Moderate variations in the human diet impact the gut microbiota in humanized mice

Abstract Aim Drastic diet interventions have been shown to promote rapid and significant compositional changes of the gut microbiota, but the impact of moderate diet variations is less clear. Here, we aimed to clarify the impact of moderate diet variations that remain within the spectrum of the habitual human diet on gut microbiota composition. Methods We performed a pilot diet intervention where five healthy volunteers consumed a vegetarian ready‐made meal for three days to standardize dietary intake before switching to a meat‐based ready‐made western‐style meal and high sugar drink for two days. We performed 16S rRNA sequencing from daily fecal sampling to assess gut microbiota changes caused by the intervention diet. Furthermore, we used the volunteers' fecal samples to colonize germ‐free mice that were fed the same sterilized diets to study the effect of a moderate diet intervention on the gut microbiota in a setting of reduced interindividual variation. Results In the human intervention, we found that fecal microbiota composition varied between and within individuals regardless of diet. However, when we fed the same diets to mice colonized with the study participants' feces, we observed significant, often donor‐specific, changes in the mouse microbiota following this moderate diet intervention. Conclusion Moderate variations in the habitual human diet have the potential to alter the gut microbiota. Feeding humanized mice human diets may facilitate our understanding of individual human gut microbiota responses to moderate dietary changes and help improve individualized interventions.