Protein-rich diet may help soothe inflamed gut

Immune cells patrol the gut to ensure that harmful microbes hidden in the food we eat don't sneak into the body. Cells that are capable of triggering inflammation are balanced by cells that promote tolerance, protecting the body without damaging sensitive tissues. When the balance tilts too far toward inflammation, inflammatory bowel disease can result.

Now, researchers at Washington University School of Medicine in St. Louis have found that a kind of tolerance-promoting immune cell appears in mice that carry a specific bacterium in their guts. Further, the bacterium needs tryptophan - one of the building blocks of proteins - to trigger the cells' appearance.

"We established a link between one bacterial species - Lactobacillus reuteri - that is a normal part of the gut microbiome, and the development of a population of cells that promote tolerance," said Marco Colonna, MD, the Robert Rock Belliveau MD Professor of Pathology and the study's senior author. "The more tryptophan the mice had in their diet, the more of these immune cells they had."

If such findings hold true for people, it would suggest that the combination of L. reuteri and a tryptophan-rich diet may foster a more tolerant, less inflammatory gut environment, which could mean relief for the million or more Americans living with the abdominal pain and diarrhea of inflammatory bowel disease.

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices. By AzaToth (self made based on PDB entry) [Public domain], via Wikimedia Commons

Postdoctoral researcher Luisa Cervantes-Barragan, PhD, was studying a kind of immune cell that promotes tolerance when she discovered that one group of study mice had such cells, while a second group of study mice that were the same strain of mice but were housed far apart from the first group did not have such cells.

The mice were genetically identical but had been born and raised separately, indicating that an environmental factor influenced whether the immune cells developed.

She suspected the difference had to do with the mice's gut microbiomes - the community of bacteria, viruses and fungi that normally live within the gastrointestinal tract.

Cervantes-Barragan collaborated with Chyi-Song Hsieh, MD, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Medicine, to sequence DNA from the intestines of the two groups of mice. They found six bacterial species present in the mice with the immune cells but absent from the mice without them.

With the help of Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor, the researchers turned to mice that had lived under sterile conditions since birth to identify which of the six species was involved in inducing the immune cells. Such mice lack a gut microbiome and do not develop this kind of immune cell. When L. reuteri was introduced to the germ-free mice, the immune cells arose.

To understand how the bacteria affected the immune system, the researchers grew L. reuteri in liquid and then transferred small amounts of the liquid - without bacteria - to immature immune cells isolated from mice. The immune cells developed into the tolerance-promoting cells. When the active component was purified from the liquid, it turned out to be a byproduct of tryptophan metabolism known as indole-3-lactic acid.

Tryptophan - commonly associated with turkey - is a normal part of the mouse and the human diet. Protein-rich foods contain appreciable amounts: nuts, eggs, seeds, beans, poultry, yogurt, cheese, even chocolate.

When the researchers doubled the amount of tryptophan in the mice's feed, the number of such cells rose by about 50 percent. When tryptophan levels were halved, the number of cells dropped by half.

People have the same tolerance-promoting cells as mice, and most of us shelter L. reuteri in our gastrointestinal tracts. It is not known whether tryptophan byproducts from L. reuteri induce the cells to develop in people as they do in mice, but defects in genes related to tryptophan have been found in people with inflammatory bowel disease.

"The development of these cells is probably something we want to encourage since these cells control inflammation on the inner surface of the intestines," Cervantes-Barragan said. "Potentially, high levels of tryptophan in the presence of L. reuteri may induce expansion of this population."

For more information visit:-

https://www.sciencedaily.com/releases/2017/08/170803141045.htm

https://en.wikipedia.org/wiki/Protein

http://www.prlabs.co.uk/lab-supplies.php?N=300l-msia-darts-protein-a&Id=19590

What molecules you leave on your phone reveal about your lifestyle

We leave behind trace chemicals, molecules and microbes on every object we touch. By sampling the molecules on cell phones, researchers at University of California San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences were able to construct lifestyle sketches for each phone's owner, including diet, preferred hygiene products, health status and locations visited. This proof-of-concept study, published November 14 by Proceedings of the National Academy of Sciences, could have a number of applications, including criminal profiling, airport screening, medication adherence monitoring, clinical trial participant stratification and environmental exposure studies.

"You can imagine a scenario where a crime scene investigator comes across a personal object - like a phone, pen or key - without fingerprints or DNA, or with prints or DNA not found in the database. They would have nothing to go on to determine who that belongs to," said senior author Pieter Dorrestein, PhD, professor in UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences. "So we thought - what if we take advantage of left-behind skin chemistry to tell us what kind of lifestyle this person has?"

Mobile phone evolution. By Anders (Own work) , via Wikimedia Commons

In a 2015 study, Dorrestein's team constructed 3D models to illustrate the molecules and microbes found at hundreds of locations on the bodies of two healthy adult volunteers. Despite a three-day moratorium on personal hygiene products before the samples were collected, the researchers were surprised to find that the most abundant molecular features in the skin swabs still came from hygiene and beauty products, such as sunscreen.

"All of these chemical traces on our bodies can transfer to objects," Dorrestein said. "So we realized we could probably come up with a profile of a person's lifestyle based on chemistries we can detect on objects they frequently use."

Thirty-nine healthy adult volunteers participated in Dorrestein's latest study. The team swabbed four spots on each person's cell phone - an object we tend to spend a lot of time touching - and eight spots on each person's right hand, for a total of nearly 500 samples. Then they used a technique called mass spectrometry to detect molecules from the samples. They identified as many molecules as possible by comparing them to reference structures in the GNPS database, a crowdsourced mass spectrometry knowledge repository and annotation website developed by Dorrestein and co-author Nuno Bandeira, PhD, associate professor at the Jacobs School of Engineering and Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego.

