Hypoglycaemic and anti-ageing activities of green alga Ulva lactuca polysaccharide via gut microbiota in ageing-associated diabetic mice

Ageing-related type 2 diabetes is a significant public health problem. Particularly, the number of cases and fatality rates of ageing-associated diabetes increase with population ageing. This study aimed to investigate the structural characterisation of Ulva lactuca polysaccharide (ULP) and the hypoglycaemic effect on ageing-associated diabetic mice using gut microbiota variation. Sugar residuals analysis showed that the purified ULP (ULP-1) comprised β-D-Xylp-(1→3)-β-D-Arap-(1→6)-β-D-Galp-(1→6)-β-D-Glcp linked to [→α-L-Rhap-(1→4)-β-D-GlcpA→]n and α-D-Manp-(1→4)-α-L-Rhap(2SO3-)-(1→2)-α-L-Rhap(4SO3-)-(1→2)-α-L-Arap-(1→2)-α-L-Rhap-(1→ as its side chains at β-D-Glcp. Moreover, ULP modulated the expression levels of p16Ink4a, MMP2, FoxO1, GLP-1/GLP-1R, STAT3, and GLUT4 to improve the status of ageing and diabetes, which was concurrent with the increased abundance of Dubosiella, Enterococcus, Romboutsia, Bifidobacterium, Kurthia, Clostridium_sensu_stricto_1, Corynebacterium, Faecalibaculum, Aerococcus and Vibrio. Notably, Dubosiella, Romboutsia, Bifidobacterium, Turicibacter and Clostridium_sensu_stricto_1 could serve as important intermediates for delaying ageing and diabetes. Additionally, the ULP-1 structure is strongly binding interaction with the target protein through hydrogen bonding and Van der Waals force, especially for GLP-1 (-10.34 kcal/mol), p16Ink4a (-10.51 kcal/mol) and GLP-1R (-8.57 kcal/mol). Moreover, the average length of the hydrogen bond was observed to be 2.36 MPa, which is smaller than that of the traditional hydrogen bond. Therefore, ULP has the potential to function as a nutraceutical to delay or prevent the development of ageing-related type 2 diabetes.