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Isoform Ratio Rather than Total Content Determines Nonlinear Bioactivity of Red Kidney Bean Phytohemagglutinin in
Rong Zhang1, Kuan Gao2, Tong Jin1
1School of Food and Biological Engineering, Engineering Research Center of Bio-Process of Ministry of Education, Anhui Province Key Laboratory of Agricultural Products Modern Processing, Hefei University of Technology, Hefei230009, Anhui, P. R. China.
Abstract:
Red kidney bean phytohemagglutinin (PHA) is an isolectin system of erythroagglutinating (PHA-E) and leucoagglutinating (PHA-L) subunits, but the biological significance of the natural ratio remains unclear. Here, natural PHA fractions with stepwise PHA-E/PHA-L ratios (N1 = 0.85, N2 = 1.24, N3 = 1.80) were tested in a BALB/c mouse sensitization model. The fractions induced nonlinear, qualitatively distinct responses. N1 and N2 both increased ileal epithelial length by approximately 10.2% relative to PBS; N2 additionally showed the highest IgG2a/IgG1 ratio, a prominent IL-17A response, and restored ZO-1 and occludin expression to PBS levels. N3 evoked the strongest IL-4-dominant Th2-like response and the highest sIgA level among PHA fractions, yet shortened the epithelium by 14.3% with a weaker barrier-gene expression. These phenotypes coincided with fraction-specific gut microbiota remodeling. Thus, the PHA isoform ratio critically determines immune, intestinal, and microbial outcomes and warrants consideration in bean lectin safety evaluation.

