Can the FUT2 Non-secretor Phenotype Associated With Gut Microbiota Increase the Children Susceptibility for Type 1 Diabetes? A Mini Review

Abstract

The global toll of type 1 diabetes (T1D) has steadily increased over the last decades. It is now widely acknowledged that T1D pathophysiology is more complex than expected. Indeed, a multifaceted interplay between genetic, metabolic, inflammatory and environmental factors exists that leads to heterogeneous clinical manifestations across individuals. Children with non-secretor phenotype and those affected by T1D share low abundance of bifidobacteria, low content of short-chain fatty acids, intestinal phosphatase alkaline and a high incidence of inflammatory bowel diseases. In this context, host-gut microbiota dyad may represent a relevant contributor to T1D development and progression due to its crucial role in shaping host immunity and susceptibility to autoimmune conditions. The FUT2 gene is responsible for the composition and functional properties of glycans in mucosal tissues and bodily secretions, including human milk. FUT2 polymorphisms may profoundly influence gut microbiota composition and host susceptibility to viral infections and chronic inflammatory disease. In this minireview, the possible interplay between mothers' phenotype, host FUT2 genetic background and gut microbiota composition will be discussed in perspective of the T1D onset. The study of FUT2-gut microbiota interaction may add a new piece on the puzzling T1D etiology and unveil novel targets of intervention to contrast T1D development and progression. Dietary interventions, including the intake of α-(1, 2)-fucosyl oligosaccharides in formula milk and the use of specific prebiotics and probiotics, could be hypothesized.

A Study on Fucosyltransferase 2 Gene Polymorphism and Secretion Status Related to Neonatal Necrotizing Enterocolitis

“…e bound L-fucose is catabolized and metabolized by a series of fucose degrading enzymes, which can ① be used as energy for bacteria; ② be internalized into fucosylated capsular polysaccharides (components of the bacterial cell wall); ③ be used to regulate the expression of fucose operon genes; ④ be used as raw material for bacteria to produce short-chain fatty acids (SCFAs). In addition, epithelial cell fucosylation can provide colonization advantages for bacteria containing fucosidase such as Bacteroides, increase the number of beneficial intestinal flora, and promote colonization resistance against opportunistic pathogens [9,10]. Some other studies have also pointed out that the composition of adult gut microbiota is related to the secretion status determined by the FUT2 gene [23], and histoblood group antigens may be a crucial genetic factor affecting the microecology of the intestinal flora [24].…”

“…She et al have examined paraffin-embedded intestinal specimens from participants and found that the NEC patients showed lower intestinal epithelial fucosylation levels than the control patients [8]. At the same time, studies have shown that fucosylation of intestinal epithelial cells participates in the maintenance of gut microbiota homeostasis, and it is also of great significance in the colonization of intestinal symbiotic bacteria [9,10].…”

Identification of biomarkers and pathways for focal segmental glomerulosclerosis using next generation sequencing data and bioinformatics analysis

“…The GO [64], PLA2G6 [65], RGS2 [66], GPS2 [67], SOX5 [68], GLUL (glutamate-ammonia ligase) [69], RYK (receptor like tyrosine kinase) [70], NFKBIA (NFKB inhibitor alpha) [71], LGR4 [102], ITGAL (integrin subunit alpha L) [103], CD27 [104], JAK3 [105], CCR5 [106], FCN1 [107], IL1RN [108], CX3CR1 [109], PDCD1 [110], TRPM2 [111], PLEK (pleckstrin) [112], CD101 [113], TNF (tumor necrosis factor) [114], CD48 [115], ALOX5 [116], TLR7 [117], CCL3 [118], C2 [119], TNFRSF1B [120], CCR2 [121], PLA2G7 [122], TH (tyrosine hydroxylase) [123], WNT7A [124], ADRB3 [125], GPBAR1 [126], SLC6A20 [127], FUT2 [128], ANK1 [129], NOS3 [130], APLNR (apelin receptor) [131], COMP (cartilage oligomeric matrix protein) [132], RETN (resistin) [133], NMU (neuromedin U) [134], S100B [135], IGFBP1 [136], COL1A1 [137], HBB (hemoglobin subunit beta) [138] and PLAC8 [139] genes plays important regulatory roles in diabetes mellitus. Various genes such as PDK4 [140], ALB (albumin) [141], EGR1 [142], RYR3 [48], CYP27B1 [143], GATA6 [144], NR4A3 [145], TET2…”

Gastrointestinal microbiome and Helicobacter pylori: Eradicate, leave it as it is, or take a personalized benefit–risk approach?

“…Non-secretors (about 20% of the population) are more susceptible to infection by some pathogens ( Escherichia coli , Neisseria meningitidis , Streptococcus pneumoniae , Haemophilus influenzae , Candida albicans ) and have aberrant gut microbiota, with a reduction of beneficial Bifidobacterium spp. The FUT2 non-secretor phenotype increases susceptibility to Crohn’s disease, ulcerative colitis, primary sclerosing cholangitis, celiac disease, psoriasis, Behçet’s disease, type 1 diabetes, and so on but at the same time protects against H. pylori , which requires fucosylated glycans in the gastric mucosa for adhesion[ 35 , 39 , 40 ].…”