IgA nephropathy (IgAN) is a common primary glomerulonephritis characterized by metabolic abnormalities that accelerate disease progression. Chitooligosaccharides (COS) exhibit notable regulatory effects on metabolism and inflammation, yet their therapeutic effects and underlying mechanisms in IgAN remain unexplored. This study identified distinct serum metabolic profiles in IgAN patients, distinguishing them from healthy controls. Notably, a significant increase in the metabolite sphingosine-1-phosphate (S1P) not only indicated the severity of IgAN progression but also induced IgAN-like pathological phenotypes in glomerular mesangial cells (including excessive proliferation and inflammation). COS with specific degree of polymerization significantly inhibited the G2/M phase of the cell cycle in glomerular mesangial cells while promoting S-phase arrest and apoptosis (P < 0.05), collectively suppressing the excessive cellular proliferation induced by S1P. Additionally, COS reduced the levels of inflammatory factors including IL-6, IL-1β, TNF-α, and MCP-1 (P < 0.05) in both cell and animal models. Mechanistically, COS alleviated S1P-induced cellular effects and improved renal function and inflammation by suppressing the expression and activity of S1PR1 and S1PR3, which was similar with the effects of S1P antagonist FTY720. Overall, this study highlighted COS as a potential functional food for mitigating IgAN progression by targeting S1P signaling.

Consuming low-glycemic index foods, such as Black Highland Barley (BHB), is essential for regulating post-meal glucose levels in individuals with type 2 diabetes mellitus (T2DM). This study examined how the starch structure of BHB affected glucose fluctuations. The incorporation of BHB enlarged starch granule size and modified the crystalline structure to an A+V type with a relative crystallinity of 31.14%. This alteration facilitated a more organized release of glucose. Population-based trials lasting six weeks had demonstrated that that BHB could reduce glucose variation, ghrelin levels, and insulin resistance in T2DM. Additionally, it increased the populations of beneficial gut bacteria such as Akkermansia, Bifidobacterium, and Lactobacillus, while also raising levels of gastric inhibitory peptides, phenolics, and specific gut metabolites. The specific digestion protocol and mathematical model of BHB disclosed its slow gastric emptying and glucose release rates, which were crucial for maintaining stable glucose levels in individuals with T2DM. Understanding the starch structure of BHB provided an effective dietary intervention for managing T2DM-related glucose fluctuations.