A universe of beauty, mystery and wonder

A universe of beauty, mystery and wonder

Wednesday, August 23, 2017


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*  Mysterious, unknown creatures live inside of us....  This is not a horror film script, but the result of a scientific study.
*  And when you think of how bacteria (particularly gut bacteria) influence our brain and emotions, then we have ask the disturbing question:  Who is in charge of us?
Stanford University:  A survey of DNA fragments circulating in the blood suggests the microbes living within us are vastly more diverse than previously known. In fact, 99 percent of that DNA has never been seen before.

A great deal of mystery DNA has been found in the human gut. Of all the non-human DNA fragments the team gathered, 99 percent of them failed to match anything in existing genetic databases.
A new survey of DNA fragments circulating in human blood suggests our bodies contain vastly more diverse microbes than anyone previously understood. What's more, the overwhelming majority of those microbes have never been seen before, let alone classified and named, Stanford researchers report August 22 in the Proceedings of the National Academy of Sciences.
Continue reading this article and one on how gut bacteria affect the brain, including the incidence of AUTISM

"We found the gamut," said Stephen Quake, a professor of bioengineering and applied physics, a member of Stanford Bio-X and the paper's senior author. "We found things that are related to things people have seen before, we found things that are divergent, and we found things that are completely novel."
Searching for rejection
The survey was inspired by a curious observation Quake's lab made while searching for non-invasive ways to predict whether an organ transplant patient's immune system would recognize the new organ as foreign and attack it, an event known as rejection. Ordinarily, it takes a tissue biopsy -- meaning a large needle jabbed into one's side and at least an afternoon in a hospital bed for observation -- to detect rejection.
The lab members figured there was a better way. In theory, they might be able to detect rejection by taking blood samples and looking at the cell-free DNA -- bits and pieces of DNA circulating freely in blood plasma -- contained therein. Apart from fragments of a patient's DNA, those samples would contain fragments of the organ donor's DNA as well as a comprehensive view of the collection of bacteria, viruses and other microbes that make up a person's microbiome.
Over the course of several studies, the first of which was published in 2013, Quake, postdoctoral fellow Iwijn De Vlaminck, and others collected samples from 156 heart, lung and bone marrow transplant recipients, along with 32 pregnant women. (Pregnancy, like immunosuppressant drugs taken by transplant patients, also changes the immune system, albeit in ways both more complicated and less well understood.)
The results of those earlier studies suggested there were identifiable changes to the microbiomes of people with compromised immune systems and that positive tests for the organ donor's DNA were a good sign of rejection.
Something weirder
But there was something else, too -- something weirder. Of all the non-human DNA fragments the team gathered, 99 percent of them failed to match anything in existing genetic databases the researchers examined.
With that in mind, Mark Kowarsky, a graduate student in Quake's lab and the paper's first author, set about characterizing all of that mystery DNA.
The "vast majority" of it belonged to a phylum called proteobacteria, which includes, among many other species, pathogens such as E. coli and Salmonella. Previously unidentified viruses in the torque teno family, generally not associated with disease but often found in immunocompromised patients, made up the largest group of viruses.
"We've doubled the number of known viruses in that family through this work," Quake said. Perhaps more important, they've found an entirely new group of torque teno viruses.
Among the known torque teno viruses, one group infects humans and another infects animals, but many of the ones the researchers found didn't fit in either group. "We've now found a whole new class of human-infecting ones that are closer to the animal class than to the previously known human ones, so quite divergent on the evolutionary scale," he said.
An unsurprising surprise?
"I'd say it's not that baffling in some respects because the lens that people examined the microbial universe was one that was very biased," Quake said, in the sense that narrow studies often miss the bigger picture. For one thing, researchers tend to go deep in the microbiome in only one part of the body, such as the gut or skin, at a time. Blood samples, in contrast, "go deeply everywhere at the same time."
For another, researchers often focus their attention on just a few interesting microbes, "and people just don't look at what the remaining things are," Kowarsky said. "There probably are some interesting, novel things there, but it's not relevant to the experiment people want to do at that time."
It was by looking at blood samples in an unbiased way, Quake said, that led to the new results and a new appreciation of just how diverse the human microbiome is. 
Predicting outbreaks
Going forward, Quake said, the lab hopes to study the microbiomes of other organisms to see what's there. "There's all kinds of viruses that jump from other species into humans, a sort of spillover effect, and one of the dreams here is to discover new viruses that might ultimately become human pandemics." Understanding what those viruses are could help doctors manage and track outbreaks, he said.
"What this does is it arms infectious disease doctors with a whole set of new bugs to track and see if they're associated with disease," Quake said. "That's going to be a whole other chapter of work for people to do."


