Green tea and lactulose- A novel support

for microbiome modulation

What is Green Tea?
Green tea originates from the leaves of Camellia
sinensis and the family Theacea.
Green tea is rich in polyphenols (catechins and gallic
acid); among the catechins of green tea,
(-)-epigallocatechin gallate (EGCG) is the most
abundant and the most extensively studied catechin,
accounting for 50-80% of the total present catechins
(See Fig 1.0). Green tea also contains carotenoids,
tocopherols, ascorbic acid (vitamin C), minerals such as
Cr, Mn, Se, or Zn, and phytochemical compounds (1).
Figure 1.0 Identified polyphenol catechins in green tea

health impacts
Green tea has been linked with a variety of health-promoting and health influencing properties. Research
supports green tea's influences in specific disease states such as obesity, type 2 diabetes, hyperlipidaemia,
cardiovascular disease, influenza prevention, liver and gastrointestinal disease, cognitive impairment, oral
health, endometriosis, polycystic ovarian syndrome, cervical dysplasia, vaginal health, urinary tract infection
and many different cancers.
Of particular interest to genitourinary and reproductive health are the potential impacts of green tea on
microbiome and inflammation modulation (2-4).

ANTIMICROBIAL ACTIVITY
Green tea's antimicrobial activity has been explored in a variety of in-vivo and in-vitro research (Fig 2.0), in
food manufacturing, dentistry, gastrointestinal microbiome modulation and antibiotic resistance.
Antimicrobial studies using various green tea extracts have shown considerable therapeutic potential (5).

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Green tea and lactulose- A novel support
for microbiome modulation

Fig 2. Identified microbial influences of Green Tea

various papers show modulating and species specific impacts. Image Source: Veeforme original 2022

Genitourinary Microbiome impacts

The microbial impacts of green tea in the literature
suggest that it may have specific roles in managing
urinary and vaginal health microbial imbalances.
Microbiome health in the vaginal and bladder
microbiome is generally represented by a low diversity
of microbial inhabitants and dominance by Lactobacillus
spp. The dominance of Lactobacilli provides
homeostatic maintenance via the production of lactic
acid, hydrogen peroxide and antimicrobial peptides
(bacteriocins) (Fig 3.0). Microbial composition in the
genitourinary tract is influenced by both internal and
external factors such as hormonal status and life stage,
nervous system health, nutritional status, Fig 3. Microbial homeostasis exerted by Lactoabcillus in the
genitourinary tract.
gastrointestinal health, hygiene factors, partner Image Source: Intimate Ecology. Reproduced with permission

interactions and medication use.

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Green tea and lactulose- A novel support
for microbiome modulation
Genitourinary Microbiome impacts: Vaginal health
Green tea has been utilised in herbal medicine for many common clinical genitourinary presentations such as
Bacterial Vaginosis (BV), Aerobic Vaginitis (AV), Vulvovaginal Candidiasis (VVC) and genital viruses of
Herpes Simplex Virus (HSV) and Human Papilloma Virus (HPV). A tradition of use is linked to green tea's
specific antimicrobial, immune and microbiome modulating effects.
The antimicrobial impacts of green tea were demonstrated successfully in-vitro against commonly implicated
vaginal pathogens, Proteus mirabilis (BV), Streptococcus pyogenes (AV), and Candida albicans (VVC).
Among the catechins, epigallocatechin gallate had the most potent anti-microbial activity (6).
A small study exploring the use of 2 mg green tea extract as a vaginal ovule found that 5-7 days of
application had the capacity to reduce objective and subjective symptoms of intermediate vaginal flora such
as vulvovaginal burning and aberrant pH in half of the participants. The effect seems to be driven by a
decrease in vaginal pH reflective of an improvement in vaginal flora. There were signs of recolonisation by
Lactobacilli bacteria but not the mixed flora implicate in vaginitis after the completion of the treatment (7).

Genitourinary Microbiome impacts: cervical health

Studies investigating the clinical efficacy of green tea components delivered vaginally and orally with cervical
HPV and dysplasia have demonstrated overall response rates of 69% in the treatment group (200mg
EGCG) compared to 10% in the untreated control group (8). A published case report of compounded green
tea extract (15%) and curcumin applied vaginally every second day showed efficacy determined by negative
cytology after only one month (9).

