Body weight heavily influenced by gut microbes: Genes shape body weight by affecting gut microbes

Body sizes (stock image). New research shows that our genetic makeup influences whether we are fat or thin by shaping which types of microbes thrive in our body. Credit: © olly / Fotolia

Our genetic makeup influences whether we are fat or thin by shaping which types of microbes thrive in our body, according to a study by researchers at King's College London and Cornell University.

By studying pairs of twins at King's Department of Twin Research, researchers identified a specific, little known bacterial family that is highly heritable and more common in individuals with low body weight. This microbe also protected against weight gain when transplanted into mice.

The results, published today in the journal Cell, could pave the way for personalised probiotic therapies that are optimised to reduce the risk of obesity-related diseases based on an individual's genetic make-up.

Previous research has linked both genetic variation and the composition of gut microbes to metabolic disease and obesity. Despite these shared effects, the relationship between human genetic variation and the diversity of gut microbes was presumed to be negligible.

In the study, funded by National Institutes of Health (NIH), researchers sequenced the genes of microbes found in more than 1,000 fecal samples from 416 pairs of twins. The abundances of specific types of microbes were found to be more similar in identical twins, who share 100 per cent of their genes, than in non-identical twins, who share on average only half of the genes that vary between people. These findings demonstrate that genes influence the composition of gut microbes.

The type of bacteria whose abundance was most heavily influenced by host genetics was a recently identified family called 'Christensenellaceae'. Members of this health-promoting bacterial family were more abundant in individuals with a low body weight than in obese individuals. Moreover, mice that were treated with this microbe gained less weight than untreated mice, suggesting that increasing the amounts of this microbe may help to prevent or reduce obesity.

Professor Tim Spector, Head of the Department of Twin Research and Genetic Epidemiology at King's College London, said: 'Our findings show that specific groups of microbes living in our gut could be protective against obesity -- and that their abundance is influenced by our genes. The human microbiome represents an exciting new target for dietary changes and treatments aimed at combating obesity.

'Twins have been incredibly valuable in uncovering these links -- but we now want to promote the use of microbiome testing more widely in the UK through the British Gut Project. This is a crowd-sourcing experiment that allows anyone with an interest in their diet and health to have their personal microbes tested genetically using a simple postal kit and a small donation via our website (www.britishgut.org). We want thousands to join up so we can continue to make major discoveries about the links between our gut and our health.'

Ruth Ley, Associate Professor at Cornell University in the United States, said: 'Up until now, variation in the abundances of gut microbes has been explained by diet, the environment, lifestyle, and health. This is the first study to firmly establish that certain types of gut microbes are heritable -- that their variation across a population is in part due to host genotype variation, not just environmental influences. These results will also help us find new predictors of disease and aid prevention.'

Source: King's College London

When you lose weight, where does the fat go? Most of the mass is breathed out as carbon dioxide, study shows

Despite a worldwide obsession with diets and fitness regimes, many health professionals cannot correctly answer the question of where body fat goes when people lose weight.
Credit: © Lovrencg / Fotolia

Despite a worldwide obsession with diets and fitness regimes, many health professionals cannot correctly answer the question of where body fat goes when people lose weight, a UNSW Australia study shows.

The most common misconception among doctors, dieticians and personal trainers is that the missing mass has been converted into energy or heat.

"There is surprising ignorance and confusion about the metabolic process of weight loss," says Professor Andrew Brown, head of the UNSW School of Biotechnology and Biomolecular Sciences.

"The correct answer is that most of the mass is breathed out as carbon dioxide. It goes into thin air," says the study's lead author, Ruben Meerman, a physicist and Australian TV science presenter.

In their paper, published in the British Medical Journal today, the authors show that losing 10 kilograms of fat requires 29 kilograms of oxygen to be inhaled and that this metabolic process produces 28 kilograms of carbon dioxide and 11 kilograms of water.

Mr Meerman became interested in the biochemistry of weight loss through personal experience.

"I lost 15 kilograms in 2013 and simply wanted to know where those kilograms were going. After a self-directed, crash course in biochemistry, I stumbled onto this amazing result," he says.

"With a worldwide obesity crisis occurring, we should all know the answer to the simple question of where the fat goes. The fact that almost nobody could answer it took me by surprise, but it was only when I showed Andrew my calculations that we both realised how poorly this topic is being taught."

The authors met when Mr Meerman interviewed Professor Brown in a story about the science of weight loss for the Catalyst science program on ABC TV in March this year.

"Ruben's novel approach to the biochemistry of weight loss was to trace every atom in the fat being lost and, as far as I am aware, his results are completely new to the field," says Professor Brown.

"He has also exposed a completely unexpected black hole in the understanding of weight loss amongst the general public and health professionals alike."

If you follow the atoms in 10 kilograms of fat as they are 'lost', 8.4 of those kilograms are exhaled as carbon dioxide through the lungs. The remaining 1.6 kilograms becomes water, which may be excreted in urine, faeces, sweat, breath, tears and other bodily fluids, the authors report.

"None of this is obvious to people because the carbon dioxide gas we exhale is invisible," says Mr Meerman.

More than 50 per cent of the 150 doctors, dieticians and personal trainers who were surveyed thought the fat was converted to energy or heat.

"This violates the Law of Conservation of Mass. We suspect this misconception is caused by the energy in/energy out mantra surrounding weight loss," says Mr Meerman.

Some respondents thought the metabolites of fat were excreted in faeces or converted to muscle.

"The misconceptions we have encountered reveal surprising unfamiliarity about basic aspects of how the human body works," the authors say.

One of the most frequently asked questions the authors have encountered is whether simply breathing more can cause weight loss. The answer is no. Breathing more than required by a person's metabolic rate leads to hyperventilation, which can result in dizziness, palpitations and loss of consciousness.

