Association of Phocaeicola vulgatus with Gut Nerve Cell Injury and Dysmotility in T2D
Faculty Mentor Information
Dr. Onesmo Balemba (Mentor), University of Idaho
Abstract
Background. Nerve cell injury, neuropathy, in the gut and subsequent gut movement-related disorders in type 2 diabetes (T2D) patients are believed to be triggered at least in part by endotoxins, short-chain fatty acid alterations, and other unknown molecules from gut microbes. However, the specific microbial species and bacteria-derived etiological factors that trigger gut neuropathy and dysmotility in T2D are not entirely known. Preliminary results from our laboratory investigations suggest increased abundance of and over-representation of the species Phocaeicola vulgatus in patients with T2D. Published results provided strong evidence showing association of P. vulgatus with insulin resistance, but it is not known whether P. vulgatus can directly cause gut neuropathy and dysmotility. We tested the hypothesis that P. vulgatus produces transudates and exudates that could decrease bowel movements by damaging nerve cells in the gut and inhibiting muscle contraction in vitro.
Methods. We analyzed the effects of filter-sterilized culture supernatants of three strains of P. vulgatus obtained from DSMZ (DSM-108234, 1447, and 3289) on contractions of cultured duodenojejunal muscle preparations from healthy mice. Tissues cultured in supernatants containing these strains were analyzed for injury to nerve cells.
Results and Conclusions. P. vulgatus DSM-3289 dramatically decreased tissue contractions after 12 hours, P. vulgatus DSM-108234 decreased contractions after 36 hours, while P. vulgatus DSM-1447 did not affect contractions. P. vulgatus DSM-3289 activated TNF-alpha expression in myenteric neurons, while P. vulgatus DSM-108234 activated TNF-alpha expression in enteric glia. They activated Caspase-11 in a similar pattern. Our findings suggest that P. vulgatus may induce gut neuropathy and dysmotility associated with type 2 diabetes in a strain-dependent manner.
Association of Phocaeicola vulgatus with Gut Nerve Cell Injury and Dysmotility in T2D
Background. Nerve cell injury, neuropathy, in the gut and subsequent gut movement-related disorders in type 2 diabetes (T2D) patients are believed to be triggered at least in part by endotoxins, short-chain fatty acid alterations, and other unknown molecules from gut microbes. However, the specific microbial species and bacteria-derived etiological factors that trigger gut neuropathy and dysmotility in T2D are not entirely known. Preliminary results from our laboratory investigations suggest increased abundance of and over-representation of the species Phocaeicola vulgatus in patients with T2D. Published results provided strong evidence showing association of P. vulgatus with insulin resistance, but it is not known whether P. vulgatus can directly cause gut neuropathy and dysmotility. We tested the hypothesis that P. vulgatus produces transudates and exudates that could decrease bowel movements by damaging nerve cells in the gut and inhibiting muscle contraction in vitro.
Methods. We analyzed the effects of filter-sterilized culture supernatants of three strains of P. vulgatus obtained from DSMZ (DSM-108234, 1447, and 3289) on contractions of cultured duodenojejunal muscle preparations from healthy mice. Tissues cultured in supernatants containing these strains were analyzed for injury to nerve cells.
Results and Conclusions. P. vulgatus DSM-3289 dramatically decreased tissue contractions after 12 hours, P. vulgatus DSM-108234 decreased contractions after 36 hours, while P. vulgatus DSM-1447 did not affect contractions. P. vulgatus DSM-3289 activated TNF-alpha expression in myenteric neurons, while P. vulgatus DSM-108234 activated TNF-alpha expression in enteric glia. They activated Caspase-11 in a similar pattern. Our findings suggest that P. vulgatus may induce gut neuropathy and dysmotility associated with type 2 diabetes in a strain-dependent manner.