March 2012 – Page 3

03.24.2012

more about bacteria

Gut bacteria and the microbiome seem to be a hot topic this month (see previous post on “the power of the gut“). Ed Yong discusses different enterotypes at Nature News:

Each of us has trillions of bacteria in our guts. These communities vary greatly between individuals, but a paper published in Nature last year¹ indicated that they fall into just three distinct types — enterotypes — defined by their bacterial composition (see ‘Gut study divides people into three types’). Each enterotype is characterized by relatively high levels of a single microbial genus: Bacteroides, Prevotella, or Ruminococcus, respectively.

But new data presented at the International Human Microbiome Congress in Paris yesterday suggest that the boundaries between the enterotypes may be fuzzier than the earlier work suggested.

…

The results, as yet unpublished, show that a genus of archaea called Methanobrevibacter joins Ruminococcus as a defining microbe in the third enterotype. And the separation between this cluster and the Bacteroides-led enterotype is no longer as clear, although these two groups remain distinct from the Prevotella-driven one.

More here. Meanwhile, at The Scientist, Kieran O’Doherty ponders the ethical implications of antibiotics and microbiome engineering as gut bacteria are such an integral part of our existence:

The issue of how stable an individual’s microbiome is over time also raises other ethical questions. For example, because human DNA is a unique identifier of individuals, there are many safeguards for ensuring the confidentiality of genetic data. In many jurisdictions laws have been enacted to prohibit insurance companies from taking the results of genetic tests into account in calculating premiums. There is also much controversy about the possibility of law enforcement agencies acquiring genetic data collected for health research. Some early studies suggest that a person’s microbiome may also be a unique identifier. And there is the possibility that microbial DNA may contain even more information about a person than does their human DNA. For example, a person’s microbiome signature may contain information about his or her country or region of origin, and might even prove presence in a certain place, if soil or water microbes unique to that location are detected. This kind of information may be sensitive for many reasons, most notably because of the obvious value such information might have for law enforcement purposes. Ethical challenges also arise, for example, in ensuring the privacy and confidentiality of individuals whose microbiome is analyzed for research purposes.

At the moment, many of these considerations are hypothetical. However, as human microbiome research progresses, these questions will become increasingly salient. And as scientific consensus emerges on such critical issues as the stability of the microbiome and the long-term implications of infants’ exposures to antibiotics and probiotics, corresponding advances need to be made in thinking about the ethical implications and frameworks to be developed.

And also this headline, “Microbiome sequencing offers hope for diagnostics“.

03.23.2012

Everyone knows that bacteria help digest our food, especially in the colon. Fewer people know that gut microbes are also important effectors of the immune system. They help stimulate cells in linings of our guts to produce antibodies to pathogens. The immune system recognizes and fights harmful bacteria, but leaves the helpful species alone. Intestinal bacteria have also been linked to asthma. It turns out that lack of exposure to intestinal bacteria in early childhood can lead to an increase chance of developing asthma. At least in mice.

From Science:

The tricky question is how microorganisms provide this protection. Mice lacking their normal microbial partners and pathogens have now given mucosal immunologist Richard Blumberg of Brigham and Women’s Hospital in Boston and colleagues an insight. Throughout their lives, these so-called germ-free mice dwell in sterile cages and nibble sterile food, so they don’t acquire the intestinal denizens of normal rodents. Compared with their microbe-populated relatives, such mice are more susceptible to colitis, a type of intestinal inflammation, and to asthma, the researchers have now found. In their lungs and intestines, the germ-free mice also harbor an unusually large number of invariant natural killer T (iNKT) cells. These immune cells trigger inflammation after sensing certain microbes or particular molecules, called antigens, made by the body.

The new study suggests that these cells are crucial for conditions such as colitis and asthma. Blumberg and colleagues discovered that genetically altered mice that lack iNKT cells are not prone to colitis, even if they are raised germ-free in sterile surroundings. Furthermore, Blumberg’s team could largely prevent the development of colitis in germ-free mice that do have iNKT cells if they treated the rodents with an antibody that blocks the cells’ ability to detect antigens.

By shifting germ-free mice to cages containing ordinary rodents that teem with bacteria, the researchers demonstrated the importance of early microbe exposure for the distribution of iNKT cells. Transferred mice quickly pick up intestinal bacteria from their cage mates. Moving adult germ-free animals did not reduce the number of iNKT cells in the colon. However, when the researchers rehoused pregnant germ-free mice, ensuring that their offspring would be immersed in bacteria from birth, the pups had fewer iNKT cells in the colon, even after they grew up, Blumberg and colleagues discovered. “It became clear from the study that [iNKT cells are] sensing the composition of the microbial community in the gut and responding to it,” Blumberg says.

Further Reading:

[Science] Torsten Olszak et al., “Microbial Exposure During Early Life Has Persistent Effects on Natural Killer T Cell Function”. Subscription required.

03.22.2012

how opioids work

A morphine-like molecule (in yellow) binds to a pocket in the mu-opiod receptor (in blue). Image from Science News. Provided by the Kobilka Lab at Stanford University.

Ever wonder how opioid drugs work their magic? Drugs like morphine, codeine and heroin? Lots of people have. And two groups of scientists, one at Stanford and one at Scripps, have made progress in figuring out how they ease pain and cause addiction. The Stanford group crystallized a morphine like molecule with the mu opioid receptor protein. Excerpted from Sceince News:

Many of today’s most powerful painkillers work by switching on one of these proteins, called the mu opioid receptor. But the relief this provides comes at a price. Derivatives of opium, such as morphine and codeine, are addictive and can cause breathing problems and constipation.

To better understand how these drugs work, an international team of researchers for the first time crystallized a small morphinelike molecule attached to a mu receptor — a technically difficult task that requires isolating the pair of molecules without unsticking them from each other. X-rays revealed how one molecule lined up with the other.

This study has limitations though: the molecule they crystallized deactivates the receptor instead of activating it like morphine or codeine, so the interactions they are looking at might not necessarily be the same interactions that are important in easy pain or causing addiction.

The Scripps group looks at a different opioid receptor, the kappa-opioid receptor. Their crystal structure reveals the binding interactions of the experimental drug JDTic with kappa-opioid receptor. This receptor is linked to stress responses moreso than pain relief, so it should tell a different story than the other.

Exciting stuff! I can’t wait to get my hands on the actual research papers.

GOLLYGEE!

Month: March 2012 (page 3 of 8)

more about bacteria

the power of the gut

how opioids work