NIEHS Senior Investigator Shyamal Peddada, Ph.D., recently received a National Institutes of Health (NIH) Office of AIDS Research (OAR) Innovation Award to improve understanding of the gut microbiome and antimicrobial resistance in persons with HIV. Antimicrobial resistance, which is on the rise worldwide due to various factors, such as infections, antibiotics, radiation, and climate change, occurs when germs become able to defeat antibiotics designed to kill them.

Peddada’s proposal builds on emerging research indicating that microorganisms lining the gastrointestinal tract may play an important role in defending against antibiotic-resistant pathogens.

“Through this proposal, we aim to address the growing clinical and public health concerns regarding the spread of antibiotic-resistant pathogens,” said Peddada.

Understanding how the microbiome affects health and disease is a major research interest for Peddada, who leads the Constrained Statistical Inference Group within the NIEHS Division of Intramural Research. He and his team work to develop biostatistical methods that can be broadly applied to toxicology, epidemiology, and various omics data.

The one-year $300,000 award, funded through the NIH Intramural Research Program, rewards meritorious projects that use innovative approaches to address significant and high-priority scientific opportunities in HIV research.

“Dr. Peddada’s proposal is a great example of NIEHS efforts to capture and measure the environment’s role in health and disease, and to share new tools and knowledge gained from these efforts across NIH,” said NIEHS Scientific Director Darryl Zeldin, M.D.

Antimicrobial resistance genes and the microbiome

To date, the relationship between antimicrobial resistance genes (ARGs) — genes in bacteria that make them resistant to antibiotics — and the microbiome is not well understood. However, people with HIV are likely to have a greater abundance of antibiotic-resistant pathogens that cannot be controlled or killed by antibiotics.

To uncover potential links between ARGs and the microbiome, Peddada and his team will develop novel statistical methods capable of incorporating a wealth of data.

Using oral wash and stool samples from participants of the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study, Peddada will describe associations between ARGs and the microbiome in people with HIV treated with antiretroviral therapy (ART), which is the standard combination of HIV medicines.

Incorporating statistical science

Differences due to gender, sexual activity, duration of HIV plus ART, and geographic regions will also be investigated, and novel computational methods will be developed to integrate the high-dimensional data.

“This award acknowledges the importance of statistical science in modern interdisciplinary research,” said Peddada. “Not only will we gain deeper insights into the interactions between ARGs and the microbiome, but this research might also generate interesting hypotheses for future studies regarding these interactions under different climatic conditions.”

Peddada will present his project’s outcomes next year at the OAR Innovation in HIV Research Symposium.