The second most frequently asked question is whether weight loss can cause global warming.

"This reveals troubling misconceptions about global warming which is caused by unlocking the ancient carbon atoms trapped underground in fossilised organisms. The carbon atoms human beings exhale are returning to the atmosphere after just a few months or years trapped in food that was made by a plant," says Mr Meerman, who also presents the science of climate change in high schools around Australia.

Mr Meerman and Professor Brown recommend that these basic concepts be included in secondary school curricula and university biochemistry courses to correct widespread misconceptions about weight loss among lay people and health professionals.

Source: University of New South Wales

Making lab-grown tissues stronger

Connective tissues like cartilage are made of cross-linked bundles of collagen fibers. UC Davis biomedical engineers have discovered that reducing oxygen or adding an enzyme called LOX can make these bundles stronger. The technique can be used to strengthen both natural cartilage kept in the lab for transplant, and artificial cartilage grown in culture. Credit: Eleftherios Makris and Kyriacos Athanasiou, UC Davis

Lab-grown tissues could one day provide new treatments for injuries and damage to the joints, including articular cartilage, tendons and ligaments.

Cartilage, for example, is a hard material that caps the ends of bones and allows joints to work smoothly. UC Davis biomedical engineers, exploring ways to toughen up engineered cartilage and keep natural tissues strong outside the body, report new developments this week in the journal Proceedings of the National Academy of Sciences.

"The problem with engineered tissue is that the mechanical properties are far from those of native tissue," said Eleftherios Makris, a postdoctoral researcher at the UC Davis Department of Biomedical Engineering and first author on the paper. Makris is working under the supervision of Professor Kyriacos A. Athanasiou, a distinguished professor of biomedical engineering and orthopedic surgery, and chair of the Department of Biomedical Engineering.

While engineered cartilage has yet to be tested or approved for use in humans, a current method for treating serious joint problems is with transplants of native cartilage. But it is well known that this method is not sufficient as a long-term clinical solution, Makris said.
The major component of cartilage is a protein called collagen, which also provides strength and flexibility to the majority of our tissues, including ligaments, tendons, skin and bones. Collagen is produced by the cells and made up of long fibers that can be cross-linked together.

Engineering new cartilage

Researchers in the Athanasiou group have been maintaining native cartilage in the lab and culturing cartilage cells, or chondrocytes, to produce engineered cartilage.

"In engineered tissues the cells produce initially an immature matrix, and the maturation process makes it tougher," Makris said.

Knee joints are normally low in oxygen, so the researchers looked at the effect of depriving native or engineered cartilage of oxygen. In both cases, low oxygen led to more cross-linking and stronger material. They also found that an enzyme called lysyl oxidase, which is triggered by low oxygen levels, promoted cross-linking and made the material stronger.

"The ramifications of the work presented in the PNAS paper are tremendous with respect to tissue grafts used in surgery, as well as new tissues fabricated using the principles of tissue engineering," Athanasiou said. Grafts such as cadaveric cartilage, tendons or ligaments -- notorious for losing their mechanical characteristics in storage -- can now be treated with the processes developed at UC Davis to make them stronger and fully functional, he said.
Athanasiou also envisions that many tissue engineering methods will now be altered to take advantage of this strengthening technique.

Source: University of California - Davis

First step: From human cells to tissue-engineered esophagus

This images shows a tissue-engineered esophagus. Credit: The Saban Research Institute

In a first step toward future human therapies, researchers at The Saban Research Institute of Children's Hospital Los Angeles have shown that esophageal tissue can be grown in vivo from both human and mouse cells. The study has been published online in the journal Tissue Engineering, 
Part A.

The tissue-engineered esophagus formed on a relatively simple biodegradable scaffold after the researchers transplanted mouse and human organ-specific stem/progenitor cells into a murine model, according to principal investigator Tracy C. Grikscheit, MD, of the Developmental Biology and Regenerative Medicine program of The Saban Research Institute and pediatric surgeon at Children's Hospital Los Angeles.

Progenitor cells have the ability to differentiate into specific types of cell, and can migrate to the tissue where they are needed. Their potential to differentiate depends on their type of "parent" stem cell and also on their niche. The tissue-engineering technique discovered by the CHLA researchers required only a simple polymer to deliver the cells, and multiple cellular groupings show the ability to generate a replacement organ with all cell layers and functions.

"We found that multiple combinations of cell populations allowed subsequent formation of engineered tissue. Different progenitor cells can find the right 'partner' cell in order to grow into specific esophageal cell types -- such as epithelium, muscle or nerve cells -- and without the need for exogenous growth factors. This means that successful tissue engineering of the esophagus is simpler than we previously thought," said Grikscheit.

She added that the study shows promise for one day applying the process in children who have been born with missing portions of the organ, which carries food, liquids and saliva from the mouth to the stomach. The process might also be used in patients who have had esophageal cancer -- the fastest growing type of cancer in the U.S. -- or otherwise damaged tissue, for example from accidentally swallowing caustic substances.

"We have demonstrated that a simple and versatile, biodegradable polymer is sufficient for the growth of tissue-engineered esophagus from human cells," added Grikscheit. "This not only serves as a potential source of tissue, but also a source of knowledge, as there are no other robust models available for studying esophageal stem cell dynamics. Understanding how these cells might behave in response to injury and how various donor cell types relate could expand the pool of potential donor cells for engineered tissue."

Additional contributors include first author Ryan G. Spurrier, MD, Allison L. Speer, MD, Xiaogang Hou, PhD and Wael N. El-Nachef, MD, of The Saban Research Institute of Children's Hospital Los Angeles. The study was supported by grants from the California Institute for Regenerative Medicine.

Source: Children's Hospital Los Angeles Saban Research Institute