Exploring the Molecular Pathways Behind the Effects of Nutrients and Dietary Polyphenols on Gut Microbiota and Intestinal Permeability: A Perspective on the Potential of Metabolomics and Future Clinical Applications

Abstract

The gastrointestinal tract hosts the largest microbial population of the human body, which works in symbiosis with the host to provide several important functions and contributes to the maintenance of host health. The diet is one of the factors that can most affect the gut microbiota, with subsequent consequences on host health. One consequence of changes in microbiota is changes in intestinal permeability (IP); disruption of this latter is related to the development of several diseases and is a frequent condition in older people. Nevertheless, the molecular pathways regulating these effects are still unclear, and a comprehensive understanding of the dietary components that can affect IP is lacking. Metabolomics, that has been widely used to study the transformation of nutrients by intestinal microbiota, could be a suitable approach for this purpose. However, up to now, the research has focused mainly on dietary fibers and tryptophan, while the activity of dietary polyphenols remains almost completely unexplored. Hence, the aim here was to review the most recent literature concerning the application of metabolomics in the study of the correlation between diet-induced alterations of gut microbiota and the effects on intestinal permeability, with a particular focus on the discovery of the molecular pathways involved. An additional aim was to give a perspective on the future research involving dietary polyphenols, given that despite their potential implication for the prevention and treatment of several diseases related to increased intestinal permeability, few studies have been reported to date.

Estimated Intakes of Nutrients and Polyphenols in Participants Completing the MaPLE Randomised Controlled Trial and Its Relevance for the Future Development of Dietary Guidelines for the Older Subjects

“…Through the administration of the selected foods, we provided mainly flavonoids (approximately four times higher compared to the amount introduced through the C-diet) and phenolic acids. These bioactives have been suggested as potential modulators of critical factors and specific targets regulating IP, including the impact on microbiota composition and activities [15,41]. Overall, our results demonstrate that it is possible to obtain a significant increase in polyphenol intake in older subjects, through the use of small amounts of well-accepted polyphenol-rich food products.…”

Polyphenols in cancer prevention: New insights (Review)

“…On the one hand polyphenols can modulate the composition of microbiota; on the other hand, the microbiota is able to metabolize them into bioactive compounds. However, it seems clear that correct eating habits, typical of the Mediterranean diet, characterized by a high intake of polyphenols, play an important role in the maintenance of intestinal functions (76).…”

Intestinal Permeability in Children with Celiac Disease after the Administration of Oligofructose-Enriched Inulin into a Gluten-Free Diet—Results of a Randomized, Placebo-Controlled, Pilot Trial

“…Several studies showed that selected strains of bacteria can positively influence the gut barrier [ 16 , 17 ]. Moreover, it is suggested that food components can strengthen the integrity of the gut barrier, mostly by affecting the gut microbiota and restoring the microbial homeostasis [ 18 , 19 , 20 ]. Therefore, prebiotics, the substrates that are selectively utilized by host microorganisms conferring a health benefit [ 21 ], were proposed as a promising intervention for gut barrier improvement [ 22 , 23 ].…”