The Research Institute of the Vall d'Hebron University Hospital demonstrates how there is a significant decrease in the secretion of inflammatory signals of the intestinal mucosa in Crohn's disease thanks to the presence of Lactobacillus casei.

A group of researchers from the Vall d'Hebron University Hospital Research Institute has shown -in vitro- how a probiotic, Lactobacillus casei, regulates inflammatory signals in Crohn's disease. This discovery, although it is a study carried out on intestinal mucosa in the laboratory and not directly on patients, demonstrates the clinical usefulness of probiotics, often much discussed. The results of the study, published in the journal Inflammatory Bowel Disease and led by Drs Maria Antolín, Marta Llopis and Francisco Guarner, represent a further step forward in the search for evidence for the use of probiotics as part of the treatment of inflammatory bowel diseases, because they demonstrate that the use of the probiotic studied prevents and counteracts the pro-inflammatory effects of bacteria present in the intestinal flora on the affected mucosa in patients with Crohn's disease. Crohn's disease is characterized by the individual's defense system attacking its own intestine and producing inflammation.

Crohn's disease is therefore an autoimmune disease. The origin of the disease is unknown, but genetic factors are known to be involved. Crohn's disease is characterized by periods of activity (outbreaks) followed by periods of inactivity in which no symptomatology is present. Symptoms can vary greatly from patient to patient, but can be summarized as follows: abdominal pain, diarrhea, vomiting, weight loss, loss of appetite, weakness; sometimes intestinal obstruction and fever. The intestinal mucosa is eroded to the point of presenting authentic ulcers in the most severe cases. Sometimes it is so severe that surgery is required to remove the damaged intestinal tract. It occurs equally among men and women. It is more common in younger people, usually appearing between the ages of 20 and 40. Currently there is no curative treatment and all therapeutic resources are oriented to palliate the symptoms.

The study and the results

The interaction of commensal or saprophytic bacteria in the intestine with the intestinal immune system is an essential factor in the development of inflammatory bowel disease. In order to understand how the pathophysiological mechanisms of this interaction occur, it is essential to study the effects of commensal bacteria in an isolated manner. This is the basis of the work of this study which has focused on the immune response of the mucosa of patients with Crohn's disease to Escherichia coli ATCC 35345 (a common intestinal bacterium) and Lactobacillus casei (a commonly used probiotic).

Samples of this inflamed intestinal mucosa were incubated with Escherichia coli in an isolated manner, with Lactobacillus casei in an isolated manner, with Lactobacillus casei DNA and with both bacterial strains together. In these samples the production of different proinflammatory molecules of the cytokine family TNF-α, INF-γ, IL-2 and IL-6 and of the chemokines IL-8, CXCL1 and CXCL2 has been studied.

The results are clear: in samples with live L. casei, "there is a significant decrease in the secretion of inflammatory signals from Crohn's disease mucosa. This effect is produced by the whole bacterium and not only its DNA", explains Dr. Marta Llopis, first signatory of the article. This probiotic decreases the expression of cytokines and chemokines involved in inflammation and therefore in the injury mechanisms of the intestinal mucosa affected by Crohn's disease. "In the mucosal samples that have been incubated with E. coli there is a clear increase in the expression of cytokines involved in mucosal inflammation, confirming that in the presence of inflammation and ulcerative lesions of the intestinal mucosa, as is the case in Crohn's disease, bacteria that are usually found in the intestine can promote the injury mechanisms and improve the situation of intestinal inflammation in patients affected by this disease", continues Dr. Llopis.

Clinical applications and current limitations

The most interesting thing is that in samples combining L. casei and E. coli, "the presence of the probiotic prevents and counteracts the proinflammatory effects of E. coli on the intestinal mucosa in patients with Crohn's disease. So it could be used as a preventive treatment in the disease, looking for a way to avoid or mitigate flare-ups," explains Dr. Maria Antolín, one of those responsible for the study. When inflammatory lesions are established, in an outbreak of Crohn's disease, for example, probiotics could be useful to counteract the effects of the intestinal flora itself on mucosal lesions. "These results give us an idea of the effects of a bacterium and a probiotic in laboratory conditions, but in real conditions, we have a lot of bacteria in the intestinal flora and we have to see how they interact with each other," continues Dr. Antolin. "It is also necessary to see how much probiotics would be needed to mitigate the effects of all the bacteria that could interact with the mucosa in the case of inflammatory lesions such as in the disease we are dealing with".

What is clear, thanks to this study and others from the same research group, is that the use of probiotics prevents alterations in the permeability of the intestinal barrier and therefore prevents or reduces the invasion of bacteria from the intestinal flora into the cells of the intestine. Furthermore, the use of probiotics reduces the recruitment of neutrophils, defense cells that come to limit the attack of the flora, but contribute to the inflammation of the mucosa, and counteracts the direct effect of bacteria, present in the flora, when there is an established intestinal lesion such as Crohn's disease.