New study shows how E. coli and B. theta grow in the gut mucus

The mucosal membrane continues to be one of the most intriguing and vexing components of the gut microbiome.  It is the interface between the body and the environment, it is inhabited many bacteria, and it is a nutritional source that shapes the populations in the gut.  There is still very little known about the specific interactions between gut mucous and bacteria, but this critical system is rapidly being studied.  In the most recent advance, scientists from Switzerland and Germany examined two very different gut bacteria that fill different mucosal niches. They published their results in the journal Nature Communications.  The two bacteria they studied were Bacteroides thetaiotaomicron (B. theta) and Escherichia coli.  B. theta is a slow growing bacteria that has high metabolic flexibility that is capable of directly using gut mucins as an energy source.  E. coli is a fast growing bacteria that is much more limited in its metabolism and can’t directly use the carbohydrates in the gut, but can take hold and rapidly proliferate after a course of antibiotics. 

The researchers meticulously researched gnotobiotic mice and made many discoveries about bacteria in their mucous.  First, they discovered that the mucosal microbiome varies across its thickness, and is sterile closest to the intestines, but rich in life closest to the lumen.  In addition, they noted that the luminal microbiome is distinct from the mucosal microbiome, even though the mucous is constantly being shed into the lumen.  To this end, they confirmed that with regards to E. coli, these bugs replicate faster than they are shed (in about 3 hours in the mucous but 8 hours in the lumen), and that their persistence is due to replication rather than uptake from the lumen.  How though, can E. coli thrive with their limited ability to break down mucins?  The scientists learned that they likely metabolize iron, in addition to atypical carbon sources such as fatty acids and glycerol.  B. theta, on the other hand, has a huge repertoire of genes to break down mucins.  They do, though, have the ability to leave the mucins and form biofilms on bits of food, such as fiber, that pass through the lumen, and this is one way they travel through the gut.  Regardless of whether they are in the lumen or the mucins they proliferate at the same rate.

Each of these bacteria occupy different niches in the gut, and each is important to our health.  The discovery that E. coli can use iron for metabolism is particularly interesting, as chemotrophy is not normally considered as important in the body, and may be important to iron regulation.  As more research is published the mucous appears to be ‘where the rubber meets the road’ in the microbiome, and new discoveries in this area will be crucial to our overall understanding of the microbiome’s interaction with the body.

New probe developed to detect specific bacteria associated with bacterial vaginosis

Confocal laser scanning images with 400x magnification of G.vaginalis biofilm in 2 vaginal slides (A and B) in a superimposed image: vaginal epithelial cells in blue and G. vaginalis specific PNA-probe in red. A: vaginal sample with dispersed bacteria; B: vaginal sample with bacteria in biofilm.

Bacterial vaginosis (BV) is a topic we have previously covered on the blog, because of its significance to women’s health. BV is a change in women’s vaginal bacterial composition, in which bacteria that are usually associated with health are at a decreased presence in comparison to BV-associated bacteria. BV is such an issue because it causes a biofilm to form that increase susceptibility HIV and other sexually transmitted infections. BV also has negative effects on pregnancy and is a threat to women of reproductive age. Clearly this is an important topic of research, and was the focus of an article recently published by PLOS ONE.

BV is usually characterized by the presence of Gardnerella vaginalis and Atopobium vaginae. A.vaginae has previously been shown to be much more common than G. vaginalis in BV patients. In the PLOS ONE study, researchers focused on finding the best way to detect these two bacteria in vaginal samples. Samples were taken from 119 women in Rwanda, between the ages of 18 and 35 years old. After testing multiple different probes that had been developed by the researchers, they found that something called the PNA FISH is a very good tool for detecting bacteria in biofilms. Through this study the scientists were able to detect that higher quantities of G. vaginalis and A. vaginae are associated with bacterial biofilms. Almost half the samples containing G. vaginalis also contained A. vaginae, whereas all of the samples that contained A. vaginae were also positive for G. vaginalis.

With the data collected, the researchers hypothesize that G. vaginalis is a main cause of vaginal biofilms when it is high enough in concentration. Hopefully with the discovery of effective probes, much more can be discovered about bacterial vaginosis.    

Saliva regulates our oral microbiome

We know that saliva is important during eating and digestion, but researchers from Harvard and MIT investigated how saliva may be influencing the microbiome.  In an article recently published in Applied and Environmental Microbiology the scientists describe results that show saliva also includes molecules that influence oral bacteria so as to prevent cavities.

Cavities are formed when bacterial biofilms form on teeth and produce acids that go on to dissolve tooth enamel.  Saliva, which flows through the mouth, works to wash away these bacteria and helps remineralize teeth.  Beyond this, it contains molecules called mucins, which are a component of body mucous that are known to influence the microbiome and which have been associated with many autoimmune disaeases.    Before now, it was unknown how salivary mucins impacted the oral microbiome.

Researchers combined the bacteria Streptococcus mutans, which is known to be one of the many bacterial culprits behind cavities, with salivary mucins in the presence of artificial teeth.  They discovered that while the mucins did not prevent the bacteria from growing and proliferating, they did in fact prevent the S. mutans from attaching to the artificial teeth.  In fact over 95% of biofilm formation (which can cause cavities) was decreased between control samples and samples with the mucins.  The scientists noted that in the samples with mucins the cells simply never formed biofilms, and stayed in the planktonic (i.e. free floating) form.  They speculate that the mucins either physically prevent binding or are somehow changing the genetics of S. mutans so as to prevent production of binding proteins.

Follow-up studies in human subjects that compare the presence of mucins with cavity abundance would be interesting to see.  We all know people who, despite brushing and flossing multiple times a day, still seem to get cavities (myself included!), and others who, despite not going to a dentist in years and never brushing, don’t get any cavities at all.  Perhaps the concentration of mucins is responsible, and perhaps we could add mucins to toothpaste and forget about cavities all together.  

Microbiota biofilms and colorectal cancer

Colorectal cancer is the 4th most deadly cancer in the world, and over 1 million people are diagnosed with it each year.  It has very few genetic indicators and it is rapidly growing in prevalence, thus researchers believe it is very likely associated with environmental causes.  An obvious environmental cause would be the microbiome, and researchers from John’s Hopkins helped establish this link with their recent publication in PNAS.  In their article they show that biofilm formation in the colon is tightly correlated with colorectal cancer.

The researchers studied a cohort of people that had colorectal cancer along with healthy people as controls.  In those people with tumors they studied the microbiome of the tumors themselves along with other, distal parts of their colons.  They discovered that the majority of people with tumors, whether benign or malignant, had thick biofilms growing on and even in the tumor.  What’s more, is that the researchers noticed that biofilms were forming all along the colon, even in the distal parts.  Biofilms were not seen in healthy patients, and in some of the patients with tumors. 

Interestingly, the bacteria in the biofilms between different patients did not necessarily correlate, and so it appeared the presence of biofilms, rather than the composition of the biofilm was critical.  Moreover, the biofilms studied decreased the gut permeability, leading to ‘leaky guts’, which we have covered on this blog before.

A normal colon has a mucous layer to prevent any bacteria from infiltrating the underlying epithelial cells.  It is possible that people with decreased mucosal integrity are at risk for bacteria to invade and form these biofilms which may eventually lead to cancer.  In fact, according to this small study, people with biofilm formation in their colon have a 5-fold increase in their likelihood to get colorectal cancer, much higher than any other known indicator.  More research on a larger scale still needs to be performed.  Still though, biofilm detection could be a useful diagnostic for colorectal cancer, and biofilm management could be a target for drugs or probiotics.