human breath analysis and individual metabolic phenotypes

plosone | The metabolic phenotype varies widely due to external factors such as diet and gut microbiome composition, among others. Despite these temporal fluctuations, urine metabolite profiling studies have suggested that there are highly individual phenotypes that persist over extended periods of time. This hypothesis was tested by analyzing the exhaled breath of a group of subjects during nine days by mass spectrometry. Consistent with previous metabolomic studies based on urine, we conclude that individual signatures of breath composition exist. The confirmation of the existence of stable and specific breathprints may contribute to strengthen the inclusion of breath as a biofluid of choice in metabolomic studies. In addition, the fact that the method is rapid and totally non-invasive, yet individualized profiles can be tracked, makes it an appealing approach.

bacteria divide people into types

NYTimes | In the early 1900s, scientists discovered that each person belonged to one of four blood types. Now they have discovered a new way to classify humanity: by bacteria. Each human being is host to thousands of different species of microbes. Yet a group of scientists now report just three distinct ecosystems in the guts of people they have studied.

Blood type, meet bug type.

“It’s an important advance,” said Rob Knight, a biologist at the University of Colorado, who was not involved in the research. “It’s the first indication that human gut ecosystems may fall into distinct types.”

The researchers, led by Peer Bork of the European Molecular Biology Laboratory in Heidelberg, Germany, found no link between what they called enterotypes and the ethnic background of the European, American and Japanese subjects they studied.

Nor could they find a connection to sex, weight, health or age. They are now exploring other explanations. One possibility is that the guts, or intestines, of infants are randomly colonized by different pioneering species of microbes.

The microbes alter the gut so that only certain species can follow them.

Whatever the cause of the different enterotypes, they may end up having discrete effects on people’s health. Gut microbes aid in food digestion and synthesize vitamins, using enzymes our own cells cannot make.

Dr. Bork and his colleagues have found that each of the types makes a unique balance of these enzymes. Enterotype 1 produces more enzymes for making vitamin B7 (also known as biotin), for example, and Enterotype 2 more enzymes for vitamin B1 (thiamine).

The discovery of the blood types A, B, AB and O had a major effect on how doctors practice medicine. They could limit the chances that a patient’s body would reject a blood transfusion by making sure the donated blood was of a matching type. The discovery of enterotypes could someday lead to medical applications of its own, but they would be far down the road.

“Some things are pretty obvious already,” Dr. Bork said. Doctors might be able to tailor diets or drug prescriptions to suit people’s enterotypes, for example.

Or, he speculated, doctors might be able to use enterotypes to find alternatives to antibiotics, which are becoming increasingly ineffective. Instead of trying to wipe out disease-causing bacteria that have disrupted the ecological balance of the gut, they could try to provide reinforcements for the good bacteria. “You’d try to restore the type you had before,” he said.

Dr. Bork notes that more testing is necessary. Researchers will need to search for enterotypes in people from African, Chinese and other ethnic origins. He also notes that so far, all the subjects come from industrial nations, and thus eat similar foods. “This is a shortcoming,” he said. “We don’t have remote villages.”

The discovery of enterotypes follows on years of work mapping the diversity of microbes in the human body — the human microbiome, as it is known. The difficulty of the task has been staggering. Each person shelters about 100 trillion microbes.

(For comparison, the human body is made up of only around 10 trillion cells.) But scientists cannot rear a vast majority of these bacteria in their labs to identify them and learn their characteristics.

the wonder of breasts

Guardian | We love breasts, yet can't quite take them seriously. Breasts embarrass us. They're unpredictable. They're goofy. They can turn babies and grown men into lunkheads.

They appear out of nowhere in puberty, they get bigger in pregnancy, they're capable of producing prodigious amounts of milk, and sometimes they get sick. But for such an enormously popular feature of the human race, it's remarkable how little we know about their basic biology.

The urgency to know and understand breasts has never been greater. Modern life has helped many of us live longer and more comfortably. It has also, however, taken a strange toll on our breasts. For one thing, they are bigger than ever. We are sprouting them at younger ages. We are filling them with saline and silicone and transplanted stem cells to change their shape. This year marks the 50th anniversary of the first silicone implant surgery in Houston, Texas.

More tumours form in the breast than in any other organ, making breast cancer the most common malignancy in women worldwide. Its incidence has almost doubled since the 1940s and is still rising.

