| Summary: | A decrease in populations of <i>Bacteroides thetaiotaomicron</i> and <i>Lactobacillus johnsonii</i> is observed during the development of colitis and fungal overgrowth, while restoration of these populations reduces inflammatory parameters and fungal overgrowth in mice. This study investigated the effect of two fatty acids from <i>B. thetaiotaomicron</i> and <i>L. johnsonii</i> on macrophages and Caco-2 cells, as well as their impact on the inflammatory immune response and on <i>Candida glabrata</i> overgrowth in a murine model of dextran sulfate sodium (DSS)-induced colitis. Oleic acid (OA) and palmitic acid (PA) from <i>L. johnsonii</i> and <i>B. thetaiotaomicron</i> were detected during their interaction with epithelial cells from colon samples. OA alone or OA combined with PA (FAs) reduced the expression of proinflammatory mediators in intestinal epithelial Caco-2 cells challenged with DSS. OA alone or FAs increased FFAR1, FFAR2, AMPK, and IL-10 expression in macrophages. Additionally, OA alone or FAs decreased COX-2, TNFα, IL-6, and IL-12 expression in LPS-stimulated macrophages. In the DSS murine model, oral administration of FAs reduced inflammatory parameters, decreased <i>Escherichia coli</i> and <i>Enterococcus faecalis</i> populations, and eliminated <i>C. glabrata</i> from the gut. Overall, these findings provide evidence that OA combined with PA exhibits anti-inflammatory and antifungal properties.
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