Original Research
Exp. Biol. Med.
Sec. Immunology/Microbiology/Virology
Volume 250 - 2025 | doi: 10.3389/ebm.2025.10468
This article is part of the IssueProceedings of the 10th Annual Conference of the Arkansas Bioinformatics Consortium (AR-BIC) - Real-World Impact of AIView all 8 articles
Effect of in utero and lactational exposure to antiretroviral therapy on the gut microbial composition and metabolic function in aged rat offspring
Chandra Mohan Reddy Muthumula1,2Yaswanthi Yanamadala1Kuppan Gokulan1Kumari Karn1Helen Cunny3
Vicki Sutherland3Janine H Santos3
Sangeeta Khare1*- 1US-Food and Drug Administration/NCTR, Jefferson, United States
- 2National Center for Toxicological Research (FDA), Jefferson, Arkansas, United States
- 3National Toxicology Program Division, National Institute of Environmental Health Sciences (NIH), Durham, North Carolina, United States
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Despite the highly effective impact of antiretroviral therapy (ART) on reducing mother-to-child transmission of human immunodeficiency virus (HIV), there are concerns of long-term impacts of ART on the health of the offspring. The implication of perinatal exposure to antiviral drugs on the gut bacterial population and metabolic function in the offspring is unclear but may influence health outcomes given the various reported effects of the microbiome in human health. This study aims to gain insight on the potential effect of in utero and lactational exposure to ART on gut microbiota populations and short chain fatty acids (SCFAs) production in aged rat offspring. Pregnant rats were administered a combination of antiretroviral drugs (abacavir/dolutegravir/lamivudine) at two different dose levels during gestation and throughout lactation, and the fecal bacterial abundance and SCFA levels of the offspring were analyzed when they reached 12 months of age. Our results showed dose-dependent and sex-based differences in fecal microbial abundance at various taxonomic levels. Specifically, we found a decline in Firmicutes in males, and an increase in Actinobacteria among males and females. Furthermore, a sex-specific distribution reorganization of Lactobacillus, Bifidobacterium, and Akkermansia was identified. No significant difference in the concentration of prominent SCFAs and IgA levels were identified. These findings provide preliminary information indicating the need to evaluate perinatal effects of ART more comprehensively on the gut bacterial and metabolic function in future studies, and their potential role in offspring health outcomes.
Keywords: antiretroviral therapy, gut microbiome, short-chain fatty acids, IgA, prenatal exposure
Received: 12 Dec 2024; Accepted: 28 Apr 2025.
Copyright: © 2025 Muthumula, Yanamadala, Gokulan, Karn, Cunny, Sutherland, Santos and Khare. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sangeeta Khare, US-Food and Drug Administration/NCTR, Jefferson, United States
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