Personalized Nutrition and the Microbiome
By Carrie Dennett, MPH, RDN
Vol. 25 No. 9 P. 38
The State of the Science and Future Possibilities
Nutrition isn’t one-size-fits-all, which is why dietitians draw on a combination of population-level recommendations, clinical guidelines, and their own professional experience when counseling individual patients. It’s also why, for example, dietitians would make different recommendations to a patient with heart disease than to one without. Taking this a step further, personalized nutrition—based on the idea that metabolic responses to foods and food components can vary from person to person—has become increasingly popular over the past several years, often with a focus on “eating for our genes.” But what about eating based on our gut microbiome?
Personalized nutrition has been defined as “individual-specific information founded in evidence-based science to promote dietary behavior change that may result in measurable health benefits.”1
A 2020 article published in the Journal of the Academy of Nutrition and Dietetics, titled “Advancements in Personalized Nutrition Technologies: Guiding Principles for Registered Dietitian Nutritionists,” emphasizes that in the traditional sense, dietitians regularly practice personalized nutrition when they assess and collaborate with a client to make nutrition care decisions based on the client’s specific needs and values and the dietitian’s clinical experience combined with the best available evidence. However, modern personalized nutrition is enabled by technology.2
The completion of the Human Genome Project in 2003 gave rise to “nutrigenomics,” the study of the relationship between diet and genetics and how their interactions affect human health in both positive and negative ways, including how variation in gene sequences between individuals can influence the bioavailability and metabolism of specific nutrients. However, compared with the human genome, the human gut microbiome—the collective genome of the gut microbiota—can fluctuate more in response to various environmental factors, one of which is diet. The relationship between diet and the gut microbiome is bidirectional, with diet affecting the health of the gut microbiota—the population of bacteria and other microorganisms inhabiting the large intestine—and the gut microbiome contributing to variability in individual physiological responses to food. All of this influences an individual’s health status, which is why there’s been growing interest in the potential of gut-mediated personalized nutrition to manage human health.3
Based on this bidirectional relationship, there are two main avenues to apply gut microbiome-mediated personalized nutrition. In one direction, if a dietitian knows the composition of a patient’s gut microbiota, they could make dietary recommendations based on what foods may be more or less beneficial for them compared with population averages and whether those benefits improve nutrition or prevent or treat disease. In the other direction, once there’s consensus in the scientific community on what a healthy gut microbiota looks like and when a patient’s microbiota deviates from that determination, the dietitian can make recommendations for diet, probiotics, and prebiotics designed to shift the patient’s microbial population to one that can help prevent or treat disease.
Why the Microbiome Affects Responses to Foods
While the diet is one major environmental factor that shapes the population of the gut microbiota, the gut microbiota and microbiome shape what our food does for us. Up to 20% of unabsorbed carbohydrates and about 10% of ingested proteins enter the colon, where they’re digested, absorbed, metabolized, and transformed by gut microorganisms.3 The gut microbiome participates in the digestion and absorption of macro- and micronutrients, increasing the bioavailability of food ingredients and synthesizing various bioactive compounds such as short chain fatty acids. But at least some of the gut microbiome’s health effects are related to metabolites produced by certain microbial species that are transported to different parts of the body.4,5 For example, most byproducts of protein fermentation—including trimethylamine N-oxide, which may increase the risk of CVD—are considered detrimental to gut and overall health, so the balance between carbohydrate and protein fermentation and the effects of increasing fiber intake are of interest, especially for cardiovascular health.6 This is one reason why altering the gut microbiome with targeted dietary interventions may be used to improve patient health.
There’s increasing interest in how microbiome “signatures” may predict individual responses to food, exploring why two people can eat the same food and have different metabolic responses to it because their respective gut microbiotas metabolized it differently. For example, dietary intervention studies involving healthy European subjects have found that a high fiber diet improves glucose metabolism in individuals who have a gut microbiota dominated by Prevotella species but not in those with microbiotas strongly populated by Bacteroides species.7 And while scientists know that human responses to the same diets may vary to a large extent depending on complex diet-host-microbiota interactions, the question is when—and how—can these interactions be used systematically to develop personalized nutrition strategies.
Johanna Lampe, PhD, RD, a research professor in the department of epidemiology at the University of Washington School of Public Health and associate director of the public health services division at Fred Hutchinson Cancer Research Center in Seattle, says there already are some companies doing this, as evidenced by the increase in home testing kits that claim to analyze consumers’ gut microbiomes and provide personalized diet and lifestyle recommendations. “I think what we’re finding is that we’re a little short on enough data at this point in supplying incredibly targeted dietary recommendations,” she says. “They’re … recommendations we might give to a patient or client regardless of whether we’ve done a microbiome analysis.”
