<P>14UCSF MAGAZINE | Spring 2014 many drug-producing genes in ground- and marine-dwelling bacteria. But I was shocked to see so many in the human microbiota. You used to have to travel to the coast of Palau to mine the ocean sediment for drugs, says Fischbach, an assistant professor of bioengineering and therapeutic sciences. Now we can just check our gut! EMBRACING OUR INNER PHARMACY Day in and day out, gastrointestinal microbes go about the care and maintenance of our bodies by extracting vitamins from the food we eat, goading our immune systems into action when need be, and producing the anti-inflammatories and antibiotics that keep us well. The human microbiome is basically a drug factory, says Fischbach. He is hard at work trying to discover its best products. He and UCSF Executive Vice Chancellor and Provost Jeffrey Bluestone, PhD, an immunologist, study a very promising gut bacte- rium called Bacteroides fragilis. It produces a chemical that resembles a well-known immunomodulatory drug that was discovered in a sponge off the coast of Japan 20 years ago. Fischbach and Bluestone, who holds the A.W. and Mary Margaret Clausen Distinguished Professorship in Metabolism and Endocrinology, predicted that the chemical would have a similar effect on the immune system, and they were right: The chemical produced by B. fragilis interacts with a type of human immune cell called a natural killer T cell. That meant it could be very useful in treating allergic and autoimmune diseases. Lactobacillus johnsonii is another gut bacterium with extraordinary therapeutic potential. Susan Lynch, PhD, an associate professor of gastroenterology, homed in on the organism when trying to explain a curious fact: Children who grow up in homes with dogs are less likely to develop allergies and asthma. She designed a study that involved exposing two sets of mice to household allergens – one set to dust from homes with dogs, and the other set to dust from homes without dogs. We found that mice exposed to the dog-associated house dust were protected against allergic inflammation or infection with a virus associated with the development of asthma, says Lynch, who directs UCSFs Colitis and Crohns Disease Microbiome Research Core. To figure out what microbes may have been at work, Lynch compared the bacterial fingerprints of the two sets of mice and found that approximately 100 different organisms were present in higher levels in the gut microbiomes of the protected mice; one of them was Lactobacillus johnsonii. She isolated this species from the mouse gut, fed it alone to another set of mice, and found that this resulted in airway protection, though to a lesser extent than exposure to dog dust did. This tells us a number of important things, says Lynch. First, that the Lactobacillus johnsonii did not act alone – it requires specific microbial partners to afford full airway protection. It also suggests that this full suite of protective organisms in the human body are not all native; they presumably can be sourced from the environment. In other words, Lactobacillus johnsonii partners with bacteria from the dog-household dust to fight off pulmonary allergens. According to Lynch, this makes perfect sense, given that a bacterium often relies on other bacteria to produce certain compounds, such as the amino acids it needs to survive. MOB RULE Overwhelming evidence suggests that one of the hallmarks of chronic inflammatory disease is an overall depletion of microbes. Thats why introducing a single organism into a microbial ecosystem that is out of whack may not always be effective; its partners may have been wiped out by the illness or, paradoxically, by an antibiotic intended to cure it. We are after the core set of microbes that are essential to creating a healthy microbial ecosystem, says Lynch. Our data supports the idea that Lactobacillus represents an anchor or keystone organism in such communities. Its presence, in other words, dictates which other organisms are present and how they behave – and that ultimately influ- ences a persons immune response. In fact, Lactobacillus johnsonii is known to play a powerful role in newborns immune systems even before their first breath. Lactobacillus johnsonii represents one of the major species in the microbial inoculum that a vaginally born newborn receives, says Lynch. We think its critical in structuring or priming development of the microbial community in early life, the period during which the immune response matures. Proof of its importance can be measured by its absence. Children born by cesarean section – and therefore not exposed to Lactobacillus johnsonii or other potentially protective species in the mothers vaginal tract – have a 30 percent higher risk of developing allergic asthma during childhood. A DELICATE BALANCE An individuals microbiome is best described as an ecosystem – a complex communal environment teeming with thousands of different types of microorganisms. Some of them are dependent upon one another for survival, while others simply coexist. In even the healthiest of microbiomes, there are microbes known to promote health and those known to cause disease. These bad actors live in check until an illness, or perhaps even an antibiotic, starts to deplete their neighbors, thereby unraveling a peaceful coexistence. All the while, the community ¯ghts to right itself by beating back the bad and replenishing the good until neighborhood demographics and order are restored.</p> <UL><LI><a href="http://www.mzines.net/publication/618/aelvmorax/1/1/">Front-Cover</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/2/2/">Inside-Front-Cover</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/3/3/">Page-1</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/4/4/">Page-2</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/5/5/">Page-3</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/6/6/">Page-4</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/7/7/">Page-5</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/8/8/">Page-6</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/9/9/">Page-7</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/10/10/">Page-8</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/11/11/">Page-9</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/12/12/">Page-10</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/13/13/">Page-11</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/14/14/">Page-12</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/15/15/">Page-13</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/16/16/">Page-14</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/17/17/">Page-15</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/18/18/">Page-16</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/19/19/">Page-17</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/20/20/">Page-18</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/21/21/">Page-19</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/22/22/">Page-20</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/23/23/">Page-21</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/24/24/">Page-22</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/25/25/">Page-23</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/26/26/">Page-24</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/27/27/">Page-25</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/28/28/">Page-26</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/29/29/">Page-27</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/30/30/">Page-28</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/31/31/">Page-29</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/32/32/">Page-30</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/33/33/">Page-31</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/34/34/">Page-32</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/35/35/">Page-33</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/36/36/">Page-34</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/37/37/">Page-35</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/38/38/">Page-36</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/39/39/">Page-37</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/40/40/">Page-38</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/41/41/">Page-39</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/42/42/">Page-40</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/43/43/">Page-41</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/44/44/">Page-42</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/45/45/">Page-43</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/46/46/">Page-44</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/47/47/">Page-45</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/48/48/">Page-46</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/49/49/">Page-47</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/50/50/">Page-48</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/51/51/">Page-49</a></LI> <LI><a href="http://www.mzines.net/publication/618/aelvmorax/52/52/">Back-Cover</a></LI> <LI><a href="http://www.mzines.net/publications/618/x/sitemap.xml" target="_blank">site map</a></LI> </UL>


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