Gut bacteria may impact body weight, fat and good cholesterol levels

Date: September 10, 2015

Source: American Heart Association

Summary:

A link has been discovered between bacteria in the gut and body weight, triglyceride and good cholesterol levels. Researchers identified 34 specific digestive tract microorganism species that influence weight and lipid metabolism.

For better cardiovascular health, check your gut. Bacteria living in your gut may impact your weight, fat and good cholesterol levels, factors necessary to help maintain a healthy heart, according to new research in Circulation Research, an American Heart Association journal.

"Our study provides new evidence that microbes in the gut are strongly linked to the blood level of HDL (good cholesterol) and triglycerides and may be added as a new risk factor for abnormal blood lipids, in addition to age, gender, BMI and genetics," said Jingyuan Fu, Ph.D., study lead author and associate professor of genetics at University Medical Center Groningen in the Netherlands.

Using state-of-the-art deep sequencing technology, researchers studied the association between gut microbes and blood lipid levels in 893 people in the Netherlands. They identified:

34 different types of bacteria contributed to differences in body fat (BMI) and blood lipids such as triglycerides and the good cholesterol known as high-density lipoprotein or HDL. Most were new associations.

Bacteria in the gut contributed to 4.6 percent of the difference in body fat, 6 percent in triglycerides and 4 percent in HDL.

Surprisingly, gut bacteria had little relationship with bad cholesterol (low-density lipoproteins or LDL ) or total cholesterol levels.

Microbes and humans have a symbiotic relationship. The human body contains trillions of microorganisms, 10 times the number of human cells. These microbes help us to digest food and train our immune systems. The bacterial community in the human gut has been referred to as an extra organ because of its important role in an individuals' health, researchers said.

"As less than 30 percent of bacteria in the human gut have been cultured, we know very little about who they are and what they do. With state-of-art deep sequencing technology, we are now able to identify them," Fu said.

While additional studies are needed in a larger and diverse population to test their hypotheses, researchers believe these findings may someday open the door to new therapies to alter the gut bacteria types that contribute to body weight, fat and cholesterol levels to help aid in the prevention of heart disease.

"We also hope our findings inspire microbiologists to continue to research the function of these bacteria and their specific role in the regulation of lipid metabolism," Fu said.

Story Source:

The above post is reprinted from materials provided by American Heart Association. Note: Materials may be edited for content and length.

Journal Reference:

Jingyaun Fu, Marc Jan Bonder, María Carmen Cenit, Ettje Tigchelaar, Astrid Maatman, Jackie A.M. Dekens, Eelke Brandsma, Joanna Marczynska, Floris Imhann, Rinse K. Weersma, Lude Franke, Tiffany W. Poon, Ramnik J. Xavier, Dirk Gevers, Marten H. Hofker, Cisca Wijmenga, and Alexandra Zhernakova. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids. Circulation Research, September 2015 DOI: 10.1161/CIRCRESAHA.115.306807

Cite This Page:

American Heart Association. "Gut bacteria may impact body weight, fat and good cholesterol levels." ScienceDaily. ScienceDaily, 10 September 2015. <www.sciencedaily.com/releases/2015/09/150910164220.htm>.

Scientists produce cancer drug from rare plant in lab

Date: September 10, 2015

Source: Stanford University

Summary:

Stanford scientists produced a common cancer drug -- previously only available from an endangered plant -- in a common laboratory plant. This work could lead to a more stable supply of the drug and allow scientists to manipulate that drug to make it even safer and more effective.

Sattely said this work is a good example of how chemistry can be applied to problems of human health. She thinks the technique she developed to find the pathway in mayapple could be applied to a wide range of other plants and drugs.

Credit: © mybaitshop / Fotolia

Many of the drugs we take today to treat pain, fight cancer or thwart disease were originally identified in plants, some of which are endangered or hard to grow. In many cases, those plants are still the primary source of the drug.

