29.7.11

Do probiotics lessen Crohn's symptoms?

Probiotic on Wikipedia
" ... live microorganisms thought to be beneficial to the host organism. ...Lactic acid bacteria (LAB) and bifidobacteria are the most common types of microbes used as probiotics; but certain yeasts and bacilli may also be helpful. Probiotics are commonly consumed as part of fermented foods with specially added active live cultures; such as in yogurt, soy yogurt, or as dietary supplements."

"What are some of the best food sources for probiotics and prebiotics?" from the world's healthiest foods
"Cultured dairy foods such as yogurt and kefir can be great sources of "healthy" or "friendly" bacteria. ... In most prepackaged, processed foods, however, it is unlikely to find any sizable quantities of live bacteria ("probiotics") due to the use of heat and chemicals in food processing. ...  it's important to select cultured dairy products that indicate "contains live cultures" or "contains active cultures" on the packaging. Some manufactures will actually report the amounts of live culture contained in the product.
Live bacterial cultures can be added to other foods besides dairy foods. Sauerkraut-another name for fermented cabbage-is an example of a cultured vegetable. An Asian version of fermented cabbage, particularly popular in Korea, is called kim chee. A basic fermentation process is used to culture the cabbage in kim chee, and chili pepper, garlic, and salt are typically added to give this cultured vegetable its pungent character. As with cultured yogurts and kefirs, these fermented vegetables may or may not contain active bacterial cultures. Once again, the manufacturers who are sensitive to these issues will often indicate the presence of live bacteria cultures (if they are present) on the packaging. Miso, a thick paste often made from soybeans, is another example of a cultured food that can contain live bacterial populations."


"Pre-, Pro-, Synbiotics and Human Health" in Synbiotics and Human Health (2010)
"The reason why attempts to reduce inflammation with the use of probiotics sometimes failed in the past might be that the pro-inflammatory pressure is simply too high due to the underlying disease, but also due to the consumption of too much of pro-inflammatory foods and prescription drugs, all with inflammation-enhancing abilities. It is likely that under certain conditions, additional measures are needed in order to achieve successful treatment with  probiotics. Measures such as reduced supply of pro-inflammatory foods, restriction in the use of pharmaceuticals and increased intake of plant foods rich in anti-inflammatory vitamins and antioxidants, especially various polyphenols, might well be needed.
...
Thousands of factors are important to maintain health and to cure disease. This might explain why single drug
pharmacy fails both to prevent a disease and to cure it, especially when chronic. Human innate immunity for a proper function much depends on continuous access to bacteria and plants. Using probiotics in combination with plants and their active ingredients remains an attractive approach for prevention and treatment of various acute and chronic diseases."

"Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism " in J Clin Invest (2011)
"... The effects of probiotics on the clinical course of Crohn disease are controversial.

Recently, three distinct and complementary cellular mechanisms for the actions of probiotics were proposed (11). First, probiotics block pathogenic bacterial effects by producing bacteriocidal substances and competing with pathogens and toxins for adherence to the intestinal epithelium. Second, probiotics regulate immune responses by enhancing innate immunity and modulating pathogen-induced inflammation via Toll-like receptor–regulated signaling pathways. Third, probiotics regulate intestinal epithelial homeostasis by promoting intestinal epithelial cell survival, barrier function, and protective responses through several signaling pathways.

The clinical application of probiotics has at least two limitations: bioavailability and biosafety. For example, bacteremia associated with probiotic therapy has been reported in very young (12) and immunocompromised patients (13). One potential approach to address these concerns may be development of probiotic bacteria–derived proteins as novel therapeutic agents. Thus, identification of probiotic-derived soluble factors that exert effects similar to those of probiotics offers not only insight into the mechanisms of probiotic action, but also significant potential for clinical application. ...

In the present study, we demonstrate that the LGG-derived soluble protein p40 activates EGFR in vivo and in vitro in colon epithelial cells. Activation of EGFR by p40 is required for inhibition of cytokine-induced apoptosis and disruption of barrier integrity in intestinal epithelial cells in vitro and ex vivo. Importantly, p40 prevents and treats DSS-induced colon epithelial injury and inflammation and ameliorates oxazolone-induced colitis, and it mediates reductions of intestinal epithelial apoptosis and disruption of barrier function in these two mouse models, in an EGFR activation-dependent manner. Therefore, our findings provide a rationale for conducting new hypothesis-driven studies to define the clinical efficacy of probiotic-derived proteins in preventive, adjunctive, or alternative treatments for intestinal inflammatory disorders. ...

A number of disorders of the gastrointestinal tract, including IBD, are characterized by elevated cytokine production and increased apoptosis, which disrupt the integrity of the protective epithelial monolayer. Therefore, strategies that promote maintenance of intestinal epithelial integrity may serve as effective approaches for treatment of IBD and other cytokine-mediated intestinal disorders. ...

However, it should be noted that aberrant EGFR activation due to overexpression and/or mutation of EGFR and autocrine growth factor loops have been related to hyperproliferative diseases such as cancer. Thus, one concern regarding probiotic therapy in IBD is an increased risk of cancer. ...

We are focusing on determining the mechanisms by which p40 regulates innate immunity. It has been reported that LGG-conditioned cell culture media decreases TNF production in macrophages, indicating that soluble molecules derived from LGG exert this immunoregulatory role (20). Therefore, we hypothesize that p40 may have direct effects on macrophages and/or lymphocytes to regulate immune responses during inflammation. This hypothesis is being tested in our laboratory. ...

Although both p40 and p75 are able to prevent cytokine-induced apoptosis, p40 appears more potent than p75 (our unpublished observations). It is likely that additional factors secreted by LGG and other probiotic bacteria may have cytoprotective or immunological effects in the gastro­intestinal tract or other tissues, and thus this field represents an important area for further investigation. ...

This is the first report to our knowledge showing delivery of probiotic-derived soluble proteins to the colon to protect mice from colitis. This effect is mediated through activation of EGFR and supports development of probiotic-derived proteins as novel reagents for preventing and/or treating ulcerative intestinal inflammatory disorders." [Emphases mine.]


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