Mannose ameliorates experimental colitis by protecting intestinal barrier integrity

Abstract

Metabolite alteration has been associated with the pathogenesis of inflammatory bowel disease (IBD), including colitis. Mannose, a natural bioactive monosaccharide that is involved in metabolism and synthesis of glycoproteins, exhibits anti-inflammatory and anti-oxidative activities. We show here that the circulating level of mannose is increased in patients with IBD and mice with experimental colitis. Mannose treatment attenuates intestinal barrier damage in two mouse colitis models, dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis in IL-10-deficient mice. We demonstrate that mannose treatment enhanced lysosomal integrity and limited the release of cathepsin B, preventing mitochondrial dysfunction and myosin light chain kinase (MLCK)-induced tight junction disruption in the context of intestinal epithelial damage. Mannose exerts a synergistic therapeutic effect with mesalamine on mouse colitis. Cumulatively, the results indicate that mannose supplementation may be an optional approach to the treatment of colitis and other diseases associated with intestinal barrier dysfunction.

D-mannose ameliorates age-associated cellular senescence in the bladder urothelium and NLRP3/Gasdermin/IL-1β -driven pyroptotic epithelial cell shedding

“…This would make D-mannose a highly effective seno-morphic as it modifies senescence risk. In line with this, mannose has been reported to protect against intestinal barrier dysfunction in a (young) mouse model of colitis (Dong et al, 2022). Moreover, we have recently reported that D-mannose prophylaxis led to a significant decrease in UTI incidence rate in patients with bTLT (Chiu et al, 2022).…”

Simultaneous N-deglycosylation and digestion of complex samples on S-Traps enables efficient glycosite hypothesis generation

“…We investigated whether PNGase F is compatible with S-Trap sample preparation using RNase B as a model glycoprotein containing one known N-glycan that results in a characteristic mass shift upon cleavage. 51 PNGase F is known to be effective at removing glycans in Protein Deglycosylation Mix Buffers 1 and 2, 52 whereas TEAB is a known to be compatible with S-Trap sample preparation and mass spectrometry analysis. 53 To test whether a single buffer system would be compatible with both PNGase F and S-Traps, RNase B was deglycosylated using PNGase F in four different buffer conditions: the two deglycosylation buffers provided with commercially available PNGase F, TEAB, and water.…”

GLUT1 is a highly efficient L-fucose transporter

“…The transport of monosaccharides provides the cell with energy and metabolic precursors used for a diverse range of processes. Understanding how these sugars are transported and utilized becomes especially important since various diseases/disorders (LADII, GFUS-CDG, SLC35A2-CDG, PGM1-CDG, colitis, various cancers) are already using or exploring “monosaccharide therapy” ( 9 , 20 , 21 ).…”