FUT2

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.{{cite journal | vauthors = Currier RL, Payne DC, Staat MA, Selvarangan R, Shirley SH, Halasa N, Boom JA, Englund JA, Szilagyi PG, Harrison CJ, Klein EJ, Weinberg GA, Wikswo ME, Parashar U, Vinjé J, Morrow AL | title = Innate Susceptibility to Norovirus Infections Influenced by FUT2 Genotype in a United States Pediatric Population | journal = Clinical Infectious Diseases | volume = 60 | issue = 11 | pages = 1631–1638 | date = June 2015 | pmid = 25744498 | pmc = 4447782 | doi = 10.1093/cid/civ165 }} Those who are homozygous for a nonfunctional allele are termed non-secretors, which has important health implications.

Non-secretors display altered susceptibility to both infectious and autoimmune diseases. While they exhibit increased resistance to certain viral pathogens like norovirus, they are more prone to developing chronic inflammatory conditions such as Crohn’s disease{{cite journal | vauthors = Tong M, McHardy I, Ruegger P, Goudarzi M, Kashyap PC, Haritunians T, Li X, Graeber TG, Schwager E, Huttenhower C, Fornace AJ, Sonnenburg JL, McGovern DP, Borneman J, Braun J | title = Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism | journal = The ISME Journal | volume = 8 | issue = 11 | pages = 2193–206 | date = November 2014 | pmid = 24781901 | pmc = 4992076 | doi = 10.1038/ismej.2014.64 }}{{cite journal | vauthors = McGovern DP, Jones MR, Taylor KD, Marciante K, Yan X, Dubinsky M, Ippoliti A, Vasiliauskas E, Berel D, Derkowski C, Dutridge D, Fleshner P, Shih DQ, Melmed G, Mengesha E, King L, Pressman S, Haritunians T, Guo X, Targan SR, Rotter JI | title = Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease | journal = Human Molecular Genetics | volume = 19 | issue = 17 | pages = 3468–76 | date = September 2010 | pmid = 20570966 | pmc = 2916706 | doi = 10.1093/hmg/ddq248 }} and type 1 diabetes.{{cite journal | vauthors = Giampaoli O, Conta G, Calvani R, Miccheli A | title = Can the FUT2 Non-secretor Phenotype Associated With Gut Microbiota Increase the Children Susceptibility for Type 1 Diabetes? A Mini Review | journal = Frontiers in Nutrition | volume = 7 | pages = 606171 | date = 2020 | pmid = 33425974 | pmc = 7785815 | doi = 10.3389/fnut.2020.606171 | doi-access = free }}

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.{{cite journal | vauthors = Cheng S, Hu J, Wu X, Pan JA, Jiao N, Li Y, Huang Y, Lin X, Zou Y, Chen Y, Zhu L, Zhi M, Lan P | title = Altered gut microbiome in FUT2 loss-of-function mutants in support of personalized medicine for inflammatory bowel diseases | journal = Journal of Genetics and Genomics = Yi Chuan Xue Bao | volume = 48 | issue = 9 | pages = 771–780 | date = September 2021 | pmid = 34419617 | doi = 10.1016/j.jgg.2021.08.003 | series = Special issue on Microbiome }} Notably, non-secretors also exhibit increased levels of butyrate-producing bacteria, which are generally considered beneficial.

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.

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{{Glycosyltransferases}}

{{gene-19-stub}}