Current Research Challenges
Despite the presence of direct-to-consumer gut microbiome test kits, the current state of the science on gut-mediated personalized nutrition remains in the laboratory, Lampe says. “I feel like it’s still in the research setting because we have so many questions that need to be answered before we can make robust recommendations. We’ve seen this with nutrigenomics, and this is similarly complex.”
While most gut microbiota-related dietary intervention studies have focused on gut bacteria on the genus level, observed differences between the functions of specific species and strains of Prevotella bacteria, for example, demonstrate that taking inventory of the gut microbiota at this deeper level is necessary to understand these differences in responses to dietary interventions.7 However, there’s currently no standardized procedure for analysis, and the same sample analyzed in multiple laboratories may produce several different profiles. When using stool samples to try to measure the composition of the gut microbiota, there are several steps, and each one is prone to error. In addition, results provide the ratio of the different bacterial species detected but not absolute numbers.8 This is just one of the challenges of getting personalized nutrition, based on the gut microbiome, ready to be applied in a clinical setting.
For example, Lampe says one area of interest is metabolites produced from bioactive components of food, such as phytochemicals. However, “We don’t have a good handle on the collection of microbes that could carry out a reaction of metabolizing a phytochemical to create a metabolite. We just don’t have all the information.” And it’s not just the microorganisms that are of interest, it’s their genes, Lampe says. Because genes contain codes for proteins, and enzymes are made of protein, different microbial genes could produce enzymes that metabolize food components in various ways. “We’re really interested in that interaction between diet and microbes and how that ultimately affects the human host.”
Another challenge in moving this area of science from the lab to the real world is that there are many influences on the composition of each individual’s gut microbiota. Our genes appear to have a relatively low impact, with other phenotypic parameters such as sex, age, and BMI demonstrating stronger, more consistent effects on gut microbiome diversity in population studies. Other significant variables identified in large cohorts are diet, medication, occupational status, ethnicity, birth mode, socioeconomic status, and geographical location. Our genes are estimated to account for between 2% and 9% of the variance in our gut microbiota, with other identified determinants accounting for 15% to 20%. That leaves much yet-to-be-identified territory.8
The first three years of life have a great impact on the development of the gut microbiota, and gut microbial diversity increases with age until it becomes stable in adulthood. Generally, the composition of the adult gut microbiota maintains this stable state, recovering quickly if disrupted by external factors, including diet. Having a high baseline of bacterial diversity makes the existing microbiota more resilient to change, whereas gut microbiotas with lower diversity may be more easily altered by dietary interventions.3,5
However, despite observations that people with certain diseases have variations in their gut microbiotas compared with healthy individuals, there’s no official definition of a “healthy” gut microbiota. Even the Human Microbiome Project, which started collecting information from average healthy individuals in 2007, hasn’t been able to define a healthy core microbiome.8
“Once we decide what the totality of a healthy gut microbiome is, getting there is a challenge,” Lampe says. “It’s very hard to change a gut microbial community, and it takes a long time, unless you’ve got a case where someone’s gut microbiome has been almost completely wiped out by heavy use of antibiotics.” She says most gut-focused dietary interventions don’t last sufficiently long enough to know how we can impact the gut microbiome, with feeding studies—especially the more controlled studies—being very short term. “It could take months or years to see what impact diet has. Feeding studies in humans don’t generally alter the gut microbiome that radically unless you have a severely impacted gut microbiome.”
Lampe says there are several research projects and initiatives in the works. One is the All of Us Research Program at the National Institutes of Health, whose goal is to build a national research cohort of at least 1 million Americans to develop a diverse health database.9 The program has a microbiome component, Nutrition for Precision Health, which is enrolling 10,000 participants from diverse backgrounds to learn more about individual responses to diet. “I think we need some longer dietary interventions to really understand what’s going on in microbial communities,” she says.
The Future of Gut-Mediated Personalized Nutrition
Once researchers have more detailed, long-term data, what might personalized nutrition look like in a clinical setting? A 2022 study in Advances in Nutrition provided such a vision, using the example of a patient with prediabetes.10 Before the first visit, the patient provides blood and stool samples and completes a questionnaire about dietary intake, lifestyle, medication use, and health history. The patient’s answers, and biometric data from the patient’s samples, would be processed through an artificial intelligence (AI) platform that provides individualized, well-validated predictions—including predictions for thousands of host-microbiota-diet metabolic interactions—based on data from a large reference population. For example, the data might indicate that based on the patient’s gut microbiome and other factors, they should respond well to interventions such as an increase in dietary fiber and a daily walk, preventing the need for prescription medication. The dietitian would have access to a dashboard of the individual’s data profile and AI-generated recommendations. The dietitian meets with the patient, shares the recommendations, and sends him or her home with a personalized intervention. The patient reports any symptoms via a phone app and returns for monitoring of blood and stool at established intervals, along with additional appointments with the dietitian as needed.
