The regulation of intestinal flora by hydroxytyrosol

I. Characteristics of Hydroxytyrosol and Its Fundamental Role in the Intestine

Hydroxytyrosol, the primary active polyphenol in olive oil and olive products, boasts strong antioxidant properties and biocompatibility. Its molecular structure (containing a catechol group) prevents rapid absorption in the intestine, allowing it to reach the large intestine and directly interact with gut microbiota. Studies indicate that hydroxytyrosol influences host health by regulating microbial composition and metabolic activity, particularly demonstrating unique potential in promoting probiotic proliferation and short-chain fatty acid (SCFA) production.

II. Proliferative Effect of Hydroxytyrosol on Probiotics

1. Selective Promotion of Beneficial Bacteria Growth

Hydroxytyrosol acts as a prebiotic substrate to selectively promote the proliferation of probiotics such as Bifidobacterium and Lactobacillus. In vitro experiments show that 0.1–1 mM hydroxytyrosol increases Bifidobacterium counts by 2–3 times, potentially via the following mechanisms:

Carbon source and energy provision: The phenolic structure of hydroxytyrosol is metabolized by probiotics into simple organic acids for carbon utilization.

Intestinal microenvironment improvement: Antioxidant activity reduces intestinal oxidative stress and decreases inflammatory factors (e.g., TNF-α), creating a suitable habitat for probiotics.

Pathogen adhesion inhibition: Hydroxytyrosol competes for intestinal epithelial cell receptors, reducing colonization by pathogens like E. coli and Salmonella, indirectly promoting probiotic implantation.

2. Clinical and Animal Experimental Evidence

In a rat model, oral administration of hydroxytyrosol (50 mg/kg/d) for 4 weeks significantly increased Lactobacillus counts in the cecum and upregulated the expression of intestinal barrier function-related genes (e.g., tight junction protein ZO-1). Human clinical trials also show that supplementing hydroxytyrosol (10 mg/d) for 8 weeks increases fecal Bifidobacterium counts by approximately 40%, with more pronounced effects in middle-aged and elderly populations.

III. Regulatory Mechanisms of Hydroxytyrosol on Short-Chain Fatty Acid Production

Short-chain fatty acids (e.g., acetic acid, propionic acid, butyric acid) are crucial metabolites from gut microbiota-fermented dietary fiber, regulating intestinal immunity and energy metabolism. Hydroxytyrosol promotes SCFA production through the following pathways:

1. Enhancement of Microbial Fermentation Activity

Hydroxytyrosol upregulates the expression of carbohydrate metabolism-related genes (e.g., β-galactosidase, xylose isomerase) in probiotics, enhancing their ability to decompose dietary fiber. For example, adding hydroxytyrosol to an in vitro fermentation system increases butyric acid production by 50–80% and propionic acid by 30–40%.

2. Optimization of Microbial Metabolic Pathways

Hydroxytyrosol inhibits the activity of methanogens (e.g., Methanobrevibacter), reducing hydrogen consumption and shifting microbial metabolism toward SCFA production. Meanwhile, its antioxidant properties protect acid-producing bacteria (e.g., Roseburia, Eubacterium) from oxidative damage, maintaining acid production efficiency.

3. Indirect Effects on the Host

SCFAs regulate intestinal peristalsis by activating G protein-coupled receptors (e.g., GPR43), promoting microbial-substrate contact. Additionally, butyric acid serves as an energy source for colonic epithelial cells, repairing mucosal damage and forming a benign cycle of "hydroxytyrosol-microbiota-SCFAs-intestinal barrier".

IV. Potential Applications and Research Prospects

1. Development of Functional Foods

Hydroxytyrosol can be compounded with dietary fiber to formulate prebiotic preparations for improving intestinal disorders like constipation and irritable bowel syndrome (IBS). For instance, an oat fiber beverage containing 0.5% hydroxytyrosol increased fecal SCFA levels by 25% and defecation frequency by 30% in clinical trials.

2. Intervention in Metabolic Diseases

Propionic acid inhibits hepatic gluconeogenesis, and butyric acid improves insulin sensitivity, so hydroxytyrosol may assist in regulating blood glucose and lipids by increasing SCFA levels. Animal experiments have confirmed that hydroxytyrosol (100 mg/kg/d) reduces fasting blood glucose by 15% and serum triglycerides by 20% in high-fat diet mice.

3. Future Research Directions

Explore the synergistic effects of hydroxytyrosol with other prebiotics (e.g., fructooligosaccharides).

Investigate the regulatory mechanism of hydroxytyrosol on specific gut microbiota (e.g., Akkermansia).

Develop intestinal targeted delivery systems to improve the bioavailability of hydroxytyrosol.

V. Conclusion

As a natural polyphenol, hydroxytyrosol demonstrates multiple advantages in gut microbiota regulation by selectively promoting probiotic proliferation and regulating SCFA production. Its mechanisms involve optimizing microbial structure, enhancing metabolic activity, and improving host intestinal barrier function, providing new insights for intestinal health intervention. In the future, clinical research combined with innovative delivery technologies will drive its application in functional foods and precision nutrition.