rs516246 — FUT2 FUT2 rs516246

FUT2 Secretor Status — The Gene That Shapes What Passes Between Mother and Infant

Your FUT2 gene determines secretor status — one of the most consequential genetic traits in human biology, influencing not just your own gut immunity but the microbial world you pass on to your children. Secretors express ABO blood group antigens¹¹ Secretors express ABO blood group antigens
H-type antigens built by alpha(1,2)-fucosyltransferase — the FUT2 enzyme — on mucosal surfaces and in saliva, tears, and breast milk. These fucosylated glycans are absent in non-secretors, who carry two loss-of-function copies of FUT2 in their intestinal mucus, saliva, and breast milk. rs516246 is an intronic proxy variant that tags this biological divide in European and African populations through strong linkage disequilibrium with the functional W143X nonsense mutation (rs601338). The T allele travels with the secretor phenotype; the C allele travels with the non-secretor phenotype.

This platform already catalogues rs601338 (the functional variant, focused on vitamin B12 metabolism) and rs492602 (a synonymous proxy focused on Crohn's disease and the gut-skin axis). rs516246 adds a distinct clinical dimension: the maternal-infant axis²² maternal-infant axis
The biological channel through which a mother's FUT2 genotype shapes the gut microbiome colonisation of her breastfed infant via the fucosylated oligosaccharides in her breast milk. This angle has direct implications for infant microbiome development and long-term immune programming.

The Mechanism

The FUT2 enzyme adds fucose residues to glycan chains on the intestinal epithelium and into secreted fluids, creating H-type 1 antigens³³ H-type 1 antigens
The carbohydrate structure H type 1 is the intestinal and secretory form of the H antigen, built on Type 1 precursor chains; H type 2 is expressed on red blood cells. Only FUT2 generates H type 1 on mucosal surfaces and in milk. In breast milk, secretor mothers produce abundant 2'-fucosyllactose (2'-FL) and lacto-N-fucopentaose I (LNFP I)⁴⁴ 2'-fucosyllactose (2'-FL) and lacto-N-fucopentaose I (LNFP I)
The two most abundant human milk oligosaccharides (HMOs) produced exclusively by secretor mothers; 2'-fucosyllactose is the most prevalent HMO in secretor breast milk at concentrations of 1.5–4 g/L, collectively termed 2'-fucosylated human milk oligosaccharides (HMOs). Non-secretor mothers produce no 2'-fucosylated HMOs.

These fucosylated HMOs are the primary carbon source for Bifidobacterium species in the breastfed infant's gut — particularly B. longum subsp. infantis, which encodes a complete suite of fucosidase enzymes to harvest fucose from HMOs. Without 2'-FL and LNFP I in the milk, the infant's developing gut receives a fundamentally different microbial substrate, shifting which Bifidobacterium species flourish and which metabolic pathways dominate early colonisation.

The Evidence

The maternal secretor-infant microbiome connection was characterised by Lewis et al. 2015⁵⁵ Lewis et al. 2015
Lewis ZT et al. Maternal fucosyltransferase 2 status affects the gut bifidobacterial communities of breastfed infants. Microbiome, 2015: infants of secretor mothers established Bifidobacterium colonisation earlier and at significantly higher levels (p<0.001), with B. longum dominant in secretor-fed infants and B. breve more prevalent in non-secretor-fed infants — a difference in species composition with distinct metabolic and immune consequences.

Durham et al. 2021⁶⁶ Durham et al. 2021
Durham SD et al. A one-year study of human milk oligosaccharide profiles in the milk of healthy UK mothers and their relationship to maternal FUT2 genotype. Glycobiology, 2021 used rs516246 directly to genotype maternal secretor status in a longitudinal cohort, tracking HMO profiles across twelve months of lactation. The study confirmed that maternal FUT2 genotype at rs516246 reliably predicts 2'-fucosylated HMO composition, though it also noted occasional phenotype-genotype discordance, suggesting that enzyme expression variation can modulate predicted HMO output.

From the infant's own perspective, Thorman et al. 2023⁷⁷ Thorman et al. 2023
Thorman AW et al. Gut Microbiome Composition and Metabolic Capacity Differ by FUT2 Secretor Status in Exclusively Breastfed Infants. Nutrients, 2023 found that infant FUT2 secretor status was an even stronger driver of early microbiome composition than maternal secretor status. Full-secretor infants showed greater alpha diversity (p=0.049) and distinct metabolic profiles, with non-secretor infants displaying enriched sucrose-degradation pathways and different enterotypes.

Beyond infant biology, the broader FUT2 literature documents substantial effects on adult immunity. Non-secretors face elevated Crohn's disease risk⁸⁸ Non-secretors face elevated Crohn's disease risk
McGovern DPB et al. Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease. Hum Mol Genet, 2010 at genome-wide significance (P=4.90×10⁻⁸) and increased type 1 diabetes susceptibility OR 1.29, 95% CI 1.20–1.37⁹⁹ OR 1.29, 95% CI 1.20–1.37
Smyth DJ et al. FUT2 nonsecretor status links type 1 diabetes susceptibility and resistance to infection. Diabetes, 2011. The trade-off is near-complete protection against symptomatic norovirus GII infection — not a single non-secretor developed symptomatic norovirus¹⁰¹⁰ not a single non-secretor developed symptomatic norovirus
Thorven M et al. A homozygous nonsense mutation (428G→A) in FUT2 provides resistance to symptomatic norovirus (GGII) infections. J Virol, 2005 among outbreak-exposed adults in the Thorven 2005 study.

Practical Actions

For non-secretors (CC), the most targeted actions address the deficit in gut microbial diversity. Without host-derived fucosylated glycans in the gut lumen, dietary prebiotic fibers serve as an alternative carbon source for Bifidobacterium species. Targeted supplementation with multiple Bifidobacterium strains can partially compensate for reduced colonisation.

For secretor mothers (CT or TT) breastfeeding non-secretor infants, or non-secretor mothers who cannot produce 2'-fucosylated HMOs, awareness of the downstream infant microbiome implications is clinically relevant. Some infant formula products now supplement with 2'-fucosyllactose, and this genotype-driven difference in milk composition may influence breastfeeding supplementation decisions in consultation with a paediatrician.

Vitamin B12 monitoring is also relevant for non-secretors: standard total serum B12 may overestimate functional status because elevated haptocorrin-bound B12 inflates the total measurement without increasing bioavailable transcobalamin-bound B12.

Interactions

rs516246 is an intronic proxy in strong LD with rs601338 (FUT2 W143X, the functional variant) and rs492602 (another synonymous proxy) in European and African populations. Carrying the C allele at rs516246 very likely means also carrying the A (non-secretor) allele at rs601338. The three entries address distinct clinical dimensions of the same biology: rs601338 covers B12 metabolism, rs492602 covers Crohn's disease and the gut-skin axis, and this entry covers maternal-infant HMO biology.

In East Asian populations, the primary non-secretor determinant is rs1047781 (A385T), since the W143X-tagged haplotype is nearly absent in that ancestry.