An emerging concept in dysbiosis and bacterial pathogenesis is that certain bacteria have the ability to utilize host substrates to gain a fitness advantage during inflammation (Fleckenstein et al., 2010; Buffie and Pamer, 2013; Winter et al., 2013). The ability to respire tetrathionate and nitrate is central to the fitness of several Enterobacteriaceae (Winter et al., 2013), as these metabolites are readily available in an inflamed gut and can be used as electron acceptors to generate ATP. We observed that tetrathionate utilization was associated with active colitis, which supports a link between enhanced oxidative stress and Enterobacteriaceae-mediated dysbiosis previously described in the TRUC model (Garrett et al., 2010). Dampening the redox stress associated with intestinal inflammation may reduce the abundance of these electron acceptors and eliminate the fitness advantage of colitogenic bacteria, thus restoring intestinal homeostasis. Enrichment of genes for microbial benzoate degradation in active colitis was unexpected. Catecholamines have garnered interest as communication molecules between host and microbes (Lyte et al., 2011). Enterobacteriaceae can degrade catecholamines and catecholamines can promote Enterobacteriaceae growth and expression of bacterial virulence factors (Eloe-Fadrosh and Rasko, 2013). The histidine sensor kinase QseC is necessary for bacterial responses to host catecholamines and a compound that inhibits QseC, LED209, has been shown to inhibit pathogen virulence in vivo and in vitro (Rasko et al., 2008). Given that LED209 selectively interferes with bacterial virulence and colonization without affecting bacterial growth, typical antibiotic resistance patterns that plague traditional antimicrobials are unlikely to develop (Rasko and Sperandio, 2010). Our observations on tetrathionate respiration and benzoate degradation highlight how gut microbiome studies in mouse models of disease are useful for identifying novel microbial therapeutic targets. Fecal transplantation represents a long-standing treatment with the potential to address IBD dysbioses and its practice is resurging. However, its use requires substantial consideration from a safety and regulatory perspective (Buffie and Pamer, 2013). We observed that the health status of a host and its gut microbiome could be transient in some cases. Despite a host being in a state of health, as confirmed by histology, transferring its gut microbiome to a GF recipient resulted in colonic inflammation. As applications for fecal transplantation develop for humans, gnotobiotic mouse models may prove useful for evaluating whether microbiomes selected for transplant will confer the intended health outcomes for the recipient. nature/ismej/journal/v8/n7/full/ismej20143a.html cc: Dr. Amy G. Lehman .. nicely compliments the story you just sent on rats eating toxic plants vis-a-vis fecal transplants, thus abrogating vulnerability associated toxicity sickness. Which is .. pretty baller. :)
Posted on: Tue, 22 Jul 2014 22:37:45 +0000
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