19 November 2012

Therapeutic parasites

Helminths protect us from Crohn's disease

Ilya Shcheglov, "Science and Life"Therapeutic manipulations with microflora: microscopic roundworms Trichuris trichiura help prevent bacterial damage to the intestinal mucosa.

Our ideas about the microorganisms inhabiting the intestine have changed radically over the past few decades. At the dawn of these studies, it was believed that the beneficial microflora of the digestive system is represented by several dozen strains that, coexisting with us, take a limited part in digestion and provide us with a certain amount of certain vitamins. No one even imagined the real scale of the impact of the quality and quantity of obligate (mandatory for the normal functioning of the intestine) and optional (optional) microflora on our body.

Today it has become clear that the diversity of microorganisms inhabiting only the digestive system (and there are also skin, mucous membranes of the respiratory tract and many other "places" of our body populated by their "resident" microflora) is so great that if these organisms were larger, they could be used to assemble an unheard-of zoo in size. The total number of microflora cells exceeds the total number of cells in our body, and the total number of genes of these microorganisms can be a hundredfold higher than the number of human genes. Moreover, our body is inhabited by representatives of all three domains of life – bacteria (the vast majority of them are in the microflora), archaea and eukaryotes (mainly unicellular), as well as viruses that do not belong to these three domains, including viruses that live in these microorganisms themselves (for example, bacteriophages).

Now, knowing the colossal scale of such a symbiosis, it is not difficult to imagine that the influence of the microbiome (a new term describing a collection of microorganisms) on its "multicellular host" can be enormous. Experimental confirmations of this are constantly appearing. The degree of influence may vary depending on the level of organization of the host. For example, in insects, cases are known and studied when the microbiota directly affects the evolution of a macroorganism by controlling its sexual behavior. In mammals, however, the matter is "limited" to the influence on the processes of development and functioning of the individual organism. For example, cases are described when violations of the qualitative and quantitative composition of the microbiota lead to malformations of the central nervous system and cause inflammatory bowel diseases.

But, given the impressive size and complexity of the organization of our microbiota, we can safely hope that even more amazing discoveries are waiting for us ahead. Recently, the authoritative journal PLOS Pathogen published the results of a study showing the possibility of therapeutic use of the microscopic parasitic worm Trichuris trichiura in order to normalize the unbalanced intestinal microflora in the case of chronic inflammatory bowel diseases (Broadhurst et al., Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon).

Many details of the pathogenesis of chronic intestinal diseases (CVD), which include ulcerative colitis and Crohn's disease, are reliably unknown, which significantly complicates the search for methods of their treatment. However, one of the key manifestations of these diseases is significant changes in the species composition and number of intestinal bacteria. It is known that this may partly be due to malfunctions in the human immune system, leading to the development of immune aggression against certain types of intestinal bacteria (normally absent).

Based on this mechanism, the authors used the well-known phenomenon of switching an immune attack from one target to another in biology and medicine. An example of such a phenomenon is the mechanism of action of the drug Pyrogenal, the active component of which is lipopolysaccharide of bacterial cell walls. Among other indications, Pyrogenal is used to treat a number of diseases associated with the development of a pathological immune response, such as allergic and some autoimmune diseases (bronchial asthma, atopic dermatitis, psoriasis and some others). When introduced into the patient's body, bacterial polysaccharides, being the most powerful antigen, "distract" the aggression of the immune system on themselves, which leads to relief of the symptoms of the target disease.

The authors conducted this study on rhesus macaques suffering from idiopathic chronic diarrhea (the main cause of mortality of these animals in captivity). (As in the case of HCV in humans, idiopathic chronic diarrhea in monkeys is characterized by the development of a pathological immune response against certain strains of intestinal microflora.) As a "distracting agent", scientists chose the helminth – whipworm (Trichuris trichiura), a microscopic round parasitic worm infecting the intestines of many mammals, including humans.

The introduction of eggs of this helminth into the intestines of monkeys led to global rearrangements of their microbiome, the qualitative characteristics of which by the end of therapy began to resemble those of healthy monkeys. Moreover, there was a significant decrease in inflammatory reactions in the intestine and a decrease in the number of bacteria attached to the intestinal wall mucus. As a result, the general condition of the monkeys improved significantly, and most of them had weight gain.


The effect of bacteria on the cells of the intestinal mucosa in colitis (A)
and induction of the immune response of Trichuris sp. (B).Thus, the authors showed that normalization of the species composition of the microbiome of monkeys suffering from idiopathic chronic diarrhea may be a sufficient condition for improving their health and preventing death.

In this regard, scientists express hope for the success of further development of this therapeutic approach for the treatment of ulcerative colitis in humans.

Scientists from different laboratories around the world have been interested in studying vlasoglav as a therapeutic agent since 2004. Then the first works appeared on the use of Trichuris suis (pig whipworm) eggs for the treatment of Crohn's disease and, to a lesser extent, ulcerative colitis in pigs. There is also evidence indicating that the treatment of inflammatory bowel diseases with these helminths leads to a decrease in the incidence of asthma, allergies, and other diseases accompanied by inflammatory processes. A prospective double cohort clinical study, the results of which were published in 2007 (doi:10.1002/ana.21067), indicate that helminths are even able to slow down the development of multiple sclerosis.

Portal "Eternal youth" http://vechnayamolodost.ru19.11.2012

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