May 5, 2017, by Brigitte Nerlich
Our microbiome: Separating hype from health
This is a blog post by Nicholas Staropoli, originally posted at the Epigenetics Literacy Project on April 18, 2017. It’s reposted here with permission. The post deals with the issue of hype, which we have discussed a lot on this blog; in this post the focus is on the microbiome.
The details of science — how to interpret empirical data — are more of a debate than lay people may know and scientists may care to admit, and it is not as cut and dry as the media sometimes present it. For example, we have been studying Alzheimer’s disease for decades and yet there is still a hotly contested debate in the science community over which protein, tau or amyloid, is more responsible for the disease’s progression. Scientific consensus is hard to come by and is generally reserved for but a few topics: gravity, vaccines, evolution and most recently the safety of GMOs, to name a few.
Debates are healthy and generally, occur when insufficient research have yet to be done on a topic and therefore the data has yet to paint a clear picture. Unfortunately, activists often get hold of some of the data on controversial topics and contort the science, and some in the media who are out of their depth on that issue get swept up in the misinformation blitz. All too often this results in an ill-equipped public attempting to incorporate this latest “science” conventional wisdom, which is sometimes anything but, into their health decisions. But because the message has been skewed there are often negative consequences.
This is exactly what is happening currently in the debate over the microbiome: the public is attempting to translate conflicting information and guidance into their daily lives but in fact, the evidence isn’t in; it is far too early for the microbiome to be at the translational medicine stage. Although we’ve known about the human microbiome (or the normal flora of bacteria living in or on us) for more than a century, research on the topic has exploded in just the last five years.
A search of the literature at PubMed for the term “microbiome” in the title and abstracts illustrates this fact well. From 1900 to 2005 there were just seven papers that used the word microbiome in their title and/or abstract; from 2006 to 2010 there were 303; and from 2011 to 2015 there were 4,072. We went 110 years with around 300 mentions but then exploded to more than three papers published per day in the last five years. (Using “normal flora” turns up slightly more results but none of these studies takes the microbiome to the level we have taken it in the last five years.) It is scientific consensus that the microbiome is important to us and affects our health significantly, however, to what extent is where the debate lies.
Microbiome in places it shouldn’t be
It may seem like everything has been connected to autism these days (even organic food), and the microbiome is no different. One key connection that proponents rely on is the idea that autistic people are more likely to suffer from GI distress than neuro-typical ones; one meta-analysis found that they are four times more likely to suffer gastrointestinal distress, but why is still uncertain. Some in the media and advocates have rushed to say this suggests a connection between the microbiome, which is significant in numbers and diversity in the gut, and autism. However, the science on this connection is weak at best.
Several studies have found differences in the composition of the gut microbiome between autistic people and neuro-typical ones, but what that actually means, is very much uncertain. One study found significantly fewer members of the genus Prevotella were present in autistic children. However, they failed to find a relationship between a reduction in the abundance of Prevotella and the severity of autism. This lack of a dose-dependent relationship is a key indicator that these findings are more likely a correlation than a causation. They also reported no correlation between severity of GI distress and severity of autism which gives credence to the idea that the GI problems are a red herring in the search for the cause of autism.
Another study found that there was a decrease in the abundance of Bacteroides fragilis in autistic children. This led researchers to attempt to “treat” autism with the introduction of this bacteria. They used a mouse model of autism and introduced high levels of Bacteroides fragilis, the results showed that some of the mouse’s autistic signs, but not all of them, were alleviated by this treatment.
What’s more likely behind the GI distress in autistic patients? One explanation is that autistic children due to their ritualistic behavior often don’t eat a nutritious enough diet which can cause GI distress. The authors of the meta-analysis think it’s likely that gene expression is the cause of this. If there is a microbiome disruption in the gut of autistic people, the genes that cause autism are driving the microbiome imbalance, and not the microbiome imbalance driving autism etiology.
Despite this tenuous connection, research continues; there is now even an international symposium on the microbiome’s role in autism. But autism isn’t the only neurological pathology that is being connected to the microbiome. One recent study found that when mice were fed a diet containing the human pathogen Campylobacter jejuni, they were less likely to approach a high ledge in their maze. Another found that antibiotic-treated mice spent less time running outside than those not treated. Some in the media say this is proof the microbiome controls your mood, however, this is the kind thinking that leads people to make dangerous decisions with their diet in an effort to keep their microbiome healthy. However, the truth is that for your microbiome we don’t actually know what healthy means.
Does anyone have a healthy microbiome?
Even before the recent microbiome boom, we knew the microbiome could have beneficial effects on human health. Many commensal bacteria, like E. coli, participate in normal digestion and produce vitamins for us. The ability of commensal organisms that live on our skin and in our gut to out-compete pathogens to keep their numbers in check is well-documented. When these communities become significantly disturbed, the tides can turn and pathogens can increase in numbers to the point where they can cause infections.
This is most certainly the case with Clostridium difficile (C. diff) infection. When patients, often hospital in-patients, are on long-term antibiotic therapy they lose much of their microbiome. What remains are those resistant to the course of antibiotics the patient is taking. C. difficile is normally in low levels in the gut, however, because it is resistant to many antibiotics, when the rest of the microbiome is knocked out, the bacteria takes over, causing severe gastrointestinal infection.
This leads us to the central problem with the microbiome: nobody knows what defines a healthy microbiome. C. difficile can cause severe pathology but can also be a member of a healthy microbiome. The same can be said of E. coli andStaphylococcus aureus. Bacteroides fragilis, the “healthy” bacteria that was used to “treat” autism in mice, is frequently the causative agent in human infections and is associated with a more than 19 percent mortality rate. Prevotella too is no stranger to causing infections.
It’s not just that we don’t know what a healthy microbiome is, it’s entirely possible that there isn’t one. Pregnant women in their third trimester have a similar microbiome to those with metabolic syndrome, yet neither the fetus nor the mother’s health is adversely affected by these changes. A quarter of healthy women do not carry the uber-healthy bacterium Lactobacillus in their vagina. One study of 300 healthy volunteers found no detectable pattern in when comparing their microbiomes.
Translating the microbiome into something useful
With all the excitement over the microbiome, some people are starting to prioritize it over other aspects of their health. This has led some to vilify practices like cesareans and antibiotics because they negatively affect our microbiome and its development. Although overuse of these practices should be monitored and antibiotics in particularly need to be used responsibly/selectively, both practices are life saving. Every doctor’s number one priority when delivering a baby must be to make sure mom and baby live, if a cesarean is necessary to save a life then that should trump all other factors. Ditto for antibiotics. Nobody should forgo antibiotics to treat an obvious bacterial infection because they are afraid the disruption of their microbiome might affect their mood.
However, there are ways in which we can use our microbiome responsibly. One example is in colorectal cancer. Several studies have now shown that there is a predictable and detectable microbiological community changes in the gut associated with these types of cancers. In fact, testing for these changes is a more sensitive way to diagnose colorectal cancer than the currently used non-invasive test, fecal occult blood. If we ignore the chicken or the egg aspect, and instead focus on the predictable nature of the changes in the microbiome associated with colorectal cancer we will have an effective tool for diagnosing cancer.
Before we can effectively translate microbiome studies into our daily life, we must identify and interpret biological mechanisms. In the meantime, don’t count on that probiotic to make you any happier.
Nicholas Staropoli is the director of the Epigenetics Literacy Project. He has an M.A. in biology from DePaul University and a B.S. in biomedical sciences from Marist College. Follow him on twitter @NickfrmBoston.