The mucosal membranes of all humans are naturally colonized by bacteria. Recent scientific evidence has documented the fact that these bacteria interact closely with cells and tissues of the body to regulate natural biological processes. It has become increasingly evident that this mucosal microflora also contributes substantially to numerous diseases affecting cells and tissues of humans.
Generally, domination of the microflora within the vagina and gastrointestinal tract, by lactobacilli and related bacteria, is associated with good health. Natural strains of lactobacilli have been administered for many years as “probiotics” for the purpose of maintaining a healthy microflora within these locations and preventing infection. It is well established that these “healthy bacteria” compete with pathogenic organisms, such as bacteria, viruses and fungi to limit the development and progression of pathogen associated diseases. Nevertheless, this microflora is a fragile and dynamic environment with the natural turnover and disruption of the healthy microflora being associated with the establishment of opportunistic infections. Consequently, approaches to maintain, or even enhance, the integrity and natural properties of the microflora, as a means of preventing or treating disease, would be coveted by the biomedical community.
Currently, the predominant mode of transmission of viruses, like human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2), is via heterosexual contact. Women are particularly at risk for infection by sexually transmitted viruses, as the efficiency of HIV and HSV-2 transmission from male to female is greater than for the reverse (al-Nozha et al., J. Acquir. Immune. Defic. Syndr. 3:193-194 (1990); Wald et al., JAMA 285:3100-3106 (2001)). The first natural line of defense against disease transmission for women during heterosexual contact is the mucosal barrier in the vagina. In healthy American and European women of childbearing age, either Lactobacillus crispatus or L. jensenii are most commonly the predominant bacteria colonizing the vaginal mucosa (Antonio et al., J. Infect. Dis. 180:1950-1956 (1999); Vasquez et al., J. Clin. Microbiol. 40:2746-2749 (2002)). These lactobacilli secrete lactic acid as a byproduct of metabolism, serving to acidify the vaginal mucosa and to keep the numbers of competing pathogenic microorganisms relatively low. Additionally, the predominance of lactobacilli in the vaginal microflora of healthy women has been associated with a lowered incidence of HIV acquisition, perhaps correlating with the observed antagonistic effects of metabolic byproducts of lactobacilli (lactic acid and peroxide), on the infectivity of the HIV virus in vitro. Therefore, the association of beneficial lactobacilli with the vaginal mucosa can be considered together as a protective “biofilm”. Sexually transmitted viruses like HIV and HSV-2 must first successfully traverse this protective matrix before infecting a host and causing disease.
The mucosal microflora contributes to many other local diseases affecting mucosal surfaces. For instance, the etiology of inflammatory bowel diseases, including ulcerative colitis and Crohn's disease may arise from inappropriate interactions between a disrupted mucosal microflora and cells and tissues of the host. A means of modulating the properties of bacteria within the mucosal flora could aid in the prevention and or treatment of these diseases, as well as related conditions affecting mucosal surfaces.
The present invention addresses these and other problems.
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