But breasts are often overlooked, at least for non-cancer scientific research. The Human Microbiome Project, for example, is decoding the microbial genes of every major human gland, liquid and orifice, from the ears to the genitals. It neglected to include breast milk.

I wanted to know more, so I went to the 15th meeting of the International Society for Research in Human Milk and Lactation in Lima. Many attendees were molecular biologists, biochemists or geneticists who are deconstructing milk bit by bit. Until recently, it was thought breast milk had around 200 components. These could be divided into the major ingredients of fats, sugars, proteins and enzymes. But new technologies have allowed researchers to look deeper into each of these categories and discover new ones.

Scientists used to think breast milk was sterile, like urine. But it's more like cultured yoghurt, with lots of live bacteria doing who knows what. These organisms evolved for a reason, and somehow they're helping us out. One leading theory is they act as a vaccine, inoculating the infant gut. A milk sample has anywhere from one to 600 species of bacteria. Most are new to science.

Then there are the sugars. There's a class of them called oligosaccharides, which are long chains of complex sugars. Scientists have identified 140 of them so far, and estimate there are about 200. The human body is full of oligosaccharides, which ride on our cells attached to proteins and lipids. But a mother's mammary gland cooks up a unique batch of "free" or unattached ones and deposits them in milk. These are found nowhere else in nature, and not every mother produces the same ones, since they vary by blood type. Even though they're sugars, the oligosaccharides are, weirdly, not digestible by infants. Yet they are a main ingredient, present in milk in the same percentage as the proteins, and in higher amounts than the fats. So what are they doing there?

They don't feed us, but they do feed many types of beneficial bacteria that make a home in our guts and help us fight infections. In addition to recruiting the good bugs, these sugars prevent the bad bugs from hanging around. "The benefits of human milk are still underestimated," said Lars Bode, an immunobiologist at the University of California, San Diego. "We're still discovering functional components of breast milk."

what bugs are in your gut?

TheScientist | Humans from different cultures and geographic locations differ in the diversity of bacteria in their guts, but the metabolic functions that those microbial communities serve are similar, according to a report out in Nature today (May 9). The findings come from a large-scale sequencing project carried out on 531 samples of human excrement from Africa, South America, and the United States.

“It’s a humungous paper, with multiple key findings,” said food scientist David Mills of the University of California, Davis. “An impressive and complex piece of work,” agreed molecular biologist Jeremy Nicholson of Imperial College, London. Neither researcher participated in the study.

The scale and complexity stem from the research team’s aim of answering a multifaceted question—“What is the degree to which these microbial communities… vary within a person, as a function of postnatal development, physiological status, cultural tradition, and where a person lives,” said geneticist Jeffrey Gordon of the Washington University in St Louis, who led the study.

To this end, the researchers collected samples of feces from villagers in rural Malawi, Amerindians in Amazonian Venezuela, and metropolis-dwelling Americans. They then performed high-throughput sequencing on DNA taken from the samples to determine both the species and strains of microbes present and which microbial genes were most abundant.

The team found a common pattern for how the microbiomes of babies develop in the three countries. “It takes 6 to 9 months to get the first 6 or 700 bugs and then another couple of years to get the adult set,” explained Nicholson. “[Gordon] finds there is the same sort of developmental time span between countries,” he said, “but that the resulting microbiomes are nonetheless distinct between, let’s call it, a third-world population and a westernized population.”

One of the most striking differences was the degree of microbial diversity, with both the Amerindians and Malawians having far greater diversity than the Americans. “But, ironically, [Americans] might have more diversity in terms of the food eaten,” said Mills, which might have been expected to correlate with microbial diversity. Gordon suggested the Westerners’ lack of diversity could result from “our lifestyle, our degree of hygiene, [and] our use of antibiotics,” though further research is needed to test these possibilities.

Despite these differences between the gut microbiomes of the three cultures, there were also striking similarities, said Gordon. For example, “across all three populations, we see this age-dependent change in vitamin biosynthesis,” he said. In infants, gut bacteria tend to carry more copies of genes involved in folate biosynthesis, while the guts of older individuals harbor microbes carrying more genes for folate metabolism. Conversely, genes involved in vitamin B-12 synthesis became more prevalent in the gut microbiome with age.

