How many bacteria vs human cells are in the body?

When people ask me what the microbiome is, part of my answer usually includes the fact that there are 10 times as many bacteria in the body as human cells in the body. Unfortunately, I may no longer be able to use that statistic. A recent study out of the Weizmann Institute in Israel states that the number of bacteria may actually be very similar to the number of human cells in the body.

The authors of the study found that the 10:1 ratio of bacterial to human cells goes back to a 1977 study by Dwayne Savage and an earlier 1972 paper estimating the number of bacterial cells in the human body. The Weizmann scientists redid the estimate and found that there were about 39 trillion bacterial cells in the body. They also estimated the number of human cells in the body, about 84% of which are red blood cells, finding there to be about 30 trillion human cells in the body.

While this results in about 1.3 bacterial cell per human cell, the numbers may vary significantly from person to person and could change significantly with each defecation. They estimate that the range of bacterial cells goes from about 30 to 50 trillion in each individual. Women may also have a higher ratio of bacterial cells than human cells because they have fewer human cells, specifically red blood cells.

While this study does not take into account fungi, viruses, and archaea which all make up the human microbiome and would increase the ratio of microbes to human cells, the often stated ratio of 10:1 for bacterial cells to human cells is most likely not accurate. While I will no longer be able to use this fun fact in my description of the microbiome, it does not take away from the importance of bacterial cells in human health. 

Can human embryonic stem cells model human nutrition?

Human embryonic stem cell colony

Scientists at Harvard University have proposed a new model for studying nutrition, human embryonic stem cells. Human embryonic stem cells are unique in their ability to turn into all the cell types in the body, including the various tissue types in the human gut.

Drs. Doug Melton and Danny Ben-Zvi propose in an essay in Cell that human embryonic stem cell derived tissues populated by gut microbiota may be an ideal system for studying the physiology of digestion and nutrition. The authors state that the mechanisms of human nutrition are largely unknown and that it is difficult to model how nutrition affects human health on a biological front. By developing systems of stem cell derived tissues, it may be possible to model the gut in the petri dish or even on a chip. Significant engineering advances have been made to model biological systems on a chip.  These chips are devices with specific cell types in chambers that are connected through microfluidic channels to better model the tissues and organs in the human body and how they interact with one another.

Chips could be developed that are made of up cells of the various organs that make up our gastrointestinal tract.  These organoids could then be populated by bacteria that make up the microbiota. Food could be passed through the chip and scientists could watch bacteria break down food that is passing through it and see how the microbiota adapts to changes in diet. Various conditions could be tested such as what bacterial strains are best at digesting complex carbohydrates? The authors state that many combinations of bacterial strains should be tested to find what bacteria conduct these tasks most efficiently. To do this in mice would require thousands of animals and this may be too restrictive to conduct such experiments. This however could be done using chips with stem cell derived tissues that make up our GI tract and connected through microfluidic channels to stem cell derived liver and pancreas cells that are important for nutrition and digestion.

Significant biological and engineering challenges still exist before this is a reality, including the ability for specific strains of bacteria to thrive in such an environment.  However, if some challenges can be overcome, the authors propose that the complexity of nutrition and digestion could be better dissected using systems of stem cell derived tissues in the dish.  This work would complement existing research using model organisms and epidemiological and other human studies to better address the questions that we ask every day about what food we should eat and the effects this has on the human body. 

What microbes are living in public bathrooms?

Do you ever wonder how clean our bathrooms are, or question what kinds of bacterial communities are lurking in the public bathrooms you use? Well lucky for you and I, a team of scientists wondered the same exact thing. Published in Applied and Environmental Microbiology, the scientists sampled the microbial communities of four public restrooms at San Diego State University to better understand how they shifted over time.

At the beginning of the study, the restrooms were sterilized using a bleach solution.  Just one-hour post sterilization, the bathrooms were already filled with microbes again and as you can imagine, a significant portion of the microbes were of fecal origin.  They found that despite varying frequency of use and sampling bathrooms of both sexes, the four bathrooms all eventually had microbial communities that were very similar to one another.