Genitourinary Microbiome impacts: URINARY HEALTH

Susceptibility studies demonstrate antimicrobial effects from green tea catechins EGCG and EGC against
common uropathogens like E. coli (10). Urinary excretion of EGC at therapeutic minimum inhibitory
concentrations has been demonstrated after ingestion of green tea, suggesting that oral green tea use may
serve as an effective mode of delivery of antimicrobial catechins to the bladder, urothelium and the
associated microbiome (10).
The role of green tea in UTI's was explored in a blinded randomised trial in conjunction with antibiotic therapy
utilising four 500mg green tea capsules daily. There was a statistically significant decrease in the prevalence
of cystitis symptoms and a statistically significant improvement in the urinalysis results except for
haematuria after three days of treatment (11). Data from the studies on the antimicrobial effects of green
tea in UTI is promising and support the need for more comprehensive human studies (12).

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Green tea and lactulose- A novel support
for microbiome modulation

Genitourinary Microbiome impacts: URINARY HEALTH

Delivery of green tea to the bladder and its microbiome can be from oral administration or via intra-vaginal
application. Delivery of therapeutic molecules to secondary genitourinary structures via intra-vaginal
application has been traditionally used in both holistic and general medical practice. An experimental animal
study demonstrated that vaginal administration of green tea in emulsion with an antibiotic penetrated the
mucous membrane and reached the target organs of kidney and bladder (13). Additionally, the vagina is a
known reservoir for uropathogens, influencing reactivation of embedded intracellular microbes implicated in
recurrent and chronic urinary tract infection (14,15). Modulating the vaginal microbiome to address the
urinary system microbiome has been shown to be efficacious in the literature (14).

Green tea synergy with genitourinary antimicrobials

Researchers have assessed how green tea catechins might work synergistically with known antibacterial
agents. These studies have focused on Staphylococcus aureus (MRSA), Staphylococcus epidermidis, and
Escherichia coli. The green tea catechins work synergistically with antibiotics like tetracycline, penicillin,
ampicillin/sulbactam, imipenem, chloramphenicol, ciprofloxacin, cefotaxime and extended-spectrum beta-
lactamase producers against isolates of resistant and non-resistant bacteria (1,12).
The susceptibility of Candida albicans to green tea catechins combined with antimycotics was evaluated
under varying pH conditions. Results indicated that EGCG enhances the antifungal effects of amphotericin
B and fluconazole against antimycotic-susceptible and resistant C. albicans. Overall, combined treatment
with green tea catechins allowed the use of a lower dose of antimycotic (1,16) .

Candida spp. BV associated bacteria

E.coli. Staphylococcus spp.

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Green tea and lactulose- A novel support
for microbiome modulation
Green tea potential impacts in gynaecology
Green tea and EGCG are the focus of research in gynaecological disorders like endometriosis, poly cystic
ovaries syndrome (PCOS) and dysmenorrhoea. The possible clinical impacts in endometriosis are through
anti-angiogenic, anti-fibrotic, anti-proliferative and proapoptotic mechanisms (3). A murine study by Ricci
et al, showed EGCG inhibited the development of endometriotic-like lesions, reducing the size of the
lesions, diminishing cell proliferation and increasing apoptotic levels (17).
In PCOS, green tea may enhance ovulation and reduces cyst formation (3). An improvement in generalised
pain, cortisol levels and uterine contractility is thought to impact dysmenorrhea (3). These beneficial effects
are summarised below (Figure 4.0).

Beneficial effects of green tea catechins on endometriosis, polycystic ovary syndrome (PCOS) and dysmenorrhea. Image Source: Kamal, D.A.M.; Salamt, N.; Zaid, S.S.M.; Mokhtar,
M.H. Beneficial Effects of Green Tea Catechins on Female Reproductive Disorders: A Review. Molecules 2021, 26, 2675. https://doi.org/10.3390/molecules26092675

