Ecological forces structure your body's personal mix of microbes

Environmental conditions have a much stronger influence on the mix of microbes living in various parts of your body than does competition between species. Instead of excluding each other, microbes that fiercely compete for similar resources are more likely to cohabit in the same individual. This phenomenon was discovered in a recent study of the human microbiome – the vast collection of our resident bacteria, , and other tiny organisms. The findings were published on July 15, in the early online edition of PNAS, the Proceedings of the National Academy of Sciences.

The study is one of the early steps toward a major goal of Dr. Elhanan Borenstein, the lead scientist on the project. His team hopes to build a  of the human microbiome as a tool to study how  can change this massive , to identify settings that promote beneficial microbiomes, and to design clinical interventions to treat currently hard-to-manage problems. For example, diet or  might be developed to manipulate the microbiome to achieve desired outcomes, such as fixing a chronic digestive inflammation.

“The large communities of  residing on and inside us are critical to our state of health or illness,” said Borenstein, a University of Washington assistant professor of  and computer science and engineering, who conducted the study with his graduate student, Roie Levy.

He explained why medical scientists are interested in the forces that structure our distinctive assemblies of microbes: This knowledge may show clinicians how to restore a more normal pattern in patients whose microbiome has been disrupted by illness, infection, toxins or injury. It can also help them better understand how disease states, such as obesity or  are reflected in and affected by the microbiome.

Ecological forces structure your body’s personal mix of microbes

“Through major genetics studies,” Borenstein noted, “scientists have made valuable progress in gathering information on the species composition of the human microbiome in health and disease.” He added that little is known, however, about the underlying ecology that determines the make-up of the human microbiome. Compositional studies alone do not explain how the various  interact, cooperate or compete to form, maintain or alter their populations.

Borenstein and his team use a systems biology approach and apply sophisticated computer modeling to understand the structure, function, and dynamics of the microbiome. In the current study, for example, they utilized genomic information from hundreds of microbial species commonly found in humans to create computer models of nutrient and energy metabolism. From these models they predicted the nutrients each species requires and the interactions between microbes. Specifically, they were able to estimate how strongly each pair of microbes competes over available nutrients or cooperates in producing necessary compounds. They then compared these predicted interactions to the abundances of microbial species across samples from different individuals.

In this way they learned that species tend to co-exist more frequently with other species with which they strongly compete for their needs, instead of winners overtaking losers. Ecologists, including those who study bigger-size plants and animals, call this habitat filtering. It means that species with similar requirements for life are selected by the environment and co-occur in the same location. Habitat filtering contrasts with another theory, species assortment, in which organisms seeking nearly identical resources clash until a victorious species triumphs.

Borenstein noted, “Species interaction plays a role, but the environment exerts a stronger effect.”

He also indicated that even when his research team corrected for the presence of obesity, inflammatory bowel disease and other factors, they still saw the previously observed pattern of competitor microbes staying together.

This suggests, he explained, that the lines along which species are filtered and microbiomes are assembled are not fully defined by major physiological abnormalities in a patient, but might take place at a finer scale.

Explore further: Your body’s microbiome has a unique ‘fingerprint’

CELLULAR COMMUNICATION DISCOVERED IN THE BRAIN – NEW INSIDES

Researchers at Johannes Gutenberg University Mainz (JGU) have discovered a new form of communication between different cell types in the brain. Nerve cells interact with neighboring glial cells, which results in a transfer of protein and genetic information. Nerve cells are thus protected against stressful growth conditions. The study undertaken by the Mainz-based cell biologists shows how reciprocal communication between the different cell types contributes to neuronal integrity. Their results have been recently published in the journalPLOS Biology.

Brain function is determined by the communication between electrically excitable neurons and the surrounding, which perform many tasks in the brain. Oligodendrocytes are a type of glial cell and these form an insulating myelin sheath around the  of neurons. In addition to providing this protective insulation, oligodendrocytes also help sustain neurons in other ways that are not yet fully understood. If this support becomes unavailable, axons can die off. This is what happens in many forms of myelin disorders, such as multiple sclerosis, and it results in a permanent loss of neuron impulse transmission.

Like other types of cell, oligodendrocytes also secrete small vesicles. In addition to lipids and proteins, these membrane-enclosed transport packages also contain , in other words, genetic information. In their study, Carsten Frühbeis, Dominik Fröhlich, and Wen Ping Kuo of the Institute of Molecular Cell Biology at Johannes Gutenberg University Mainz found that oligodendrocytes release nano-vesicles known as ‘exosomes’ in response to neuronal signals. These exosomes are taken up by the neurons and their cargo can then be used for neuronal metabolism. “This works on a kind of ‘delivery on call’ principle,” explained Dr. Eva-Maria Krämer-Albers, who is leading the current study. “We believe that what are being delivered are ‘care packages’ that are sent by the oligodendrocytes to neurons.”

While studying cell cultures, the research group discovered that the release of exosomes is triggered by the neurotransmitter glutamate. By means of labeling them with reporter enzymes, the researchers were able to elegantly demonstrate that the small vesicles are absorbed into the interior of the neurons. “The entire package of substances, including the genetic information, is apparently utilized by the neurons,” said Krämer-Albers. If neurons are subjected to stress, cells that have been aided with ‘care packages’ subsequently recover. “This maintenance contributes to the protection of the neurons and probably also leads to de novo synthesis of proteins,” stated Carsten Frühbeis and Dominik Fröhlich. Among the substances that are present in the exosomes and are channeled to the are, for instance, protective proteins such as heat shock proteins, glycolytic enzymes, and enzymes which counter oxidative stress.

