New studies show link between gut bacteria and the risk of heart attack and weight gain

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1 Body & Health New studies show link between gut bacteria and the risk of heart attack and weight gain By Sharon Oosthoek 11:59am, December 1, 2014 Gut bacteria can turn a nutrient in red meat into a chemical that increases the risk of hardened arteries. The new finding helps explain why eating lots of red meat might foster heart disease. NIGHTANDDAYIMAGES/ISTOCKPHOTO Vast hordes of bacteria live in our intestines. Some promote disease. Certain others can help people digest food or fight off infection. But scientists have yet to learn what impacts most of these bacteria may be having on us. And with our bodies housing 10 times as many bacterial cells as human ones, there is much to learn. Two new studies one about heart attacks and the other about weight gain are helping to fill those gaps in our knowledge. For instance, scientists have known for at least two decades that gut bacteria can play a role in an individual s tendency to gain weight. Genes also can influence an individual s risk of plumping up. There were even hints that those genes might work by creating an environment that encouraged certain bacteria to move into our guts. New research now strengthens that last idea. 1 of 5 12/8/2014 2:37 PM

2 Michelle Beaumont is working on her Ph.D. at King's College in London, England. There she s been studying genetics and molecular medicine. This field of research probes how molecules in our bodies affect health. It also points to possible treatments for diseases that occur when these molecules don't work as they should. Beaumont and her team isolated bacteria from the feces (poop) of 416 pairs of twins. Yes, it s yucky science. But the payoff proved big. The researchers studied germs found in the feces of identical twins (siblings who share the exact same genes). They also studied germs found in the feces of fraternal twins (siblings who are no more similar to each other than any other sister or brother would be). The identical twins shared more of the same types of bacteria than did fraternal twins even though both types of twins had access to the same meals and home environment. This indicates that human genes influence both the mix and amounts of at least some gut microbes, Beaumont concludes. Different bacteria prefer different conditions. Beaumont now suspects that our genes have a big role in what conditions develop in the gut. Slimming bacteria sensitive to genes A person s genes will not influence most gut bacteria, Beaumont observes. But one family of bacteria is sensitive to them: Christensenellaceae (KRIS-ten-sehnel-LAA-see-ay). Identical twins Cherilyn Reinholtz and Charmane Kay, 35, live in London, England. They took part in a study to determine whether genes influence gut bacteria, and the risk of weight gain. TwinsUK People who remain trim tend to host more of these bacteria in their guts than do people who have trouble holding down their weight. And this link has shown up even among people who were eating the same types and amounts of food. In the new study, slim twins had more of this family of bacteria in their guts than did overweight twins. And slim identical twins were more likely to each have similar amounts of Christensenellaceae in their guts than did slim fraternal twins. Beaumont decided to see if the same findings showed up in mice. The researchers started with rodents who were similar in size and food consumption. Then they transplanted some of the special slim germs into the guts of half of the mice. They continued feeding all of the mice the same foods. Mice given the slimming gut bacteria gained less weight than did mice without those special bacteria. Beaumont s group reported its findings November 6 in Cell. These data even suggest a way to treat people who are obese, Beaumont says. Those who don t have many Christensenellaceae in their guts might take a pill containing the helpful microbes. Pills already exist that supply the gut with beneficial bacteria. Right now, however, none contain these slimming bacteria. But Beaumont would like to see scientists develop such capsules. Yet there may a catch, she admits. We know Christensenellaceae prevents weight gain, she says. At this time, she points out, We are not sure if it helps you lose weight. Peter Turnbaugh studies how bacteria in and on our bodies affect health. He works at the University of California, San Francisco. Despite these interesting findings, he says that many questions remain. For example: What genes are responsible? How strong is the influence of genes versus other 2 of 5 12/8/2014 2:37 PM

