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NIH grant 1R01AI202116-01: Lactic Acid–Mediated Protection of the Cervicovaginal Epithelium
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Katherine Nelson. Award: $649728.
Start: 2026-08-21T00:00:00.
ABSTRACT
Sexually transmitted infections (STIs) are among the most prevalent infections in the United States and
impose a significant public health and economic burden. Susceptibility to STIs is strongly influenced
by the cervicovaginal microenvironment, particularly the composition of the resident microbiota, pH,
and oxygen tension. However, the specific mechanisms by which these factors regulate epithelial
responses to infection remain poorly understood, limiting prevention and leaving antibiotics as the primary
treatment. One factor known to play a role is the lactic acid produced by the optimal resident microbiota, which
decreases microenvironmental pH. We hypothesize that lactic acid can be used as a therapeutic to prevent
and resolve STIs, thereby reducing reliance on antibiotics. However, the interconnected system makes it
challenging to study pathogenesis and protection in controlled settings. Animal models of the cervicovaginal
region are limited in their ability to provide human-relevant results; therefore, while more reductionist, in vitro
models provide the most relevant conditions and experimental control. Microfluidic microphysiological
systems (MPS) are in vitro models that provide tight control while enabling complex interactions between
cells and their microenvironment. We have developed a cervical MPS in which microbiota consortia can be
cultured and Chlamydia trachomatis can infect, uniquely enabling isomer-specific dissection of lactic acid
effects under physiologic oxygen tensions; an advance not possible in prior static transwell or organoid
models. Using this advanced system, we will define the mechanistic role of lactic acid as a function of oxygen
tension in the cervical epithelium and test its ability to protect against and resolve chlamydia infection as an
alternative to antibiotics. This proposal uses a human-relevant non-animal model (NAM) to define the causal
mechanisms linking lactic acid isomers, oxygen, and microbial states to STI susceptibility, while testing a
translational therapeutic. If successful, this work will reduce reliance on antibiotics, decrease reinfection rates,
and establish broadly applicable strategies to engineer protective mucosal states in women’s health.document fetched 2026-08-30 02:46