Polyphenolic Modulation of Gut Microbiome and Cardiometabolic Disease
Insulin resistance is a problem that is strongly associated with obesity due to excess body fat and diabetes. However, growing evidence suggests that gut microbiota (GM) is tightly linked to the presence of these comorbidities. Besides this, it is well-known that genetic, age, antibiotics, and particularly nutrition interact with each other promoting or disrupting the delicate balance of symbiosis. With this being mentioned, dietary polyphenols seem to intervene with GM functions modulating membrane permeability, therefore influencing the GM immune and anti-inflammatory purpose.
The gut microbiota (GM) is a collective community of microorganisms, and it is believed that this component is highly variable among human beings. In fact, numerous factors influence the approximately 100 trillion gut microorganisms. For example, genetic background, colonization in utero, birth delivery, breastfeeding, nutritional intake, prolonged antibiotics, and physiological factors such as aging, stress, and exercise.
Besides, dysbiosis, dysfunction caused by GM and the environment’s interaction can be caused by age, stress, drugs, xenobiotics, dietic intake, and lack of excessive exercise.
Leading roles of Gut microbiota
|Structural functions||· Regulation of gut architecture.
· Regulation of intestinal permeability.
· Education of host immunity.
|Protective functions||· Prevention of pathogens colonization
· Colonization resistance.
· Regulation of innate and adaptive immunity
|Metabolic functions||· Absorption of fats and vitamins.
· Regulation of lipid energy metabolism.
· Production of SCFA and bile composition.
· Regulation of glucose homeostasis.
· Synthesis of amino acids.
Gut microbiota, disease, and polyphenols
Although it seems obvious that gastrointestinal conditions such as inflammatory bowel disease (IBD), ulcerative colitis (UC), colorectal cancer (CRC), and Crohn’s disease (CD) are linked to a dysbiosis of the GM, cardiometabolic conditions are as well related to this dysfunction. Consequently, obesity, diabetes, insulin resistance, and macro-and microvascular complications seem to start in the gut.
Dysbiosis and disease
When gut microbiota dysbiosis is present due to a decrease in the number of symbionts, an overgrowth of pathobionts, or a loss of diversity, these aforementioned conditions accompany environmental factors begin a cascade of responses that result in the pathophysiology of numerous metabolic diseases.
Dysbiosis affects gut microbiota composition:
- A decrease in the Firmicutes to Bacteroides
- Breastmilk oligosaccharides influence the Lactobacillus and Bifidobacterium content in the infant’s gut.
- High-fat and high- sugar diet can influence GM and result in increased adiposity, inflammatory molecules proliferation such as lipopolysaccharide (LPS).
- Artificial sweeteners can upset the GM’s balance by promoting Clostridia, Bacteroides, and aerobic bacteria.
This dysbiosis can be the promoter of trimethylamine- N-oxide (TMA-O), associated with CVD and renal diseases. Furthermore, choline, a nutrient component derived from lipid metabolism, gets transformed into trimethylamine (TMA) that afterward converts into TMA-O by flavin mono-oxygenase 3 (FMO3) in the liver.
Gut microbiota and cardiometabolic conditions
A disbalance of gut microbiota ultimately results in a gut barrier breakdown, affecting the tight junctions’ expression (proteins that link together the epithelial wall in the gut). Consequently, this breakage would result in permeability, facilitating the infiltration of bacteria fragments (LPS) into the bloodstream.
In brief, this infiltration would cause a pro-inflammatory response mediated by the microbe-associated molecular pattern (MAMP) and toll-like factor 4, promoting the release of pro-inflammatory cytokines. Furthermore, this uncontrolled pro-inflammatory response would culminate with the disruption of insulin metabolisms and signaling.
The combinations of advanced glycation end (AGE) products and oxidative stress promoted by oxidative pathways can inflict further damage and contribute to obesity and diabetes development. Overall, pathogenic molecules’ translocation through the impaired intestinal barrier to the systemic circulation can contribute to the pro-inflammatory and pro-oxidative profile found in diabetic nephropathy and retinopathy.
