Olive Leaf Extract and its Effects on the Human Microbiome.

Introduction

Microbes and humans establish a symbiotic relationship from the beginning of life but as we move away from traditional lifestyles, diet and environment this changes how microbes behave within the human body.^1,2 Studies have linked these changes with reduced microbial diversity and fewer species numbers which is associated with disease or conditions such as inflammation, irritable bowel syndrome, infections, obesity, insulin resistance and more.^1,3 Diet and herbal medicine can make positive changes to the microbes and overall microbiota.

The olive tree (Olea europaea) has a long history of nutritional and medicinal benefits.⁴ Evidence shows the olive tree was grown commercially as far back as 3000 BC where ancient Egyptians used the leaves to mummify Pharaohs.⁴ Olive leaf extract (OLE) use dates back over 7000 years and was valued as a famous folk remedy to treat fever and some tropical diseases such as malaria.^1,5

Medicinal plants still used today like Olea europaea contain bioactive compounds with the ability to reduce disease and promote health by having a positive effect on the microbiota. These bioactive compounds include biophenols which studies indicate to have antimicrobial actions.⁶

Naturopathy as Complementary Medicine

Most commercial and herbal drugs currently used are of plant origin or ‘folk remedy’, now more commonly known as complementary medicine (CM). CM incorporates a diverse collection of clinical practices including acupuncture, massage therapy and naturopathy.^6,7 Reid et al conducted a database search to identify peer reviewed original research published from January 1 2000 to December 31 2014 investigating the nature of CM use amongst the Australian population, results indicated CM use is substantial across Australia and is an important subject in the Australian primary health care system. The number of licensed Naturopathic doctors in the US is continually increasing with patients seeking disease preventative health advise and chronic disease wellness advice.⁸ Naturopathy is an evidence-based alternative and complementary medicine with a profound belief in the ability of the body to heal itself, given the proper opportunity. Using a broad range of diagnostic and therapeutic skills such and nutritional and herbal medicines.^7,9,10,11 A core belief of Naturopathic medicine is that ‘disease starts in the gut’. To begin the healing process or maintain health, a naturopath will research the microbiota state of the individual.^10,11

The Human Microbiota

The human Microbiota refers to the population of organisms (microbes; bacteria, viruses, fungi, and/or eukaryotes) in an anatomical location and Microbiome refers to the collective genes encoded by all microbes of that location.^12,13 The human gastrointestinal tract (GIT) includes the mouth, esophagus, stomach, small and large intestines and rectum which comprises of around 2kg biomass bacterial microbes. There are over 1000 species of bacteria encoding more than 3 million bacterial genes (microbiome) greatly exceeding our human genome by 150-fold.¹ The microbial strains differ the whole way along the GIT tract.^1,2,12,13 Duenas states that homeostasis and resilience in the human body are because of highly diverse gut microbiota in healthy people, whereas inflammatory, metabolic disorders and infections are linked to disturbances or changes in the composition and/or functions of the gut microbiota for example viruses or an overabundance of a pathogenic bacteria.² A bidirectional relationship links the human GIT microbiota and immunity, the gut microbiota works together as a team to maintain diverse metabolic functions, making them adaptive to the everchanging environment they live in.^1,14 The microbiome transforms throughout life, it gains diversity and complexity and contributes to host metabolic, immunologic, and cognitive development and to normal physiology.¹⁵

What Effects the Microbiota – Dysbiosis

The microbiota composition is continuously influenced by internal and external factors like genetics, medications, diet, infection and lifestyle.² Zhang et al reported, “dietary alterations are responsible for 57% of the gut microbiota’s entire variation, whereas genetic background explains only 12%” ¹³ When the microbiota is negatively influenced this can lead to dysbiosis: an imbalance in a biological system such as the types and number of bacteria in the gut which leads to illness and diseases¹² or more broadly defined, “dysbiosis is any change to the composition of resident commensal communities relative to the community found in healthy individuals” thereby affecting the status of the host.^16,17 A list of studies on the microbiota in recent years have implicated dysbiosis in a growing list of Western diseases, such as metabolic syndrome, inflammatory bowel disease, and cancer.¹⁵ From birth to the age of three there is a vast introduction of different microbes that will colonies the gut, from here, microbiota communities will fluctuate throughout life.¹⁸ Antibiotic exposure, neonatal nutrition, adult nutrition, stress, age, degree of hygiene and bacterial infections all contribute to the development of an individual’s unique microbial composition and as a result, susceptibility to several diseases.²⁰

The microbiota is important for the maturation and development of appropriate intestinal immune responses.¹⁷ Human Microbiota aid in drug metabolism, prevention of colonization of pathogenic microorganisms by providing an intestinal barrier function as well as nutrient metabolism of carbohydrates to synthesis short chain fatty acids; butyrate, acetate and propionate.¹⁸

