The microbiome affects celiac severity in mice

In non-celiac people, gluten is broken down into its constituent proteins and does not elicit any immune response.  In celiac disease, however, the gluten proteins cause inflammation, which can result in a number of GI issues.  The microbiome has long been thought to play a role in this disease, because of its importance to immune mediation, and its role in gluten breakdown.  An international group of scientists recently tested the role of various different characteristic microbiome communities on the immune reaction in mice with celiac disease.  They published their results last week in the American Journal of Pathology.

The scientists used a mouse model for celiac disease that involved genetically modified mice that had an immune response to gluten.  They split the mice into three groups, one group had a typical healthy microbiome, the next had a healthy microbiome but without proteobacteria, and the final group was germ free (i.e. completely lacking a microbiome).  When the germ free mice were challenged with gluten they had the highest inflammatory response.  This included increases in immune cells, and breakdown of the intestinal villi.  Unsurprisingly, when the germ free mice were colonized with normal microbiota, their inflammatory response was attenuated.   The scientists then discovered an important relationship between celiac’s and Proteobacteria.  The mice that harbored this phylum had more severe responses to gluten, suggesting that these bacteria somehow worsen the inflammatory response to gluten.  Antibiotic treatment that increased the amounts Proteobacteria, and the relative abundances of Escherichia, Helicobacter, Pasteurella, and Lactobacillus, also increased the inflammatory response.

The exact mechanisms by which the microbiome are mediating the immune response are unclear.  Bacteria are known to induce various immune cells and also break down gluten, and these mechanisms may be involved.  In either case gluten sensitivity and celiac disease are clearly affected by the microbiome.

Decreased bladder microbiome diversity associated with urinary tract infections

A catheter

Urinary tract infection is one of the top healthcare-associated infections along with pneumonia and gastrointestinal illness, according to the Centers for Disease Control and Prevention. In nursing homes, UTIs are the most common type of infection and are often caused by catheters. Catheters are used to collect urine in both male and female patients. Older patients tend to need catheters for a longer period of time, putting them at higher risk for infections as it allows for the greater colonization of infectious bacteria. In an article published in the Journal of Infection, researchers in Houston, Texas experimented with a catheter coated in a specific strain of Escherichia coli to see if it would prevent catheter-associated urinary tract infections (CAUTIs) in older patients.

Eight men and two women, with a mean age of 70.9, were enrolled in the study. All but one subject received antibiotics prior to the insertion of the catheter. This antibiotic regime most likely caused a significant disruption to the existing microbial balance in the bladder. Despite the antibiotic use, the subjects’ urine still showed the presence of microorganisms after antibiotic treatment and immediately prior to catheter insertion. The study catheters that each patient received were previously colonized in the lab by E. coli strain HU2117, which is a strain that is missing an essential infection-allowing gene. By using the benign strain without this papG gene, the patients were safe from any harm. The hypothesis was that this E. coli strain would be delivered to the bladder and compete with infectious bacteria, not allowing the pathogens to colonize the bladder.

Urine samples were collected from the subjects on days 0, 1, 3, 7, 14, 21, and 28 after catheter insertion. After that, samples were collected monthly until no E. coli was detected. Three of the subjects suffered from febrile UTI, and two from urosepsis/bacteremia, another form of UTI. In these five subjects E. coli was not the predominant bacteria and was not even detected during infection in some cases. From the results of this study we can conclude that E. coli HU2117 is most-likely not effective enough in preventing other pathogenic bacteria from infecting the bladder.  

The researchers explain that the reason why their experiment had a negative result was that the E. coli did not increase bacterial diversity in the bladder. Diversity in colonization is usually what protects from infection and in this study, decreased diversity led to UTIs. This is a theme we have seen over and over again on the blog. Further informative studies could include those that help us understand the healthy and diverse microbiome of the bladder, and subsequently use that information to decrease UTI occurrence.  

Understanding the nasal microbiome

Electron micrography of Staphylococcus aureus.

The nasal microbiome remains largely unstudied despite its potential importance to many diseases, such as rhinosinusitis, allergies, and staph infection (incuding MRSA).  Staphylococcus aureus is probably the most well-known nasal resident, but simple questions, such as which species of bacteria are most prevalent in the nose, are still not answered.  Understanding all the residents of the nasal microbiome, the influence of our genetics and the environment on defining their populations, and the influence each one has on others may be critically important to preventing diseases such as staph infection, and more research is needed.  Fortunately, a new study out of Johns Hopkins that investigated sets of twins shed light on many of these questions, and was published in Science Advances last week.

The scientists sequenced the nasal microbiomes of 46 identical and 43 fraternal pairs of twins.  First, thy learned that these people’s nasal microbiomes could be classified into 7 different phenotypes or community state types (CST) which broadly described their nasal microbiomes.  These 7 types are defined by their most abundant bacteria, and are as follows: CST1 – S. aureus, CST2 - Escherichia spp., Proteus spp., and Klebsiella spp., CST3 - Staphylococcus epidermidis, CST4 - Propionibacterium spp., CST5 - Corynebacterium spp., CST6 - Moraxella spp., and CST7 - Dolosigranulum spp.   The most common CTS was CTS4 with 29% of the sampled population having that CTS, whereas CTS4 was the least popular, coming in at 6% of the individuals tested.  The researchers noted that many of these bacteria, such as Proteus, were not considered to be important to the nasal microbiome at all, so their dominance in some noses was surprising.  The scientists learned that genetics plays nearly no role in the microbiome community composition, but does influence the overall microbiome population.  In addition, gender influenced the overall population, with women having about half as many total bacteria in their noses as men.

