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Probiotics, Crohn's Disease, and Tumor Necrosis Factor (TNF)

February 7, 2007

The British Medical Journal Gut published a study which investigated the effect of probiotics on the production of tumor necrosis factor (TNF), a substance which plays a key role in Crohn's disease. Before describing the results of the study, here is a brief description of TNF:

What is TNF?
TNF is produced by white blood cells and inhibits the growth of malignant cells. However, overproduction of TNF results in inflammation and causes the autoimmune response seen in Crohn's disease. (sources: wikipedia, northwestern university)
Remicade and TNF
Newer drugs such as Remicade and Humira are often called "anti-TNF" drugs. These medicines inhibit the production of TNF, therefore stopping the inflammatory response. WebMd describes Remicade's actions as follows:

"Anti-TNF [remicade] removes TNF from the bloodstream before it reaches the intestines, thereby preventing inflammation".

However, a side effect is lowering the body's immunity when dealing with other infections--leading to extensive side effects.

Probiotics and TNF
In the Gut journal study, researchers used intestinal tissue specimens from 10 patients with Crohn's disease (CD) as well as 5 control patients who did not have CD. They then followed the basic steps below:

(1) measured the TNF levels produced by the specimens

(2) exposed the specimens to either a "probiotic" strain or a "blank". The probioic strains cultures used were: Lactobacillus casei, L. bulgaricus, L. crispatus, or Escherichia coli

(3) waited 24 hours and re-measured the TNF levels

The results:

(1) In the control patients' specimens (with no inflammation), nothing happened

(2) The Crohn's patients' specimens (with inflammation) showed a significant decrease in TNF level when exposed to L. casei or L. bulgaricus.

(3) The Crohn's specimens (with inflammation) exposed to the "blanks" showed significant increase in TNF levels.

(4) L. crispatus and E. coli had no significant effect on lowering TNF level.

Conclusion: Probiotic strains L. casei and L. bulgaricus induced changes which significantly reduced TNF levels.

Or as the medical journal article put it:

In summary, in the present study we have established that certain probiotic bacteria are capable of interacting with immunocompetent cells using the mucosal interface and thus can modulate locally the production of proinflammatory cytokines [TNF] by inflamed tissue. Our findings provide a basis for future clinical trials of probiotic bacteria in the treatment of active Crohn's disease.

The authors also write:

"These results suggest that cross talk between bacteria and mucosal cells does exist, and that certain bacteria downregulate the degree of activation of intestinal lymphocytes."

In other words, the effective "probiotics" trigger a change in the intestinal mucosa, and the mucosal cells reduce their TNF production.

Here's to hoping for more research on probiotics!