A Comparison of Lower Genital Tract Glycogen and Lactic Acid Levels in Women and Macaques: Implications for HIV and SIV Susceptibility

Abstract

Understanding factors that affect heterosexual transmission of HIV in women is of great importance. Lactobacilli in the lower genital tract of women utilize glycogen in vaginal epithelial cells as an energy source and produce lactic acid. The resultant vaginal acidity is believed to provide protection against HIV infection. Conversely, bacterial vaginosis (BV) is characterized by less lactic acid and a higher pH, and is associated with increased susceptibility to HIV infection. Because vaginal infection of macaques with simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) is used as a model to study HIV sexual transmission, and because previous studies have shown a paucity of lactobacilli in rhesus macaques' lower genital tract, we compared lactic acid and glycogen levels in the genital fluid of rhesus and pigtail macaques with levels found in humans. The levels of lactic acid were lower in both rhesus (median=1.2 mol lactate/mg protein) and pigtail macaques (median=0.7 mol/mg) compared to women with healthy genital microbiota (median=4.2 mol/mg). Glycogen levels were significantly lower in both rhesus (median=0.004 μg glycogen/μg protein) and pigtail macaques (median=0 μg/μg) than in women (median=0.2 μg/μg). No significant differences in glycogen or lactate levels were observed comparing longitudinally collected samples from cycling pigtail macaques. These data show that the previously reported scarcity of lactobacilli in macaques correlates with low glycogen and lactic acid levels. These findings have important implications for studies of vaginal infection of macaques with SIV or SHIV and further our understanding of how the bacterial microbiota influences HIV infection.

The vaginal mycobiome: A contemporary perspective on fungi in women's health and diseases

“…In contrast to oft-used animal models, the vagina of reproductive-age women is distinctly acidic (pH of 4.5 or less), owing to the presence of lactic-acid producing bacteria that thrive in this anaerobic niche 27 not otherwise described in the Class Mammalia. 28 Further intricacies of the vaginal environment in humans include cycles of growth, production of glycogen and its breakdown products by human a-amylases 29 , and shedding of the epithelium in response to reproductive hormones, and primarily innate (as opposed to adaptive) mucosal immune protection. [30][31][32] These physiologic features are certainly key determinants of microbial colonization of the vaginal mucosa.…”

The primate vaginal microbiome: Comparative context and implications for human health and disease

“…2003; Watts et al, 2005;Oakley et al, 2008;Mirmonsef et al, 2012). Lactobaccilli competitively exclude pathogens such as Prevotella, Atopobium, Gardnerella, Sneathia, Megasphaera, and Mobiluncus, from binding sites on vaginal epithelial cells, and also produce antimicrobial compounds and can enhance the host immune response to pathogens (Klebanoff et al, 1991;Boskey et al, 2001;Kaewsrichan et al, 2006;Voravuthikunchai et al, 2006;Ma et al, 2012).…”

“…In contrast, Lactobacillus is not prevalent among NHPs (Rivera et al, 2010a(Rivera et al, , 2010bSpear et al, 2010;Yildirim et al, 2011), constituting 5% or less of the NHP vaginal microbial communities (Spear et al, 2010). The paucity of Lactobacillus correlates with significantly lower glycogen and lactic acid levels in NHPs compared to women with healthy vaginal microbiota (Mirmonsef et al, 2012; Table 3). Data from vervets, baboons, and mangabeys (Street et al, 1983;Johnson et al, 1984) as well as rabbits, mice and rats (Linhares et al, 2011) also indicate that the vaginal environment of these species is characterized by a higher, near neutral pH.…”

“…At such times, we predict that greater Lactobacillus abundance would confer protection from pathogens and microbial disruptions when such protection is most important. Although no significant differences in glycogen or lactate levels have been observed in longitudinally collected samples from cycling pigtail macaques (Mirmonsef et al, 2012; see also Spear et al, 2010), NHP species have not been well sampled across their ovulatory cycle to evaluate this hypothesis and more data are clearly necessary.…”

The Barrier to HIV Transmission Provided by Genital Tract Lactobacillus Colonization

“…Our initial studies showed that humans have much higher levels of genital glycogen than macaques 42 providing a possible explanation for the lack of colonization by Lactobacillus in this important animal model of genital HIV infection. More recent studies by our group (manuscript submitted) show that in 185 lavage samples collected from women in the Women's Interagency HIV Study (WIHS), free glycogen was strongly and significantly associated with a low vaginal pH and the fraction of the microbiota consisting of Lactobacillus as determined by pyrosequencing.…”