The present invention refers to the use of one or more bacterial strains to reduce the level of oxidative stress factors in mammals including man.
Oxidative stress factors is the common term for a number of molecules primarily causing prooxidant conditions in the body. Said factors, such as IL-1, IL-6, ROS (reactive oxygen species), IL-8,8-isoprostaglandin, VCAM (vascular cell adhesion molecule) and ICAM (intracellular adhesion molecule) are present at an elevated level in proinflammatory and inflammatory states.
The oxidative stress factors can also be designated inflammatory markers, which expression, however, in addition comprises so called secondary molecules, which are initiated by the oxidative stress factors, for example acute phase proteins.
ROS, as well as the other oxidative stress factors, are produced by the monocytes and lymphocytes. Normal production of the specific level serve to maintain homeostasis in the body.
An elevated level of oxidative stress factors is typical for acute and chronic inflammation. In chronic inflammation there is a risk of an increased ageing process, atherosclerosis and cancer. Chronic inflammatory states are for instance induced by heavy smoking or by chronic infections with viruses and bacteria. Another group of chronic inflammatory diseases comprises autoimmune conditions such as rheumatic diseases and psoriasis.
Chronic inflammation patients are today treated with antibiotics, high doses of vitamins or other drugs. The use of antibiotics should for several reason be avoided and the use of drugs is mostly associated with different unwanted side-effects. Rheumatic diseases are for instance treated with the drug ibuprofen which is effective but expensive and gives gastric side-effects. For psoriasis patients there is no real medication.
EP 0 649 603 A1 in the name of Otsuka Pharmaceutical Co., Ltd. refers to an antioxidant food comprising a fermentation product of a food containing a manganese-containing natural material, such as tea leaves, by means of a microbe such as Lactobacillus plantarum. The reason for choosing said bacterium is said to be the catalase activity as well as superoxide dismutase-like activity thereof, which brings about an antioxidant activity in the body, but only in the presence of manganese.
Nenonen, MT., et al., British Journal of Rheumatology, March 1998, 37(3) p 274-81, describes the effect of uncooked lactobacilli-rich vegan food in rheumatoid patients. Half of the patients experienced adverse effects such as nausea and diarrhoea and therefore stopped the experiment, but the other half experienced a subjective release of symptoms. It is speculated that a daily consumption of lactobacilli might have a positive effect also on objective measures of rheumatoid arthritis.
U.S. Pat. No. 4,314,995 in the name of Seikenkai refers to a process for treating a patient having an infection or an inflammation caused by an infectious disease, which comprises administering at least one Lactobacillus which has different nutritional requirements compared to known strains of Lactobacillus, that is which has the ability to grow on a special low nutrition culture medium. Five different strains of Lactobacillus are mentioned as being of the invention.
International Journal of Food Microbiology, 42 (1998) 29-38, discloses a significant increase in the total faecal concentration of the short-chain fatty acids (SCFA) acetic acid and propionic acid after 3 weeks of intake of 400 ml/d of a rose-hip drink containing oats fermented with the probiotic Lactobacillus plantarum. This increase, which is said to be independent from the basal diet, can either be explained by a production of SCFA by the administered probiotic strain or by said strain stimulating or suppressing other SCFA producing bacteria in the colon.
The present invention refers to the use of a bacterial strain giving rise to increased amounts of propionic acid in the gut for the manufacture of a medicament for reduction of the level of oxidative stress in mammals including man.
The invention especially refers to the use of a bacterial strain giving rise to increased amounts of propionic acid in the gut for the manufacture of a medicament for reduction of the level of IL-6, ROS, and the adhesion of monocytes to endothelial cells in mammals including man.
A high level of oxidative stress factors, such as the cytokines interleukin 1 and interleukin 6, ROS, and the adhesion of monocytes to endothelial cells is a characteristic of proinflammatory and inflammatory states.
The bacterial strain giving rise to increased amounts of propionic acid in the gut is preferably a strain of Lactobacillus or Propionibacterium. 
According to a preferred embodiment of the invention the bacterial strain is a Lactobacillus plantarum strain. A preferred strain of Lactobacillus plantarum is the strain Lactobacillus plantarum 299v, which has been deposited at the DSM, Deutsche, Sammlunq von Mikroorganismen von Zellkulturen GmbH, Mascheroder Weg1b Braunscheweig, Germany, under the accession number DSM 9843.
The invention also refers to the use of a bacterial strain giving rise to increased amounts of propionic acid in the gut for the manufacture of a medicament for the prophylaxis and/or treatment of chronic inflammatory diseases. Chronic inflammatory or proinflammatory diseases which can be treated according to the invention can be induced by different bacteria, such as Chlamydia pneumoniae and Helicobacter pylori, or toxic substances, such as nicotine. It has for instance been demonstrated that the number of antibodies against Helicobacter pylori was reduced after one month consumption of Pro Viva, a rose-hip drink containing oats fermented with Lactobacillus plantarum DSM 9843 (5xc3x97107 cfu/ml) in an amount of 400 ml/d.
A preferred use according to the invention is for the prophylaxis and/or treatment of autoimmune diseases, such as rheumatic diseases, and psoriasis.