Journal Reference:
  1. Mark Kowarsky, Joan Camunas-Soler, Michael Kertesz, Iwijn De Vlaminck, Winston Koh, Wenying Pan, Lance Martin, Norma F. Neff, Jennifer Okamoto, Ronald J. Wong, Sandhya Kharbanda, Yasser El-Sayed, Yair Blumenfeld, David K. Stevenson, Gary M. Shaw, Nathan D. Wolfe, Stephen R. Quake. Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA. Proceedings of the National Academy of Sciences, 2017; 201707009 DOI: 10.1073/pnas.1707009114



A new study has found that there is a three-way relationship between a type of gut bacteria, cortisol, and brain metabolites. This relationship, the researchers hypothesize, may potentially lead to further insight into autism, but more in-depth studies are needed.

Research previously covered by Medical News Today suggested that there might be a link between bacteria found in the gut and the development of autistic behavior. Recent studies continue to establish links between the gut microbiome and autism spectrum disorders (ASD).
However, the exact way in which gut microbes might influence brain development is still subject to debates and further studies.
Now, researchers from the University of Illinois at Urbana-Champaign have found that there may be a three-way mechanism of communication between gut microbes and brain metabolites, involving cortisol as the channel through which the "message" is transmitted.
First study author Austin Mudd, a doctoral student at the University of Illinois, explains that brain metabolites can have a strong impact on the development of infants, and that these could be influenced by the gut microbiome.
"Changes in neurometabolites during infancy can have profound effects on brain development, and it is possible that the microbiome - or collection of bacteria, fungi, and viruses inhabiting our gut - plays a role in this process," he says.
It was this mysterious interaction between the brain and the gut that motivated the researchers to investigate the mechanism at play. The researchers' findings were published in the journal Gut Microbes and are available online.

Gut bacteria predict brain metabolites

In this study, the scientists used 1-month-old piglets, since they are the animals with most similarities to human infants when it comes to the development of the brain and the gut microbiome.
"Using the piglet as a translatable animal model for human infants provides a unique opportunity for studying aspects of development which are sometimes more difficult or ethically challenging to collect data on in human infants," explains Mudd.
"For example, in this study we wanted to see if we could find bacteria in the feces of piglets that might predict concentrations of compounds in the blood and brain, both of which are more difficult to characterize in infants," he adds.
First, the researchers found that the Bacteroides and Clostridium bacteria, identified in the animals' feces, predicted higher levels of myo-inositol, which is a substance that plays a role in cell signaling. Bacteroides could also predict higher quantities of creatine - an amino acid-like compound - in the brain.
The scientists also noticed that Butyricimonas bacteria could positively predict n-acetylaspartate (NAA), an amino acid found in the brain. At the same time, they found that an abundance of Ruminococcus bacteria in the feces correlated with lower concentrations of NAA in the brain.
Mudd highlights the fact that previous research had already suggested a link between abnormal NAA and the development of ASD, but so far, nothing had led scientists to note correlations between gut bacteria and NAA.
"These brain metabolites have been found in altered states in individuals diagnosed with autism spectrum disorder [...], yet no previous studies have identified specific links between bacterial genera and these particular metabolites."
Austin Mudd

Cortisol acts as communication channel

Next, the researchers sought to establish whether these types of bacteria could also predict the concentration of certain compounds in the blood.
Study co-author Ryan Dilger, who is an associate professor at the University of Illinois, explains that collecting fecal samples and blood biomarkers from infants would be more feasible than carrying out other tests. If this approach is proven effective, it would enable easier tests that could flag up potential ASD predictors.
"Blood biomarkers are something we can actually collect from an infant, so it's a clinically relevant sample. It would be nice to study an infant's brain directly, but imaging infants is logistically and ethically difficult. We can, however, obtain feces and blood from infants," says Prof. Dilger.
It was found that the microbes from feces could predict levels of serotonin and cortisol, both of which are influenced by gut bacteria. Bacteroides bacteria were linked with higher levels of serotonin, and abundant Ruminococcus were associated with lower levels of both compounds.
The study authors note that their findings support the results of existing studies that separately observed the associations between ASD and altered levels of serotonin and cortisol, on the one hand, and an abundance of Bacteroides and Ruminococcus in the feces, on the other.
Using "mediation analysis," a statistical method, the researchers tested the existence of a three-way relationship between Ruminococcus, NAA, and cortisol.
They found that cortisol in the blood acted as a sort of "channel of communication" between fecal Ruminococcus and cerebral levels of NAA. This suggests that Ruminococcus influence changes in the brain indirectly, through serum cortisol.
The researchers conjecture that this three-way mechanism could play a role in determining ASD symptoms, but they caution that this must be confirmed by further in-depth studies.
"We remain cautious and do not want to overstate our findings without support from clinical intervention trials, but we hypothesize that this could be a contributing factor to autism's heterogenous symptoms," says Mudd.


More articles on the fascinating subject of bacteria and viruses on this blog


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