Weizmann Institute’s Science Tips: “Microbiome” of Microbes in Human Body Form “Second Genome”, and more

Germs, Humans and Numbers

How many microbes inhabit our body on a regular basis? For the last few decades, the most commonly accepted estimate in the scientific world puts that number at around ten times as many bacterial as human cells. In research published today in the journal Cell, a recalculation of that number by Weizmann Institute of Science researchers reveals that the average adult has just under 40 trillion bacterial cells and about 30 trillion human ones, making the ratio much closer to 1:1.

The bacteria living in our bodies are important for our health. The makeup of each person’s microbiome plays a role in both the tendency to become obese and in each individual’s reaction to drugs. Some scientists have begun referring to it as the “second genome, ” recognizing that it needs to be taken into account when treating patients.

The rising importance of the microbiome in current scientific research led the Weizmann Institute’s Prof. Ron Milo, Dr. Shai Fuchs and research student Ron Sender to revisit the common wisdom concerning the ratio of “personal” bacteria to human cells.

Their research was undertaken as part of their work for the book Cell Biology by the Numbers, which was recently published by Milo and Prof. Rob Philips of the California Institute of Technology. The book, as the name suggests, is a compilation of insights gained from calculations and estimates about living cells.

The original estimate that bacterial cells outnumber human cells in the body by ten to one was based on, among other things, the assumption that the average bacterium is about 1, 000 times smaller than the average human cell. The problem with this estimate is that human cells vary widely in size, as do bacteria. For example, red blood cells are at least 100 times smaller than fat or muscle cells, and the microbes in the large intestine are about four times the size of the often-used “standard” bacterial cell volume. The Weizmann Institute scientists weighted their computations by the numbers of the different-sized human cells, as well as those of the various microbiome cells. They also weighted their calculations for the quantities of “guest” bacteria in different organs in the body. For example, the bacteria in the large intestine dominate, in terms of overall numbers, all the other organs combined.

Milo says, “It is truly important to understand our microbiome, and research into this fascinating field is crucial for biomedical research. In the life sciences, which involve “messy” highly dynamic and variable systems, researchers sometimes tend to rely on qualitative rather than quantitative statements. But performing educated estimates in cell biology can serve as an extremely powerful tool. For those researchers who are proficient at hearing what the numbers tell them, estimates serve as a ‘sixth sense’ for understanding the lives of cells.”

Calculating Whiskers Send Precise Information to the Brain

As our sensory organs register objects and structures in the outside world, they are continually engaged in two-way communication with the brain. In research recently published in Nature Neuroscience, Weizmann Institute scientists found that for rats, which use their whiskers to feel out their surroundings at night, clumps of nerve endings called mechanoreceptors located at the base of each whisker act as tiny calculators. These receptors continuously compute the way the whisker’s base rotates in its socket, expressing it as a fraction of the entire projected rotation of the whisker, so that the brain is continually updated on the way that the whisker’s rotation is being followed through.

Whiskers, like our eyes or fingers, must move to sense the stationary things in their environment. Prof. Ehud Ahissar and his group in the Institute’s Neurobiology Department, including Dr. Knarik Bagdasarian, have been investigating the rat’s active sensing system for over a decade, applying a method in which the experimenter “does the whisking” for an anesthetized rat. This method enables them to study so-called active sensation, but the whisker’s movement could not mimic that of awake rats – in which sensing and the act of whisking are tightly bound.

In the present study they combined their method with one developed by Dr. Avner Wallach, at that time a postdoctoral fellow in Ahissar’s lab, whose PhD research with Profs. Shimon Marom and Ron Meir in the Technion had involved work on integrating computers into biological systems. Wallach, Bagdasarian and Ahissar further developed a combined method: a closed-loop system in which the rat whisking system and the computer form a sort of “rat-computer hybrid” that recreates the whisking movement and the way it is regulated in awake, freely-moving rats.

The discovery that the mechanoreceptors within the whisker follicle were actually calculating the whisker’s motion phase “online” came as a surprise to the researchers, because knowing the phase implies predictive knowledge of how the whisker motion will develop. The assumption was that specialized neuronal circuits would perform this calculation using raw data from both the receptor and the brain’s motion-planning circuits.
“On second thought, ” says Ahissar, “this work division is sensible. The sensory organs are not merely ‘signal converters.’ Rather, they are broad, inclusive interfaces between organisms and their environments, providing everything the brain needs for making sense out of their signals.” Next, the researchers would like to know how the sensory organ physically calculates this predictive information.

The combined method might, in future research, be used to explore other closed-loop algorithms in the brain. “By investigating sensing with a machine-brain interface, we were able to obtain a sort of insider’s insight into the communications between the whisker and brain, ” says Wallach. “This ‘inside agent’ can be moved around to explore other complex motor-sensory loops underlying perception.”

“The more the sensory organs are studied, the more their complexity and sophistication are revealed, ” adds Ahissar. “It seems that their evolution is a key factor in the evolution of perception.”

Prof. Ehud Ahissar’s research is supported by the Lulu P. and David J. Levidow Fund for Alzheimers Diseases and Neuroscience Research; Lord David Alliance, CBE; the Berlin Family Foundation; and the Harris Foundation for Brain Research. Prof. Ahissar is the incumbent of the Helen Diller Family Professorial Chair in Neurobiology.