The study has demonstrated that exosomes from oligodendrocytes participate in a previously unknown form of bidirectional cell communication that could play a significant role in the long-term preservation of nerve fibers. “An interaction like this, in which an entire package of substances including  is exchanged between cells of the nervous system, has not previously been observed”, stated Krämer-Albers, summarizing the results. “Exosomes are thus similar to viruses in certain respects, with the major difference that they do not inflict damage on the target cells but are instead beneficial.” In the future, the researchers hope to develop exosomes as possible ‘cure’ packages that could be used in the treatment of nerve disorders.

New mode of cellular communication discovered in the brainNew mode of cellular communication discovered in the brain

 Explore further: New research points to potential treatment strategies for multiple sclerosis

THE BRAIN IS SHAKING & MOVING ON ITS OWN

Pioneering experiments back in 1982 by Tasaki and Iwasa at the NIH revealed that action potentials in neurons are more than just the electrical blips that physiologists readily amplify and record. These so-called “spikes” are in fact multi-modal signalling packages that include mechanical and thermal disturbances propagating down the axon at their own rates. Nobel Laureate Francis Crick published a paper that same year, in which he postulated potential mechanisms that would explain twitching in dendritic spines, adding to an emerging picture of a brain more vibrant and motile than had been previously imagined. More recently, researchers have developed diffusion-based MRI methods, like diffusion tensor imaging (DTI), to trace the trajectories of axons, and perhaps more intriguingly, determine their directional polarity. Working at the EPFL in Switzerland, Denis Le Bihan and his co-workers have been using diffusional MRI in slightly different way. They now appear to be able to directly measure neuronal activity from the subtle movements of membranes, the water within them, and in the extracellular space around them. Their work, just published in PNAS, provides a much needed conceptual shift away from currently established, but typically nebulous, ideas regarding neurovascular coupling of brain activity to blood flow.

Present-day imaging methods, like -dependent (BOLD) MRI, are only indirectly and remotely related to the cortical activity they often claim to measure. In 2006, Le Bihan reported a water “phase transition” response that preceded the neurovascular response normally detected by functional MRI. He attributed the changes in water diffusion to previously established effects involving membrane expansion and cell swelling secondary to activity. At the biophysical level, interpreting  as is a little off the beaten path from traditional neurobiology, but it can be an informative approach when to trying to understand what might be going on when cells fire.

As biophysicist Gerald Pollack has previously pointed out, spikes may involve the propagation of the line of transition of water from the ordered phase, (as patterned by hydrophic interactions nucleated at the surfaces of membranes and proteins) to a disordered phase.
Traditionally, the so-called bound surface water only extends out a only a couple of molecules from the surface of nondiffusable features. That idea may need to be revisited in light of more recent understanding when attempting to account for the diffusion of water in . A decrease in water diffusion as measured by MRI may be in part explained by a decrease in extracellular space, and that has been suggested from experiments measuring intrinsic optical effects. The larger picture of water diffusion, however, is likely a bit more complicated than this.

In his new study, Le Bihan stimulated the forepaw of a rat and looked at responses in the somatosensory cortex. The key experiment was to infuse nitroprusside in attempt to inhibit neurovascular coupling. It is a tricky alteration because nitroprusside apparently has many diffuse effects. It can induce potent vasodilation, particularly on the vascular end (mainly the smaller venules), after it breaks down to produce nitric oxide. It is also a diamagnetic molecule, and each molecule releases five cyanide ions, which are presumably detoxified by the mitochondrial enzyme rhodanese. The experiments were done under isoflurane anesthesia, which also introduces a few uncertainties, particularly with regard to responses to different frequencies of forepaw stimulation.

If nitroprusside is indeed a realistic experimental proxy for neurovascular uncoupling, then the results of Le Bihan appear to show that the diffusion response is not of vascular origin, and that it is closely linked to neural activation. He found that the standard BOLD MRI responses were completely quenched under nitroprusside, whereas the diffusion MRI responses were only slightly suppressed. Local field potentials were also simultaneously measured and suggested at least, that the neuronal responses were also intact.

The work of Le Bihan indicates that diffusion-based MRI can be used to infer neural activity directly from the structural changes that affect the molecular displacements of water. The ability to use shape changes in neurons, astrocytes, or even spines, raises the question of whether these kinds of techniques might eventually be of use in creating larger scale, and more detailed, Brain Activity Maps (BAMs). I asked Konrad Kording, author on the recent theoretical paper which discussed the theoretical limits to MRI and other activity recording methods, whether methods that probe water movements might be applied to this end.

Kording observed that the spatial resolution of standard MRI is ultimately limited by the diffusion of water, but more importantly perhaps, the temporal resolution of all known MRI methods is nowhere near that required to create spike maps. None-the-less, detecting mechanical responses in the brain could provide many unique insights into function. For example, experiments using agents that dissolve the extracellular matrix, like the clot-busting drug TPA, result in more twitching, or vibration if you will, in dendritic spines. Other studies have shown that the greater the electrical drive on a spine, the less it tends to twitch or change size, particularly during periods of rapid development.

Similarly, sensory deprivations appear to increase these kinds of movements as neurons grow and reorganize connections. While these effects are far below that which could be detected by any large external method of MRI, new tools may permit us to access these newly-revealed activities. Diffusional MRI in particular, can be done with a little modification of the standard MRI procedure. For example, to determine directional diffusion parameters, or diffusion tensors, typically six gradients are used to measure three directional vectors. As these capabilities become more common, hopefully the results of Le Bihan can be further explored and verified.

Next to come: Reading, writing and playing games may help aging brains stay healthy