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Irritable bowel syndrome (IBS) is a common gastroenterological disorder with triggers such as fructose. We showed that our IBS patients suffering from socioeconomic challenges have a significantly high consumption of high-fructose corn syrup (HFCS). Here, we characterize gut microbial dysbiosis and fatty acid changes, with respect to IBS, HFCS consumption, and socioeconomic factors. Fecal samples from IBS patients and healthy controls were subjected to microbiome and lipidome analyses. We assessed phylogenetic diversity and community composition of the microbiomes, and used linear discriminant analysis effect size (LEfSe), analysis of compositions of microbiomes (ANCOM) on highly co-occurring subcommunities (modules), least absolute shrinkage and selection operator (LASSO) on phylogenetic isometric log-ratio transformed (PhILR) taxon abundances to identify differentially abundant taxa. Based on a Procrustes randomization test, the microbiome and lipidome datasets correlated significantly (p = 0.002). Alpha diversity correlated with economic factors (p < 0.001). Multiple subsets of the phylogenetic tree were associated with HFCS consumption (p < 0.001). In IBS patients, relative abundances of potentially beneficial bacteria such as Monoglobaceae, Lachnospiraceae, and Ruminococcaceae were lower (p = 0.007), and Eisenbergiella, associated with inflammatory disorders, was higher. In IBS patients, certain saturated fatty acids were higher and unsaturated fatty acids were lower (p < 0.05). Our study aims first to underscore the influence of HFCS consumption and socioeconomic factors on IBS pathophysiology, and provides new insights that inform patient care.