This Clinician’s View opinion piece is written by Karen Corbin, PhD, RD, investigator at the AdventHealth Translational Research Institute.
With obesity a major health concern, impacting more than 40% of American adults, the effect of the gut microbiome on weight regulation has emerged as an important topic of scientific research. However, most studies to date have been conducted on mice, and the few human studies completed have lacked the precise methodologies and rigorous controls necessary to draw causal conclusions regarding human health. At the AdventHealth Translational Research Institute (TRI), we developed an innovative study to tackle this topic and recently published the results in Nature Communications.
Using a microbiome enhancer diet designed to deliver more dietary substrates to the colon and therefore modulate the gut microbiome, we quantified microbial and host contributions to human energy balance in a controlled feeding study with a randomized crossover design in young, healthy, weight stable males and females. Our study compared the calorie absorption (also called metabolizable energy) of the a high-fiber, whole foods diet called the “microbiome enhancer diet” versus a traditional Western diet in each participant. We found that the microbiome enhancer diet resulted in a significant decrease in the amount of energy participants absorbed. This suggests that switching to a more microbiome-friendly diet could make weight loss and healthy weight maintenance easier to achieve, potentially with less restriction of calories.
The Microbiome Enhancer Diet vs. A Traditional Western Diet
We know that processed foods are more quickly absorbed in the upper gastrointestinal tract, translating to more calories for the body and fewer traveling down to the gut microbiome, located in the large intestine. By contrast, higher-fiber foods aren’t absorbed as easily and are able to make the full journey.
For our study, we created a diet that was designed to feed and modulate the colonic gut microbiome. This diet was higher in fiber and resistant starch, known substrates for microbial fermentation. Understanding that fine grinding of foods makes nutrients more bioavailable to the person eating them and less available to their gut microbes, we also provided larger food particles as part of the microbiome enhancer diet. This meant foods like whole nuts instead of nut butter. Additionally, we minimized processed foods. By contrast, the highly digestible Western diet fed to study participants lacked fiber and resistant starch and included highly processed foods like margarine, hot dogs, and pre-packaged entrees, desserts, and snacks.
Controlling the Research Environment — An Innovative Study Design
Because of the TRI’s unique research environment, which includes a state-of-the-art metabolic kitchen and one of only approximately 20 whole-room calorimeters in the world, we were able to do what no one else had done before when researching the gut microbiome: a randomized, controlled, cross-over feeding study in humans that precisely measured the entire energy balance equation: energy intake, energy expenditure and fecal energy loss. Included participants were 17 young, healthy, weight-stable individuals so that we could quantify whole-body bioenergetics without the confounding effects of age and metabolic disease. This approach also allowed us to establish a baseline of comparative data for future studies on people with various health conditions.
We provided the study participants all their meals. Each study diet — microbiome enhancer and Western — was provided in random order and followed for 22 days. Both diets provided the same number of calories and similar percentages of protein, fat and carbohydrates. With this approach, each person served as their own control, increasing our ability to see a signal.
For half their time on each diet, participants lived in the TRI’s metabolic ward where we could ensure adherence to the diet and control physical activity levels. They also spent six days of each diet in our whole room calorimeter, allowing us to determine exactly how many calories they burned. We measured energy intake, energy expenditure and both fecal and urinary energy output. Measuring fecal energy was especially important to understanding the role of the gut microbiome on participants energy balance .
The primary endpoint was the within-participant difference in host metabolizable energy between experimental conditions — the control/Western diet versus the microbiome enhancer diet. Secondary endpoints included enteroendocrine hormones, hunger/satiety and food intake.
The Power of a Microbiome Enhancer Diet
Our study revealed what we suspected — that our gut microbes are in a tug of war with our bodies for calories and that the traditional Western diet doesn’t sufficiently feed the gut microbes. In fact, when study participants were on the fiber-rich microbiome enhancer diet, they absorbed significantly fewer calories compared to when they were eating the more processed, Western diet. This created a negative energy balance, which is required for weight loss.
Specific findings pointing to the benefits of the microbiome enhancer diet included the following:
- An average loss of 217 calories a day, about 116 more than was lost on the Western diet, with some participants losing nearly 400 calories daily
- A significant increase of approximately 8 1/2 times more microbial biomass in the feces
- Higher circulating levels of short-chain fatty acids in the stool, signaling that the gut microbes were multiplying and fermenting
- Increased levels of hormones such as GLP-1 and pancreatic polypeptide, which promote satiety
Educating Patients That Not All Calories are Handled Equally
While physicians have been encouraging their patients for years to eat a high-fiber, whole-food diets with fewer ultra-processed foods, our study sheds some light on “the why” behind this advice. It may also provide new motivation through the discovery that it’s not always about cutting calories — it’s about putting higher-quality calories into our bodies. Helping patients better understand the reasons for shifting their eating habits could empower them to become more active participants in setting and achieving health goals.
Opportunities for Future Research
As exciting and significant as these findings are, this study was just the first step in better understanding the critical role the gut microbiome plays in healthy weight management. We still have unanswered questions:
- What are the long-term effects of diet on the microbes and the human host? Are there additional changes not detected in our short-term study?
- Are there host signals that might alter microbes?
- Are there differences based on host health status?
- Are the microbes on the causal chain of body weight regulation or merely a reflection of host metabolic status?
- Can we find a biomarker of healthy microbial function?
At the TRI, we are already pursuing grants to further explore several of these topics and look forward to growing and sharing our knowledge of the gut microbiome. We are excited about its potential power to inform new precision nutrition approaches that could further our global efforts to reduce obesity and other chronic health conditions.
