bombay haplotypes among 250,000 Taiwanese". Annals of Clinical and Laboratory Science. 34 (3): 314–318. PMID15487706.
Pang H, Soejima M, Koda Y, Kimura H (October 2004). "A novel tetrameric short tandem repeat located in the 3' flanking region of the human ABO-secretor gene (FUT2) and association between FUT2 and FUT2/01 loci". Human Biology. 76 (5): 789–795. doi:10.1353/hub.2005.0008. PMID15757249. S2CID1201579.
