Fucose is an L-configuration sugar found abundantly in the mammalian gut. were not found by a broadly reactive fucose-specific lectin (1). Fut1 expression is restricted to M cells a rare intestinal epithelial population (3). In rodents the stomach and parts of large intestine are constitutively fucosylated while that in the small intestine is variable and can be induced by a variety of environmental factors. This concentration of fucose in tissues that are in intimate contact with the highest density of microbes immediately suggests a connection. Indeed fucosylation of the distal small intestine increases in rats and mice around weaning (3-4 weeks) when a shift in bacterial populations occurs (7 8 Germ-free (GF) mice do not maintain ileal fucosylation after weaning but colonization with bacteria from conventionally-housed mice restores it (8 9 Not all bacteria are capable of causing fucosylation nor can it be recapitulated by oral administration of ICG-001 a bacterial TLR ligand such as LPS to GF mice (10). Monocolonization of mice with segmented filamentous bacteria (SFB)(11) or (8) is effective while is not (12)). Conversely certain oral antibiotics can abolish fucosylation in conventional mice (12). Clearly some bacteria have the ability to cause fucosylation while others do not. How do gut bacteria cause fucosylation? The model human gut symbiont provides one interesting example. When monocolonizing mice at sufficiently high densities it triggers fucosylation of the ileum (8) and since it resides in the lumen this must be done via a soluble signal secreted by the bacteria. Genetic experiments suggest that the putative signaling molecule is controlled by fucose availability. That is the fucose-inducing signal is regulated by the same mechanisms as the bacteria’s fucose catabolism genes via a fucose-responsive transactivator (13). This co-regulation strongly suggests that host-derived fucose is energetically useful for this symbiont. The identity of the putative signal and how it activates fucosylation on the host remains unknown. Another common gut resident SFB also cause increased fucosylation in the ileum that they populate (11). SFB came to prominence based on their induction of IL-17 and IL-22 production in the small intestine lamina propria and the effects of this on the immune system (14). Ileal fucosylation in SFB-harboring specific pathogen-free (SPF) mice was shown to depend on IL-22 and TNF family member lymphotoxin alpha (LTα)(12). IL-22 is a cytokine of the IL-10 ICG-001 family whose expression can be induced by commensal and pathogenic bacteria (15). Its receptor is expressed on epithelial cells and can activate defense and tissue repair mechanisms via STAT3 signaling (16). LTα is involved in lymphoid tissue organogenesis and has been implicated in maintenance of IL-22 production (17). In contrast to IL-22 its expression was not affected by antibiotic treatment. To cause fucosylation IL-22 and LTα both needed ICG-001 to be produced by innate lymphoid cells (ILCs) which require the transcription factors RORγt and Id2 for development. Acute blockade of IL-22 or the lymphotoxin beta receptor (which LTα signals through) abolished fucosylation in the ileum (12). Unlike most gut bacteria SFB is in intimate physical contact with epithelial cells but the molecular mechanisms that allow it to activate PGK1 IL-22 and fucosylation are not yet clear. The innate and adaptive arms of the immune system combine to sequester most bacteria in the lumen of the ileum and large intestine. In several mouse strains that lack components of the adaptive immune system (RAG ?/? scid nude pIgR ?/?) there is increased small and large intestine fucosylation (12 18 One explanation is that certain members of the gut community (such as SFB (19)) that are normally limited by secreted IgA antibodies could trigger excess fucosylation when uncontrolled (either by expanding in numbers invading or altering their behavior). Fucosylation in this case could be part of an increased innate immune response compensating for the absence of adaptive immunity (20). A mouse model ICG-001 of cystic fibrosis also results ICG-001 in increased fucosylation of small intestine mucins (21) which could be.