3 factors, such as diet? And can altering gut microbes prevent obesity or limit malnutrition? Answering these questions will help us understand why each person has a distinctive mixture of bugs [bacteria], with the goal of predicting and preventing disease, says Turnbaugh. Some gut microbes may make meat harmful Studies have linked eating red meat to an increased risk of cardiovascular disease, including stroke and heart attack. Why has remained unknown. Now, a new study points to certain gut bacteria that can turn a nutrient in red meat into a disease-fostering chemical. Stanley Hazen is a scientist and medical doctor at Cleveland Clinic's Lerner Research Institute in Ohio. He studies how diet choices and other behaviors may play a role in raising someone's risk of heart disease. Hazen and his team knew that gut bacteria feed on nutrients in the food we eat. And like us, those germs don't use up everything they eat. They leave behind some wastes. Scientists refer to those breakdown products as metabolites (Me-TAB-oh-lites). Last year, Hazen s group showed that gut bacteria break down a nutrient called L-carnitine (KAR-neh-teen). Rich sources of it include red meat and some energy drinks. As bacteria feed on L-carnitine, they leave behind a metabolite called trimethylamine (TRY-METH-ul-a-MEEN). Inside the human gut, this waste product gets converted to trimethylamine-n-oxide (TMAO), they showed. And that s worrisome. TMAO increases the risk that someone will develop hardening of the arteries, which is also known as atherosclerosis (ATH-er-oh-sklah-ROW-sis). This hardening is caused by an unhealthy buildup of a fatty substance known as plaque (PLAK) inside the walls of our arteries. Over time, that plaque can block blood flow, leading to a heart attack or stroke. TMAO doesn't increase the level of cholesterol (Ko-LES-ter-all) a component of plaque in your blood, Hazen s group found. But it does increase how much plaque builds up on the walls of someone s arteries. That helps explain why eating lots of red meat might foster heart disease. His team s new research finds that another type of bacteria can up heart risks even more. When the researchers fed mice foods rich in L-carnitine, these bacteria produced a different breakdown product. It's called gamma-butyrobetaine (BU-teer-oh-BEE-teh-en). This chemical, too, can break down into TMAO. Therefore, at least two types of gut bacteria help make TMAO, the new data show. Hazen s team reported its findings November 4, in Cell Metabolism. Red meat is not the only food from which gut bacteria make TMAO. Hazen published a second study in 2013 about another nutrient choline (KO-leen). It's found in eggs, shellfish, high-fat dairy products and red meat. Gut bacteria also can convert choline into TMAO, that study showed. Hazen would now like to see other scientists use his research to figure out how to turn off the process of TMAO production that is jump-started by gut bacteria. This is important, says Hazen. After all, heart disease is the number one cause of death and disability in the United States. Edward Fisher studies cardiovascular disease at New York University, in New York City. He cautions that Hazen's study does not mean eating red meat is bad. As a source of high-quality protein, this food offers important health benefits, he notes. The issue is whether excessive consumption of 3 of 5 12/8/2014 2:37 PM

4 meat may be a risk factor in some people, says Fisher. Overdoing anything, he notes, can pose risks. Together, these new studies on the impacts of gut bacteria may help science figure out how to better treat disease. In fact, the more we learn about the bugs in our bellies, the better chance we have of staying healthy in the first place. Power words atherosclerosis A disease that is also known as hardening of the arteries. It happens when fat, cholesterol, and other substances build up in the walls of arteries and form hard structures called plaques. Over time, these plaques can block blood flow in the arteries. This can lead to heart attack or stroke. bacterium (plural bacteria) A single-celled organism. These dwell nearly everywhere on Earth, from the bottom of the sea to inside animals. cardiovascular An adjective that refers to things that affect or are part of the heart and the system of vessels and arteries that move blood through the heart and tissues of the body. chronic A condition, such as an illness (or its symptoms, including pain), that lasts for a long time. feces A body s solid waste, made up of undigested food, bacteria and water. The feces of larger animals are sometimes also called dung. gene (adj. genetic) A segment of DNA that codes, or holds instructions, for producing a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves. gut Colloquial term for an organism s stomach and/or intestines. It is where food is broken down and absorbed for use by the rest of the body. metabolism The set of life-sustaining chemical reactions that take place inside cells. These reactions enable organisms to grow, reproduce, move and otherwise respond to their environments. metabolite The compounds left behind after metabolism. microbe Short for microorganism. A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell. microbiome The community of microorganisms that live in our body. molecular medicine The branch of medicine that deals with the structure and function of molecules essential to life. Ph.D. (also known as a doctorate) A type of advanced degree offered by universities typically after five or six years of study for work that creates new knowledge. People qualify to begin this type of graduate study only after having first completed a college degree (a program that typically takes four years of study). red meat A term used to describe beef, lamb or other meats that appear red when uncooked and 4 of 5 12/8/2014 2:37 PM

5 not light-colored (as chicken breast is) when cooked. stroke (in biology and medicine) A condition where blood stops flowing to part of the brain or leaks in the brain. S. Oosthoek. Germs explain some animal behaviors. Science News for Students. Aug. 19, S. Ornes. Slimming germs. Science News for Students. Oct. 4, S. Ornes. The power of microbes. Science News for Students. July 11, S. Ornes. Gut instinct. Science News for Students. June 22, Original Journal Source: S. Hazen et al. y-butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-Carnitine to TMAO. Cell Metabolism, Nov. 4, doi: / /j.cmet Original Journal Source: J. Goodrich, et al. Human genetics shape the gut microbiome. Cell, Nov. 6, doi: Original Journal Source: W.H. Tang, Z. Wang and... S.L. Hazen. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. New England Journal of Medicine, Vol. 368, April 25, 2013, p doi: /NEJMoa Original Journal Source: R.A. Koeth, Z. Wang... S.L. Hazen. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Medicine, Vol. 19, Published online April 7, 2013, p doi: /nm Source URL: 5 of 5 12/8/2014 2:37 PM