Inactivated probiotic bacteria also protect against colitis
The non-specific (innate) immune response is the first line of defense against infectious diseases. It is generally carried out on factors invading pathogens (lipopolysaccharides (LPS, endotoxin), bacterial lipoproteins, lipoteichoic acids, peptidoglycans, CpG nucleic acids). The first challenge for the host is to track down the pathogen and initiate a rapid defense reaction. A group of proteins comprising the Toll or Toll-like receptor family performs this function in vertebrates and invertebrates. The TLRs (Toll-like receptors) serve as so-called pattern recognition receptors in mammals and play an essential role in the recognition of microbial components. They are expressed on macrophages, dendritic cells and B lymphocytes, among other things, and recognize antigenic structures that are highly conserved in the living environment, so-called pathogen-associated molecular patterns. TLR2 is activated by bacterial lipoproteins, TLR3 by dsRNA, TLR4 by LPS, and TLR9 is activated by CpG DNA. CpG motifs are regularly found in bacterial and viral genomes, but not in vertebrate genomes. Receptor-related adapter proteins, e.g. B. the signal transmitter MyD88 involved.
A group of researchers from Israel, USA. and Japan (RACHMILEWITZ et al.: Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis) now investigated whether the weakening of experimentally produced colitis by live probiotic bacteria can be attributed to their immunostimulatory DNA, whether TLR signaling is required, and whether non-live probiotic bacteria are also effective. For this purpose, before the targeted induction of colitis in test mice, methylated and non-methylated genomic DNA from probiotic bacteria of a commercial preparation (mixture of Lactobacillus casei, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium bacterium infantis, Streptococcus salivarius subsp.thermophilus) and DNA of these probiotic bacteria treated with DNAse and from Escherichia coli DH5a administered intragastrically (ig) or subcutaneously (sk). Live or radiation-inactivated probiotic bacteria were administered ig to wild-type mice and mice lacking TLR or adapter protein MyD88 10 days before the mice were given dextran sodium sulfate (DSS) in their drinking water and for 7 days after DSS -gift. Both ig and sc administered DNA from probiotic bacteria and from E. coli resulted in a more favorable course of the DSS-induced colitis in the mice. In contrast, methylated DNA from probiotic bacteria, calf thymus DNA and DNAse-treated probiotics showed no effect. The severity of colitis was attenuated by ig administration of killed, irradiated, and live probiotics alike. Mice lacking MyD88 showed no response to irradiated probiotics. Mice without TLR2 and TLR4 reacted significantly less to DSS-induced colitis when given irradiated probiotics, while mice without TLR9 showed no reaction under the same conditions.
The authors conclude that the protective effects of probiotics are mediated through their own DNA and not through their metabolites or their ability to colonize the colon. TLR9 signaling is essential for mediating the anti-inflammatory effects of probiotics. Live microorganisms are not needed to attenuate experimentally induced colitis since non-live probiotic bacteria are just as effective.
Source: Kulmbach [KRÖCKEL]
