Scientist culture critical gut bacteria

Example of a segmented filamentous bacteria.

Scientists from France recently announced in Nature that they had successfully cultured segmented filamentous bacteria (SFBs) for the first time.  These bugs likely exist in the intestines of all mammals, including humans, and research has shown they may be amongst the most important commensal bacteria we have.  Previous research has shown that the existence and abundance of SFBs is directly linked to the induction and recruitment of immunity cells, like T cells.  The SFBs exist right on the mucosal boundary of the gut and appear to intimately interact with it.  This close interaction allows the bacteria to use the gut to survive, but also to send molecular signals to the body.

The scientists were able to culture the bacteria by first culturing epithelial cells (i.e. the cells that line the gut) and then culturing the SFBs in close proximity.  During their experimentation they discovered that the bacteria grew best when they were physically touching the epithelial cells, but that they could survive so long as they were close by.  The scientists also discovered many of the important requirements for successful colonization and growth of SFBs, and we invite anyone interested in learning more to read the article.

While the results of this study may not sound very exciting to the lay-man, they are in fact significant.  If these SFBs turn out to indeed be a critical component to mediating the immune system, being able to culture and perform experiments on them in the lab will be essential.  Future studies could possibly identify the key molecules that are critical in signaling host immunity by the microbiome, and important compounds could be made into therapeutics.

What happens to our microbiome when we get sick?

Editors Note:  Yesterday a piece about the AMI was published by the website Gut Microbiota for Health.  Read about it here.

When people get sick, what happens to their gut bacteria? Does their microbiome become weaker like the rest of their body? A recent study led by a group at the University of Chicago and published in Nature found that in mice, the intestines begin producing a specific type of sugar, fucose, to keep the bacteria in their guts healthy when the rest of their body becomes ill. 

To observe this occurrence, the team of scientists exposed different sets of mice to a molecule that causes them to get sick, simulating infection. When the first set of mice was given this molecule, fucose was quickly and abundantly produced in their intestine. When the second set of mice, mice that were bred to lack a specific gene (Fut2) that allows them to produce fucose, was made to become sick, the mice recovered from the illness much slower than the mice able to produce fucose.

This study showed that these sugars keep the microbiome healthy when its host gets sicks and help the host recover faster. What does this mean for humans?  Do we too produce this sugar when we become sick?

Unfortunately, approximately 20% of humans lack this important gene for producing fucose and these same people have been associated with a higher incidence of Chrohn’s disease.  In this study, the gut microbes of the mice engineered to lack the gene for creating fucose had greater harmful bacteria in their gut than normal mice. It is likely that the production of fucose in our bodies not only helps feeds our healthy bacteria, but it also helps stave off potentially pathogenic bacteria from proliferating.

This important interaction may lead to new therapeutics that directly influence the microbiome.  So remember, always 'feed' your cold.

Can we prevent C. diff infections with other bacteria?

The microbiome of the mammalian gut helps protect the body from intestinal colonization of harmful pathogens. Antibiotic use can destroy the beneficial bacteria in our gut and allow for harmful bacteria to colonize it. Specifically, Clostridium difficile (C. diff) infection is a condition that is frequently seen in patients taking antibiotics and is often fatal.  A study published in Nature last week led by scientists at Memorial Sloan Kettering Cancer Center identified another bacteria, Clostridium scindens, that helped fight against C. diff infection. This study opens a new avenue to better predict what patients are at a higher risk of C. diff infection as well as the development of products that could prevent or even treat this condition.

A few weeks ago we wrote about an study published in the Journal of the American Medical Association that described the treatment of patients suffering from C. diff infection with a pill containing fecal material of healthy individuals.  The pill restored the microbiome to a healthy state and prevented future infection. However, little is known about what specific bacteria are responsible for resistance to infection. Why do some patients taking antibiotics get C. diff and others do not?

The scientists conducting this study identified 24 human patients undergoing allogeneic hematopoietic stem-cell transplantation, 12 who had C. diff infections and 12 who were C. diff carriers but were not infected after their transplant.  In the human study, as well as in mouse studies, they found that Clostridium scindens, an intestinal bacterium, is connected with resistance to C. diff infection. C. scindens produces an enzyme necessary for secondary bile acid synthesis, which was shown to be absent in the gut of patients infected with C. diff but present in recovered patients. This study suggests that it may be possible for doctors to better predict what patients are at a higher risk of C. diff infection by measuring the presence of C. scindens in the patient’s gut.  C. scindens could also be used in the development of preventative agents or therapeutics given to patients at higher risk or infected with C. diff.

The microbiome and osteomyelitis, an autoinflammatory bone disease

The Gross Clinic, famous oil portrait depicting osteomyelitis surgery from 1875.

A recent paper in the journal Nature discusses experiments that provide a link between a certain gut bacteria, diet, and osteomyeltis (an autoinflammatory bone disease).  Osteomyelitis occurs when there is a bacterial infection of the bone marrow.  It is often treated with antibiotics but sometimes surgery and amputation are necessary. 

In the study, the researchers induced osteomyelitis in a group of mice.  They then gave half the mice high fat diets and half the mice low fat diets.  They discovered that the mice eating the high fat diets were protected from osteomyelitis and showed little bone inflammation, while those eating a low fat diet developed the disease.  

The discovery that diet could alter the progression of the disease led the researchers to investigate the microbiome of these mice.  The mice with low fat diets had higher amounts of Prevotella and lower amounts of Lactobacillus when compared to normal mice.  The reverse was true for the high fat diet mice, they had much less Prevotella and much more Lactobacillus in their guts, which better represents the composition in normal mice.

To further investigate if Prevotella may be causing the disease, the researchers gave antibiotics to the low fat diet mice, which destroyed the Prevotella population, and decreased the symptoms of the disease.

Finally, the researchers performed microbiome transplants into germ-free mice that were susceptible for osteomyeltis.  Any germ-free mouse that received a transplant high in Prevotella and then was fed a low fat diet developed the disease.  However, any mouse that received a transplant that was low in Prevotella, even if that mouse was on a low fat diet, did not develop the disease.  

These results show that dietary intake can alter the microbiome and greatly influence osteomyelitis outcomes.