The role of intestinal microbiota and microRNAs in the anti-inflammatory effects of cranberry: from pre-clinical to clinical studies

Abstract

Cranberries have known anti-inflammatory properties, which extend their benefits in the context of several chronic diseases. These benefits highly rely on the polyphenol profile of cranberries, one of few foods rich in A-type proanthocyanidin (PAC). A-type PAC comprises flavan-3-ol subunits with an additional interflavan ether bond in the conformational structure of the molecule, separating them from the more commonly found B-type PAC. PACs with a degree of polymerization higher than three are known to reach the colon intact, where they can be catabolyzed by the gut microbiota and biotransformed into lower molecular weight organic acids that are available for host absorption. Gut microbiota-derived metabolites have garnered much attention in the past decade as mediators of the health effects of parent compounds. Though, the mechanisms underlying this phenomenon remain underexplored. In this review, we highlight emerging evidence that postulates that polyphenols, including ones derived from cranberries, and their metabolites could exert anti-inflammatory effects by modulating host microRNAs. Our review first describes the chemical structure of cranberry PACs and a pathway for how they are biotransformed by the gut microbiota. We then provide a brief overview of the benefits of microbial metabolites of cranberry in the intestinal tract, at homeostasis and in inflammatory conditions. Finally, we discuss the role of microRNAs in intestinal health and in response to cranberry PAC and how they could be used as targets for the maintenance of intestinal homeostasis. Most of this research is pre-clinical and we recognize that conducting clinical trials in this context has been hampered by the lack of reliable biomarkers. Our review discusses the use of miRNA as biomarkers in this context.

Supplementation with a cranberry extract favors the establishment of butyrogenic guilds in the human fermentation SHIME system

“…This includes in vitro and in vivo studies, as well as some clinical trials involving PAC supplementations from different sources (e.g., grape [15] , aronia berry [16] , blueberry [17] , avocado [18] ). These studies have consistently observed a stimulation of bifidobacteria and lactobacilli [19][20][21][22] . Moreover, Roseburia species and Faecalibacterium praustnitzii seem to flourish after PAC supplementation, while the response of Enterobacteriaceae is not consistent across studies [19,22] .…”

Effects of Cranberry Extract (Vaccinium macrocarpon) Supplementation on Lipid Peroxidation and Inflammation in Patients with Chronic Kidney Disease (Stages 3-4): A Randomized Controlled Trial

“…Interpreting polyphenol findings in cranberry studies is complex and requires consideration of various cranberry-derived products. Moreover, several individual factors may influence the metabolism, absorption, interaction, and effects of polyphenols, such as genetic polymorphisms of enzymes and transporters, age, sex, the presence of diseases, diet, modulation of transcription factors, variation in gut microbiota, and interactions between the microbiota and miRNAs [ 57 ]. Only a few studies have investigated plasma polyphenol dose-response profiles after the intake of polyphenol-rich supplements or food, and there is only a linear dose-response among the distinctive polyphenols.…”

Sports-Related Gastrointestinal Disorders: From the Microbiota to the Possible Role of Nutraceuticals, a Narrative Analysis

“…Cranberry polyphenols, not fully absorbed in the small intestine, reach the colon, where they are metabolized by intestinal bacteria into bioactive compounds, including organic acids. These metabolites, along with cranberries themselves, influence the composition of the intestinal microbiota, promoting the growth of beneficial bacteria such as Lactobacillus, Bifidobacterium, and Akkermansia muciniphila [125]. Modulating the intestinal microbiota is associated with various health benefits, including improved weight management, reduced inflammation, and enhanced protection against metabolic disorders like obesity and diabetes.…”

“…Furthermore, consumption of cranberry powder was shown to positively influence the production of short-chain fatty acids (SCFAs), important for intestinal and energy metabolism health. Cranberry polyphenols, in addition to influencing the composition of the intestinal microbiota, can also modulate gene expression at the intestinal level through their action on microRNAs (miRNAs) [125]. This complex interaction between cranberry polyphenols, the intestinal microbiota, and miRNAs may contribute to the beneficial effects of these fruits on health.…”