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