Nature Reviews Gastroenterology and Hepatology 8, 182 (April 2011) doi:10.1038/nrgastro.2011.26
IBD: Modified Lactobacillus acidophilus may regulate intestinal inflammation
Lactobacillus acidophilus that lack lipoteichoic acid (a major component of the cell walls of Gram-positive bacteria) have an anti-inflammatory effect in mice that results in resistance to colitis, according to a US research group.“The gastrointestinal microbiota and the immune system are closely tied, and constantly influence each other,” explains lead author Mansour Mohamadzadeh from Northwestern University, Chicago, IL.
Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4623-30. Epub 2011 Jan 31.
Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid.
Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611, USA. email@example.com
Imbalance in the regulatory immune mechanisms that control intestinal cellular and bacterial homeostasis may lead to induction of the detrimental inflammatory signals characterized in humans as inflammatory bowel disease. Induction of proinflammatory cytokines (i.e., IL-12) induced by dendritic cells (DCs) expressing pattern recognition receptors may skew naive T cells to T helper 1 polarization, which is strongly implicated in mucosal autoimmunity. Recent studies show the ability of probiotic microbes to treat and prevent numerous intestinal disorders, including Clostridium difficile-induced colitis. To study the molecular mechanisms involved in the induction and repression of intestinal inflammation, the phosphoglycerol transferase gene that plays a key role in lipoteichoic acid (LTA) biosynthesis in Lactobacillus acidophilus NCFM (NCK56) was deleted. The data show that the L. acidophilus LTA-negative in LTA (NCK2025) not only down-regulated IL-12 and TNFα but also significantly enhanced IL-10 in DCs and controlled the regulation of costimulatory DC functions, resulting in their inability to induce CD4(+) T-cell activation. Moreover, treatment of mice with NCK2025 compared with NCK56 significantly mitigated dextran sulfate sodium and CD4(+)CD45RB(high)T cell-induced colitis and effectively ameliorated dextran sulfate sodium-established colitis through a mechanism that involves IL-10 and CD4(+)FoxP3(+) T regulatory cells to dampen exaggerated mucosal inflammation. Directed alteration of cell surface components of L. acidophilus NCFM establishes a potential strategy for the treatment of inflammatory intestinal disorders.
PMID: 21282652 [PubMed - in process]PMCID: PMC3063598 [Available on 2011/9/15]