Exploring the human intestinal microbiome in health and disease

摘要

In this thesis, molecular tools were used to study bacteria inhabiting the gastrointestinal tract of humans. One aim was to determine whether certain lifestyle factors, such as an anthroposophic lifestyle, or living on a farm, had an impact on the bacterial composition in fecal samples collected from 90 children. The bacterial composition was determined by terminal restriction fragment length polymorphism (T-RFLP). Each child had a unique bacterial community, but anthroposophic children had a higher bacterial diversity than farm children. A second aim was to study the bacterial communities in fecal samples and biopsies collected from patients with Crohn's disease (CD), compared to healthy individuals. Several molecular approaches were used to characterize the microbiota in identical twins, including healthy twins pairs and twins that were discordant (one has CD and one is healthy) or concordant (both have CD). The bacterial profiles of healthy twins were highly similar whereas in twins discordant for CD they were very different. An imbalance in the microbiota was observed in a subset of individuals with CD and was correlated with the ileal disease phenotype (ICD). A reduced diversity of Firmicutes, and in particular, a depletion of Faecalibacterium prausnitzii was correlated with ICD. By contrast there was an increased prevalence and abundance of E. coli in ICD individuals. These findings suggest that specific members of the gut microbiota play a functional role in ICD and this could have clinical significance. A third aim was to characterize the microbiota in stomach biopsies from individuals with stomach cancer compared to healthy individuals. The gastric cancer microbiota had a high bacterial diversity and a similar composition to that in dyspeptic controls. In both cases, the bacterial composition was dominated by streptococci and other Firmicutes and a low abundance of Helicobacter pylori, contradicting earlier reports of H. pylori dominance in the stomach. In conclusion, the bacterial community in the human gastrointestinal tract is more complex than originally thought and disturbances in this community are indicative of some disease states.