Molecular mechanisms linking food processing to the human gut microbiome and metabolic health: A critical review

Abstract Food processing can improve safety, shelf life, digestibility and sensory quality, but it can also alter the food matrix, remove microbiota‐accessible substrates and introduce additives or heat‐derived compounds that modify host–microbe interactions. This critical review evaluates how mechanical, thermal, fermentative and ultra‐processing practices influence the human gut microbiota and metabolic health. A structured literature search of PubMed/MEDLINE and Google Scholar was conducted for peer‐reviewed studies published from January 2010 to July 2026, with priority given to human controlled‐feeding trials, randomized interventions and large observational studies. The strongest human evidence indicates that processing‐related effects are heterogeneous rather than uniformly harmful. Refined and ultra‐processed dietary patterns can increase energy intake and are associated with adverse metabolic outcomes, while small controlled studies show that specific emulsifiers and non‐nutritive sweeteners can alter microbiota composition or function in susceptible individuals. Conversely, whole‐grain and fermented‐food interventions can increase short‐chain fatty acid production, microbial functional capacity or diversity. Mechanistically, food processing acts through changes in particle size, starch structure, fibre accessibility, polyphenol bioavailability, additive exposure, advanced glycation end products, bile acid metabolism and intestinal barrier integrity. However, much of the mechanistic literature remains preclinical, and processing level is frequently confounded by nutrient quality and dietary pattern. Future research should use standardized processing descriptors, metagenomic and metabolomic endpoints, adequately powered controlled diets and long‐term multi‐ethnic cohorts. Food design should preserve beneficial matrices and fermentable substrates while minimizing unnecessary additives and excessive thermal damage.