With this information, the researchers developed a personalized lifestyle "read-out" from each phone. Some of the medications they detected on phones included anti-inflammatory and anti-fungal skin creams, hair loss treatments, anti-depressants and eye drops. Food molecules included citrus, caffeine, herbs and spices. Sunscreen ingredients and DEET mosquito repellant were detected on phones even months after they had last been used by the phone owners, suggesting these objects can provide long-term composite lifestyle sketches.

"By analyzing the molecules they've left behind on their phones, we could tell if a person is likely female, uses high-end cosmetics, dyes her hair, drinks coffee, prefers beer over wine, likes spicy food, is being treated for depression, wears sunscreen and bug spray - and therefore likely spends a lot of time outdoors - all kinds of things," said first author Amina Bouslimani, PhD, an assistant project scientist in Dorrestein's lab. "This is the kind of information that could help an investigator narrow down the search for an object's owner."

There are limitations, Dorrestein said. First of all, these molecular read-outs provide a general profile of person's lifestyle, but they are not meant to be a one-to-one match, like a fingerprint. To develop more precise profiles and for this method to be more useful, he said more molecules are needed in the reference database, particularly for the most common foods people eat, clothing materials, carpets, wall paints and anything else people come into contact with. He'd like to see a trace molecule database on the scale of the fingerprint database, but it's a large-scale effort that no single lab will be able to do alone.

Moving forward, Dorrestein and Bouslimani have already begun extending their study with an additional 80 people and samples from other personal objects, such as wallets and keys. They also hope to soon begin gathering another layer of information from each sample - identities of the many bacteria and other microbes that cover our skin and objects. In a 2010 study, their collaborator and co-author, Rob Knight, PhD, professor in the UC San Diego School of Medicine and Jacobs School of Engineering and director of the Center for Microbiome Innovation at UC San Diego, contributed to a study in which his team found they could usually match a computer keyboard to its owner just based on the unique populations of microbes the person left on it. At that time, they could make the match with a fair amount of accuracy, though not yet precisely enough for use in an investigation.

Beyond forensics, Dorrestein and Bouslimani imagine trace molecular read-outs could also be used in medical and environmental studies. For example, perhaps one day physicians could assess how well a patient is sticking with a medication regimen by monitoring metabolites on his or her skin. Similarly, patients participating in a clinical trial could be divided into subgroups based on how they metabolize the medication under investigation, as revealed by skin metabolites - then the medication could be given only to those patients who can metabolize it appropriately. Skin molecule read-outs might also provide useful information about a person's exposure to environmental pollutants and chemical hazards, such as in a high-risk workplace or a community living near a potential pollution source.

For more information visit:

https://www.sciencedaily.com/releases/2016/11/161114152820.htm

http://www.prlabs.co.uk/lab-supplies.php?N=caffeine-usp-grade&Id=679

Oxygen oasis in Antarctic lake reflects Earth in distant past

At the bottom of a frigid Antarctic lake, a thin layer of green slime is generating a little oasis of oxygen, a team including UC Davis researchers has found. It's the first modern replica discovered of conditions on Earth two and a half billion years ago, before oxygen became common in the atmosphere. The discovery is reported in a paper in the journal Geology.

The switch from a planet with very little available oxygen to one with an atmosphere much like today's was one of the major events in Earth's history, and it was all because some bacteria evolved the ability to photosynthesize. By about 2.4 billion years ago, geochemical records show that oxygen was present all the way to the upper atmosphere, as ozone.

What is not clear is what happened in between, or how long the transition - called the Great Oxidation Event - lasted, said Dawn Sumner, professor and chair of earth and planetary sciences at UC Davis and an author on the paper. Scientists have speculated that here may have been "oxygen oases," local areas where was abundant before it became widespread around the planet.

The new discovery in Lake Fryxell in the McMurdo Dry Valleys could be a modern example of such an ancient oxygen oasis, and help geochemists figure out what to look for in ancient rocks, Sumner said.

Lake Fryxell. Credit: Tyler Mackey, UC Davis 

Sumner and collaborators including Ian Hawes of the University of Canterbury, New Zealand have been studying life in these ice-covered lakes for several years. The microbes that survive in these remote and harsh environments are likely similar to the first forms of life to appear on Earth, and perhaps on other planets.

The discovery occurred "a little by accident," Sumner said. Hawes and Tyler Mackey, a UC Davis graduate student working with Sumner, were helping out another research team by diving in Lake Fryxell. The lakes of the Dry Valleys typically contain oxygen in their upper layers, but are usually anoxic further down, Sumner said. Lake Fryxell is unusual because it becomes anoxic at a depth where light can still penetrate.

During their dives below the oxygen zone, Hawes and Mackey noticed some bright green bacteria that looked like they could be photosynthesizing. They took measurements and found a thin layer of oxygen, just one or two millimeters thick, being generated by the bacteria.

Something similar could have been happening billions of years ago, Sumner said.

"The thought is, that the lakes and rivers were anoxic, but there was light available, and little bits of oxygen could accumulate in the mats," she said.

The researchers now want to know more about the chemical reactions between the "oxygen oasis" and the anoxic water immediately above it and sediments below. Is the oxygen absorbed? What reactions occur with minerals in the water?

Understanding how this oxygen oasis reacts with the environment around it could help identify chemical signatures preserved in rocks. Researchers could then go looking for similar signatures in rocks from ancient lake beds to find "whiffs of oxygen" prior to the Great Oxidation Event.

For more information visit:-

http://www.sciencedaily.com/releases/2015/09/150901140759.htm

https://www.prlabs.co.uk/lab-supplies.php?N=oxygen-emptied-cylinder&Id=60499