Thinking with your gut

Via Science Daily:

For the first time, researchers at McMaster University have conclusive evidence that bacteria residing in the gut influence brain chemistry and behaviour.

The findings are important because several common types of gastrointestinal disease, including irritable bowel syndrome, are frequently associated with anxiety or depression. In addition there has been speculation that some psychiatric disorders, such as late onset autism, may be associated with an abnormal bacterial content in the gut.

“The exciting results provide stimulus for further investigating a microbial component to the causation of behavioural illnesses,” said Stephen Collins, professor of medicine and associate dean research, Michael G. DeGroote School of Medicine. Collins and Premysl Bercik, assistant professor of medicine, undertook the research in the Farncombe Family Digestive Health Research Institute.

The research appears in the online edition of the journal Gastroenterology.

For each person, the gut is home to about 1,000 trillion bacteria with which we live in harmony. These bacteria perform a number of functions vital to health: They harvest energy from the diet, protect against infections and provide nutrition to cells in the gut. Any disruption can result in life-threatening conditions, such as antibiotic-induced colitis from infection with the “superbug” Clostridium difficile.

Working with healthy adult mice, the researchers showed that disrupting the normal bacterial content of the gut with antibiotics produced changes in behaviour; the mice became less cautious or anxious. This change was accompanied by an increase in brain-derived neurotrophic factor (BDNF), which has been linked to depression and anxiety.

When oral antibiotics were discontinued, bacteria in the gut returned to normal. “This was accompanied by restoration of normal behaviour and brain chemistry,” Collins said.

To confirm that bacteria can influence behaviour, the researchers colonized germ-free mice with bacteria taken from mice with a different behavioural pattern. They found that when germ-free mice with a genetic background associated with passive behaviour were colonized with bacteria from mice with higher exploratory behaviour, they became more active and daring. Similarly, normally active mice became more passive after receiving bacteria from mice whose genetic background is associated with passive behaviour.

While previous research has focused on the role bacteria play in brain development early in life, Collins said this latest research indicates that while many factors determine behaviour, the nature and stability of bacteria in the gut appear to influence behaviour and any disruption , from antibiotics or infection, might produce changes in behaviour. Bercik said that these results lay the foundation for investigating the therapeutic potential of probiotic bacteria and their products in the treatment of behavioural disorders, particularly those associated with gastrointestinal conditions such as irritable bowel syndrome.

Humans were not the first farmers

And it might be the case that ants weren’t, either. A Rice University graduate student may have discovered proto-agricultural behavior in amobeas:

It’s too bad they don’t make microscopic overalls. The amoeba Dictyostelium discoideum could use a pair. A new study finds that the single-celled organism is a farmer of sorts. It picks up bacteria, carries them to new locations, and harvests them like crops.

D. discoideum, or “Dicty,” is a so-called social amoeba, formerly classified as a slime mold. An individual amoeba cell can live independently, slurping up bacteria in the soil. When the food is gone, it joins with its comrades, forming a sluglike organism about half a centimeter long that can wriggle to greener pastures (see video). Once there, the slug becomes a stalk with a fruiting body—a tiny globe on top that releases spores, each spawning a single amoeba—to start the cycle all over again.

Debra Brock, a graduate student in ecology and evolutionary biology at Rice University in Houston, Texas, spent a lot of time looking at Dicty under a microscope before she started graduate school; she worked as a technician in a lab that studies the organism’s development. Most labs that work on Dicty order strains from a catalog, almost all of which are descended from one clone collected decades ago. But the lab where Brock is getting her Ph.D. has a large collection of clones from the wild. It was Brock’s first time looking at spores from wild amoebae, and she saw something she’d never seen before: bacteria hanging out in the fruiting body. “I was going, ‘This is really odd,’ ” she says.

At least Brock thought the specks she saw were bacteria. But she couldn’t be sure. So she embarked on a series of experiments, described online today in Nature. First, she stuck a very thin pipette tip into a Dicty fruiting body, sucked out the contents, and spread them on a plate for growing bacteria. After 2 days, some of the plates had patches of bacteria, suggesting that some Dicty clones harbor the bugs within their spores.