Polyphenols and gut microbiota
The interplay between polyphenols and GM is dependent on the chemical constitution of the polyphenolic compounds. However, the polyphenolic chemical structure is very similar; they all have aromatic rings and phenol rings. Polyphenols can come from various foods, for example, fruits, teas, coffee, cereals, dark chocolate, vegetables, wine, and cocoa. The main groups of dietary polyphenols are:
Where to find your resveratrol?
The combination of molecules, exercise, and dietary habits can promote a better healthy life.
The digestive and metabolic interplay of these polyphenolic compounds is vital for the modulation of oxidative stress. In brief, only a low number of dietary polyphenols are digested by the small intestine and then are metabolized in the liver by Phase I enzymes (oxidation, reduction, and hydrolysis) and then mainly by Phase II enzymes (conjugation). However, while the 5-10% of polyphenols are absorbed in the small intestine, the remaining undigested (more complex) 90-95% of polyphenols travel to the large intestine interplay GM starts. These 90-95% of polyphenols stay a more extended period of time in the gut’s lumen, which gives them a prolonged interaction with the host gut bacteria.
|Polyphenol interaction with gut microbiota and cardiometabolic effects|
|Flavonol supplementation in humans showed and stimulated the growth of Bifidobacterium spp. and Lactobacillus spp. This resulted in a decline of C-reactive protein levels and pro-inflammatory biomarkers.|
|In vitro, water-soluble cocoa fractions were able to promote Bifidobacterium spp. and Lactobacillus spp growth, consequently reducing the CRP concentration and plasma triglycerides levels dropped.|
|The consumption of red wine polyphenols is associated with reductions in blood pressure, plasma triglycerides, and higher HDL-C levels. These benefits are associated with the higher concentrations of Bacteroides spp.-induced by red wine polyphenols.|
|Weight reduction is tightly associated with green tea, fruits, and vinegar wine consumption. Bacteroides’ polyphenol-induced growth is believed to influence the glycan- degradation of end products, promoting protection against adiposity. Also, metabolites from these polyphenols seem to interplay with the TNF-a pathway inhibiting IL-6 and IL-1B production.|
|Polyphenolic components in turmeric, cinnamon, anise, and ginger lower cardiometabolic risk by modulating the gut glucose uptake and diminishing appetite.|
Body composition and polyphenols
While is true that polyphenols have been studied and resulted in positive outcomes when it comes to adiposity and weight-loss, it safe to understand that the combination of a healthy exercise routine and a proper diet can positively influence body composition. Indeed, the only way weight loss is positive is if the percentage of body fat decreases while maintaining muscle mass. To learn more about this, BIA can provide a better look into this situation.
The metabolic pathways are yet too complicated to follow and modulate. However, now there’s an extra player in this process, the gut microbiome. The maintenance of gut permeability ensures our immune response’s proper function that nowadays it’s getting a tough reputation. Indeed, the controlled immune response is vital for our body’s protection. However, when excessive translocation emerges, our immune response becomes exaggerated, leading to a pro-inflammatory response that can promote cardiometabolic conditions.
Polyphenolic compounds interact with our antioxidant pathways and can ultimately modulate the pro-inflammatory response, lowering the risk of cardiometabolic disease development. Also, the complexity of their chemical structure allows them to interact for a more extended period of time with our gut microbiome inducing beneficial bacteria’s growth. Overall, these interactions result in a lower production of metabolites like TMA and promote beneficial metabolites that conclude lower plasma triglycerides, CRP, and IL-6. IL-1B and higher HDL-C concentrations. – Ana Paola Rodríguez Arciniega, MS
Kumar Singh, Amit et al. “Beneficial Effects of Dietary Polyphenols on Gut Microbiota and Strategies to Improve Delivery Efficiency.” Nutrients vol. 11,9 2216. 13 Sep. 2019, doi:10.3390/nu11092216
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Dr. Alex Jimenez DC, MSACP, CCST, IFMCP*, CIFM*, CTG*
Licensed in Texas & New Mexico