As an individual with more than a passing interest in nutrition (okay, I’m a total geek when it comes to this stuff) it is easy to become trigger happy with pressing the ‘share’ button on social media when I read about exciting new research results. But I have quickly learned to curb my enthusiasm, because, for one, I often come across very different headlines describing the same study and secondly when I read the actual journal article, the results are at best over-interpreted and at worse inaccurate. So I’m adding “a look beyond the headlines” as a regular feature on my blog. This is a post where I will review the actual study described by a recent news headline and give you my take on the results and their implications for your life.
First up is a study (well two studies) published on April 29th in the journal Science that identified how health, diet and lifestyle factors influence the composition of our gut flora, aka your microbiome. “My what?” I hear you ask, followed by “Why should I give two hoots about my gut flora, surely microbes are two small to be of any consequence?”.
It just so happens that a scientific review was published this week that may help to answer these questions. In this paper, Milani et al summarized our current state of knowledge on the fascinating underworld of our bellies. Here’s what you need to know ….
- Our gastrointestinal tract is home to trillions of bacteria that together make up our intestinal microbiota or gut flora.
- The total number of bacterial cells residing in our intestine is 10 times greater than the number of human cells, with the highest density being found in the large bowel (colon).
- The microbiota is made up of communities of commensal (normal), symbiotic (mutually beneficial), and pathogenic (disease-causing) bacteria.
- Together these gut microorganisms form a complex ecosystem. The composition and overall balance of this ecosystem determines whether health is maintained or disease occurs.
- The gut microbiota functions to:
- Protect against pathogenic bacteria
- Ferment complex carbohydrates
- Support the immune system
- Produce vitamins and short chain fatty acids (used as energy for colonic cells)
- The term microbiome is often used interchangeably with microbiota but it technically refers to the genome of the microbiota rather than the microorganisms.
- It is believed that babies are born with a sterile gut (some colonization of the gut occurs in utero through the amniotic fluid) but the majority of bacterial colonization occurs immediately after birth and is influenced by mode of delivery, type of feeding, infections and antibiotic use.
- There is some data to suggest that a disturbance in the balance of gut microbiota may be associated with metabolic disorders such as obesity, allergic diseases and gut diseases such as inflammatory bowel disease and colon cancer.
- There is a potential to identify specific microbiome-based biomarkers that could be used clinically for diagnosis of diseases just like blood tests.
- The composition of gut microbiota is influenced by genetic and environmental factors (e.g. diet, medications etc.), but our understanding of the relationship between our gut microbiome, these factors, and our health is in its infancy. Before we can modify the microbiome to prevent and cure disease we first need to improve our understanding of these relationships through large-scale population studies.
What did the headlines say?
How was the study conducted?
This is a little tricky as the headlines referred to two similar population-based studies reported in the same issue of the journal Science. In the first study, investigators analysed data from 1179 individuals participating in a Dutch cohort study named LifeLines-DEEP. They assessed physical and biochemical measures, disease status, medication use, smoking status, and dietary intake. These factors were correlated with participants variation in microbial composition and diversity (determined from participants stool samples). In the second study, the investigators analysed data from 1106 individuals who volunteered to participate in the Belgian Flemish Gut Flora Project (FGFP). Participants underwent a health assessment (e.g. height, weight, blood pressure, blood sample, medication use) and completed an online questionnaire providing information on their current and past health, early life events, current lifestyle, diet, and bowel habits. On the same day as the health assessment, participants provided a stool sample. The stool samples were frozen and later the DNA extracted and gene sequencing of the microbiota performed. The investigators combined this gut microbiome data with 5 other datasets (including the Dutch LifeLines-DEEP) to describe the richness, diversity, and evenness of the human core microbiota. Several statistical analyses were completed to identify health and lifestyle factors that were associated with microbiome variation and composition. This analysis was also replicated using the dataset from the first study.
What were the results?
