guts

‘Wildly weird’ RNA bits discovered infesting the microbes in our guts

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Rod-shaped structures named ‘obelisks’ are even smaller than viruses but can still transmit instructions to cells.

Coloured transmission electron micrograph of two Streptococcus sanguinis bacteria.
Streptococcus sanguinis bacteria live in the human mouth and are hosts to a newly described group of RNA entities.

The human microbiome just gained a new dimension: scientists have discovered tiny bits of RNA — even smaller than viruses — that colonize the bacteria inside human guts and mouths1. Too minimal to be considered a standard life form, these scraps of genetic material are among the smallest known elements to transfer information that can be read by a cell, and the sequences that they encode are new to science.

“That’s, like, wildly weird,” says cell and developmental biologist Mark Peifer at the University of North Carolina at Chapel Hill, who was not involved in the work. The research rekindled his sense of the joy that scientific discovery can bring, he says. “The world is just full of new things. And once you start to look, you find them.”

The work was posted on the bioRxiv preprint server on 21 January, and has yet to be peer reviewed.

New neighbours

Obelisks, as preprint co-author and biochemist Ivan Zheludev at Stanford University in California and his colleagues are calling the newly discovered elements, are flattened circles of RNA. The authors’ analysis suggests that these circles are folded into rod-like structures.

Flattened circles have been seen before, in the form of ‘viroids’ — structures made of RNA that are similar to viruses, but are much smaller. They were first discovered in the 1970s, when some were found to cause diseases in plants. Soon scientists discovered a similar element that can cause hepatitis in humans. A flurry of studies in the past five years have reported viroid-like elements in a range of animals2,3 and fungi4, and a study5 last year provided the first hint that they might be present in bacteria.

Zheludev and his colleagues took advantage of the characteristic circular RNA of viroids to search for similar elements in databases of RNA from human stool. And there, they found the obelisks.

Although obelisks have the same shape as many viroids, their genetic sequences are very different — implying that they comprise a separate but related group. Follow-up searches turned up a plethora of obelisks in stool samples taken from people across every continent. The authors found evidence of the elements in almost 10% of samples of gut and oral microbiota collected from 472 individuals, most of them from North America.

The study is “a milestone” because it presents the best available evidence that such elements are widespread in the bacterial world, and not just in more complex organisms, says molecular biologist Joan Marquez-Molins at the Swedish University of Agricultural Sciences in Uppsala, who was not involved in the work. “It’s not really something sporadic or isolated in the population — it’s really affecting a considerable amount of the sample,” he says.

Tipping the balance

Nobody knows how obelisks might affect human health. The components of the microbiome — including bacteria, fungi and other organisms — “all exist in a balance”, says virologist Anamarija Butković at the Pasteur Institute in Paris, who was not involved in the work. “It’s interesting to think what obelisks are doing there, and how they might affect this whole balance.”

The answer could come from the common mouth bacterium Streptococcus sanguinis, in which the researchers found a family of obelisks. Because S. sanguinis is easy to grow, Marquez-Molins and Buković hypothesize that scientists might be able to use these bacteria to address questions about how obelisks replicate, how they affect bacteria and what their proteins do.

Such experiments could reveal truths about the origin of life itself. Some scientists have speculated that, because viroids and their relatives are small, simple and have the capacity to self-replicate, they are the precursors of all life on Earth, Butković says. Although scientists have just seen obelisks for the first time, they might have shaped us from the start.

Some Guts Get More Energy From the Same Food

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The results indicate that being overweight might not be related only to how healthily a person eats or the amount of exercise they get. It may also have something to do with the composition of their gut microbes. (sankalpmaya/iStock)

The results indicate that being overweight might not be related only to how healthily a person eats or the amount of exercise they get. It may also have something to do with the composition of their gut microbes.

New findings are a step towards understanding why some people gain more weight than others, even when they eat the same diet.

The research indicates that some Danish people have a composition of gut microbes that, on average, extracts more energy from food than do the microbes in the guts of their fellow Danes. Part of the explanation could be related to the composition of their gut microbes.

