Xiaofang Jiang, Ph.D.

The gut microbiome shapes human physiology through chemistry the body cannot perform on its own. Gut bacteria transform bile pigments, steroid hormones, cholesterol, and dietary compounds into metabolites that influence jaundice risk in newborns, hormone balance, cardiometabolic health, and inflammatory disease. For many of these transformations, the responsible enzymes remain unknown, leaving clinicians without the mechanistic markers or intervention targets that would make this biology actionable.

My group identifies these enzymes and establishes their relevance to human health. We use comparative genomics to pinpoint candidate genes, confirm their activity through collaborations with experimental laboratories, and measure their prevalence across human cohorts to connect specific microbial genes to clinical phenotypes. Because existing methods were not built for this kind of question, we also develop the computational tools the work requires: for linking genes to phenotypes across species, for delineating enzyme families and the residues that distinguish them, and for mapping enzyme prevalence at cohort scale. This combined approach has uncovered previously uncharacterized enzyme families throughout the gut microbiome.

Among these, we identified BilR and BilV as complementary bacterial bilirubin reductases, resolving a long-standing question about the microbial basis of bilirubin reduction; BilR is nearly universal in healthy adults yet frequently absent in early infancy, the window of greatest jaundice risk. We defined enzymes behind microbial steroid hormone metabolism, including a fusion enzyme that produces the neurosteroid epipregnanolone, with implications for fertility, menopause, and neuropsychiatric conditions. And we identified SpiR as the enzyme initiating cholesterol-to-coprostanol conversion, whose abundance tracks favorable lipid profiles and is reduced in metabolic syndrome. We apply related approaches to microbial and viral enzymes more broadly.

Dr. Xiaofang Jiang is a tenure-track investigator in the Division of Intramural Research at the National Library of Medicine, where she has led a research group since 2019. Her laboratory combines comparative genomics, structural modeling, and machine learning with experimental collaborations to identify gut microbial enzymes that shape human metabolism and disease, and develops computational methods to support that work. She received her B.S. in Life Science from Wuhan University and her Ph.D. in Genetics, Bioinformatics, and Computational Biology from Virginia Tech, and completed postdoctoral training at MIT and the Broad Institute of MIT and Harvard.