Now Elizabeth Sattely, an assistant professor of chemical engineering at Stanford, and her graduate student Warren Lau have isolated the machinery for making a widely used cancer-fighting drug from an endangered plant. They then put that machinery into a common, easily grown laboratory plant, which was able to produce the chemical. The technique could potentially be applied to other plants and drugs, creating a less expensive and more stable source for those drugs.

"People have been grinding up plants to find new chemicals and testing their activity for a really long time," Sattely said. "What was striking to us is that with a lot of the plant natural products currently used as drugs, we have to grow the plant, then isolate the compound, and that's what goes into humans."

In her work, published Sept. 10 in the journal Science, Sattely and her team used a novel technique to identify proteins that work together in a molecular assembly line to produce the cancer drug. Her group then showed that the proteins could produce the compound outside the plant -- in this case, they had put the machinery in a different plant, but they hope to eventually produce the drug in yeast. Either the plant or yeast would provide a controlled laboratory environment for producing the drug.

This work could lead to new ways of modifying the natural pathways to produce derivative drugs that are safer or more effective than the natural source.

"A big promise of synthetic biology is to be able to engineer pathways that occur in nature, but if we don't know what the proteins are, then we can't even start on that endeavor," said Sattely, who is also a member of the interdisciplinary institutes Stanford Bio-X and Stanford ChEM-H.

Finding the machinery

The drug Sattely chose to focus on is produced by a leafy Himalayan plant called the mayapple. Within the plant, a series of proteins work in a step-by-step fashion to churn out a chemical defense against predators. That chemical defense, after a few modifications in the lab, becomes a widely used cancer drug called etoposide.

The starting material for this chemical defense is a harmless molecule commonly present in the leaf. When the plant senses an attack, it begins producing proteins that make up the assembly line. One by one, those proteins add a little chemical something here, subtract something there, and after a final molecular nip and tuck, the harmless starting material is transformed into a chemical defense.

The challenge was figuring out which of the many proteins found in the mayapple leaf were the ones involved in this pathway. Sattely started with the realization that the proteins she needed to find weren't always present in the leaf. "It's only when the leaf is wounded that the molecule is made," she said.

And if the molecule is only made after wounding, the proteins that make that molecule are probably also only around after a wound as well.

The question then became, "What are all the molecules that are there after wounding?" Sattely said.

It turns out that after damaging the plant leaf, 31 new proteins appeared. Sattely and her team put various combinations of those proteins together until they eventually found 10 that made up the full assembly line. They put genes that make those 10 proteins into a common laboratory plant, and that plant began producing the chemical they were seeking.

Drugs from yeast

The eventual goal is not simply moving molecular machinery from plant to plant. Now that she's proven the molecular machinery works outside the plant, Sattely wants to put the proteins in yeast, which can be grown in large vats in the lab to better provide a stable source of drugs.

Producing a drug in yeast also provides some flexibility that isn't present when isolating a drug from plants.

"We can only use what the plant gives us," Sattely said.

In yeast, scientists can modify the genes to produce proteins with slightly different functions. For example, they could nip a little more off the chemical or add a slightly bigger side chain, or subtly alter the function of the eventual drug.

It may also be possible to feed the yeast a slightly different starting product, thereby changing the chemical that the molecular assembly line churns out. These approaches would provide a way of tweaking existing drugs in an effort to improve them.

Sattely said the work is a good example of how chemistry can be applied to problems of human health, which is the goal of Stanford ChEM-H. She thinks the technique she developed to find the pathway in mayapple could be applied to a wide range of other plants and drugs.

"My interests are really identifying new molecules and pathways from plants that are important for human health," she said.

Story Source:

The above post is reprinted from materials provided by Stanford University. The original item was written by Amy Adams. Note: Materials may be edited for content and length.

Journal Reference:

Warren Lau and Elizabeth S. Sattely. Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone.Science, September 2015 DOI: 10.1126/science.aac7202

Cite This Page:

Stanford University. "Scientists produce cancer drug from rare plant in lab." ScienceDaily. ScienceDaily, 10 September 2015. <www.sciencedaily.com/releases/2015/09/150910144044.htm>.