Background: Recent studies have shown an association between weight change and the makeup of the intestinal microbiota in humans. Specifically, Lactobacillus, a part of the entire gastrointestinal tract's microbiota, has been shown to contribute to weight regulation. Aim: We examined the association between the level of oral Lactobacillus and the subsequent 6-year weight change in a healthy population of 322 Danish adults aged 35-65 years at baseline. Design: Prospective observational study. Results: In unadjusted analysis the level of oral Lactobacillus was inversely associated with subsequent 6-year change in BMI. A statistically significant interaction between the baseline level of oral Lactobacillus and the consumption of complex carbohydrates was found, e.g. high oral Lactobacillus count predicted weight loss for those with a low intake of complex carbohydrates, while a medium intake of complex carbohydrates predicted diminished weight gain. A closer examination of these relations showed that BMI change and Lactobacillus level was unrelated for those with high complex carbohydrate consumption. Conclusion: A high level of oral Lactobacillus seems related to weight loss among those with medium and low intakes of complex carbohydrates. Absence, or a low level of oral Lactobacillus, may potentially be a novel marker to identify those at increased risk of weight gain.