Gastrointestinal microbiome IMPACTS

Green tea polyphenols demonstrate selective inhibition and prebiotic effects in the gastrointestinal tract by
limiting the increase of pathogenic bacteria, whilst supporting the survival of beneficial intestinal bacteria
such as Bifidobacteria (18).
Gastrointestinal bacteria metabolise green tea compounds and produce bioactive molecules. It is currently
estimated that between 10 and 20% of dietary polyphenols are absorbed in the small intestine (2).
Therefore, most of them reach the colon and are metabolized by gut microbes into smaller compounds. The
metabolism of green tea compounds by gut microbes seems to be related to many of the green tea health
benefits, namely antioxidant capacity (2). Some green tea oral supplementation studies demonstrate
conflicting impacts of green tea on microbiome composition which require further exploration and
clarification in addition to methodology refinement (19).
Overall, in microbiome focused studies green tea phenolic compounds (i.e., catechins) have show inhibitory
effects on some bacteria such as Bacillus cereus, Campylobacter jejuni, Clostridium perfringens, Escherichia
coli, Helicobacter pylori, Legionella pneumophila, and Mycobacterium spp. (2).
Green tea compounds may correct dysbiosis originated by high-fat diets, impacting the microbial dysbiosis
associated with a variety of disease states. Modulation of bacterial dysbiosis reduces the production of pro-
inflammatory substances (either by inhibiting the growth of LPS-producing bacteria or by altering their
secretion) (2).
Green tea and lactulose- A novel support
for microbiome modulation
What is lactulose?
Lactulose is a non-absorbable sugar that has prebiotic applications in both the gastrointestinal and vaginal
microbiome.
Lactulose therapeutic impacts
As a prebiotic carbohydrate, it can stimulate the growth of health-promoting bacteria in the gastrointestinal
tract, such as bifidobacteria and lactobacilli, and simultaneously inhibit growth of pathogenic bacteria such as
Salmonella (20,21). Lactulose can be used in small doses orally and vaginally to impact overall microbial
composition (22). Lactulose orally has a laxative effect when used in larger doses (20). Low-dose oral
lactulose has also been shown to enhance the absorption of minerals such as calcium and magnesium from
the gut, which may aid bone health in peri-menopause and menopause (23,24).
Research and clinical use also support the use of small amounts of lactulose applied intra-vaginally. Lactulose
was found to broadly and specifically stimulate vaginal lactobacilli, including the strongly health-associated
species L. crispatus, and significantly, not to stimulate microbes implicated in Bacterial Vaginosis or
Vulvovaginal Candidiasis (22).

Mechanism of action of lactulose and significance of the bacterial metabolism of lactulose

Mechanism of action of lactulose and significance of the bacterial metabolism of lactulose. Image Source: Schumann, C. (2002). Medical, nutritional
and technological properties of lactulose. An update. European Journal of Nutrition, 41(1), i17-i25.

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Green tea and lactulose clinical Applications

Green tea and lactulose synergy

When combined, the overall prebiotic and microbiome modifying actions of both green tea and lactulose
may be an effective supportive therapeutic when applied either topically in the vagina or taken orally to
support genitourinary, reproductive and gastrointestinal health.
INTRA-VAGINAL INSERTION
Green tea extract and pure powdered lactulose can be inserted into the vaginal canal via a capsule form. The
contents will dissolve over 12-24 hours. For most applications 7 day treatment periods are required.

Support in microbiome flora restoration: An initial intra-vaginal induction application of 30 days may be
appropriate for some microbial imbalances followed by 7 days a month at high risk time e.g assess cyclical
variation for symptom patterns and apply prophylactically before risk period, repeat monthly for a minimum
period of 3 months. For high risk clients post-coital insertion may be appropriate. Companion prescribing
with probiotics is indicated.

Synergistic support for antimicrobial treatment: Insert vaginally during the course of antimicrobial treatment
and for a week post treatment cessation before moving into a monthly 7 day pattern. If antimicrobial
treatment is intra-vaginal apply at opposite end of the day.

Support for cervical health: Insert vaginally for at least 7 days a month after menstruation or equivalent
pattern, repeat monthly for 3-6 months. Longer time periods of applications are also appropriate.

Support for urinary health: Insert vaginally 7 days a month at high risk time, usually in a low estrogen period,
repeat monthly for a minimum period of 3 months. An initial induction application of 30 days may be
appropriate for some microbial imbalances.

SAFETY CONSIDERATIONS
The suitability of topical and intravaginal application of green tea/lactulose should be made on a case by case
basis.
Individual allergies should be considered prior to use. In the clinical trial setting, green tea extracts and
lactulose used vaginally were well tolerated.
However, in vaginal dysbiosis levels of tissue inflammation can vary. If increased irritation is experienced from
vaginal use, discontinue and reassess.
Intra-vaginal use in pregnancy should consider individual client pregnancy risks (past and present) and cervical
competency.

