Bile-microbe to fight germs behind chronic diarrhea

15:46
Bile-microbe to fight germs behind chronic diarrhea -

Scientists have identified a natural microbial advocate in the fight against the organization Clostridium difficile . The deadly bacteria inducing diarrhea and sometimes lurks in hospitals and develops in patients with intestinal microbes were decimated by antibiotics. Now, a series of experiments shows that a normal microbial resident mouse and the human intestine, called Clostridium scindens seems to help limit C. difficile infection in rodents, creating bile acids in the intestine. If this is true in people, pills containing bacteria can be both a preventive measure in patients at risk and an alternative to the successful strategy, putting to many, fecal transplants.

In the United States, about 14,000 people a year die of C. difficile , and cases are on the rise. The researchers learned that deplete resident microbes, antibiotics make the body to hospital C. difficile spores. More recently, they have found that fecal transplants appear to restore balance to the bacterial community, such as faeces-filled capsules.

But many researchers are eager to move beyond crap, said Trevor Lawley, a microbiologist at the Wellcome Trust Sanger Institute in Hinxton, UK "If you show a patient, you need to identify a donor, get them to poo in a pot, then put it in a pill. " the process takes time, unpleasant, and not without risks, he said. The ideal treatment would be an isolated mixture of beneficial bacteria, "You can just go to your fridge and take your capsules and tell them to take a few." First, however, scientists need to know which individual bacteria are most useful, and why.

For 4 years, researcher in infectious diseases Eric Pamer and his colleagues at Memorial Sloan Kettering Cancer Center in New York studied the elaborate defense mechanisms of the body against C. difficile . In previous research, they found that certain antibiotics caused more severe and more lasting sensitivity to infection than others. Knowing that each treatment has a unique effect on the composition of the microbiome, the collection of microorganisms within us, "we used different antibiotics as tools," Pamer said, "to begin to identify which bacteria are associated resistance. "

The new research began in the mice who received one of three antibiotics and were then fed C. difficile spores. Having identified 11 bacterial guts of rodents that correlate with resistance to intestinal infection, Pamer and his group turned to humans. They sequenced the bacterial DNA in the stools of 24 bone marrow transplant patients who received antibiotics. Half of them had developed C. difficile infection, while the other half were colonies of C. difficile in their intestines, but no disease, which suggests something about their microbiomes made it more resilient. Senior microbial defenders in mice and people are not identical, but a senior species on both lists: C. scindens .

That news was encouraging, Pamer said, because what is already known about C. scindens fits right into the story of how C. difficile interacts with the intestine. Other groups have shown that C. scindens makes the enzymes that chemically modify bile acids produced in the liver, turning them into so-called secondary bile acids in the colon. And these secondary bile acids have been shown to inhibit C. growth difficult in a dish.

Indeed, the feeding mice a dose of C. scindens after antibiotics reduced the number of C. difficile bacteria that were able to proliferate in intestine about 100 times. And a group of mice treated with C. scindens mixed with three other similar bacteria strains identified by DNA sequencing lost less weight of about 10% to nearly 20% among witnesses- and had better survival rate-100% against 50% -after exposure to C. difficile . (The multibacteria cocktail gave better results than C. scindens alone, although researchers do not know its mechanisms of action.) C. scindens also increased the abundance of secondary bile acids in the intestine, Pamer and his colleagues report online today in Nature .

This is not the first study to suggest a role for certain bacteria to resist C. difficile , said Vincent Young, a microbiologist and infectious disease physician at the University of Michigan, Ann Arbor. His group found that the bacterial family Lachnospiraceae also has a suppressive effect, for example. But the clear connection for bile production makes this important discovery because the precise mechanisms of bacterial defense were largely absent from existing studies, he said. "We know who is there, but we do not necessarily know what they are doing."

Lawley should understand how this bacterium protects against C. difficile , it will be a stronger candidate for potential tests in man down the line. "We must be careful what we put into the patients, because most of these bugs, we do not understand their biology," he said. "I think having a mechanism, it gives us a bit more confidence . "He says C. scindens does not completely get rid of the disease in mice, which is important to eliminate the risk of relapse. But as the group Pamer and several others begin concocting free excrement C. difficile treatments, Lawley believes that "this is probably a bug that could be considered in the mix."

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