Researchers at the University of Copenhagen’s department of nutrition, exercise, and sports studied the residual energy in the feces of 85 Danes to estimate how effective their gut microbes are at extracting energy from food. At the same time, they mapped the composition of gut microbes for each participant.

The results show that roughly 40% of the participants belong to a group that, on average, extracts more energy from food compared to the other 60%. The researchers also observed that those who extracted the most energy from food also weighed 10% more on average, amounting to an extra nine kilograms (about 20 pounds).

“We may have found a key to understanding why some people gain more weight than others, even when they don’t eat more or any differently. But this needs to be investigated further,” says associate professor Henrik Roager.

The results indicate that being overweight might not be related to how healthily a person eats or the amount of exercise they get. It may also have something to do with the composition of their gut microbes.

As reported in the journal Microbiome, participants were divided into three groups, based on the composition of their gut microbes. The so-called B-type composition (dominated by Bacteroides bacteria) is more effective at extracting nutrients from food and was observed in 40% of the participants.

Following the study, the researchers suspect that having gut bacteria that are more effective at extracting energy may result in more calories being available for the human host from the same amount of food.

“The fact that our gut bacteria are great at extracting energy from food is basically a good thing, as the bacteria’s metabolism of food provides extra energy in the form of, for example, short-chain fatty acids, which are molecules that our body can use as energy-supplying fuel. But if we consume more than we burn, the extra energy provided by the intestinal bacteria may increase the risk of obesity over time,” says Roager.

From mouth to esophagus, stomach, duodenum, and small intestine, large intestine, and finally to rectum, the food we eat takes a 12-to-36-hour journey, passing several stations along the way, before the body has extracted all the food’s nutrients.

The researchers also studied the length of this journey for each participant, all of whom had similar dietary patterns. Here, the researchers hypothesized that those with long digestive travel times would be the ones who harvested the most nutrition from their food. But the study found the exact opposite.

“We thought that there would be a long digestive travel time would allow more energy to be extracted. But here, we see that participants with the B-type gut bacteria that extract the most energy, also have the fastest passage through the gastrointestinal system, which has given us something to think about,” says Roager.

The new study in humans confirms earlier studies in mice. In these studies, researchers found that germ-free mice that received gut microbes from obese donors gained more weight compared to mice that received gut microbes from lean donors, despite being fed the same diet.

Even then, the researchers proposed that the differences in weight gain could be attributable to the fact that the gut bacteria from obese people were more efficient at extracting energy from food. The new research confirms this theory.

“It is very interesting that the group of people who have less energy left in their stool also weigh more on average. However, this study doesn’t provide proof that the two factors are directly related. We hope to explore this more in the future,” says Roager.

Some Guts Get More Energy From the Same Food

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The results indicate that being overweight might not be related only to how healthily a person eats or the amount of exercise they get. It may also have something to do with the composition of their gut microbes. (sankalpmaya/iStock)

The results indicate that being overweight might not be related only to how healthily a person eats or the amount of exercise they get. It may also have something to do with the composition of their gut microbes. (sankalpmaya/iStock)

New findings are a step towards understanding why some people gain more weight than others, even when they eat the same diet.

The research indicates that some Danish people have a composition of gut microbes that, on average, extracts more energy from food than do the microbes in the guts of their fellow Danes. Part of the explanation could be related to the composition of their gut microbes.

Researchers at the University of Copenhagen’s department of nutrition, exercise, and sports studied the residual energy in the feces of 85 Danes to estimate how effective their gut microbes are at extracting energy from food. At the same time, they mapped the composition of gut microbes for each participant.

The results show that roughly 40% of the participants belong to a group that, on average, extracts more energy from food compared to the other 60%. The researchers also observed that those who extracted the most energy from food also weighed 10% more on average, amounting to an extra nine kilograms (about 20 pounds).

“We may have found a key to understanding why some people gain more weight than others, even when they don’t eat more or any differently. But this needs to be investigated further,” says associate professor Henrik Roager.

The results indicate that being overweight might not be related to how healthily a person eats or the amount of exercise they get. It may also have something to do with the composition of their gut microbes.

