Recent years have seen mounting interest in the impact of diet on the gut microbiome, gastrointestinal inflammation, and the development of inflammatory bowel diseases.
To investigate the connection between diet and gut inflammation, the study group known as the Crohn’s and Colitis Canada Genetic, Environmental, Microbial Project Research Consortium recruited a large cohort of healthy first-degree relatives of patients with Crohn’s disease (CD). The recruited individuals provided stool samples and answered a validated food frequency questionnaire reflecting their habitual diets during the year before sample collection.
The study results appeared in Gastroenterology, and co-authors Kenneth Croitoru, MDCM, and Williams Turpin, PhD, of Mount Sinai Hospital in Toronto, discussed the findings in the following interview with the Reading Room.
Why did your group decide to take on this study?
Croitoru/Turpin: The incidence of CD is increasing globally, with notable rapidity reported in newly industrialized countries within Africa and Asia. These rapid changes in CD epidemiology indicate a significant environmental influence on disease development. One such environmental component is the diet, potentially via modulation of bacterial composition and gut inflammation. The Mediterranean diet is described as a potential tool capable of preventing disease onset; however, it remains unclear if this is true or what mechanisms are involved in the process.
What did earlier research show about the possible link between a Mediterranean diet and gut inflammation?
Croitoru/Turpin: Epidemiological studies suggest that diet is an important contributor to CD risk, potentially via modulation of bacterial composition and gut inflammation. Previous studies have identified certain dietary patterns such as those of the Dietary Inflammatory Index I and II that are capable of predicting disease onset. However, microbiome measures were not assessed in this index, and this scoring system used circulating inflammatory biomarkers.
Other studies have shown that diet can modify the composition of the gut microbiome, so that a lack of dietary fiber, for example, could lead to a bloom of Coprobacillus or Lachnospiraceae, which in turn promotes gut inflammation. Contrarily, a diet rich in vegetables, leafy greens, and fish could promote the growth of generally recognized beneficial bacteria, such as Lactobacillus of Bifidobacterium, which are capable of fermenting those fiber-rich foods and producing anti-inflammatory metabolites such as short-chain fatty acids.
What was the composition of the study cohort?
Croitoru/Turpin: The study cohort comprised 2,289 healthy individuals who were first-degree relatives of CD patients. The median age was 18, and 1,083 (47.3%) participants were male. A total of 1,951 participants (85.2%) were recruited in Canada, while the remaining 338 were recruited in the U.S.
What were the main findings?
Croitoru/Turpin: We identified a dietary pattern resembling a Mediterranean diet that was associated with lower levels of gut inflammation. Mediation analysis suggested that lower subclinical inflammation was partially mediated by the microbiota.
We also found that associations of specific food items with inflammation or individual bacteria were generally weak. However, when considering a general dietary pattern, we detected a more robust association with larger effect sizes. Consequently, this study suggests that baseline microbiome characteristics should be considered when starting a dietary intervention, as the success of the intervention may be dependent on the presence of a microbiome capable of responding to dietary change.
Furthermore, the findings suggest that dietary intervention should aim at modifying dietary patterns, rather than promoting the consumption of specific food items.
Did your findings align with prior research?
Croitoru/Turpin: Our findings align with and complement very well previous findings for the most part. However, we were expecting that dietary patterns would be correlated with microbiome patterns, since it is reasonable that specific bacterial communities would adapt to specific dietary patterns.
Perhaps the weak correlation between dietary patterns and microbiome patterns observed in this study could be explained by the unsupervised clustering method used to define groups of bacteria. Indeed, the concept of enterotypes is controversial and distance matrices or criteria, such as the optimal number of clusters, could affect the enterotype stratification and thus impact reproducibility.
What is the mechanism of action by which diet influences the intestinal microbiome and its propensity for abnormal immune responses?
Croitoru/Turpin: Our causal inference analysis suggests that the microbiome may contribute to almost 50% of the anti-inflammatory properties of a Mediterranean-like diet. This suggests that both diet and microbiome contribute equally to immune response. The mechanisms of action from the microbiome and the diet might be different, and the exact mechanisms involved remain to be explored. However, it is reasonable to assume that a Mediterranean-like eating pattern, which is rich in fiber-dense foods such as fruits, could directly modulate the function of the microbiome through a fermentation process.
We observed that the Mediterranean-like dietary pattern was characterized by an increase of Faecalibacterium, a bacterial taxa known for its anti-inflammatory potential and maintenance of immune homeostasis.
Moreover, an ingested food item could also affect the immune response via a different pathway. For example, the Mediterranean-like dietary pattern was characterized by a higher consumption of tomatoes, a food rich in antioxidant lycopene known to be involved in immune response processes. However, this compound was not directly measured in this study, so further analysis is required to better understand this observation.
What does future research look like?
Croitoru/Turpin: Our studies as well as others have shown that the consumption of a diet supplemented with Mediterranean diet staples reduces inflammatory biomarkers, and that such a diet may protect against development of CD. However, it remains to be seen which specific components of diet contribute to these effects.
With the development of artificial intelligence, it is now possible to assess and predict personalized response to nutrition modification, while considering an individual’s microbiome composition. We are currently exploring personalized prediction models to assess each individual’s response to an identical diet, based on microbiome composition and dietary intake using a mixed-effect Bayesian network. This work will allow us to identify food items capable of modulating microbiome communities at a personal level to reduce the risk of developing CD.
What is the bottom line?
Croitoru/Turpin: General dietary patterns rather than individual food items provide a more realistic goal in altering dietary habits that may impact gut microbiome and subclinical inflammation. Since the human microbiome is a major player in an anti-inflammatory diet, we believe baseline microbiome composition should be considered in the design of any dietary intervention study.