How to keep the Microbiota Happy

The microbial diversity (species and number) in the GIT of healthy individuals are vastly different however the functions of these microbes are the same in everyone which suggests function is more important than the species providing it.¹² An increased microbiota diversity leads to improved health and reduced disease risk.¹⁶ Recent studies have reported biophenol extract dietary intervention modulates the human gut microbiota towards a more ‘health-promoting profile’ by increasing the number of prebiotics; non-digestible carbohydrates, oligosaccharides or short polysaccharides and probiotics like bifidobacteria and lactobacilli that can change the composition and activity of the GIT microbes.¹² Epidemiological studies indicate that the intake of a diet high in fruit and vegetables and therefore biophenols is inversely associated with chronic disease risk such as coronary heart disease, cancers, neurodegenerative disease, infection and can modulate the microbiota.² Biophenol rich sources incorporated in the diet (e.g. cloves, berries, apples, plums hazlenuts, pecans, almonds, red onion and spinach) can influence the abundance of different bacterial groups within the microbiota, reducing pathogen numbers of certain bacteria and enhancing mainly beneficial probiotics Clostridia, bifidobacteria and lactobacilli, this statement raises the possibility that foods, herbs and supplements have the ability to regulate the microbiota community structure and function, contributing to the health of the host.^2,12,19

Olive Leaf Extract and Biophenols – what the good microbes like to eat

Biophenols are abundantly found as secondary metabolites in a wide variety of fruits, vegetables herbs and seeds with a great deal of potential health benefits and implications in preventing chronic diseases.²¹ Phenolic compounds have shown antioxidant, antimicrobial, anti-inflammatory, antihypertensive and anticancer properties.^6,21 For phenolic compounds to be absorbed in the gut there must be a mutual relationship between them and gut microbiota, therefore they must be bioavailable to exert their functional influence.²¹ Human digestive and microbial enzymes help to release native biophenols from the food matrix, which is an essential mechanism for them to pass through the intestinal barrier.²¹ Boiphenols also interact with other nutrients or ingredients that influence their bioavailability. Protein-phenolic interactions generally decrease bioavailability, as do associations with dietary fiber. However, lipids in the diet enhance the bioavailability of phenolic compounds.²¹ Biophenols modulate the composition of the gut microbial community through the inhibition of pathogenic bacteria and the stimulation of beneficial bacteria. They may act as a prebiotic metabolite and enrich the beneficial bacteria. Therefore, the interactions of dietary biophenols and gut microbiota may elicit the health benefits.²¹

Olive leaves yield a high concentration of the biophenols such as oleuropein and hydroxytyrosol, these biophenols exert potent antimicrobial and antiviral effects, the concentration of these specific biophenols is far greater in the leaves than in the fruit or fruit oil.^22,23 Oleuropein exerts its antimicrobial activity against both Gram negative and positive bacteria, including Lactobacillus plantarum, Bacillus cereus, Helicobacter pylori and Salmonella spp, these bacteria in excess can lead to illness²⁴.  For its antimicrobial properties, oleuropein can be used as a food additive and for the treatment of human intestinal or respiratory tract infections. Oleuropein also possesses a well-documented antiviral activity through a viricidal effect, reducing how the virus infect the human body, probably acting on the virus envelope.²³ Phenolic compounds, present in almost all parts of the Olea europaea, have been shown to exhibit a wide range of physiological, properties, such as anti-allergenic, anti-atherogenic, anti-inflammatory, anti-microbial, antioxidant, anti-thrombotic, anti-cancer, cardioprotective, and vasodilatory effects.^25,5 Abaza reported that the antioxidant capacity of olive leaf extract was higher than Vitamin C and E or pure Hydroxytyrosol, indicating that olive leaf extract is a very strong antioxidant as a whole herbal extract.²⁵

In a study by Masoko where plant material of the olive tree (Olea africana) was extracted using different solvents to yield the highest antioxidant, antibacterial and antifungal activities, results indicated the highest total activity was found in methanol extract with the value of 1068 mL against E. faecalis while the lowest total activity was displayed by the hexane extract with the values of 25 mL against both P. aeruginosa and S. aureus. Oleuropein inhibited the growth of Salmonella spp. and Staphylococcus aureus with minimum inhibitory concentration.⁶ Hydroxytyrosol, derived from oleuropein by enzymatic hydrolysis was reported to have a broader spectrum and higher potency by inhibiting pathogenic bacteria and viruses compared to other phenolic compounds.⁶ A thorough review of the latest studies on the effect of phenolic compounds on gut microbiota by Ozdal, stated that “phenolic compounds and their metabolites contribute to beneficial gastrointestinal health by modulating gut microbial balance with the simultaneous inhibition of pathogens and stimulation of beneficial bacteria”.²¹ These latest studies indicate that the concept of prebiotics is not limited to non-digestible carbohydrates, but also applies to phenolic compounds that can show prebiotic action Therefore, the regular consumption of phenolic compound–rich foods and herbal extracts in a diet may beneficially balance the gut microbiota and exert beneficial health effects.²¹

Conclusion

The mutual relationship between gut microbiota and phenolic compounds increases the bioavailability of biophenols and provides increased health benefits. Phenolic compounds can alter the gut microbiota community, resulting in a greater abundance of beneficial microbes. Olive leaf extract of provides high amounts of biophenols; oleuropein and hydroxytyrosol that improve and maintain the health of microbiota and reduce illness and disease.

Areas of further research should include increased human studies examining the impact of polyphenols on more diverse human gut microbiota, not just specific strains of bacteria.

Researching the synergistic effects of the whole olive leaf extract as herbal medicine instead of individual constituents of the plant.

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