Chronic treatment with prebiotics,probiotics and synbiotics attenuated cardiac dysfunction by improving cardiac mitochondrial dysfunction in male obese insulin-resistant rats

European Journal of Nutrition - In metabolic syndrome, the composition of gut microbiota has been disrupted, and is associated with left ventricular (LV) dysfunction. Several types of prebiotics,...     

Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota

Conventional wisdom holds that microbes support their growth in vertebrate hosts by exploiting a large variety of nutrients. We show here that use of a specific nutrient (ethanolamine) confers a marked growth advantage on Salmonella enterica serovar Typhimurium (S. Typhimurium) in the lumen of the inflamed intestine. In the anaerobic environment of the gut, ethanolamine supports little or no growth by fermentation. However, S. Typhimurium is able to use this carbon source by inducing the gut to produce a respiratory electron acceptor (tetrathionate), which supports anaerobic growth on ethanolamine. The gut normally converts ambient hydrogen sulfide to thiosulfate, which it then oxidizes further to tetrathionate during inflammation. Evidence is provided that S. Typhimurium's growth advantage in an inflamed gut is because of its ability to respire ethanolamine, which is released from host tissue, but is not utilizable by competing bacteria. By inducing intestinal inflammation, S. Typhimurium sidesteps nutritional competition and gains the ability to use an abundant simple substrate, ethanolamine, which is provided by the host.     

Altered gut microbiota ameliorates bone pathology in the mandible of obese–insulin-resistant rats

The chronic consumption of a high-fat diet (HFD) induces obese–insulin resistance and impairs jawbone health via gut dysbiosis-stimulated inflammator     

Contribution of Flagellin Pattern Recognition to Intestinal Inflammation during Salmonella enterica Serotype Typhimurium Infection

Salmonella enterica serotype Typhimurium causes acute inflammatory diarrhea in humans. Flagella contribute to intestinal inflammation, but the mechanism remains unclear since most mutations abrogating pattern recognition of flagellin also prevent motility and reduce bacterial invasion. To determine the contribution of flagellin pattern recognition to the generation of innate immune responses, we compared in two animal models a nonmotile, but flagellin-expressing and -secreting serotype Typhimurium strain (flgK mutant) to a nonmotile, non-flagellin-expressing strain (flgK fliC fljB mutant). In vitro, caspase-1 can be activated by cytosolic delivery of flagellin, resulting in release of the interferon gamma inducing factor interleukin-18 (IL-18). Experiments with streptomycin-pretreated caspase-1-deficient mice suggested that induction of gamma interferon expression in the murine cecum early (12 h) after serotype Typhimurium infection was caspase-1 dependent but independent of flagellin pattern recognition. In addition, mRNA levels of the CXC chemokines macrophage inflammatory protein 2 and keratinocyte-derived chemokine were markedly increased early after serotype Typhimurium infection of streptomycin-pretreated wild-type mice regardless of flagellin expression. In contrast, in bovine ligated ileal loops, flagellin pattern recognition contributed to increased mRNA levels of macrophage inflammatory protein 3α and more fluid accumulation at 2 h after infection. Collectively, our data suggest that pattern recognition of flagellin contributes to early innate host responses in the bovine ileal mucosa but not in the murine cecal mucosa.Salmonella enterica serotype Typhimurium is a major cause of gastroenteritis in humans, which is characterized by acute intestinal inflammation and diarrhea (11, 36). One of the serotype Typhimurium virulence factors contributing to intestinal inflammation are flagella. Nonflagellated serotype Typhimurium mutants have been shown to cause less inflammation than their isogenic parents do after infection of bovine ligated ileal loops (59), streptomycin-pretreated mice (65, 74), and chickens (24).Several possible mechanisms by which flagella may contribute to eliciting proinflammatory responses have been proposed. Flagella are surface appendages of serotype Typhimurium that are required for motility and chemotaxis. Motility contributes to serotype Typhimurium invasion of intestinal epithelial cell lines by increasing bacterial contact with host cells (26, 27). The invasion-associated type III secretion system (T3SS-1) is important for inducing intestinal inflammation in animal models (1, 20, 70, 81). Nonmotile serotype Typhimurium mutants may thus cause reduced intestinal inflammation in vivo because the efficiency of T3SS-1-mediated invasion is reduced.In addition to its role in motility and invasion, the proteinaceous monomer of the flagellar filament, flagellin, has been shown to be a potent activator of the innate immune response in tissue culture models. Flagellin is an agonist of Toll-like receptor 5 (TLR5) (21), a pattern recognition receptor (PRR) of the innate immune system expressed on the basolateral surface of intestinal epithelial cells (15, 16) and on the surface of a subset of intestinal dendritic cells (71). In addition, flagellin is delivered into the cytosol of macrophages by the T3SS-1 of serotype Typhimurium (12, 38, 68), where it activates the cytosolic interleukin-1β (IL-1β) converting enzyme-protease activating factor (IPAF), a nucleotide-binding and oligomerization domain-like receptor (NLR) of the innate immune system. Recognition of flagellin by IPAF leads to activation of the inflammasome (i.e., caspase-1), followed by proteolytic activation of IL-1β and IL-18 (12, 38).Although the molecular mechanisms by which flagella influence interaction with host cells have been determined using tissue culture models, it remains unclear which of these mechanisms are operational in vivo. The principal reason for this is that most mutations that prevent the biosynthesis of flagella are associated with a pleiotropic phenotype, including an absence of motility, reduced invasion and reduced stimulation of TLR5 and IPAF. For example, inactivation of the two flagellin genes (fliC and fljB) reduces inflammation in vivo (24, 59, 65, 74), but it is not clear whether the lack of motility or the lack of flagellin pattern recognition exhibited by the fliC fljB mutant is responsible for this observation. Because of the pleiotropic phenotypes of the mutants under study, genetic approaches used in previous reports were not able to distinguish between a reduction in pattern recognition and a reduction in invasiveness as possible causes for reduced inflammatory responses elicited by nonmotile serotype Typhimurium mutants. Therefore, conclusive evidence for a contribution of flagellin pattern recognition to inflammation in vivo is still lacking.Here, we applied a combination of innovative bacterial genetics, mouse genetics, and bovine ligated ileal loop experiments to overcome current limitations and test the hypothesis that flagellin pattern recognition contributes to the initiation of inflammation in vivo.