As reported in the journal Microbiome, participants were divided into three groups, based on the composition of their gut microbes. The so-called B-type composition (dominated by Bacteroides bacteria) is more effective at extracting nutrients from food and was observed in 40% of the participants.

Following the study, the researchers suspect that having gut bacteria that are more effective at extracting energy may result in more calories being available for the human host from the same amount of food.

“The fact that our gut bacteria are great at extracting energy from food is basically a good thing, as the bacteria’s metabolism of food provides extra energy in the form of, for example, short-chain fatty acids, which are molecules that our body can use as energy-supplying fuel. But if we consume more than we burn, the extra energy provided by the intestinal bacteria may increase the risk of obesity over time,” says Roager.

From mouth to esophagus, stomach, duodenum, and small intestine, large intestine, and finally to rectum, the food we eat takes a 12-to-36-hour journey, passing several stations along the way, before the body has extracted all the food’s nutrients.

The researchers also studied the length of this journey for each participant, all of whom had similar dietary patterns. Here, the researchers hypothesized that those with long digestive travel times would be the ones who harvested the most nutrition from their food. But the study found the exact opposite.

“We thought that there would be a long digestive travel time would allow more energy to be extracted. But here, we see that participants with the B-type gut bacteria that extract the most energy, also have the fastest passage through the gastrointestinal system, which has given us something to think about,” says Roager.

The new study in humans confirms earlier studies in mice. In these studies, researchers found that germ-free mice that received gut microbes from obese donors gained more weight compared to mice that received gut microbes from lean donors, despite being fed the same diet.

Even then, the researchers proposed that the differences in weight gain could be attributable to the fact that the gut bacteria from obese people were more efficient at extracting energy from food. The new research confirms this theory.

“It is very interesting that the group of people who have less energy left in their stool also weigh more on average. However, this study doesn’t provide proof that the two factors are directly related. We hope to explore this more in the future,” says Roager.

Babies born by caesarean section are more likely to be obese, study finds

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Obesity is a lot more complex than we think.

Babies born by caesarean section are more likely to experience obesity than children delivered via vaginal birth, a new study has found.

The study suggests that babies from caesarean deliveries don’t only experience greater incidence of obesity as children, but also later on in life – with the effects persisting through teenage years and into adulthood.

“Caesarean deliveries are without a doubt a necessary and lifesaving procedure in many cases,” says nutritionist and epidemiologist Jorge Chavarro from Harvard University.

“But cesareans also have some known risks to the mother and the newborn. Our findings show that risk of obesity in the offspring could another factor to consider.”

The researchers analysed data from more than 22,000 young adults who took part in the Growing Up Today Study (GUTS) – an ongoing project launched in 1996 to examine the factors that influence health and weight as people age.

The participants, who were children aged between 9 to 14 when the study commenced, had their body mass index (BMI) tracked over 16 years. The researchers also collected information on factors that might affect obesity, including their mothers’ pre-pregnancy BMI, smoking status, and age when the participants were born.

Once these factors were accounted for, the data showed that participants born via caesarean deliveries (22 percent of the group) were 15 percent more likely to be obese on average than those who came into the world via vaginal birth (the other 78 percent).

The association showed up in across genders and different age segments, but was at its strongest when the participants were younger.

Participants born via C-section were 23 percent more likely to be obese when aged 9–12; 16 percent more likely to be obese when aged 13 to 18; and 10 percent more likely when aged 19 to 28.

Strangely, the increased risk of obesity was at its highest when pregnant women had elected to have caesarian births without a documented health reason for the C-section, with their babies found to be 30 percent more likely to experience obesity than children delivered via vaginal birth.

Also of note is the fact that participants in the study with siblings – 12,903 of the overall 22,068 group – who were delivered by caesarian had a 64 percent higher risk of obesity than their brothers or sisters from a vaginal birth.

While researchers have previously observed this association between caesarean sections and obesity, this is the largest and most comprehensive investigation yet into the relationship between birthing methods and future weight outcomes.

