Nowadays we understand that the human microbiome plays a major role in many diseases, either in the development of illness, or in terms of prevention and recovery [1,2].

The microbiome comprises all the microorganisms that exist in and on the human body and together with the human cells, it forms a kind of superorganism. We have already described this system in another article (The human superorganism).

The vaginom

However, individual aspects of this superorganism receive more attention than others, a fact that is somewhat due to their physical size. It is now clear to many people that a healthy ecosystem in the gut is of great importance for health. Other areas are discussed much less frequently, such as the microbiome of the female genital tract, which has been termed “the vaginome”.

Here too, there is a complex ecosystem, with important functionality for health, as well as defence against potential pathogens. This ecosystem is dominated by Lactobacilli, which represent 80-95% of the resident microorganisms [3,4]. These produce lactate, which lowers the pH, supports the innate immune system and has a direct impact on harmful bacteria [5].

Disruption or changes in the vaginal flora play an essential role in the development of problems such as bacterial vaginosis, sexually transmitted diseases, urinary tract infections and premature childbirth [6-8].

Bacterial vaginosis

One of the most common diseases in the vaginal area is bacterial vaginosis. Antibiotics are often prescribed to deal with this, a measure that does not always lead to long-term resolution [5].

Studies which investigated the use of lactoferrin in bacterial vaginosis have been quite successful.

A 2017 study showed that lactoferrin was able to reduce the number of pathogenic germs while simultaneously increasing the concentration of lactobacilli. These measurable differences were still present 2 weeks after the vaginal treatment with lactoferrin [5].

Pregnancy and premature childbirth

The vaginome has other profound influences, closely related to fertility and how the pregnancy progresses.

We know that infections caused by pathogens can play a role in premature births. The presence of these pathogens can stimulate the release of various pro-inflammatory messengers, ultimately triggering a premature labour via the formation of prostaglandins [9].

A healthy vaginal microflora is essential here, helping prevent colonisation by pathogens.

Giunta et al. investigated the possibilities of using lactoferrin in women who showed an increased risk of premature childbirth due to infection. Oral administration of lactoferrin was correlated with a reduced level of Interleukin 6 (IL-6), a pro-inflammatory cytokine, in the vaginal secretions, with a  normalising of the vaginal microbiome and a reduced risk of premature delivery [9].

A smaller study of six women with a history of miscarriage, premature birth and bacterial vaginosis also showed a significant improvement in the vaginal microbiome following administration of lactoferrin [10]. The authors referred to similar results in animal studies [11] and were optimistic that lactoferrin could help reduce the risk of premature births as related to infections.

Independent of microbiome research, this effect of lactoferrin was already presented in previous human studies [12].

Chlamydia infection also deserves a mention: this often requires long-term treatment with antibiotics, with a significant increased risk of antibiotic resistance.  It has been shown that lactoferrin used as a suppository intravaginally can be successful [13].

Fertility problems

Vaginal dysbiosis, i.e. an imbalance in the vaginal microbiome, is also associated with reduced pregnancy rates [14].

After examining microbial diversity, a recent study was able to predict whether In Vitro Fertilisation (IVF) would be successful or not [15].

Thanks to new methods of analysis, interventions can be tailored to be more specific. A pilot study has examined triple therapy of antibiotic, probiotic plus lactoferrin in managing endometrial dysbiosis [16], with the conclusion that the restoration of the microbiome could mean a distinct advantage with regard to fertilisation.

More research, along with the use of new technologies and new therapeutic approaches could open the door for a completely new range of treatments.

Lactoferrin lives up to its role as a multifunctional protein and may be an essential component of such innovative concepts.

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2        Gut Microbiota in Health and Disease. Physiological Reviews.

3        Forsum U, Holst E, Larsson PG, Vasquez A, Jakobsson T, Mattsby-Baltzer I. Bacterial vaginosis–a microbiological and immunological enigma. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 2005; 113: 81–90.

4        Cribby S, Taylor M, Reid G. Vaginal microbiota and the use of probiotics. Interdisciplinary perspectives on infectious diseases 2008; 2008: 256490.

5        Pino A, Giunta G, Randazzo CL, Caruso S, Caggia C, Cianci A. Bacterial biota of women with bacterial vaginosis treated with lactoferrin: an open prospective randomized trial. Microbial ecology in health and disease 2017; 28: 1357417.

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7        Hyman RW, Fukushima M, Jiang H, Fung E, Rand L, Johnson B, Vo KC, Caughey AB, Hilton JF, Davis RW, Giudice LC. Diversity of the vaginal microbiome correlates with preterm birth. Reproductive sciences (Thousand Oaks, Calif.) 2014; 21: 32–40.

8        Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. The New England journal of medicine 2000; 342: 1500–1507.

9        Giunta G, Giuffrida L, Mangano K, Fagone P, Cianci A. Influence of lactoferrin in preventing preterm delivery: a pilot study. Molecular medicine reports 2012; 5: 162–166.

10     Otsuki K, Imai N. Effects of lactoferrin in 6 patients with refractory bacterial vaginosis. Biochemistry and cell biology = Biochimie et biologie cellulaire 2017; 95: 31–33.

11     Yakuwa K, Otsuki K, Nakayama K, Hasegawa A, Sawada M, Mitsukawa K, Chiba H, Nagatsuka M, Okai T. Recombinant human lactoferrin has a potential to suppresses uterine cervical ripening in preterm delivery in animal model. Archives of gynecology and obstetrics 2007; 275: 331–334.

12     Paesano R, Pietropaoli M, Berlutti F, Valenti P. Bovine lactoferrin in preventing preterm delivery associated with sterile inflammation. Biochemistry and cell biology = Biochimie et biologie cellulaire 2012; 90: 468–475.

13     Sessa R, Di Pietro M, Filardo S, Bressan A, Rosa L, Cutone A, Frioni A, Berlutti F, Paesano R, Valenti P. Effect of bovine lactoferrin on Chlamydia trachomatis infection and inflammation. Biochemistry and cell biology = Biochimie et biologie cellulaire 2017; 95: 34–40.

14     Bernabeu A, Lledo B, Díaz MC, Lozano FM, Ruiz V, Fuentes A, Lopez-Pineda A, Moliner B, Castillo JC, Ortiz JA, Ten J, Llacer J, Carratala-Munuera C, Orozco-Beltran D, Quesada JA, Bernabeu R. Effect of the vaginal microbiome on the pregnancy rate in women receiving assisted reproductive treatment. Journal of assisted reproduction and genetics 2019; 36: 2111–2119.

15     Haahr T, Humaidan P, Elbaek HO, Alsbjerg B, Laursen RJ, Rygaard K, Johannesen TB, Andersen PS, Ng KL, Jensen JS. Vaginal Microbiota and In Vitro Fertilization Outcomes: Development of a Simple Diagnostic Tool to Predict Patients at Risk of a Poor Reproductive Outcome. The Journal of infectious diseases 2019; 219: 1809–1817.

16     Kyono K, Hashimoto T, Kikuchi S, Nagai Y, Sakuraba Y. A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium. Reproductive medicine and biology 2019; 18: 72–82.