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Milk plays an important role in supplying essential nutrients that help meet daily requirements. However, lactose, one of its components, is often associated with digestive discomfort in individuals with lactose intolerance or reduced lactase activity. Yet, recent findings suggest that this ingredient may have prebiotic properties. We propose that lactose may positively affect both the structure and metabolism of the gut microbiota. To test that, we first explored the acute impact of lactose ingestion on gut microbiota from lactose-tolerant adults using a short-duration (48 hours) in vitro batch colonic model (mini-xGIbiomics®). Subsequently, a long-duration (5 weeks in total with 14 days of treatment) in vitro dynamic colonic model (xGIbiomics®) was employed to evaluate the chronic effects of lactose administration on gut health. In both models, a selected mixture of lactose, galactose, and glucose was administered to simulate lactose metabolism and absorption in lactose-tolerant adults. This is the first study that, to our knowledge, has assessed the effect on the microbiota of this biologically relevant proportion of lactose metabolites that reach the colon and, therefore, are available to the gut microbiota. Our findings challenge the common assumption that lactose negatively impacts gut health, revealing a prebiotic effect of this ingredient on both composition and metabolism of the microbiota across three simulated doses, equivalent to the consumption of half, one, and two glasses of cow’s milk. The dynamic colonic model confirmed these positive changes in gut microbiota, increasing the relative abundance of well-known beneficial bacterial genera such as Lactobacillus, Akkermansia, and Faecalibacterium, while reducing Clostridium, a genus composed by many pathogenic species. Furthermore, we observed an increase in the production of health-promoting metabolites (acetic, propionic, and lactic acids). These results underscore the prebiotic potential of lactose consumption, offering new insights into how lactose may support gut health and contribute to overall well-being.
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