Science journalism is an essential medium for keeping the general public well informed about ground breaking and exciting science. But in the process of translating complex research into attractive material for general consumption important details and subtleties are often lost. Unfortunately these losses can result in misleading representations of science, communicating preliminary and correlative data as nearly proven fact. Separating truth from hype isn’t easy as a reader or even writer. There are many examples of media distorting or overselling science, but right now there is probably no better example than much of the coverage of research on the human microbiome and how its manipulation might impact human mental health.

The Human Microbiome

Over the past decade, research into the microbial organisms that live in and on human beings has exploded dramatically. Collectively termed the human microbiota, it is estimated that there are perhaps 10x more microbial than human cells cohabiting our bodies[1]. Scientists have become increasingly interested in studying the human microbiota because these organisms contribute a huge amount of genetic material to the overall human genome. The genomes of our microbiota, and the way they interact with the human host, are collectively termed the microbiome. The fundamental hypothesis that is driving, and increasingly validated by, human microbiome research is that all of this microbial activity adds up to a significant impact on human physiology. More and more we are developing an understanding of what kinds of microbes are living where, and how they are intimately involved in human health and disease.

Figure 1~ A quick search for “Microbiome” in scienctific journals online demonstrates how significantly this field of research has been growing over the past ten years [2].

While microbial communities are present in all areas of they human body, the highly complex intestinal microbiome has become one of the core areas of research. Scientists have already demonstrated that the gut microbiome is importantly involved in the development of the human immune system, and that abnormalities in microbial diversity are correlated with several inflammatory diseases, as well as colon cancer, diabetes, and obesity [1].

The Microbiome-Brain Connection

Recently our understanding of the scope of this microbial involvement has taken a surprising turn. The past few years has seen a significant increase in scientific publications that examine if and how the microbiome may also influence our mood and behavior. The idea being that the microbial cultures in our guts are interacting with our nervous systems through the molecules and proteins they secrete. Altogether, the accumulating body of scientific literature has provided early glimpses at potential links between our gut bacteria and conditions such as anxiety, depression, schizophrenia, and autism [3].

Popular Perceptions

This microbiome-gut-brain connection has stirred up public interest as well as scientific curiosity. The suggestion that our intestinal bacteria are involved in behavior and mood has been particularly marketable, as it is an appealingly simple explanation for depression, anxiety, eating behavior, and even memory. Feeling sad? Have some yogurt.

In reality, while there is strong preliminary evidence (primarily in rodents) that alterations to or the entire absence of gut microbiota correlates with changes in mood and behavior, there has also been a significant amount of misleading journalism about what scientists really know.

Prebiotics and Probiotics

Much of the hype surrounding the human microbiome and how it may influence mental health stems from a long standing belief that manipulating the gut microbiota confers positive health benefits to the host. There are two primary ways of altering the intestinal microbiota, either with probiotics, which are live microorganisms, or prebiotics which are essentially bacterial food sources that cannot be metabolized by the host organism. If there is a link between the intestinal microbiota and the brain then pre and probiotics present exciting avenues for psychological therapies.

Figure 2 ~ Pre- vs. Probiotics [1].

So what are some of the important points that many news outlets misrepresent? Looking at two very recent studies that report a link between human intestinal microbiota and the brain we can start to get an idea. By examining their methods, conclusions, the various interest groups involved, and the accompanying media coverage we can get a sense of both what is known, where the research is headed, and the aspects that have been skewed in the media.

Prebiotics

Last December, researchers at Oxford University conducted a trial that tested for emotional and physiological effects of prebiotics on a small group of human volunteers. The Huffington Post reported that “the researchers found that supplements designed to boost healthy bacteria in the gastrointestinal tract (“prebiotics”) may have an anti-anxiety effect” [4]. Other news outlets reported something to the same effect. In reality, the trial showed that volunteers

given a prebiotics course had lowered levels of salivary cortisol, a common hormone related to stress response, and showed decreased attention towards negative stimuli [5].

The researchers gave a group of 45 healthy volunteers (22 male and 23 female) a fructooligosaccharide (FOS), Bimuno®-galactooligosaccharide (B-GOS), or a placebo (maltodextrin) every day for 3 weeks. FOS and B-GOS are both commercially available prebiotics. Immediately after waking on the mornings of the first and final days of the trial, participants self-collected samples of saliva. Subjects were then given a series of emotional processing tasks in which attention to positive versus negative stimuli was measured.

.Figure 3 ~ Subjects were quickly presented paired words on a screen and then shown either 1 or 2 stars and asked to quickly determine the number. The amount of time it took participants to complete that task gave researchers an idea of how much attention volunteers paid to the different types of stimuli. For example, if patients were able to count the number of stars in the same location as the positive stimulus more quickly that those in the location of the neutral stimulus, this indicated that they were more attentive to positive stimuli. Researchers observed that those given prebiotics tended to be less attentive to negative stimuli [5].

The paper’s primary result was an observed decrease in the amount of salivary cortisol after waking in subjects given the B-GOS supplement. In general, we experience a significant increase in cortisol levels within the first hour of getting up in the morning, theorized to be a physiological means of preparing for anticipated stress during the day [6]. This correlation between prebiotic consumption and lower cortisol levels may demonstrate a connection between the gut microbiome and the human nervous system. The researchers suggest that this correlation may point to prebiotics having an anti-anxiety affect that is similar to existing pharmaceuticals.

In addition, when attention to negative versus positive words was measured, B-GOS supplementation correlated to increased focus on positive stimuli (Figure 3). The majority of other emotional tests showed no significant difference in response between the test groups.

