Bilemaking microbe fights off germ behind chronic diarrhea

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first_imgScientists have identified a natural microbial defender in the body’s fight against Clostridium difficile. The diarrhea-inducing and sometimes life-threatening bacterium lurks in hospitals and flourishes in patients whose intestinal microbes have been decimated by antibiotics. Now, a set of experiments shows that a normal microbial resident of the mouse and human gut, called Clostridium scindens, seems to help curtail C. difficile infection in rodents by creating bile acid in the intestine. If that holds true in people, pills containing the bacteria could be both a preventative measure in patients at risk and an alternative to the successful strategy, off-putting to many, of fecal transplants.In the United States, about 14,000 people a year die from C. difficile, and cases are on the rise. Researchers have learned that by depleting resident microbes, antibiotics make the body more hospitable to C. difficile spores. More recently, they’ve found that fecal transplants appear to restore balance to the bacterial community, as do feces-filled capsules.But many researchers are eager to move past the poop, says Trevor Lawley, a microbiologist at the Wellcome Trust Sanger Institute in Hinxton, U.K. “If you have a patient show up, you have to identify a donor, get them to poop in a pot, and then put it in a pill.” The process is time-consuming, unpleasant, and not without risks, he says. The ideal treatment would be an isolated mixture of helpful bacteria: “You could just go to your refrigerator and grab your capsules and tell them to take a few.” First, though, scientists need to know which individual bacteria are most helpful, and why. For 4 years, infectious disease researcher Eric Pamer and his colleagues at Memorial Sloan Kettering Cancer Center in New York City have studied the body’s elaborate defense mechanisms against C. difficile. In earlier research, they had found that certain antibiotics caused more severe and longer lasting susceptibility to the infection than others. Knowing that each treatment has a unique effect on the makeup of the microbiome, the collection of microorganisms inside us, “we used the different antibiotics as tools,” Pamer says, “to start to pin down which bacteria are associated with resistance.”That new research began in mice, which received one of three antibiotics and were then fed C. difficile spores. After identifying 11 bacteria from rodent guts that correlated with resistance to the intestinal infection, Pamer and his group turned to humans. They sequenced bacterial DNA in the feces of 24 bone marrow transplant patients who had received antibiotics. Half of them had developed C. difficile infection, whereas the other half had colonies of C. difficile in their intestines but no disease, suggesting that something about their microbiomes made them more resilient. The top microbial defenders in mice and people weren’t identical, but one species ranked high on both lists: C. scindens.That was encouraging news, Pamer says, because what’s already known about C. scindens fits right into the story of how C. difficile interacts with the gut. Other groups have shown that C. scindens makes enzymes that chemically alter the bile acids made in the liver, transforming them into so-called secondary bile acids in the large intestine. And these secondary bile acids have been shown to inhibit C. difficile growth in a dish.Indeed, feeding mice a dose of C. scindens after antibiotics reduced the number of C. difficile bacteria that were able to proliferate in the gut roughly 100-fold. And a group of mice treated with C. scindens mixed with three other bacteria similar to the strains identified by DNA sequencing lost less weight—about 10% versus nearly 20% in controls—and had better survival rates—100% versus 50%—after exposure to C. difficile. (The multibacteria cocktail yielded better results than C. scindens alone, though the researchers don’t know its mechanisms of action.) C. scindens also increased the abundance of secondary bile acids in the gut, Pamer and his colleagues report online today in Nature.This isn’t the first study to suggest a role for certain bacteria in resisting C. difficile, says Vincent Young, a microbiologist and infectious disease physician at the University of Michigan, Ann Arbor. His group has found that the bacterial family Lachnospiraceae also has a suppressant effect, for example. But the clear link to bile production makes this an important finding because the precise mechanisms of bacterial defense have been largely missing from existing studies, he says. “We know who’s there, but we don’t necessarily know what they’re doing.”Lawley agrees that understanding how this bacteria protects against C. difficile will make it a stronger candidate for potential testing in humans down the line. “We have to be careful about what we’re putting into patients, because most of these bugs, we don’t understand their biology,” he says. “I think by having a mechanism, it gives us a little bit more confidence.” He points out that C. scindens didn’t completely get rid of disease in the mice, which would be important for eliminating the risk of relapse. But as Pamer’s group and several others start concocting feces-free C. difficile treatments, Lawley believes “this is probably one bug that could be considered in the mix.” Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Click to view the privacy policy. 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