Jianbo (Bob) Zhang, Griffith Lab, MIT

for the The Parsons Lab Microbial Systems Seminar Series @MIT

Abstract:

Gut microbiome has emerged as a key factor in human health and diseases. Despite numerous insights on the host-microbe crosstalk using animal models, it is challenging to study human-microbe interactions in vitro because of two reasons. First, healthy intestinal epithelia experiences the deepest oxygen gradient in human body, make it difficult to maintain in vitro. Second, many commensal bacteria, especially those in human colon, are extremely oxygen sensitive, making it challenging to co-culture these bacteria with intestinal cells. Here we established a GuMI physiome platform that recapitulates a gut-microbe interactions under physiologically relevant microenvironment. Colon stem cells in GuMI were differentiated into different cell subtypes that are observed in vivo. In addition, GuMI can maintain the growth of obligate anaerobes without compromising the barrier function of colon monolayers. To test if colon epithelial cells respond to the physiologically relevant stimuli such as hypoxia and bacteria, we performed transcriptomic analysis, immunofluorescent staining, bacterial metabolite profiling. We found that the cells had significantly different gene expression patterns in response to oxygen gradient, luminal flow, commensal anaerobes, and bacterial fermentation metabolites. Moreover, the NFKB pathway was downregulated by F. prausnitzii, a promising anti-inflammatory bacterium, suggesting that GuMI recaptures the anti-inflammatory effects of F. prausnitzii. We envision that GuMI could be a useful tool to study host-microbe interactions in vitro.