New gut ecosystem model?

A new class of organisms may be cutting in on the classic, co-evolutionary, immune system-boosting tango between mammals and the beneficial bacteria that inhabit their guts: parasitic worms.

Trichuris muris eggs with Escherichia coli
Image courtesy of Kelly Hayes, University of
Manchester

Researchers at the University of Manchester in the United Kingdom report this week in Science that they have found that parasitic worms of the genus __Trichuris__ -- inhabitants of many a mammal's large intestine -- are dependent upon common gut bacteria, such as __E. coli__, to reproduce inside their mammalian hosts. This means that the worms likely evolved alongside the bacteria that share their host and may play a more crucial role in building and modulating mammalian immune responses than previously expected. "Having a low number of worms that don't cause disease may be effective in developing a robust and effective immune response," University of Manchester microbiologist linkurl:Ian Roberts;http://www.ls.manchester.ac.uk/people/profile/?id=521 told __The Scientist__. "You end up with a kind of beneficial ecosystem." Looking at a species of __Trichuris__ that commonly infects mice, Roberts and his colleagues found that the worm's eggs would only hatch in the presence of bacterial cells, which clustered around tiny trap doors in the oblong egg capsules through which the worms would emerge. When bacteria were absent, hatching ceased. This strategy makes sense for the worms, Roberts added, because their dispersal to different hosts depends upon a life spent in the nether regions of the digestive tract, during which they hatch out of eggs and lay more that are released in the host's feces. __Trichuris__ worms don't hatch in stomachs or small intestines -- only in large intestines, where large numbers of bacteria also reside. linkurl:Richard Grencis,;http://www.ls.manchester.ac.uk/people/profile/index.aspx?id=401 University of Manchester immunologist and senior author on the paper, told __The Scientist__ that other species of __Trichuris__ worms infect up to 1 billion humans, most of whom live in subtropical regions. "The majority of the people that are known to be infected have low level but chronic infection," he said. "The low levels of infection enable the parasite to survive, probably modulating host immunity to its own advantage." Indeed, worms may have broader effects on the host's immunity to a range of foreign invaders, in much the same way that the presence of gut bacteria modulates immunity. Science has long known that beneficial gut bacteria are crucial to their host's immune function. Soon after birth, beneficial bacteria begin colonizing mammalian guts, where they incite the release of specific lymphocytes that help the host's immune system combat pathogenic bacteria while leaving them in peace. But this paper, said Yale University evolutionary biologist linkurl:Stephen Stearns,;http://www.yale.edu/eeb/stearns/ builds a bridge between that model of immune modulation and the epidemiological evidence that autoimmune diseases are rare in areas where intestinal worm infections are common. "This [interaction between worm and bacterium] is unexplored and, it's particularly relevant because of its medical significance," Stearns told __The Scientist__.

__Trichuris muris__ emerging from eggs
stimulated to hatch by __Escherichia coli__
Image courtesy of Kelly Hayes, University of
Manchester

Recent research has explored using low-level parasitic worm infections to treat autoimmune diseases. Some treatments, though still controversial, exist for disorders such as Crohn's Disease and ulcerative colitis. The theory is that intestinal worms tone down overactive immune responses that typify autoimmune disorders. In light of these new findings, Stearns said, the health of gut bacteria must be considered in concert with the hypothesized immune modulatory effect of the worms. For now, though, Roberts and Grencis are focusing more on the novelty of the three-way interaction between worms, bacteria and mammalian hosts that they've uncovered. Both said it was too early and there were too many additional aspects of the interaction to explore to draw clinical conclusions about what Roberts called the "three-legged stool" interaction. But Roberts did venture a vision of how the research might be useful in the future. "I think if we understand how our immune systems develop and are built then it gives us a greater opportunity to manipulate that," he said. "It gives us the opportunity to potentially prime the immune system by different kinds of tailored probiotics or even by potentially delivering different types of worms. Who knows?"
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[17th April 2010]*linkurl:Charting the Human Metabolome;http://www.the-scientist.com/article/display/55640/
[May 2009]*linkurl:Stopping Hookworm;http://www.the-scientist.com/article/display/53318/
[Jul 2007]