“I think that our findings – particularly those that show a dramatic difference in obesity risk between those born via caesarean and their siblings born through vaginal delivery – provide very compelling evidence that the association between caesarean birth and childhood obesity is real,” says Chavarro.

“That’s because, in the case of siblings, many of the factors that could potentially be playing a role in obesity risk, including genetics, would be largely the same for each sibling – except for the type of delivery.”

But the question remains, why is this happening?

At this stage, nobody knows for sure, but children born by caesarian section do have less exposure to their mother’s vaginal and gastrointestinal microbiota, and this could play a role in their dietary development and weight as they age.

“Children born via C-section harbour less diverse gut bacteria and these patterns of less diversity have been linked to increased capacity for energy harvest by the gut microbiota,” one of the researchers, Audrey Gaskins, told Hannah Devlin at The Guardian. “You can think of it as a slower metabolism.”

It’s important to remember that, for many women, giving birth via a C-section is a medical necessity to safeguard the health of the mother and her baby – so the researchers are not suggesting that women avoid using this method in a bid to lower their child’s risk of developing obesity.

A definitive biological cause is yet to be identified to explain this correlation, so until the link can be confirmed, we need to wait and see what further evidence reveals. But one thing’s for sure – getting to the bottom of what’s really going on here will be beneficial for all.

“Most often caesarean births are as a result of medical necessity, rather than elective,” biomedical researcher Simon Cork from Imperial College London in the UK, who wasn’t involved with the study, told The Guardian. “[A]s such, this risk would outweigh any concerns mothers should have regarding the possibility of future weight issues.”

Scientists think a whole new type of life form could be living in our guts

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Our digestive system is home to a weird and wonderful collection of bacteria, and we’re only just beginning to understand how these unique populations are not just having an effect how we digest our food, but potentially even how we think and behave.

And now new research has found that the situation in our guts is even stranger than we thought, with biologists suggesting that we may need to define a whole new type of life form to describe these tiny residents.

A team from the Pierre and Marie Curie University in Paris, France has been attempting to redefine the way we classify the organisms living inside our colons. By studying 86 different gene families, they’ve discovered DNA sequences that are different enough to suggest they’re beyond the three forms of life that we currently recognise.

Those forms are classified as bacteria, archaea, and eukaryotes. Archaea were once bundled with bacteria, but have a different biochemical make-up and can survive in more extreme conditions, whereas eukaryotes refers to fungi, plants, and animals.

What the Paris team, led by Philippe Lopez and Eric Bapteste, found makes the case for a fourth type being added to that list, but it’s important not to get ahead of ourselves – it might also mean that the existing types are more genetically diverse than we thought.

New Scientist explains the findings, published in the journal Biology Direct.

“They analysed microbiome samples, recovering about 230,000 DNA sequences that are related to known sequences in those 86 gene families. They then used these sequences as the starting point for a second analysis – a little like digging deeper into your ancestry by using your parents’ DNA rather than your own to guide the search. This revealed an additional 80,000 stretches of microbial DNA that belonged in the 86 gene families.

But the sequence of bases was highly unusual in about one-third of the DNA – it shared just 60 percent or less of its identity with any known gene sequences. That degree of difference is what you might expect to separate different domains of life, such as bacteria and archaea.”

But before a fourth domain can be added, scientists will need to isolate and study these organisms in a lab environment, and that’s no easy task. Right now, around 99 percent of microbes can’t be grown in the lab, which is why there’s still so much we don’t know about these basic forms of life. Plus many genes are swapped around between microbes, further adding to the confusion, which is one of the reasons why this research focuses on gene families that don’t often cross over.

“These results underline how limited our understanding of the most diverse elements of the microbial world remains, and encourage a deeper exploration of natural communities and their genetic resources, hinting at the possibility that still unknown yet major divisions of life have yet to be discovered,”concludes the report.

There’s still a lot of work to do, but these findings are definitely cause for excitement if you’re a keen biologist. “Let’s wait to see how unusual the organisms are,” Bapteste told New Scientist. “Scientists have found a huge diversity of microbes in the human gut, so I would not expect it to be necessarily hostile to different life forms.”