Reconstruction and dynamics of human intestinal microbiome observed in situ

Gut microbiome are studied primarily using fecal samples in humans and we gained vital knowledge of compositional and functional capacities of gastro-intestinal microbial communities. Yet, fecal materials limit our ability to investigate microbial dynamics in different locations along GI-tract (in situ), nor in finer temporal scales as they are infrequent. With a technology developed originally for fecal material transplantation, colonic transendoscopic enteral tubing, we were able to sample ileocecal microbiome twice daily, and carried out metagenomic as well as metatranscriptomic analyses. Ileocecal and fecal microbiome are similar in metagenomic profiling, yet their active genes (in metatranscriptomes) are highly distinct. Both were perturbed after laxatives and then became more similar to microbiome prior to treatment, demonstrating resilience as an innate property of gut microbiome. Ileocecal microbiome transcriptomes sampled during day and night revealed diurnal rhythmes exist in certain bacterial species and functional pathways, in particular those related to short-chain fatty acid production. Lastly, metabolomic analysis in fecal and urine samples mirrored the perturbance and recovery in gut microbiome, indicating crucial contribution of gut microbiome to many of the key metabolites involved in host health. Our study provides interesting novel insights into human gut microbiome, and demonstrates the inner resilience, diurnal rhythmes and potential consequences to the host.