The scientists found one specific bacterium, Staphylococcus, was prevalent in all the restrooms. One kind of staph can be very pathogenic, specifically when it is resistant to antibiotics (MRSA), however Staphylococcus does often live harmless in our bodies.  They did not find any Staphylococcus that was resistant to antibiotics in any of the restrooms. The restrooms were cleaned regularly using soap and water over the course of this study, yet the microbial communities remained largely stable.

You may read this and be grossed out about bacteria being prevalent in public restrooms even after regular cleaning, but they are most likely harmless, or even beneficial. Perhaps bleaching a bathroom may be like taking antibiotics - it leaves open the possibility for harmful bacteria to colonize, like what Clostridium difficile does in the gut.

How our body's normal bacteria avoid destruction by the immune system

The human gut is exposed to toxins, pathogens, dietary changes, antibiotics, and other disturbances that can cause alterations to our microbiome. So how is it that the gut of healthy individuals remains largely stable despite these perturbations? When we get sick, why is it that our body’s “good” bacteria remain in the gut while the bacteria causing the infection are killed off by our immune system?  A study out of Yale, published last week in Science, identified a single gene in bacteria that allows for these bacteria to resist inflammation-associated antimicrobial peptides that are released by the body to kill off harmful bacteria.

The scientists found that this gene, lpxF, encodes for an enzyme in the cell membrane of bacteria to be slightly altered from bacteria lacking this specific gene.  To figure this out, they exposed 17 commensal (or normal) bacteria to antimicrobial peptides (AMPs) and found that they were more resistant than pathogens that were also exposed to the same AMPs. They then mutated the genes of five species of Bacteroidetes at various points and checked to see which ones became less resistant to AMPs.  They found one gene that was common across all five species, lpxF.

They also did experiments in which they genetically manipulated bacteria to knock out the lpxF gene and put these bacteria into germ free mice along with the same bacteria with the functional lpxF gene. In the absence of a pathogen, the bacteria lacking the lpxF gene performed just as well as the bacteria with the gene.  When a pathogen was introduced into the mouse, inducing an immune response, the bacteria lacking the lpxF gene was greatly reduced in comparison to the other bacteria with functional lpxF.  This showed that the gene was protecting the bacteria from the AMPs. 

Lastly, they took fecal samples from twelve individuals and exposed bacteria from them to AMPs. They found that in comparison to pathogens that did not survive very well after exposure, the commensal bacteria performed very well.  This is a very important study as it opens up a new understanding of how bacteria in the body are saved from an immune response after exposure of a pathogen in the body.  There are most likely many more genes that play similar roles to lpxF and this work opens up new avenues to better understand how commensal microbes interact with the human body as well as pathogens in the body.   

New antibiotic discovered that may not lead to resistance

iChip - the device used to identify the new antibiotic (image by Slava Epstein/Northeastern University)

Antibiotic resistance is a topic that we’ve written about extensively in the blog and a major public health concern in today’s society. In the US alone, over 20,000 deaths are caused by antibiotic resistant bacteria every year and several million illnesses can also be attributed annually to antibiotic resistant bacteria. Research led by Dr. Kim Lewis at Northeastern University resulted in the identification of a new antibiotic called teixobactin that looks as if it may not cause antibiotic resistanace. This discovery is being hailed as groundbreaking and a promising avenue to treat previously untreatable chronic infections.

The research published on Wednesday in Nature identified this new antibiotic by culturing bacteria that were previously difficult to grow in the laboratory.  Only about 1% of microbes can be grown in the laboratory making the identification of new antibiotics very difficult (antibiotics are generally developed using microbes).  Using a device called the iChip, they were able to successfully grow up to 50% of bacteria that were previously unable to be grown in the lab. 

Cells from different bacterium were placed individually into a chamber on the iChip that holds several hundred chambers. The device is then placed under the soil where the bacteria are able to grow in their natural environment. After they form colonies, the device was brought to the laboratory and the bacterial colonies were placed on a petri dish.  A target bacteria is then covered over the bacteria that were growing in the soil. If they see that there is no growth over a specific area, they know that the bacteria in that chamber is releasing a potential antibiotic. Through this method, the scientists identified 25 promising novel antibiotics in which teixobactin was the most promising. 

