Commensal microflora induce host defense and decrease bacterial translocation in burn mice through toll-like receptor 4

Abstract

BackgroundMajor burn is associated with decreased gut barrier function and increased bacterial translocation (BT). This study is to investigate whether commensal microflora induce host defense and decrease BT in burn mice.MethodsFirst, we treated Wild type (WT) mice with antibiotics in drinking water for 4 weeks to deplete gut commensal microflora. At week 3, drinking water was supplemented with lipopolysaccharide (LPS); a ligand for TLR4, to trigger TLRs in gut. The intestinal permeability, glutathione level, NF-κB DNA-binding activity, TLR4 expression of intestinal mucosa, BT to mesenteric lymph nodes (MLNs), and bacterial killing activity of peritoneal cells were measured after thermal injury. Second, lung of animals were harvested for MPO activity and TNFα mRNA expression assay. Third, WT animals were treated with oral antibiotics with or without LPS supplement after burn. At 48 hr after burn, TLR4 expression of intestinal mucosa and bacterial killing activity of cells were examined. Finally, bacterial killing activity and BT to MLNs after thermal injury in C3H/HeJ (TLR4 mutant) mice were measured.ResultsBurn induced BT to MLNs in WT mice. Commensal depletion decreased TLR4 expression as well as NF-κB activation of intestine, myeloperoxidase (MPO) activity as well as TNFα expression of lung, and bacterial killing activity of peritoneal cells. Oral LPS supplement markedly reduced 81% of burn-induced BT and increased TLR4 expression, MPO activity of lung, as well as bacterial killing activity of peritoneal cells. LPS supplement did not change BT or bacterial killing activity in C3H/HeJ mice.ConclusionsCollectively, commensal microflora induce TLR4 expression of intestine and bacterial killing activity of inflammatory cells in burn. TLR4 ligand increases bacterial killing activity and decreases burn-induced BT. Taken together with the abolition of LPS effect in TLR4 mutant mice, we conclude that commensal microflora induce host defense and decrease bacterial translocation in burn mice through toll-like receptor 4.

The microbiome of translocated bacterial populations in patients with and without inflammatory bowel disease

“…2 The passage of bacteria from the lumen through the gastrointestinal mucosa to normally sterile tissues, such as the mesenteric lymph nodes, is referred to as bacterial translocation. 5 It has been hypothesised for decades that microorganisms are involved in the aetiology of inflammatory bowel diseases (IBD; Crohn disease (CD) and ulcerative colitis (UC)). Murine models have suggested that bacterial commensals reduce bacterial translocation in the presence of severe illness through toll-like receptor 4-mediated host defences.…”

“…Murine models have suggested that bacterial commensals reduce bacterial translocation in the presence of severe illness through toll-like receptor 4-mediated host defences. 5 It has been hypothesised for decades that microorganisms are involved in the aetiology of inflammatory bowel diseases (IBD; Crohn disease (CD) and ulcerative colitis (UC)). 6 Previous culture-based studies have demonstrated bacterial translocation to be more common in those with IBD: 5-24% of controls, compared with up to 33-48% of patients with IBD, have had organisms isolated from mesenteric lymph nodes.…”

Effect of melatonin and misoprostol on bacterial translocation in portal hypertensive rats

“…1,2 Bacterial translocation (BT) is defined as the passage of intestinal bacteria and bacterial products from the intestinal lumen to the extraintestinal sites, such as the mesenteric lymph node (MLN), the blood, and distant tissues. [3][4][5][6][7][8][9][10][11][12] BT is reported to occur after thermal injury, 3 hemorrhagic shock, 4,12 intestinal obstruction, 11,13 pancreatitis, 6 intestinal ischemia-reperfusion inury, 14 obstructive jaundice, 15 portal hypertension, 2,5 chirrosis 5,7 and Crohn's disease. 10 In various studies it has been reported that bacteria from the gut were detected in peritoneal fluid, MLN, and blood cultures follow-ing PHT.…”

Intestinal dysbacteriosis contributes to decreased intestinal mucosal barrier function and increased bacterial translocation

“…These microbes, collectively referred to as the commensal microflora, have an important role in human nutrition and health, promoting nutrient supply, preventing pathogen colonization, and shaping and maintaining normal mucosal immunity (Chen et al . ). The majority of these microbes reside in the intestines as part of the intestinal microbiota, with microbiota levels ranging from <10 5 bacteria per gram of digesta in the upper parts of the small intestine to >10 12 bacteria per gram of digesta in the colon (Sekirov et al .…”