Precision Nutrition Matching the Diet to Individual Microbiome Profile
Acknowledgement: This article is a summary of “Dietary Interventions to Modulate the Gut Microbiome— how far away are we from precision medicine” recently published in Inflammatory Bowel Diseases by Francesca De Filippis, PhD, Paola Vitaglione, PhD, Rosario Cuomo, MD, Roberto Berni Canani, PhD, and Danilo Ercolini, PhD. The article was written by Nataly Shtraizent, PhD, Research Manager at the Crohn’s & Colitis Foundation.
The human body is home to at least 100 trillion microorganisms, the majority of which reside in the gut. These microorganisms, including bacteria, viruses, fungi, and a few other single-cell organisms, are collectively called microbiota, sometimes referred to as the microbiome (1). The composition of the microbiota can vary among individuals (2). It is believed that this interpersonal variation is due to complex interaction of the genetics and environmental factors, such as, diet, lifestyle, physical activity, etc. Microbial organisms interact with each other and with the host, contributing to both healthy functions and disease (3,4). In a healthy organism, there is a symbiotic relationship between the human host and the microbiome. The former provides nutrients from the food; the latter facilitates digestion and absorption and synthesizes essential vitamins. In addition, microbiome can influence human health by secreting products of bacterial metabolism, called metabolites (5,6). These are small chemical molecules that can travel in the intestinal lumen and be beneficial or detrimental to intestinal function. In patients with inflammatory bowel diseases (Crohn’s and ulcerative colitis) the microbial balance is disrupted and there is an abundance of certain bacterial and fungal species. However, it remains unclear whether the changes in the microbiome are a result of chronic inflammation in IBD or whether it is the microbiome disbalance that causes the onset of IBD (7).
From the recent studies focused on co-evolution of humans and their gut microbiota, it is clear that diet and lifestyle affect the composition of microbiota and play a role in human health. Westernization of diet leads to loss of bacterial diversity and our microbiome loses the ability to digest plant-derived fiber and to produce beneficial metabolites such as anti-inflammatory short-chain fatty acids (8-13).
Several studies confirmed association between a high animal protein diet and fat intake, with increased risk of developing IBD; while a diet rich in olive oil, fish, vegetable, fruit, grains, and nuts has the opposite association, i.e. fewer cases of IBD were reported among people consuming the latter type of diet (14-16). Multiple studies are ongoing to establish which types of diet can have a therapeutic effect on intestinal health in general and specifically in IBD. From an observational study that compared omnivore, vegetarian or vegan diets it was reported that Mediterranean diet is associated with a healthier microbiome-related profile. Exclusive enteral nutrition (EEN) induced remission of Crohn’s disease and is therefore the firstline therapy in many parts of the world (17, 18). However, the researchers could not confirm that this improvement is due to changes in microbiota and that the microbiome can be modified by nutrition therapy. Thus, the mechanism through which nutritional therapies work remains unclear, as does the role of microbiome in the progression of IBD and whether specific nutrients can help to reinstate a healthy microbial balance in the gut of an IBD patient (19-20). Overall the efficacy of dietary therapies is still controversial.
In order to design new dietary therapies and expand our understanding of the causal relationship between the microbiome and IBD, we first need to obtain more evidence of the effects of individual nutrients on microbiota in properly designed clinical trials. There are a few critical factors to be considered in nutritional studies (21). Clinical trials need to focus on testing individual nutrient, by giving or omitting this nutrient from otherwise homogeneous diet, without patients knowing which type of diet they are getting to avoid the placebo effect. This type of clinical study is called blinded randomized control trial. In addition, the number of patients enrolled in the study should be large enough to produce statistically significant results. If the subject sample size is too small the effects of diet on the microbiome can be hidden by high interpersonal variability. Namely, one nutrient can have different effect on different baseline microbiomes and if there are not enough samples of each kind, scientist can’t see a pattern of cause and effect and thus the results of the study will be inconclusive. What can help to minimize the variability of baseline microbiome and the variation in the metabolic response to a diet is if the criteria for patients’ enrollment are uniform: close age, similar health status, and lifestyle. It would be ideal to follow the clinical and biological parameters (biomarkers) as well, such as host metabolism, inflammation, and gut microbiota composition, to quantify the effect of nutrition on the disease-relevant biological processes, to monitor the response to different doses of nutrient and to different timing of administration. This will also allow excluding patients with unique baseline parameters which can potentially amplify or counteract the effects of nutritional therapy. Screening for these biomarkers before enrollment in a clinical study or clinical trial may increase the costs of the study but will enable more consistent data to be obtained from a small group of patients. During the study, monitoring the nutrient intake though questionnaires, measurement of the nutrient level in biological fluids should be done to endure ensure compliance with the standard research protocol.
While studying separate nutrients, scientist also recognize that habitual consumption of healthy and diverse diet is important to shape the microbiome and to maintain its healthy state. Different people may have distinctive metabolic response to the same food. It is likely that through metabotyping - grouping individuals with similar metabolic profile – more effective, personalized nutritional therapy can be achieved. Scientists are trying to apply machine learning (complex computer algorithms) to design personalized healthy nutrition based on the biomarkers of the microbial composition, anthropological characteristics, metabolites, dietary habits, physical activity, and lifestyle (22). In support of these efforts, the Crohn’s & Colitis Foundation and the Patient Centered Outcomes Research Institute (PCORI) are sponsoring the DINE-CD research study to compare two different diets – the Mediterranean Diet and the Specific Carbohydrate Diet™. Adult patients with active Crohn’s Disease will receive food for the duration of 6 weeks, after which symptomatic and clinical remission, as well as reduction in inflammation will be assessed. This is an open-label (not blinded), randomized, multicenter clinical trial. The estimated completion date for this trial is July 2019. In the meantime, guided by the association studies, gastroenterologists and IBD nutritionist can suggest one of the special IBD diets and assess case by case the compatibility of a patient with a particular diet, based on the symptomatic remission. These special IBD diets are described in more detail on the Foundation’s website (http://site.crohnscolitisfoundation.org/what-are-crohns-and-colitis/diet-and-nutrition/special-ibd-diets.html).
In summary, development of personalized nutrition based on the features of the microbiome is currently being attempted. Despite the aforementioned challenges, modulating and manipulating the gut microbiome with a personally designed dietary intervention to induce changes in its composition and functions is surely a promising application for both therapeutic and preventive clinical strategies (21).
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