The Blaser hypothesis: The microbiome is programmed to kill us

Editors note: I understand that the title to this blog is a bit sensationalist, but if ever a microbiome paper called for a sensationalist headline, this is the one.

Microbiome scientist Marty Blaser (and member of our scientific advisory board) and mathematician Glenn Webb published a remarkable hypothesis last week in Mbio .  The hypothesis states that the microbiome is ‘programmed’ to protect us in our youth and reproductive ages, and then kill us in our old age.

First we must consider the enormous influence the microbiome has on our health, both positive and negative, and that we have only explored the tip of the iceberg as to the true impact the microbiome has.  Then, we must remember that the microbiome has evolved with us for hundreds of millions of years, from mother to child, and that from the microbiome’s perspective, humans are just a vehicle for reproduction.   Finally, we must acknowledge that the microbiome is subject to the same evolutionary principles as any organism or community, and that the laws of nature dictate that it attempts to fundamentally organize itself so as to optimize its population.  Once we accept these three things we can investigate how the microbiome could exert its influence on humans so as to improve its population.

A mathematical analysis was performed that showed the most prospering populations of humans, and by extent our microbiomes, occur when young children survive through reproductive ages, but then die shortly after reproductive age.  Long lasting, post-reproductive humans can actually diminish the overall population because they drain certain resources.  With that in mind it is not a stretch to consider that the microbiome may be dictating this type of population structure.  That is, the microbiome prospers when it kills its host (us) shortly after reproductive age, and that it is evolutionarily ‘programmed’ to do just that.  This type of population structure occurs in other animals, and the human age structure is unique in the animal kingdom.  Humans are pre-reproductive (pre-pubescent) for a longer time than most animals, and then are post-reproductive (senescent) for a much longer time than other animals.    

The authors go on to give examples of how bacteria may be dictating the ideal age structure (protecting children and killing senescent humans).  We know of many bacteria that exist in children that are protective but then decrease in population into adulthood.  In addition there are examples of bacteria, like Helicobacter pylori, that confer protection early in life, but then the very same bacteria can become pathogenic and cause disease later in life.  Other bacteria which cause acute infections that kill their host seem only to strike older adults.  Finally, the inflammation caused by the microbiome gets worse into old age.  In fact, many of the frailties associated with old age can be traced to the microbiome. 

It is an interesting hypothesis, and one that the reader should ponder.  While it likely can’t ever be proven, this hypothesis supports the idea that it’s a bacterial world, and we are just living in it.

New study correlates antibiotic use in infants and childhood obesity

Childhood obesity is increasing in the United States (Figure is from the CDC, not from the linked study)

One of my favorite things about working in the microbiome field is telling my friends and family about my work and about the human microbiome. In the days and weeks following my conversations, I often get emails from them about news articles they've read pertaining to the microbiome. Earlier this week, my good friend Kyle sent me an article about an important study published in JAMA Pediatrics that showed a correlation between antibiotic use in children during their first two years of life and early childhood obesity. While we see many studies in the field, there is so much going on and we can't see everything.  If any of our readers come across a study or article that may be of interest for the blog, we'd love to hear from you so please email us at blog@microbiomeinstitute.org.

In this particular study, researchers at Johns Hopkins Bloomberg School of Public Health, Children’s Hospital of Philadelphia, and University of Pennsylvania reviewed the health records of over 64,000 children seen between 2001 and 2013 in local Philadelphia health clinics. They found that children who were given several courses of antibiotics before the age of 2 (four or more courses), were more likely to become obese by the age of 5. Specifically, broad spectrum antibiotics were causing this increase in obesity while narrow spectrum antibiotics were not.  Narrow spectrum antibiotics target specific bacteria while broad spectrum antibiotics attack a much wider range of bacteria. 

People have long hypothesized and shown that the overuse of antibiotics is resulting in several public health problems in today's society, including obesity, due to their altering the composition of the gut microbiome, and this study correlates with those predictions.  Parents worry about the health of their child and may receive an antibiotic from a doctor "to be safe" in case the child has a bacterial infection that needs treatment. But children today are often being given antibiotics when they are not needed or may be receiving a broad spectrum antibiotics when a narrow spectrum antibiotic would suffice. 