From this data, the researchers conclude that the B-GOS supplement has similar effects as some anti-depressant and anti-anxiety pharmaceuticals, and that prebiotic usage has behavior effects in humans[5]. These are bold claims, and while they openly acknowledge that their findings are preliminary, the suggestion that prebiotic consumption will effect human behavior is simply not conclusive from the correlations they observe.

Perhaps what is most worrisome about this research is that there is a glaring conflict of interest, as a major source of funding came from Clasado Ltd. Clasado is a biotech company that primarily sells prebiotics, namely Bimuno®-galactooligosaccharide — the same supplement that these researchers report can impact affective function in humans.. Such a situation is common across industry-funded research, and underlines the persistent tension between financial and academic interests threatening scientific objectivity.

Probiotics

Another paper similarly examined the impact of a probiotic on brain function in humans. Authored by Dr. Kristen Tillisch an associate professor of medicine at UCLA in 2013, the study involved 36 women given either a milk product supplemented with probiotics, milk without probiotics, or no intervention over the course of 4 weeks. Fecal samples from the volunteers were analyzed for Bifidobacterium lactis, which was the active probiotic in the supplement, such that potential control subjects were screened to be B. lactis negative. This allowed the researchers to look at only those effects related to the presence or absence of this particular bacterial species.

To test how the consumption of this probiotic cocktail impacted neurological function, the researchers used a combination of fMRI, which scans and monitors brain activity, and a face-matching attention task. Brain activity was monitored during a resting state and while subjects performed tasks that had them identify certain emotions in human faces [7].

Figure 4 ~ To test how probiotics might impact brain function, researchershad subjects perform this type of emotional task while monitoring their brain activity using fMRI [7].

What they found was that the group given the probiotic supplement had a lower amount of activity in several areas of the brain during the experimental task. In particular they note there were noticeable changes in the periaqueductal gray region of the midbrain, a region of the midbrain that is involved in pain regulation[7].

While the data is very preliminary and provides no direct evidence of a bacterial dependent mechanism for these changes, it is interesting to see in humans what has for sometime been observed in rodents: that the presence or absence of certain bacterial strains in the gut appear to affect the brain. This is the basis of the excitement that stirred the media response (see below).

It is, however, important to note that this study on probiotics shares the same controversy in terms of conflict of interest as the previously-discussed Oxford paper on the effect of prebiotics: it was funded by the Groupe Danone, the makers of Dannon Yogurt. Dannon both funded part of this research as well as provided the probiotic milk product that this trial tested.

The Media Lens

Setting aside a discussion about the strengths and weaknesses of these papers or their possible conflicts of interest, it is most interesting to look at how this research has been reported in the media.

For instance, the prebiotics paper has been picked up by multiple news outlets around the world, in one form or another reporting that “some people feeling stressed, anxious or depressed could receive relief by downing probiotics and prebiotics,” or that “[prebiotics] may have an anti-anxiety effect”[4,8]. Though popular articles may describe some of the particulars and vagaries of the research, they seriously misrepresent the correlations and data by presenting preliminary evidence as something close to proven fact.

The coverage of the Tillisch et al. paper on the effects of fermented probiotic milk has been similarly misleading. Forbes magazine wrote that this research showed how “brains of people ingesting a probiotic for four weeks had less activity in brain areas associated with excessive anxiety”[9]. While the general idea is accurate, making the connection to anxiety is still a stretch and grossly oversimplifies the research.

Of course, the critical viewpoint presented in this piece by no means renders the field meritless. There is promising evidence that the microbiome is intimately involved in human health, including brain function and behavior. But there is equally clear evidence that media coverage walks far ahead of the scientific work it intends to report, too often condensing preliminary, correlative and complex data into pat headlines. As a result, the public impression of microbiotic research differs from the present-day reality, creating the serious risk that pre/probiotics will be marketed as miracle cures for a laundry list of physical and psychological ailments under a pseudo-academic purview. The likely end result is the degradation of public trust in the integrity and validity of scientific research.

Matthew Niederhuber is a Research Assistant in the Silver Lab in Department of Systems Biology at Harvard Medical School.

References

1. Rauch, M., Lynch, SV. The potential for probiotic manipulation of the gastrointestinal microbiome. Current Opinion in Biotechnology 2012. 23,2:192-201.

2. PubMed. http://www.ncbi.nlm.nih.gov/pubmed/?term=microbiome#

3. Mayer et al. Gut Microbes and the Brain: Paradigm Shift in Neuroscience. The Journal of Neuroscience 2014. 34:15490-15496.

4. Gregoire, Carolyn. The Surprising Link Between Gut Bacteria And Anxiety. The Huffington Post 2015. http://www.huffingtonpost.com/2015/01/04/gut-bacteria-mental-healt_n_6391014.html

5. Schmidt et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology 2014. http://link.springer.com/article/10.1007/s00213-014-3810-0/fulltext.html

6. Fries, E., Dettenborn, L., and Kirschbaum, C. The cortisol awakening response (CAR): Facts and future directions. International Journal of Psychophysiology 2009. 72:67-73.

7. Tillisch et al. Consumption of Fermented Milk Product With Probiotic Modulates Brain Activity. Gastroenterology 2013. 144:1394-1401.

8. Perry, Douglass. Depression, anxiety come from the gut: Surprising new research suggests ‘prebiotics’ can help. The Oregonian 2015. http://www.oregonlive.com/living/index.ssf/2015/01/depression_anxiety_come_from_t.html

9. DiSalvo, David. Gut Feeling: How Intestinal Bacteria Could Manipulate Your Brain. Forbes 2014. http://www.forbes.com/sites/daviddisalvo/2014/08/17/a-different-kind-of-gut-feeling-how-intestinal-bacteria-could-manipulate-your-brain/