We have demonstrated that the presence of key gut bacteria at the time of neutrophil recovery can be used to predict risk of GVHD after HCT. This observation opens the potential to use the microbiota to assess risk of GVHD after HCT and determine if manipulation of the gut microbiota leads to a reduction in GVHD risk. We have also demonstrated connections between the gut microbiota and immune reconstitution after HCT, providing a mechanism for how the microbiota may influence inflammation and GVHD after HCT.
Golob JL, Pergam SA, Srinivasan S, Fiedler TL, Liu C, Garcia K, Mielcarek M, Ko D, Aker S, Marquis S, Loeffelholz T, Plantinga A, Wu MC, Celustka K, Morrison A, Woodfield M, Fredricks DN. The Stool Microbiota at Neutrophil Recovery is Predictive for Severe Acute Graft versus Host Disease after Hematopoietic Cell Transplantation. Clin Infect Dis. 2017 Aug 18. doi: 10.1093/cid/cix699. [Epub ahead of print]. PMCID: PMC5850019.
We have developed and validated a panel of real-time quantitative PCR assays for measuring concentrations of specific bacterial species in the genital tract. We have used these assays to measure the response to antibiotic therapy for BV and the dynamics of vaginal bacterial communities in women with and without BV. We have also developed a high throughput method for characterizing the human microbiota based on broad range 16S rRNA gene PCR / high throughput sequencing with identification of bacteria to the species levels using our bioinformatics pipeline.
Srinivasan S, Morgan MT, Fiedler TL, Djukovic D, Hoffman NG, Raftery D, Marrazzo J, Fredricks DN. Metabolic Signatures of Bacterial Vaginosis. MBio. 2015 Apr 14;6(2). pii: e00204-15. doi: 10.1128/mBio.00204-15. PMCID: PMC4453549.
Bacterial Vaginosis (BV) has been epidemiologically associated with multiple adverse health outcomes including HIV acquisition and transmission, cervicitis, pelvic inflammatory disease, and non-gonococcal urethritis (NGU) in men. The specific bacterial drivers of these associations were unknown. We demonstrated that vaginal BVAB3 and Leptotrichia/Sneathia species were associated with increased shedding of HIV in women from the US and Kenya. We have data showing that BVAB3 is also associated with idiopathic cervicitis in women, which may provide a mechanism for increased shedding of HIV in the genital tract.
McClelland RS, Lingappa JR, Srinivasan S, Kinuthia J, John-Stewart GC, Jaoko W, Richardson BA, Yuhas K, Fiedler TL, Mandaliya KN, Munch MM, Mugo NR, Cohen CR, Baeten JM, Celum C, Overbaugh J, Fredricks DN. Key Vaginal Bacteria Associated with Increased Risk of HIV Acquisition in African Women: A Nested Case-Control Study. Lancet Infect Dis. 2018 May;18(5):554-564. doi: 10.1016/S1473-3099(18)30058-6. Epub 2018 Jan 26. PMID: 29396006.