New diabetes drug incorporates microbiome therapy

Chemical formula of metformin

MicroBiome Therapeutics is an early stage company based in Broomfield, CO that is developing drugs that affect the microbiome in beneficial ways.  They are currently investigating diabetes and obesity, which has led them to study the diabetes drug metformin.  

Metformin is the most popular drug for people with type 2 diabetes, however it often causes diarrhea in 20% of those who take it.  MicroBiome Therapeutics has developed a drug that is a combination of metformin and a proprietary secondary component (maybe a probiotic or prebiotic of some sort?).  In recent clinical trials their drug proved to help diabetic patients better control their blood glucose levels than metformin with a placebo co-administered.  The next step is to increase the size of clinical trials and eventually reach FDA approval.

This is very exciting news not only for diabetics but for microbiome scientists.  It is a direct application of microbiome research to improve an existing drug, and thus improve the quality of life for patients.  We at the AMI are excited to see what happens with this drug, and we look forward to all the microbiome drugs that are in the development pipeline.

A gluten free diet and IBD

The University of North Carolina recently published the results of a study based on a longitudinal internet survey conducted by the Crohn's and Colitis Foundation of America (CCFA).  Almost 1700 people with inflammatory bowel disease (IBD) participated in the study including many people with Celiac disease, others who were gluten-sensitive, and even more who had tried a gluten free diet.  In the study, 66% of participants who were on a gluten free diet had improved gastro-intestinal symptoms, and 38% reported improvement of IBD flares. This study shows that potential role that diet, especially a gluten free diet, may have in IBD management.

However this study was only based on a longitudinal internet survey, and not as rigorous as clinical trials.  We must also keep this in mind in light of a recent study that suggested a gluten free diet placebo effect, though these studies were hardly robust and had their problems as well. 

While this post is not necessarily focused on the microbiome, there have been clear associations between Celiacs, IBD, nutrition, and the microbiome.

'Framing' the microbiome

At the Harvard Probiotics Symposium last week I was interviewed by Kristina Campbell about the AMI.  Kristina is on the publishing team for the website Gut Microbiota for Health, a website that connects experts in the microbiome field with the latest research.  She is also a member of the Canadian Science Writers' Association and the author of a great microbiome blog.

She recently wrote an excellent piece for the Canadian Science Writers' blog titled "Picking a Metaphor for Your Microbiome" about the importance of language surrounding the microbiome, and how the microbiome shifts our perspectives on our body and the environment.  

In the blog post she writes,"Every article has its own way of framing the microbiome, whether the writer does it consciously or not," and lists examples when language choice frames the conversation. She goes on to discuss how these perspectives have real consequences, such as the classification of fecal microbiota transplants (FMTs) as drugs rather than organs.

This article resonates with me, especially since my experience with writing this blog for the last month.  I realize the connotation that the word 'microbiome' elicits is hugely important.  Many people fear bacteria and 'germs' to varying degrees.  This manifests in the overuse of antibiotics and in compulsive cleansing.  How we view our own microbiome as friend, foe, or something in between is shaped by our culture.  Some small piece of the cultural attitude is influenced by bloggers and science writers.   It is important to 'frame' the microbiome with as honest a depiction as possible, even when we don't know all the facts.  At the end of the day, each individual will form his or her own mental acquaintance with his or her microbiome.

One of the goals of the AMI is to raise the profile of microbiome science to the general public. We hope we are doing so diligently and responsibly.

Gut helminths and the microbiome

Hookworms attached to intestine.

Helminths are worms, like roundworms or hookworms, that can live in human intestines.  They are not as prevalent in developed nations, like the United States, but are very common in more traditional societies; nearly 20% of people world wide have helminths, and upwards of 70% of people in some communities have them.  There has been recent speculation that the presence and absence of helminths can lead to the so-called "diseases of wealth", due to their positive effects on the microbiome and reducing the inflammatory effects of the immune system.  This has even led to a cottage industry providing helminthic therapy, where helminths are purposely ingested.  

An article was recently published in PLoS ONE about the effect of gut helminths on the microbiome.  In the study, a cohort of 51 individuals from Malaysia had their stool samples tested for microbial diversity and for the presence of helminths.  The study showed that people with helminths had a richer diversity and greater number of bacteria in their gut.  They also discovered a greater amount of specific bacterial taxa from those that had helminths and those that didn't.  In addition, the authors mention other studies done in developed nations that have shown the same effect.  The paper concludes that helminths may be increasing gut microbial diversity, and increased diversity has been repeatedly linked to improved health, but as always this association does not necessitate causation.  

While an interesting paper, we don't suggest any of our readers to go out and eat ringworm  any time soon.  Helminths can of course, have other negative consequences!

The lung microbiome changes after transplant

People don't generally consider the lungs as an important component of the human microbiome.  Of course, our lungs are not sterile and have their own diverse bacteria with functions and influence that are still under investigation.  Unfortunately, lung bacteria can also cause an inflammatory response, which can be especially harmful after lung transplant as it can lead to pneumonia and bronchiolitis obliterans syndrome (BOS) - both of which can lead to death.

A recent study published in PLoS ONE by researchers at the University of Michigan investigated the bacterial population and diversity of bacteria in 33 people undergoing lung transplants.  They discovered that after lung transplant the bacterial diversity of the lung microbiome decreases.  Furthermore, based on controls with non-transplant populations, that low diversity of lung microbiome is associated with higher risk for infection.  Finally, they discovered that one particular bacteria, Pseudomonas aeruginosa, was associated with BOS.  This is especially interesting because Pseudomonas fluorescens, a different species of Pseudomonas, was not associated with BOS, meaning clinical sampling of bacterial families and genera are not valuable in diagnosing risk of BOS.  

Like any major surgery, transplant patients receive antibiotics to fight infection.  Perhaps with this evidence that lung microbiome diversity is important to lung health, lung probiotics should be considered after transplantation. 

Let's talk about necrotizing enterocolitis

Radiograph of infant with necrotizing enterocolitis.

A rather contentious issue at the recent Harvard Probiotics Symposium, which AMI was fortunate enough to attend, was the use of probiotics in treating necrotizing enterocolitis (NEC).  NEC occurs in 7% of very low birth weight babies, and is caused by a bacterial infection in the gut.  The mortality rate of children who suffer from NEC is around 25%.  Many studies have shown that using human milk, rather than formula, to feed low birth weight infants, reduces risk of NEC, presumably by encouraging commensal bacterial growth, and this is now common practice in NICUs in the United States.

Several countries, including Australia and New Zealand, but not the United States, give a prophylactic probiotic to low birth weight infants immediately following birth to prevent NEC.  Double blind randomized clinical trials demonstrate that using probiotics in these infants decreases both risk of NEC and mortality from NEC by half in each case.

Reviews of all the clinical data on using probiotics have shown that the studies have not been robust enough for US regulators to develop clinical guidelines regarding probiotics.  These trials have occurred outside the US, so are under even more scrutiny. Adding more complexity to the issue is the fact that many of the studies used different probiotics, so how can they be compared?  Now however, many of the countries providing probiotics to low birth weight infants require the probiotic administration as a course of treatment, thereby making controlled randomized trials unethical. Withholding probiotics would place these infants at a greater risk for NEC.  

A recent commentary on the subject in the Journal Pediatrics points to the need for a robust randomized clinical trial to occur in the United States, to truly determine whether probiotics are useful in treating NEC.  The AMI has not yet adopted a formal position on the subject, but we agree more work is needed.