Helminths may increase sensitivity to insulin

Different helminth eggs

Countries that are becoming more exposed to Westernization have experienced many positive health impacts, such as decreases in infectious disease rates.  At the same time, however, there have been some negative consequences, such as increases in type 2 diabetes (T2DM) patients in these developing countries.  T2DM is linked to disruptions in energy balance and increases in systemic inflammation.  Interestingly, helminth infections – i.e., the parasitic worms that can reside in the intestines – have been previously shown to enhance glucose tolerance in animal models as well as induce anti-inflammatory immune responses.  Researchers sought to explore this relationship in humans, hypothesizing that insulin resistance is lower in subjects with soil-transmitted helminth infection. 

A homeostatic model assessment for insulin resistance (HOMAIR) test was used to examine insulin resistance in 646 adult study participants on Flores Island in Indonesia.  Soil-transmitted helminth (STH) infection is common on this island.  The HOMAIR model measures insulin in blood samples in a well-validated insulin-resistance assay.  Stool samples were also collected from the subjects, and microscopy and PCR were used to detect various helminth species. 

Of the 646 participants, 424 were STH-infected while 222 were not.  In the STH-infected cohort, participants were further categorized by how many different species were found.  Body mass index and waist to hip ratio were significantly lower in the STH-infected group, suggesting STH-infection may be beneficial toward glucose metabolism.  Furthermore, there was an association between the number of distinct STH species present and HOMAIR.  For every additional species found in a subject, there was an incremental decrease in homeostatic insulin resistance. 

These experiments display an interesting causal relationship between STH species and insulin resistance, however there were certainly limitations.  No association was found between subjects in systemic inflammation in infected versus non-infected groups, failing to elucidate modulations of inflammatory pathways that could be correlated with the observed trends.  Additionally, the changes in insulin resistance may be related to a change in body-mass index rather than helminth infection.  Specifically, participants located in more rural areas may have more active, healthier lifestyles, and would be subsequently leaner and thus more sensitive to insulin.  On top of this, patients with helminths tend to exhibit lower weight in general as these parasites significantly affect metabolism. 

Despite these limitations, this study points to an interesting relationship that is deserving of more examination.  This epidemiology research will impact global health policy and can offer good perspective as more nations around the world are on the path toward development.  

Strange, parasitic microbiome bacteria may responsible for inflammatory diseases

Electron micrograph of a type of Actinomyces, the genus of the natural host of TM7, discussed in the paper.

There are many bugs in the microbiome that cannot be cultivated, and thus are incredibly difficult to study using normal culturing techniques.  We only know about these bugs through DNA sequencing, and it often difficult to draw any substantial conclusions from this information.  One such group of bugs that is highly abundant in the microbiome is the bacterial phylum TM7.  TM7 has been associated with numerous inflammatory diseases, like vaginosis, inflammatory bowel diseases and periodontitis, and DNA analysis shows that this bug has the ability to create many toxins.  Studying this bug could lead to breakthroughs in microbiome diseases, but until now it was unculturable.  Recently though, a team of scientists from around the United States were able to cultivate these bacteria and in doing so learned what makes this bacteria so unique, and possibly so pathogenic.  The results were published in PNAS.

The team aimed their investigation at the oral microbiome, because TM7 is abundant in the mouth and highly associated with periodontitis.  They took samples of spit and realized that TM7 only could grow when another bacteria, Actinomyces odontolyticus, was present.  When they cultured these bacteria together in a saliva-like media they realized that the TM7 was physically attached to the surface of A. odontolyticus.  Through further experimentation they learned that TM7 could never grow on its own, and needed A. odontolyticus to replicate.  Furthermore, TM7 is parasitic, and kills A. odontolyticus when they are starved.

The researchers then investigated the pathogenicity of TM7.  They learned that TM7 can evade detection by the immune system for itself and A. odontolyticus.  They also discovered that the particular strain of TM7 they were studying was antibiotic resistant.  Furthermore, sequencing of the TM7 showed the strain had amongst the smallest genomes ever discovered, and relies on the A. odontolyticus for production of many essential molecules, like amino acids.  However, TM7’s small genome is very dense in the production of virulent molecules and toxins, perhaps necessary for its parasitic nature, which could also affect its human host.

This study raises many interesting points about pathogens in the microbiome.  DNA sequencing is a great start to defining the microbiome, but often times culture, or in this case co-culture is necessary to drill down into the true virulence of bacteria.  For instance, prior to this study A. odontolyticus was considered to be associated with many inflammatory diseases, but these researchers showed that it is likely TM7, not A. odontolyticus that is the true culprit.  Alas, the complexity of the microbiome often times reveals many more questions than answers.

Gut bacteria protect against malaria transmission

Malaria is a deadly disease transmitted through mosquitoes and most widespread in tropical and subtropical regions around the world, especially in Africa. According to the Center for Disease Control and Prevention (CDC), 627,000 people died in 2012 and there were a total of 207 million cases worldwide. Through studying the microbiome, scientists last week published a major discovery in Cell that may lead to better vaccinations for malaria that could help prevent the disease from being transmitted.

Scientists in Portugal, collaborating with colleagues in the United States, Australia, and Mali, found that the parasite the causes malaria, Plasmodium, expresses the same sugar molecule that is seen in a type of Escherichia coli (E. coli).  This sugar molecule from the E. coli called alpha-gal (a-gal) results in the body’s immune system producing antibodies against this molecule and therefore also protecting against the malaria parasite. It is known that adults who are exposed to malaria are at lower risk of contracting the disease than children under the age of 5 and the researchers hypothesized that this was due to the children lacking this specific E. coli in their body and therefore unable to fight back against Plasmodium exposure.   

The scientists studied the gut bacteria of a group of individuals in Mali who had very high rates of malaria transmission. They found that those who had higher levels of anti-a-gal antibodies had lower risk of transmitting malaria and those with low levels of these antibodies had greater risk of transmitting the disease.  This showed that children are at greater risk for the disease because they do not produce enough anti-a-gal antibodies to prevent the parasite from infecting the body.

The scientists also found that the transmission of the parasite is blocked almost immediately following its introduction into the body through the skin. The antibodies against a-gal attach to the Plasmodium as soon as it is exposed to the body, and a part of the immune system called the component cascade is activated, killing the parasite before it can leave the skin and reach the blood stream.   

They found that by vaccinating mice against a kind of a-gal, the mice produced enough anti-a-gal antibodies that were highly efficient in protecting the mice from malaria transmission.  The scientists believe that it may now be possible to translate this work to humans and develop vaccines that would increase anti-a-gal antibodies and prevent malaria transmission. If successful, vaccinations could be given to children who are at high risk for the disease and could prevent hundreds of thousands of deaths every year.  These findings also illustrate the protective aspects of the microbiome in regulating immunity, and the potential treasure-trove of molecules produced by the microbiome that could be used in therapeutics.