medRxiv (Medicine)
2026-06-24
DOI: HASH:030e128eccbb9576c5814c77142b58c4
Consumption of ultra-processed foods is rising globally and has been implicated in inflammation and metabolic dysfunction, yet the impact of specific food additives on the human gut microbiota remains poorly understood. Using dietary data from the Food & You study (approximately 1000 participants in Switzerland), we identified 257 unique additives from 4,119 unique packaged products to quantify each participant's daily additive exposure. Higher exposure to a combination of high intensity sweeteners and sugar polyols, commonly found in low calorie products, was independently associated with reduced gut microbial Shannon diversity (beta = -0.39, p < 0.001), after adjustment for demographics, diet quality, BMI and bowel movement frequency. At a broader level, total additive exposure and fast food consumption were each negatively associated with gut microbial diversity; however, additive exposure remained independently associated and also specifically attenuated the diversity benefits of vegetable rich diets. Furthermore, microbial log ratio signatures linked to additive exposure showed strong negative correlations with Shannon diversity, including emulsifiers and thickeners (r = -0.66) and preservatives and antioxidants (r = -0.56). Integrating additive exposure with healthy dietary components such as HEI, fruits, or vegetables strengthened associations with gut microbial diversity; for example, vegetable linked correlations with Shannon diversity increased from r = 0.52 to r = 0.65 when contrasted against preservative-antioxidant exposure. Concordantly, microbial signatures associated with the sweeteners and sugar polyols additive combination showed depletion of fiber associated commensal taxa, and enrichment of pathways involved in polyol and aromatic compound metabolism. Notably, these associations emerged despite packaged foods representing only approximately 15% of logged dietary intake, underscoring the sensitivity of gut microbial diversity to limited exposure, and demonstrating that without integrating additive and processed-food metrics, one of the largest effect-size phenomena in human gut microbiota diversity would remain undetected.