Two diseases we’ve discussed on the blog previously are MRSA (methicillin resistant Staphylococcus aureus) and Clostridium difficile infection. C. diff is a disease usually caused when the healthy bacteria in the gut are killed by an antibiotic and C. diff colonizes the gut. This can be very difficult to treat and a last resort is often a fecal microbiota transplant (FMT). An exciting development from this research is that this new antibiotic was particularly effective against both C. diff and S. aureus as well as the bacteria that causes tuberculosis. 

This is an incredibly exciting development but as an organization focused on the microbiome, we need to think about what the implications are on the microbiome.  The development of new antibiotics is incredibly important and we have seen the field move very slowly in recent times, but we still need to be careful with the overuse of antibiotics. Even if bacteria do not become resistant to this antibiotic, the same issues we’ve discussed pertaining to the overuse of antibiotics still exist.  This antibiotic seems to be quite powerful and ridding our guts of bacteria on a regular basis can cause increased levels of obesity in children among countless other public health problems. It is important that just because an antibiotic does not cause resistance, we do not overuse it. 

We look forward to the further developments with teixobactin and hope to see this move to clinical trials in the near future. This new antibiotic has only been tested so far in mice and will need to be tested further in animals and later humans.  The authors estimate that if all goes well, this new antibiotic could be on the market in about 4 or 5 years (they hope to be in clinical trials in two years with clinical trials taking an additional two to three years).  

How an antibiotic resistant bacteria is raising concerns for the 2016 Summer Olympics

About a month ago we wrote about an antibiotic resistant bacteria called MRSA, or methicillin-resistant Staphylolococcus aureus, and gave an example of an athlete who had contracted the bacteria.  There is now another antibiotic resistant bacteria making international headlines and it is once again a relationship with sports that is bringing it to the forefront of our attention.  Recent reports out of Rio De Janeiro, Brazil show that an antibiotic resistant “superbug” has been found in the Cariorca River that runs through Rio and empties into the Atlantic Ocean at the famous Flamengo Beach.

This report from scientists at the Instituto Oswaldo Cruz is particularly concerning as the bacteria have been found close to the Marina da Gloria, site of the 2016 Olympic sailing competitions. This bacterium is of the Enterobacteriaceae family and produces an enzyme called KPC that is resistant to most forms of antibiotics.  This bacterium is usually only found in hospitals, so how is that it was found in three separate sites of the Cariorca River?

Well, its not yet clear how the bacteria made its way to the river, but the scientists did note that the bacteria were not found before the river made it’s way through town. This leads to the belief that it was likely sewage and waste from hospitals that transmitted the bacteria into the environment. There are several hospitals along the river and fecal matter in the sewage very well could have been host to the bacteria. Officials in Rio had stated their goal was to reduce the sewage and waste by 80% but officials have recently acknowledged that this number was not going to be reached in preparation of the 2016 Olympic games.

Like other bacteria, it is possible that someone who comes in contact with the bacteria may not get sick from it but they could carry it and pass it on to someone else. Those who do contract this bacterium will need to be hospitalized and studies have shown that KPC producing bacteria result in a 50% mortality rate. Antibiotic resistant bacteria are a major concern in today’s society and something that we feel does not get enough attention.  A recent report out of the UK that was commissioned by Prime Minister David Cameron and supported by the Wellcome Trust found that antimicrobial resistance resulted in approximately 700,000 deaths a year and this number was going to increase to 10 million people a year by 2050.  This is a staggering figure and is one of the fastest rising figures in the cause of deaths around the world. 

Almost every two years there is some major health concern at the Olympics. At the 2002 winter games in Salt Lake City we saw influenza running rampant, in 2010 at the winter games in Vancouver, Canada there was a measles outbreak, and earlier this year in Sochi we had stray dogs running loose. Now, we have antibiotic resistant bacteria on the loose in Rio and it will be interesting to see how officials in Brazil get this under control in preparation for the 2016 Summer Olympics. 

This is our last post for the week. We hope everyone has a happy holiday season and we will be back with another post on Monday.