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Green tea and lactulose- A novel support
for microbiome modulation
oral supplementation
Start by taking 1 capsule orally a day, providing an equivalent of 80mg EGCG and 500mg lactulose.
For some individuals lactulose tolerance may need to be titrated, as the prebiotic action may initially cause
gas or bloating. Over time dosage may be gradually increased to 4 capsules a day.
The green tea/lactulose combination can be used concurrently with pharmaceutical antimicrobial treatment.

Urinary tract infection: To support in infection and prophylaxis of UTI take 4 capsules orally a day in divided
doses. Consider concurrent intra-vaginal therapy.

Cervical health: 3 capsules orally a day in divided doses. Consider lactulose tolerance by increasing dose
gradually over time. Minimum course 12 weeks with concurrent intra-vaginal therapy for best results.

Gynaecological conditions: 4 capsules orally a day in divided doses. Consider lactulose tolerance by increasing
dose gradually over time.

Gastrointestinal conditions: 4 capsules orally a day in divided doses. Consider lactulose tolerance by
increasing dose gradually over time.

REFERENCES
1. Bansal S, Syan N, Mathur P, Choudhary S. Pharmacological profile of green tea and its polyphenols: a review. Medicinal Chemistry Research. 2012;21:3347-3360.
2. Pérez-Burillo S, Navajas-Porras B, López-Maldonado A, Hinojosa-Nogueira D, Pastoriza S, Rufián-Henares JÁ. Green tea and its relation to human gut microbiome.
Molecules. 2021;26:3907.
3. Kamal DAM, Salamt N, Zaid SSM, Mokhtar MH. Beneficial effects of green tea catechins on female reproductive disorders: A review. Molecules. 2021;26:2675.
4. Ratnani S, Malik S. Therapeutic Properties of Green Tea: A Review. Journal of Multidisciplinary Applied Natural Science. 2022;2:90-102.
5. Reygaert WC. The antimicrobial possibilities of green tea. Frontiers in microbiology. 2014:434.
6. Kim SH, Bae SM, Lee BR. Antimicrobial and antifungal effects of a green tea extract against vaginal pathogens. Journal of Womens Medicine. 2008;1:27-36.
7. Tuzil J, Filkova B, Jircikova J, et al. Tea Extract Vaginal Ovule for Intermediate Flora: Randomized Blinded Vehicle-Controlled Multicenter Pilot Clinical Trial with
Microbiome Analysis. Journal of Biologically Active Products from Nature. 2020;10:357-372.
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2003:383-390.
9. Agbi KE, Hover S, Carvalho M. Case Report of a Human Papillomavirus Infection Treated with Green Tea Extract and Curcumin Vaginal Compounded Medications.
International Journal of Pharmaceutical Compounding. 2018;22:196-202.
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11. Kheirabadi Z, Mehrabani M, Sarafzadeh F, Dabaghzadeh F, Ahmadinia N. Green tea as an adjunctive therapy for treatment of acute uncomplicated cystitis in
women: a randomized clinical trial. Complementary Therapies in Clinical Practice. 2019;34:13-16.
12. Reygaert W, Jusufi I. Green tea as an effective antimicrobial for urinary tract infections caused by Escherichia coli. Frontiers in microbiology. 2013;4:162.
13. Atinderpal K, Kapoor N, Gupta S, et al. Development and characterization of green tea catechins and ciprofloxacin-loaded nanoemulsion for intravaginal delivery to
treat urinary tract infection. Indian Journal of Pharmaceutical Sciences. 2018;80:442-452.
14. Lewis AL, Gilbert NM. Roles of the vagina and the vaginal microbiota in urinary tract infection: evidence from clinical correlations and experimental models. GMS
Infectious Diseases. 2020;8.
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periodontal research. 2002;37:433-438.
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Journal of Applied Pharmaceutical Science. 2011:149-152.
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22. Collins SL, McMillan A, Seney S, et al. Promising prebiotic candidate established by evaluation of lactitol, lactulose, raffinose, and oligofructose for maintenance of a
lactobacillus-dominated vaginal microbiota. Applied and environmental microbiology. 2018;84.
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