But were the bacteria just an infection? To find out, Brock killed them by giving antibiotics to the Dicty clones. She then placed the amoeba on a fresh patch of bacteria. The clones that had originally harbored bacteria picked up the bugs again, indicating that they were collecting bacteria. “That was like Nirvana,” Brock says. “I was going around in the lab going, ‘Yay! Yay!’ “

Other experiments showed that the amoebas “planted” their new environments with food. “They can carry [the bacteria], they disperse them, and they seed them in new places, and they actually harvest,” Brock says. “We felt that was sufficient to be designated a farmer.”

Only about a third of the clones that Brock and her colleagues tested were farmers. That means farming must not give a consistent advantage, or it would have taken over. Indeed, she found that farming wasn’t great in all environments. Farmers thrived if their spores were placed on a plate with no bacteria, because they could plant their own. But on a plate that already had bacteria, nonfarmers did well, whereas farmers struggled—possibly because they stop eating before the food is gone.

Researchers have already discovered several animals that farm: ants and termites that grow fungus, damselfishes that tend algae, and intertidal snails that tend fungus. Dicty, the first microbe shown to farm, is less sophisticated. The fungus-farming ants, for example, carefully tend their crops, fertilizing them and killing pests. “It’s really amazing the amount of care they give to their crop. An amoeba cannot do that,” Brock says.

Koos Boomsma, an evolutionary biologist at the University of Copenhagen who did not work on the study, is not surprised that farming is scattered through the tree of life. “But if I would’ve had to predict where I would have next expected farming to be discovered, I would never have predicted a slime mold,” he says.

“It’s a wonderful paper,” says evolutionary biologist Bernard Crespi of Simon Fraser University in Burnaby, Canada. Still, he says, “It really is the first data that’s out there, so there’s always going to be questions.” For example, he’d like to see more data about the environments where farmers and nonfarmers are found in the wild—whether farmers are in places where the food is patchier. Such research might even allow comparisons to early human agriculture. “You’re always looking for convergences” in evolutionary biology, Crespi says. “Slime molds and humans is one of the more unusual comparisons.”

A new (which is to say very old, but recently discovered) human ancestor?

Ewen Callaway writing in Nature News:

The ice-age world is starting to look cosmopolitan. While Neanderthals held sway in Europe and modern humans were beginning to populate the globe, another ancient human relative lived in Asia, according to a genome sequence recovered from a finger bone in a cave in southern Siberia. A comparative analysis of the genome with those of modern humans suggests that a trace of this poorly understood strand of hominin lineage survives today, but only in the genes of some Papuans and Pacific islanders.

Named after the cave that yielded the 30,000–50,000-year-old bone, the Denisova nuclear genome follows publication of the same individual’s mitochondrial genome in March¹. From that sequence, Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and his colleagues could tell little, except that the individual, now known to be female, was part of a population long diverged from humans and Neanderthals.

Her approximately 3-billion-letter nuclear genome, reported in this issue of Nature², now provides a more telling glimpse into this mysterious group. It also raises previously unimagined questions about its history and relationship to Neanderthals and humans. “The whole story is incredible. It’s like a surprising Christmas present,” says Carles Lalueza Fox, a palaeogeneticist at Pompeu Fabra University in Barcelona, Spain, who was not involved in the research.

When the ancient genome was compared to a spectrum of modern human populations, a striking relationship emerged. Unlike most groups, Melanesians — inhabitants of Papua New Guinea and islands northeast of Australia — seem to have inherited as much as one-twentieth of their DNA from Denisovan roots. This suggests that after the ancestors of today’s Papuans split from other human populations and migrated east, they interbred with Denisovans, but precisely when, where and to what extent is unclear.

More answers could come from a closer look at Denisovan, human and even Neanderthal DNA. So far, conclusions about interbreeding have been drawn from a relatively small number of human genomes using conservative DNA-analysis methods, says David Reich, a geneticist at Harvard Medical School in Boston, Massachusetts, who led the Denisova analysis. “There may have been many more interactions,” he says. Pääbo says it may be possible to determine roughly when humans interbred with Denisovans by examining the length of DNA segments lurking in various human genomes, with shorter segments corresponding to more shuffling of genes and a longer elapsed time.

