Aspergillus fumigatus, a pathogenic filamentous fungus, possesses a distinctive surface polysaccharide known as galactomannan that comprises mannose and galactofuranose residues. Although galactomannan is less abundant than other polysaccharides, such as chitin and β-glucans, its functional importance is evident: deletion of genes encoding enzymes involved in galactomannan biosynthesis leads to pronounced growth defects. These findings underscore the critical role of galactomannan in maintaining cell wall integrity. In this review, we describe the recent advances in our understanding of galactomannan biosynthesis in filamentous fungi.

Glycans expressed by intestinal epithelial cells, particularly O-linked glycans on mucins, play critical roles in maintaining the mucosal barrier and regulating the gut microbiota. These glycans support the polymerization and viscosity of mucins, forming a protective mucus layer that prevents bacterial invasion. Specific glycan structures, including fucosylated, sialylated, and sulfated glycans, vary by intestinal region and are essential for mucus integrity. Glycosyltransferase-deficient mice have revealed that disruption of these glycans compromises barrier function and increases susceptibility to intestinal inflammation. Additionally, host glycans serve as nutrient sources for commensal bacteria, such as Akkermansia muciniphila and Bacteroides thetaiotaomicron that rely on mucin degradation for colonization and growth. Alterations in glycosylation patterns of mucins affect microbial composition and functions, and increase the susceptibility to intestinal inflammation. Genome-wide association studies have linked glycosylation-related genes, such as FUT2, B3GALT5 and GAL3ST2, to inflammatory bowel disease (IBD). However, the precise mechanisms by which glycan changes contribute to IBD pathogenesis remain unclear. Further research is needed to clarify these interactions, which may lead to a novel glycan-based therapeutic approach for IBD, including prebiotic or mucin-targeted treatments.

Muscular dystrophies are a group of hereditary intractable diseases, among which a subgroup known as dystroglycanopathies is caused by defective glycosylation of a membrane-associated protein in muscle cells. In Japan, the prevalence of this disorder is relatively high due to a founder effect, and the development of disease-modifying therapies has long been awaited. Recent advances in glycobiology and genetic medicine have led to the emergence of therapeutic approaches based on underlying disease mechanisms, with some candidate drugs already entering clinical trials. In this review, we present our research on drug development using disease model mice for dystroglycanopathy, and outline global trends and challenges in therapeutic development for dystroglycanopathy.

Aspergillus fumigatus, a pathogenic filamentous fungus, possesses a distinctive surface polysaccharide known as galactomannan that comprises mannose and galactofuranose residues. Although galactomannan is less abundant than other polysaccharides, such as chitin and β-glucans, its functional importance is evident: deletion of genes encoding enzymes involved in galactomannan biosynthesis leads to pronounced growth defects. These findings underscore the critical role of galactomannan in maintaining cell wall integrity. In this review, we describe the recent advances in our understanding of galactomannan biosynthesis in filamentous fungi.

Glycans expressed by intestinal epithelial cells, particularly O-linked glycans on mucins, play critical roles in maintaining the mucosal barrier and regulating the gut microbiota. These glycans support the polymerization and viscosity of mucins, forming a protective mucus layer that prevents bacterial invasion. Specific glycan structures, including fucosylated, sialylated, and sulfated glycans, vary by intestinal region and are essential for mucus integrity. Glycosyltransferase-deficient mice have revealed that disruption of these glycans compromises barrier function and increases susceptibility to intestinal inflammation. Additionally, host glycans serve as nutrient sources for commensal bacteria, such as Akkermansia muciniphila and Bacteroides thetaiotaomicron that rely on mucin degradation for colonization and growth. Alterations in glycosylation patterns of mucins affect microbial composition and functions, and increase the susceptibility to intestinal inflammation. Genome-wide association studies have linked glycosylation-related genes, such as FUT2, B3GALT5 and GAL3ST2, to inflammatory bowel disease (IBD). However, the precise mechanisms by which glycan changes contribute to IBD pathogenesis remain unclear. Further research is needed to clarify these interactions, which may lead to a novel glycan-based therapeutic approach for IBD, including prebiotic or mucin-targeted treatments.

Muscular dystrophies are a group of hereditary intractable diseases, among which a subgroup known as dystroglycanopathies is caused by defective glycosylation of a membrane-associated protein in muscle cells. In Japan, the prevalence of this disorder is relatively high due to a founder effect, and the development of disease-modifying therapies has long been awaited. Recent advances in glycobiology and genetic medicine have led to the emergence of therapeutic approaches based on underlying disease mechanisms, with some candidate drugs already entering clinical trials. In this review, we present our research on drug development using disease model mice for dystroglycanopathy, and outline global trends and challenges in therapeutic development for dystroglycanopathy.