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The global increase in depression represents a significant public health burden, emphasizing the need to identify modifiable risk factors for Major Depressive Disorder (MDD). Over the past two decades, evidence has suggested systemic inflammation as a potential risk factor. Crucially, gut inflammation and disruptions in gut microbiota composition have been shown to influence systemic inflammation. It is hypothesized that dietary interventions could positively impact this disruption and through the microbiota-gut-brain (MGB) axis impact depression-related-inflammation. However, results from previous studies investigating this relationship are inconsistent or may lack important mediators. Specifically, a fiber-rich diet may offer therapeutic benefits for depression by promoting the production of short-chain fatty acids (SCFAs), known for their anti-inflammatory properties. Therefore, this thesis aimed to explore the immune-modulating effects of dietary fiber on stress and affective state as an endophenotype for depression in the general population and the effect of putative mediators SCFAs, gut inflammation and systemic inflammation. A cross-sectional study involving 83 participants from the general Belgian population was conducted, utilizing the Perceived Stress Scale, 10-items (PSS-10), and momentary measures of stress, positive affect (PA), and negative affect (NA) as indicators of mental well-being. Serum hs-CRP levels served as a marker of systemic inflammation, while fecal calprotectin levels indicated gut inflammation. Daily dietary fiber intake was assessed using a Food Frequency Questionnaire (FFQ), and fecal SCFA levels were measured as a representative marker of colonic concentrations. Spearman correlations and mediation analysis were performed to assess direct and indirect effects. Our findings did not reveal significant associations between dietary fiber intake, stress and affective state, aligning with inconsistent findings in existing literature on this relationship. Interestingly, we observed a significant negative association between hs-CRP and acute momentary stress (p = 0.042) and NA (p < 0.0001). However, caution is needed in interpreting this result due to the absence of controlled confounders. Furthermore, mediation analysis did not identify significant indirect effects, but a direct negative effect of dietary fiber on momentary NA (95% CI [-0.50; -0.0031]). Future research should include taxonomic analyses of the microbiome and serum SCFAs with a larger sample size to deepen our understanding of the relationship between dietary fiber and depressive symptoms and possible mediators.