Dietary monosodium glutamate disrupts neutrophil-mediated bacterial clearance in association with circulating glutamate-glucose metabolic remodeling.

Abstract

This study investigated the association of chronic high-dose dietary monosodium glutamate (MSG) exposure with neutrophil abnormalities and paternal intergenerational changes in antibacterial defense. Male SD rats received MSG in drinking water for 90 days and were subsequently mated with unexposed females to produce F1 offspring. Assessments included absolute neutrophil counts, serum immune proteins and inflammatory cytokines, co-culture with Escherichia coli, untargeted metabolomics in F0 rats, and biochemical and pancreatic histopathological analyses in both generations, complemented by in vitro experiments. Both F0 and F1 rats exhibited neutropenia and altered neutrophil antibacterial effector responses, accompanied by hyperglycemia, disrupted glutamate metabolism, and pancreatic/islet abnormalities. Colony formation following co-culture of peripheral blood with E. coli showed opposite patterns across generations, decreasing in F0 and increasing in F1. These findings suggest that colony formation may reflect the combined effects of neutrophil antibacterial function and the direct effects of MSG and glucose on E. coli growth. In vitro, high glucose concentrations enhanced the inhibitory effect of MSG on the viability of neutrophil-like differentiated HL-60 (dHL-60) cells. Both MSG and glucose exerted concentration-dependent biphasic effects on E. coli growth, although the concentrations required to produce comparable effects differed markedly. These results suggest that disrupted glutamate-glucose metabolism may contribute to MSG exposure-associated neutrophil abnormalities and paternal intergenerational changes in antibacterial defense. However, the causal relationships and underlying mechanisms remain to be established.

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