We have learned countless times that overusing antibiotics, especially in children, is altering our gut bacteria and having serious implications on our health.  Antibiotics are absolutely critical to the health and wellbeing of children and adults around the world but it is important that we become better educated on this subject and ask better questions when we see a doctor, such as the likelihood of a certain infection being viral or bacterial.

In one our posts from earlier this month we talked about the research of one of our scientific advisors, Dr. Marty Blaser from NYU School of Medicine, that showed that antibiotics caused an increase in obesity in infantile mice. This is a very popular topic and I don't think this is going to be the last time we hear about it.

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!

Antibiotics, obesity, and the microbiome

A paper published last month in Cell by AMI Scientific Advisory Board member Marty Blaser at NYU investigated the role and conseqeunces of low dose antibiotics early in life in mice.  Blaser and his team took two groups of infantile mice, and exposed one group with low doses of penicillin and left the other group alone.  The mice that were given the low doses of antibiotics ended up becoming overweight later in life compared to the group that was not given antibiotics.  Then, the team took the microbiome of each group and transplanted it into germ-free infantile mice that were given no antbiotics.  The germ-free mice that were given the microbiome of the lean mice were lean later in life, while the germ free mice that were given the microbiome of the obese mice were obese later in life.  In addition, when both groups of mice were given high fat diets, the group with low dose antibiotics gained more weight.

Interestingly, the antibiotic group of mice still had an abundance of highly diverse bacteria, however these mice were lacking certain strains that were found in the normal mice, and thus may be critical to later health.  The team discovered rather unambiguously that the obesity was induced by the microbiome.  The mechanism for how this occurs is still unknown, but the researchers suggested changes to normal metabolic processes and the immune system that could occur.  Overall this study shows the importance of a healthy microbiome early in life and the dangers of antibiotics early in life, because they both can have lasting consequences into adulthood.

The great fecal microbiota transplant debate

An article was published today in the Atlantic that does a really nice job of describing the controversy surrounding fecal microbiota transplants (FMTs).  Basically, FMTs have been highly effective (>90% effective) in treating C. Difficile infections, and this efficacy has been even used as proof of the causal role of dysbiosis in C. Diff infection.  

The problem though, is that FMTs are currently unregulated, and the real question is how does the FDA regulate this new treatment, especially with how little is known about the microbiome.  The first question the FDA has to answer is whether or not fecal microbiota is a drug or a tissue.  Currently it is considered a drug but many common definitions would call it a tissue.

In addition, no one knows any long term consequences with FMTs, or what diseases to look for in donors, or how to screen FMTs at all.  Fecal microbiota is obtained just as you would imagine, through stool samples, and everything in that stool is transferred, the entire microbiota, including viruses.  It is a really complex issue that comes down to ethics, the responsibility of government, and the science of the microbiome.  Without guidance though, many have resorted to DIY FMTs which is not a good idea!

At the AMI we are aligned with the editorial written by a consortium of microbiome scientists, including our very own Marty Blaser and Rob Knight.  They support the FDA's cautious approach and note that past transplant procedures, like with blood, have resulted in unexpected disease transfer.  They also do see the benefit of FMTs and want to move forward with research to develop proper protocols, registries, and databases, as well as thorough clinical trials.  

A fellow non-profit here in Cambridge, Open Biome, based out of Eric Alm's lab at MIT, has created the first stool bank.  Organizations such as this will be essential to centralizing data and clinical outcomes, and we support their efforts.

Finally, drugs are being developed for C. Diff infection that are working.  Seres Health is a start-up in Cambridge, that has had great success in an oral treatment to C. Diff.  This may very well be the treatment for C. Diff in the future, but with so many diseases being linked to the microbiome, FMTs will again be at the forefront of therapeutics, even if they have not been successful for more complex diseases such as IBS and ulcerative colitis.