In a combined dataset representing nearly 4,000 individuals representing the western population, 664 different bacterial groups or genera were detected, with 17 genera making up the ‘core’ microbiota shared by 95% of the tested individuals. In the LifeLines-DEEP dataset, out of a total of 207 factors, 126 were found to correlate with a measure of variability of microbial composition, together these factors explained 18.7% of microbial variation. 
In the FGFP dataset, out of a total of 503 health and lifestyle factors considered, the investigators identified 69 that correlated significantly with microbiome community variation. The top 3 ranked factors being stool consistency, red blood cell count, and uric acid. In addition to bowel habits and blood parameters, other significant factors included health status/medication use (e.g. antibiotics) anthropometric measures (e.g. BMI), dietary intake (e.g. fruit), and lifestyle features (e.g. smoking). Of the 26 similar variables in the LL-DEEP dataset, 24 were found to be significantly correlated with microbiome variation, thus supporting the findings of the FGFP dataset. However, the 69 identified factors only explained up to 14.7% of microbiome variation. Of the factors considered, medication appeared to have the most influence on the microbiome with 13 of the 69 significant factors being medications. Further analysis also showed that medications may affect the relationship between the other non-medication factors identified and microbiome variation. Interestingly, early life events, with the exception of residence type during early childhood, were not found to influence microbiome variation in this study.
What does this all mean?
The results of these large population based studies can be tricky to interpret. We sometimes refer to these types of analyses where investigators look at multiple factors from different angles as fishing expeditions, when you cast your net wide enough you are bound to come up with something. But the question that remains is, have you discovered “the catch of the day” or just some rubbish dredged from the ocean floor? There are some statistical approaches that one can adopt when making these multiple comparisons to temper the results and limit the chances of false findings. It is also important that the researchers themselves adopt a conservative approach when interpreting the data. I believe that the investigators have done so in these papers.
In a new area of research like this one, these large exploratory studies are crucial for helping to define parameters to be used in future investigations. Mapping the human core microbiota of the general population is key to understanding what a healthy microbiome looks like, and combining large datasets enables us to get closer to this goal. Furthermore, investigating the relationship of numerous factors with microbiome composition, functions to inform and refine future research questions. For example, identifying stool consistency and medication use as key predictors warrants further investigation and brings awareness to the importance of measuring these aspects in future human gut microbiome studies. In these studies, despite considering hundreds of factors, those identified as significant only explained a small amount of microbiome variation, which means that there are yet unidentified external factors that strongly influence the gut and/or there are aspects of the gut environment and how these microorganisms interact that we do not fully appreciate yet.
But when it comes to changing your own behaviour, the results of such studies in isolation should be taken with a grain of salt. However, some of the observed associations reported in these studies have been shown to be beneficial to health in other contexts; such as consuming a diet rich in carbohydrate, plant proteins and fruit; drinking alcoholic drinks, probiotic beverages and coffee, preferring dark to milk chocolate, and eating whole grain rather than white bread. These are dietary habits that are worth pursing. While consuming sugar sweetened sodas, a high calorie intake, and having a high BMI may have negative consequences on the diversity of gut microbiota and likewise should be avoided.
Should I believe the headlines?
Ummm, no. These studies did not find that drinking wine and eating chocolate are good for your gut… they observed that among other factors alcohol consumption and a preference for eating dark chocolate have a small influence on your gut microbiome variation. It is likely that your bowel habits and medication use are more important but I guess the headline “Study finds a daily log better than weekly rabbit droppings for gut flora vitality” doesn’t quite appeal to the masses!
I don’t know about you but my head is spinning. The gut microbiome and potential role in health and disease is fascinating. We are just starting to scratch the surface when it comes to understanding its function. As I was writing this post the White House announced the National Microbiome Initiative, providing $121 million and $400 million in private funds to support microbiome research …. So I guess it is safe to say that while you shouldn’t believe every headline, you should definitely watch out for more exciting developments on this topic! Which also means a lot more poop talk from me!
References
Milani et al Diet and Human Gut Microbiota Journal of Human Nutrition and Dietetics May 2016
White House Announcement the National Microbiome Initiative May 13, 2016
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