The HMI™ module: a new tool to study the host-microbiota interaction in the human gastrointestinal tract in vitro

Background: Recent scientific developments have shed more light on the importance of the host-microbe interaction, particularly in the gut. However, the mechanistic study of the host-microbe interplay is complicated by the intrinsic limitations in reaching the different areas of the gastrointestinal tract (GIT) in vivo. In this paper, we present the technical validation of a new device - the Host-Microbiota Interaction (HMI) module - and the evidence that it can be used in combination with a gut dynamic simulator to evaluate the effect of a specific treatment at the level of the luminal microbial community and of the host surface colonization and signaling. Results: The HMI module recreates conditions that are physiologically relevant for the GIT: i) a mucosal area to which bacteria can adhere under relevant shear stress (3 dynes cm-2); ii) the bilateral transport of low molecular weight metabolites (4 to 150 kDa) with permeation coefficients ranging from 2.4 x 10(-6) to 7.1 x 10(-9) cm sec(-1); and iii) microaerophilic conditions at the bottom of the growing biofilm (PmO2 = 2.5 x 10(-4) cm sec(-1)). In a long-term study, the host's cells in the HMI module were still viable after a 48-hour exposure to a complex microbial community. The dominant mucus-associated microbiota differed from the luminal one and its composition was influenced by the treatment with a dried product derived from yeast fermentation. The latter - with known anti-inflammatory properties induced a decrease of pro-inflammatory IL-8 production between 24 and 48 h. Conclusions: The study of the in vivo functionality of adhering bacterial communities in the human GIT and of the localized effect on the host is frequently hindered by the complexity of reaching particular areas of the GIT. The HMI module offers the possibility of co-culturing a gut representative microbial community with enterocyte-like cells up to 48 h and may therefore contribute to the mechanistic understanding of host-microbiome interactions

Microbial inhibition of oral epithelial wound recovery: potential role for quorum sensing molecules?

Awareness of the impact of microbiota in both health and disease is growing. Using a new in vitro oral mucosa co-culture model, we recently showed a clear inhibition of epithelial wound healing in the presence of an oral microbial community. In this paper, we have used the same model in combination with specific oral microbial species to obtain a better insight into the role of the oral microbiota in wound healing. Monocultures of Klebsiella oxytoca and Lactobacillus salivarius significantly inhibited wound healing with similar to 20%, whereas Streptococcus mitis and S. oralis enhanced the healing process with similar to 15% in 24 h. Yet, neither S. oralis or S. mitis were able to counteract the inhibitory effects from K. oxytoca on wound healing. Other tested microbial species had no effect on wound healing. Apart from this species-dependency, the inhibitory effect on wound healing depended on a microbial threshold concentration. Further mechanistic experiments with K. oxytoca excluded different microbial factors and hypothesized that quorum sensing molecules might play a role in the inter-kingdom signalling during wound healing. These results are important for the development of new strategies for the management of (infected) wounds and ulcerations