“What’s really fascinating about those results,” said Mills, “is that it is reflecting what the host needs.”

breath straight kicking like cancer....,

thescientist | Fusobacterium nucleatum is a Gram-negative oral commensal microbe, but it has the potential to become pathogenic, occasionally causing periodontal disease. In October 2011, two separate teams from Canada’s BC Cancer Agency and the Broad Institute in Cambridge showed that the bacterium could also be found in the gut, where its abundance was associated with colorectal cancer. Now, two new studies present functional evidence to help explain how F. nucleatum spurs the development of cancer.

In papers published in Cell Host & Microbe today (August 13), teams led by Harvard Medical School’s Aleksandar Kostic and Case Western Reserve University’s Mara Roxana Rubinstein used a mouse model of intestinal tumorigenesis and human colon cancer cells, respectively, to show that F. nucleatum induces proinflammatory and oncogenic activities that promote the growth of colorectal cancer.

“It is usually impossible to infer whether microbes are causative or opportunistic colonizers without functional studies,” said Robert Holt, who led the BC Cancer Agency team that in 2011 reported an association between F. nucleatum in the gut and colorectal cancer but was not involved in the present studies. “Identifying an infectious origin for disease almost always starts with observing an association between the presence of a microbe and the presence of a particular pathology, but an understanding of causality—or lack thereof—requires the gradual accumulation of experimental and epidemiological evidence,” such as that reported today.

The Washington University School of Medicine’s Gautam Dantas agreed that the new work helps distinguish cause from consequence. “Is an observed altered microbiome state in a diseased individual the cause of the disease, or a symptom?” Dantas, who was not involved in the studies, wrote in an e-mail to The Scientist. The papers published today “report on significant strides towards . . . identifying the mechanisms by which a human commensal bacterium, Fusobacterium nucleatum, promotes colorectal cancer.”

gut microbes influence behavior

TheScientist | Gut microbes acquired early in life can impact brain development in mice and subsequent behavior, such as decreasing physical activity and increasing anxiety, according to a study published this week in the Proceedings of the National Academy of Sciences.

"This paper opens the door to new studies in at least two directions," Yale University microbiologist Andrew Goodman, who was not involved in the research, told The Scientist in an email. "First, determining how differences between complete host-associated microbial communities lead to differences in behavior, and second, exploring the contributions of microbes during specific developmental periods in the host."

Gut microbiota often colonize their hosts early in life, either during pregnancy or following birth, and play an integral role in the health of developing organisms. Previous research has shown that the bacteria affect the development of liver function, the protection epithelial cells afford underlying digestive tissue, gut regulation and the growth of new capillary blood vessels. But this is the first time gut flora have been linked to brain development and behavior.

Harmful microbial infections, on the other hand, have been linked to neurodevelopmental disorders, including autism and schizophrenia. And rodents infected by microbial pathogens before and after birth demonstrated behavioral abnormalities, such as anxiety-like behavior and impaired cognitive function, leading Rochellys Diaz Heijtz, a neurobiologist at the Karolinska Institute in Sweden, and her colleagues to wonder if the gut's normal microbial residents may similarly influence brain development.

The researchers tested exploratory activity in germ-free mice and mice with normal gut microbiota by tracking their movements across open space. They also tested anxiety of the two groups in two classic rodent behavioral tests -- the light-dark box and the elevated maze. Spending more time in lit areas and along unwalled, elevated maze portions equated to less anxiety.

Germ-free mice appeared to be more exploratory than mice with normal microbiota, venturing farther and to more areas of the space provided. Germ-free mice also spent more time in the light and engaged in riskier behavior in the maze, indicating they suffered from less anxiety than their microbe-filled counterparts.

The team then infected germ-free mice with normal gut microbiota when they were born to test whether the gut flora could alter the mice's activity and anxiety levels. Sure enough, the newly infected mice spent less time exploring and engaging in risky behavior, like the normal mice in the initial experiments. The results further supported the argument that the microorganisms can affect brain and behavior when introduced early enough in development.