Other interventions may include increasing short-chain fatty acid populations in the large intestine to reduce systemic inflammation or reducing levels of trimethylamine N-oxide in the bloodstream through targeted dietary, prebiotic, or probiotic recommendations. This depends on generations of more phenotypic data from longitudinal human trials, in which individual responses to diet, prebiotics, and probiotics are tracked. Those data can help refine the AI models that generate predictions.10
In the public health sphere, modulating the gut microbiome to efficiently use available food may protect vulnerable populations from gut undernutrition and even malnutrition when food intake is reduced or altered. Globally, agricultural losses due to extreme weather conditions may compromise the food supply, leading to famine, so having a gut microbiome with high nutritional efficiency may help buffer the individual effects of this type of acute nutritional stress. In areas where malnutrition is chronic, an efficient gut microbiome also may prevent the development of nutritional deficiencies.11 That’s significant because, according to the World Health Organization, approximately 462 million adults currently are underweight, while in 2020, 194 million children under age 5 were wasted or stunted because of malnutrition.12 Even when available nutrients aren’t limited, modulation of the gut microbiome could treat iron deficiency, the most prevalent micronutrient deficiency worldwide, by increasing iron absorption, or prevent osteoporosis by increasing calcium absorption.11
The race towards personalized nutrition began with the genome and has progressed to include the microbiome. There’s also interest in the epigenome and other-omics. The question is, do the best hopes lie with one of these domains or potentially all of them?
“You could imagine that all these pieces come into play. We’ve had access to GWAS [genomewide association study] data for a lot longer and have some information about possibly eating to your genotype, but there’s really a limited number of genes that are applicable,” Lampe says. “I think in the context of an actionable component of health, the microbiome shows promise. One problem is that it’s determined early in life, at the time of weaning. I think a focus on early nutrition and infant nutrition needs to happen to start kids and their microbiome off on the right foot.”
As research on the role of gut microbiome-mediated responses to dietary interventions continues to evolve, consumer confidence in personalized nutrition is likely to grow. Until then, it’s important that companies and organizations developing personalized nutrition programs take science-based, ethical, and rigorous approaches in developing their guidance so personalized nutrition maintains credibility and provides real benefits. Similarly, it’s important that dietitians and other health care providers don’t get ahead of the science by selling or overpromising.1,13
Guidance from the Academy of Nutrition and Dietetics is clear that for healthy individuals, dietitians should look to population-based recommendations from national authoritative bodies.2 They also need to compare current evidence and evidence-based guidelines to recommendations from personalized nutrition technology companies to determine the appropriate strategies for the patient sitting in front of them. In addition, RDs need to be transparent and communicate the potential effects or noneffects of the technology to the client in terms he or she can understand, and disclose any benefits they’ve received from the company, including meals or speaking fees.
“The important part would be for dietitians to look at what their clients are getting in the way of information and think about whether there are potential risks in responding to recommendations,” Lampe says. “What are you going to be excluding from your diet, and do you need to think about nutritional adequacy? If someone wants to try to follow those recommendations, maybe it’s worth a shot, but what does that mean in terms of the rest of your health? This is a very active area of research, and there’s a lot going on, so stay tuned.”
— Carrie Dennett, MPH, RDN, is the nutrition columnist for The Seattle Times, owner of Nutrition By Carrie, and author of Healthy for Your Life: A Non-Diet Approach to Optimal Well-being.
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8. Simon MC, Sina C, Ferrario PG, Daniel H; Working Group “Personalized Nutrition” of the German Nutrition Society. Gut microbiome analysis for personalized nutrition: the state of science. Mol Nutr Food Res. 2023;67(1):e2200476.
9. All of Us Research Program. National Institutes of Health website. https://allofus.nih.gov/
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12. Malnutrition. The World Health Organization website. https://www.who.int/news-room/fact-sheets/detail/malnutrition. Published June 9, 2021.
13. Bush CL, Blumberg JB, El-Sohemy A, et al. Toward the definition of personalized nutrition: a proposal by the American Nutrition Association. J Am Coll Nutr. 2020;39(1):5-15.