Changes in the Phenotype and Metabolism of Peritoneal Macrophages in Mucin-2 Knockout Mice and Partial Restoration of Their Functions In Vitro After L-Fucose Treatment

In the development of inflammatory bowel disease (IBD), peritoneal macrophages contribute to the resident intestinal macrophage pool. Previous studies have demonstrated that oral administration of L-fucose exerts an immunomodulatory effect and repolarizes the peritoneal macrophages in vivo in mice. In this study, we analyzed the phenotype and metabolic profile of the peritoneal macrophages from <i>Muc2^-/-</i> mice, as well as the effect of L-fucose on the metabolic and morphological characteristics of these macrophages in vitro. The investigation utilized flow cytometry, quantitative PCR (qPCR), measurement of the intracellular ATP and Ca²⁺ concentrations, an analysis of mitochondrial respiration and membrane potential, and transmission electron microscopy (TEM) for ultrastructural evaluations. The <i>Muc2^-/-</i> mice exhibited lower intracellular ATP and Ca²⁺ levels in their peritoneal macrophages, a higher percentage of stellate macrophages, and an increased oxygen consumption rate (OCR), combined with a higher percentage of mitochondria displaying an abnormal ultrastructure. Additionally, there was a five-fold increase in condensed mitochondria compared to their level in C57BL/6 mice. The number of CD209⁺ peritoneal macrophages was reduced three-fold, while the number of M1-like cells increased two-fold in the <i>Muc2^-/-</i> mice. L-fucose treatment enhanced ATP production and reduced the expression of the <i>Parp1</i>, <i>Mt-Nd2</i>, and <i>Mt-Nd6</i> genes, which may suggest a reduction in pro-inflammatory factor production and a shift in the differentiation of peritoneal macrophages towards the M2 phenotype.