"These microorganisms communicate in a systemic fashion to the developmental programming of a new individual and can influence fundamental aspects of behavior," said Diaz Heijtz. "We should start to consider the possibility that the microbiome and/or its composition may contribute to psychiatric problems."

microbiomes-R-us

NYTimes | In 2008, Dr. Khoruts, a gastroenterologist at the University of Minnesota, took on a patient suffering from a vicious gut infection of Clostridium difficile. She was crippled by constant diarrhea, which had left her in a wheelchair wearing diapers. Dr. Khoruts treated her with an assortment of antibiotics, but nothing could stop the bacteria. His patient was wasting away, losing 60 pounds over the course of eight months. “She was just dwindling down the drain, and she probably would have died,” Dr. Khoruts said.

Dr. Khoruts decided his patient needed a transplant. But he didn’t give her a piece of someone else’s intestines, or a stomach, or any other organ. Instead, he gave her some of her husband’s bacteria.

Dr. Khoruts mixed a small sample of her husband’s stool with saline solution and delivered it into her colon. Writing in the Journal of Clinical Gastroenterology last month, Dr. Khoruts and his colleagues reported that her diarrhea vanished in a day. Her Clostridium difficile infection disappeared as well and has not returned since.

The procedure — known as bacteriotherapy or fecal transplantation — had been carried out a few times over the past few decades. But Dr. Khoruts and his colleagues were able to do something previous doctors could not: they took a genetic survey of the bacteria in her intestines before and after the transplant.

Before the transplant, they found, her gut flora was in a desperate state. “The normal bacteria just didn’t exist in her,” said Dr. Khoruts. “She was colonized by all sorts of misfits.”

Two weeks after the transplant, the scientists analyzed the microbes again. Her husband’s microbes had taken over. “That community was able to function and cure her disease in a matter of days,” said Janet Jansson, a microbial ecologist at Lawrence Berkeley National Laboratory and a co-author of the paper. “I didn’t expect it to work. The project blew me away.”

Scientists are regularly blown away by the complexity, power, and sheer number of microbes that live in our bodies. “We have over 10 times more microbes than human cells in our bodies,” said George Weinstock of Washington University in St. Louis. But the microbiome, as it’s known, remains mostly a mystery. “It’s as if we have these other organs, and yet these are parts of our bodies we know nothing about.”

voices from within: gut microbes and the central nervous system

springer |  Recent advances in research have greatly increased our understanding of the importance of the gut microbiota. Bacterial colonization of the intestine is critical to the normal development of many aspects of physiology such as the immune and endocrine systems. It is emerging that the influence of the gut microbiota also extends to modulation of host neural development. Furthermore, the overall balance in composition of the microbiota, together with the influence of pivotal species that induce specific responses, can modulate adult neural function, peripherally and centrally. Effects of commensal gut bacteria in adult animals include protection from the central effects of infection and inflammation as well as modulation of normal behavioral responses. There is now robust evidence that gut bacteria influence the enteric nervous system, an effect that may contribute to afferent signaling to the brain. The vagus nerve has also emerged as an important means of communicating signals from gut bacteria to the CNS. Further understanding of the mechanisms underlying microbiome–gut–brain communication will provide us with new insight into the symbiotic relationship between gut microbiota and their mammalian hosts and help us identify the potential for microbial-based therapeutic strategies to aid in the treatment of mood disorders.

a universe of us

NYTimes | We think of ourselves as individuals — perhaps, in philosophical moments, as the merger of body and soul. Most of us are barely aware of the estimated 10 trillion individual cells that make up the human body or of the 100 trillion or more bacteria that live collaboratively and benignly within and upon us. Whatever else we are, we are also a complex ecosystem, a habitat.

Scientists now have discovered another realm within our habitat — the virome, a large community of viruses. These are not the viruses that make us sick. These are an integral part of the microbiotic universe that makes us healthy.

In a recent paper in Nature, a team led by Jeffrey Gordon, a microbiologist at Washington University, reports that each of us has, so to speak, a viral identity — a pattern of viral DNA that is highly stable and highly distinct, even among closely related humans. This is unlike bacterial communities, which tend to evolve over time and to be similar among family members.

This discovery is part of a rapidly growing interest in the microbiome — an effort to understand the diversity and complexity of the trillions of organisms living within each of us. The basic exploratory technique is broad-scale DNA sequencing of the genetic contents of the human gut. The result is a significantly different view of who we are.

We are not just the expression of an individual human genome. We are, as Dr. Gordon writes, “a genetic landscape,” a collective of genomes of hundreds of different species all working together — in ways that leave our minds mysteriously free to focus on getting our bodies to the office and wondering what’s for lunch.