I-Corps: Development of a gut bacterial strain to stimulate mucus-secreting cells of the colon to treat leaky-gut

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The broader impact/commercial potential of this I-Corps project is to address leaky gut and improve the microbiome. Leaky gut, or increased intestinal permeability, is an unhealthy gut lining that may allow partially digested food, toxins, and microbes to be released. This may trigger inflammation and changes in the normal gut flora that could lead to problems within the digestive tract. Currently, there are no products on the market with clinical evidence of ability to address leaky gut. The proposed technology may relieve leaky gut and its associated inflammation, as well as improve the host’s microbiome. The proposed technology increases the presence of beneficial bacteria indiscriminately by making the gut a more suitable place for probiotics to live and thus does not decrease microbiome diversity. This I-Corps project is based on the development of a bacterial strain called Lactobacillus paracasei D3.5 that was discovered by screening hundreds of human-isolated bacterial strains to treat leaky gut. The bacterial strain was selected for its unique ability to stimulate mucus-secreting cells of the colon called goblet cells. Because the components of the bacteria responsible for these effects become more bioavailable after killing the bacteria with heat, the heat-treated version called Postbiotic LPD3.5 was used for a subsequent preclinical study. In this study, the preparation was found to restore the thickness of the colonic mucosal layer in aging mice, which then led to the recovery in tightness of the connections between epithelial cells lining the gut. Both of these effects prevented bacteria and toxins from leaking through the digestive tract into the blood stream, and relieved the associated inflammation, a condition referred to as leaky gut. Moreover, Postbiotic LPD3.5 also was shown to strengthen the host’s bacterial community, decrease anxiety, and improve insulin sensitivity, muscle function, and memory. In order to test whether Postbiotic LPD3.5 is able to stimulate the mucus production in humans, human goblet cells were treated in vitro. The effects seen in human goblet cells were the same as those observed in goblet cells of mice.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.