With regards to S. aureus, while it existed in 56% of the individuals studied, it was associated with other bacterial.   For example, the researchers discovered that Dolosigranulum, and Propionibacterium granulosum were negatively correlated to the existence of S. aureus, whereas S. epidermidis was positively correlated with S. aureus abundance.  This lends itself to the idea that specific bacteria can create colonization resistance against S. aureus, and thus could be used to prevent the disease.  The researchers suggest a probiotic should be tested for its therapeutic value in preventing S. aureus colonization, and hopefully they move forward with those trials.

The oral microbiome of children, and its relation to dental caries

The oral microbiome is a popular area of exploration because bacteria are a prominent part of dental health, and because it is one of the most heavily colonized and easily accessible niches in the body. Many studies have been discussed on this blog concerning adult oral microbiomes, and its relations to bodily issues such as cystic fibrosis and periodontitis. It is also very useful to investigate children and the ways that their bacterial communities first inhabit and develop. A study done in Sweden at the Umeå University, and published by Plos One, takes a look at the maturation of the oral microbiome from infants at 3 months old to children at 3 years old.

The Swedish researchers performed a longitudinal study that followed children from 3 months to 3 years of age, looking for microbial characteristics of children with dental caries (i.e. cavities) compared to those without. There were 207 original participating 3 month olds that were consented by their parents to be in the study. The parents provided information on mode of feeding, mode of delivery, use of antibiotics or probiotics, health issues like allergies, and presence of teeth. At 3 months and later at 3 years samples were taken from the buccal mucosa, tongue, and alveolar ridges. Teeth were also scraped for plaque and saliva was collected. Of the original 207 participants, 155 returned for sampling at 3 years of age, and 13 of those children had dental caries.

After sequencing the bacterial DNA samples, it was found that Escherichia coli, Staphylococcus epidermidis, and various Pseudomonas species were significantly more prevalent in 3 month olds. However, there were 23 genera that were more significantly prevalent at 3 years of age than at 3 months.

By comparing the children with and without caries, the scientists were able to make several conclusions.  The researchers identified seven taxa that appear to be associated with healthy teeth.  On the other hand, Streptococcus mutans seemed to be more prevalent in the children with caries, than in those without caries. Additionally, the colonization of this species was most prevalent in girls. This is possibly because girls develop faster, so earlier tooth eruption allows for a longer time for the colonization of these bacteria.

The results of this study show us that during the first three years of life, species richness and diversity seems to increase significantly in the mouth. While there is an increase in the type of the bacteria, there are also some taxa that are lost with age. The researchers also concluded that the oral microbial composition of the mouth at 3 months does not appear related to the development of dental caries. With this information, it might be smart to perform a related study that collects oral microbiome samples in children within the time frame of 3 months to 3 years, because it could show a clearer picture of the changes that take place in bacterial composition.

The giant panda’s microbiome isn’t doing it any favors

Panda bears are quite unique in the animal kingdom because they are nearly strictly herbivores yet they are descended from omnivores.  In fact, scientists aren’t quite sure why panda’s made the transition to eating bamboo, because it is a relatively inefficient energy source.  Making matters worse for the panda, its gastrointestinal tract is rather short, and resembles other carnivores, whereas most herbivores have very long gastrointestinal tracts that allow for long retention times for the microbiome to do its work.  This microbiome, of course, breaks down plant material into usable sources of energy for the host and it is critical in all herbivores.  Scientists from China recently investigated the panda’s microbiome, and to their surprise discovered that it too, resembled carnivores’ microbiomes, rather than herbivores’ as one might expect.  They published their results last week in MBio.

The scientists measured the fecal microbiomes of 45 captive pandas over the course of one year, including cubs, juveniles, and adults.  They then compared these microbiome samples with previously reported microbiomes of 54 other species, and wild, rather than captive pandas.  Their first discovery was that the panda’s microbiome was not as diverse as many of these other species, and as our regular readers know, low diversity has been implicated in many diseases in humans.  Next, they found that the panda’s microbiome was actually much more similar to other carnivorous species, especially other bears and tigers, than herbivorous species, and was dominated in Escherichia/Shigella, and Streptococcus, rather than bacteria that are known to degrade cellulose from plant matter, such as Ruminococcaceae, and Bacteroides.  Finally, of particular interest in light of the recent research on the importance of diurnal changes in the microbiome, the scientists noted that the panda microbiome undergoes huge shifts in accordance with the seasons, although they do not speculate as to the effects these shifts may be having.

These discoveries are quite surprising, but they help explain why pandas must eat around 25 lbs. of bamboo every day.  Their microbiomes are just not well equipped to digest this food.  In fact, the lack of cellulose degrading bacteria in pandas’ guts has led some scientists to speculate that pandas are merely living off the cellular contents of each plant cell, rather than the energy dense cellulytic plant cell wall.  Whichever the case, their inefficient digestion certainly is not helping them thrive as a species.