*Note: this study was performed in 2014 when the Knight Lab was still located at CU Boulder in Boulder, CO and therefore references the city of Boulder and CU Boulder.
By Luke Thompson, Ph.D.
Few things typify Boulder, Colorado like doing a dietary cleanse to detox your body and restore your digestive health. Walk through the aisles of Whole Foods Market and you’re likely to hear someone discussing their “juice cleanse” or “master cleanse”. Many of us assume that these cleanses have some beneficial effect on digestion and health — but what do they actually do to your gut microbiome?
At the Knight Lab, we decided to apply some CU-Boulder expertise to this Boulder kind of problem. Several of us in lab tried a dietary cleanse and monitored our gut “output”. Stool samples are commonly collected as a proxy for the colon microbial community. We joined forces with Tim Spector’s group at King’s College London, who were planning a similar study of dietary interventions.
Samples were shipped over from the UK or brought in from home freezers in Boulder to the Knight Lab. Back in the lab, we extracted microbial DNA from the fecal samples and analyzed it using DNA sequencing to determine the relative abundance of different microbes (bacteria and archaea). The results reveal how the gut microbial community changes (or does not change) when an individual changes his or her diet in extreme or moderate ways.
The images below depict all gut samples of all 19 individuals, colored by person. The closer the points are to each other, the more similar the microbial communities in those samples. The image on the left shows three dimensions of variation (principal coordinates), while the image on the right shows two dimensions of variation plus time.
Relative to everyone else, each person tends to have a unique and relatively stable combination of microbes. The microbial community may change from day to day or in response to the intervention, but those changes are small enough that the community is still recognizable as belonging to a certain person distinct from others.
To see gut microbiome changes that happen during and after dietary changes, the researchers looked at each individual separately, allowing them to see fine-scale changes that are harder to detect when looking at everyone together. What they found was that individuals fell into different groups. Some had stable microbiomes that showed a clear perturbation by the intervention followed by a rebound to their original state. Others had more variability pre-intervention but still showed obvious changes with the diet. Still others had so much variability that it was difficult to detect any effect of the diet intervention. How a person’s gut responds to dietary changes may have just as much to do with the individual and their starting gut microbiome as the dietary intervention itself.
Among the different dietary interventions, cleanses and fasts seemed to elicit a more pronounced change than the cheese and yogurt diet. This may depend on the baseline diet of the individuals. All of the participants were from the US or UK and generally consumed a Western-style diet. A diet of only fruits and vegetables, or mostly water, may be a more significant deviation from the Western diet than a diet heavy in cheese and yogurt.
The animated GIF below, also available on Imgur and YouTube, depicts the gut samples of three individuals (US 1-3), colored by person. Samples were taken for three days before the cleanse, three days during, and then four more times every third day thereafter. Just like the still image above, the closer the points are to each other, the more similar the microbial communities in those samples.
The animation shows that each individual is different from the other two, but all three undergo a shift in microbial community following the cleanse. Within a week after returning to “normal” or “Western” food, the microbiome has shifted back to its original state. Many thanks to Justine Debelius, who rendered and edited the movie, and Yoshiki Vasquez-Baeza, who developed the EMPeror visualization software.
We were especially interested in the specific microbial taxa that change the most during the course of the dietary interventions. As shown below, individuals following the Dr. Oz fruit and vegetable cleanse saw an increase in the microbial groups Enterobacteriaceae (E. coli) and Akkermansiaimmediately following the cleanse. The gray box shows samples collected on the three days of the intervention (shifted 1 day to the right to account for gut transit time). Data are average over the three individuals who undertook this particular intervention.
The genus Akkermansia is negatively correlated with obesity. Specifically, Akkermansia is thought to help prevent metabolic diseases like diabetes by aiding mucin turnover and production, causing thickening of the gut wall. Gut wall health is also aided by butyrate, a short-chain fatty acid. Several of the “good” microbes in common probiotics function to maintain health of the gut. These include Lactobacillus and Faecalibacterium, which ferment lactose and fiber, respectively, in the diet. Fermentation produces acidic compounds, lowering gut pH to a healthier level. For more on the importance of fiber and gut pH, see Human Food Project founder Jeff Leach’s blog posts here and here.
Deeper investigation of the microbial groups that increase or decrease following dietary interventions will lead to deeper mechanistic understanding of the changes of gut community in response to diet.
For Boulder and the world, then, it seems there is something to the idea of subjecting yourself to a cleanse. Diets high in plants help foster microbes that degrade fiber and keep the gut healthy. But you have to keep up the diet in order to maintain that community of good bacteria. A cleanse may help jumpstart your gut to a new microbial state, but everyday fiber intake is the fuel the keeps it going.
As to why there was variability in the magnitude and direction of individual responses, my principal investigator Rob Knight reminded me that there’s a lot more diversity in our gut DNA than in our human DNA. “Like every other study of diet and exercise, including the recently published study in Nature on artificial sweeteners, we find tremendous differences between different people,” said Knight. “This might be explained by the huge differences between different people’s microbiomes, rather than the small differences in their human genomes.”
Luke Thompson is a Research Associate in the Knight Lab at the University of Colorado Boulder. He holds a B.S. in Biological Sciences from Stanford University and a Ph.D. in Microbiology from MIT.