A molar discovered in the same cave also yielded mitochondrial DNA resembling that of the finger bone. But the Denisovans were probably more widespread, says Pääbo. Some fossils from China, for example, resemble neither Neanderthals nor modern humans — nor Homo erectus, an earlier human ancestor. Pääbo wonders whether they could be more closely related to Denisovans. His Russian collaborators plan to search for more complete Denisovan fossils that could be matched to others from China.

Chris Stringer, a palaeoanthropologist at London’s Natural History Museum, agrees that Asian fossils, such as the 200,000-year-old Dali skull from central China, could have links to the Denisovans. But he says that firm conclusions about such relationships will have to await the discovery of more complete Denisovan fossils.

Preserved DNA from other Asian fossils would also provide a clearer picture of the Denisovans, which Pääbo, to sidestep controversy, has opted not to call a new species or subspecies of hominin. The challenge will be to make sense of such discoveries and put them in the context of ancient human history, says Lalueza Fox. Palaeoanthropologists are just beginning to scrutinize the Neanderthal genome published earlier this year³ for clues to ancient human history. With the Denisova genome, “they will need to deal with another surprise”, he says.

Is the As-bacterium overhyped? ctd

Carl Zimmer, writing in Slate, considers the evidence:

None of the scientists I spoke to ruled out the possibility that such weird bacteria might exist. Indeed, some of them were co-authors of a 2007 report for the National Academies of Sciences on alien life that called for research into, among other things, arsenic-based biology. But almost to a person, they felt that the NASA team had failed to take some basic precautions to avoid misleading results.

When the NASA scientists took the DNA out of the bacteria, for example, they ought to have taken extra steps to wash away any other kinds of molecules. Without these precautions, arsenic could have simply glommed to the DNA, like gum on a shoe. “It is pretty trivial to do a much better job,” said Rohwer.

In fact, says Harvard microbiologist Alex Bradley, the NASA scientists unknowingly demonstrated the flaws in their own experiment. They immersed the DNA in water as they analyzed it, he points out. Arsenic compounds fall apart quickly in water, so if it really was in the microbe’s genes, it should have broken into fragments, Bradley wrote Sunday in a guest post on the blog We, Beasties. But the DNA remained in large chunks—presumably because it was made of durable phosphate. Bradley got his Ph.D. under MIT professor Roger Summons, a professor at MIT who co-authored the 2007 weird-life report. Summons backs his former student’s critique.

But how could the bacteria be using phosphate when they weren’t getting any in the lab? That was the point of the experiment, after all. It turns out the NASA scientists were feeding the bacteria salts which they freely admit were contaminated with a tiny amount of phosphate. It’s possible, the critics argue, that the bacteria eked out a living on that scarce supply. As Bradley notes, the Sargasso Sea supports plenty of microbes while containing 300 times less phosphate than was present in the lab cultures.

But why rush a critically flawed paper to publication? Zimmer speculates:

“I suspect that NASA may be so desperate for a positive story that they didn’t look for any serious advice from DNA or even microbiology people,” says John Roth of UC-Davis. The experience reminded some of another press conference NASA held in 1996. Scientists unveiled a meteorite from Mars in which they said there were microscopic fossils. A number of critics condemned the report (also published in Science) for making claims it couldn’t back up. And today many scientists think that all of the alleged signs of life in the rocks could have just as easily been made on a lifeless planet.The controversy over the Martian meteorite still sputters on today because they contain only a few alleged fossils, rather than living bacteria. There are only a limited number of tests that scientists can run on the rocks, and their results remain murky. Fortunately, that’s not the case for GFAJ-1. Critics say that a few straightforward tests on the bacteria would show whether they really do have arsenic-based DNA once and for all. And the NASA scientists say they’re ready to hand out GFAJ-1 to researchers who want to study it. This controversy may be burning brightly at the moment, but it probably won’t burn for long.