Research
Our research is focused on the role of the microbiome, or all microorganisms that live in or on us, in urologic disease. We conduct clinical, pre-clinical, and in vitro studies using microbiological, biochemical, and multi-omic approaches to understand the mechanisms through which the microbiome promotes or inhibits urologic disease and associated co-morbidities.
Biography
At the Cleveland Clinic, I am the head of the Urology Translational Research Laboratory and faculty in the Microbiome Center for Human Health. My research program seeks to understand how the microbiome contributes to the onset of renal and urologic diseases. The ultimate goal of this research is to develop a suite of diagnostic and therapeutic strategies to reduce systemic inflammation, biofilm formation, renal crystallization, vascular calcification, and plaque accumulation, along with the health burdens it produces. Towards this end, I have developed a successful, internationally recognized research program, which has led to over 40 peer-reviewed publications and successful fundings. My laboratory has been the leader in applying multi-omics technologies to studies of urologic disease and has published numerous clinical and animal studies that utilize multi-omics techniques. Additionally, our work has also led to the discovery of a diverse renal microbiome in both clinical and animal specimens, which has implications for viral and bacterial diseases of the urinary system. Through our work, we have identified specific microbial consortia in the gut that are responsible for the metabolism of dietary toxins, such as oxalate, that have a strong impact on the urinary system. Our work has fundamentally shaped the microbiome-urologic field as more investigators expand upon our past work. Since starting my position at Cleveland Clinic over six years ago, I have developed a productive research program in collaboration with physicians and investigators that span multiple benign urologic and nephrologic diseases including chronic kidney disease, urinary stone disease, benign prostatic hyperplasia, urinary tract infections, erectile dysfunction, and biofilms of indwelling devices. My research integrates clinical, animal, and in vitro study systems, using multi-omics and bioinformatics as a means of interrogation. The innovative approaches of my program has led to the discovery of a rich trans-domain microbiome throughout the nephrons and we have identified factors, such as glomerular dysfunction and antibiotic use that modulate this microbiome. Over the course of my career, I have mentored 21 trainees, ranging from undergraduates to postdocs and fellows, to carry out several clinical and basic investigations that take a systems biology approach. I have helped to secure external funding for several of these trainees for their research.
Education & Professional Highlights
The Ohio State University, Columbus, Oh B.S. 06/2004 Zoology
Nova Southeastern University M.S. 05/2006 Marine Biology
Florida International University Ph.D. 05/2012 Biology
University of Utah Postdoc 01/2016 Biology
Research
Research in my lab is focused on the confluence of the diet, microbiome, and host factors in the development of chronic urologic disease and co-morbidities. Chronic urologic diseases such as kidney stones, urinary tract infections, and chronic kidney disease are age-related disorders that have been increasing in prevalence over the last 50 years, consistent with co-morbid cardiometabolic diseases. We take a multi-omics approach using a combination of in vitro studies involving commensal bacteria with or without host cells, pre-clinical studies, and clinical studies to understand how the microbiome influences urinary tract health and factors such as vascular calcification and plaque accumulation that underpin many age-related chronic diseases. The goal of this research is to understand what factors have led to an increasing prevalence of urologic and cardiometabolic disease, the underlying commonalities among these co-morbidities, and to develop efficacious bacteriotherapies designed to alleviate the burdens of chronic disease.
Our Team
Selected Publications
45. Hong C., Eichinger F., Atta M., Estrella M., Fine D., Ross M.J., Wyatt C., Hwang T.H., Kretzler M., Sedor J.R., O’Toole J. F., Miller A.W.*, Bruggeman L.A. 2022. Kidney microbiome compartmentalization and association of viral infections and microbiome diversity with kidney disease. Kidney International. *Co-senior author
44. Agudelo J., Fedrigon D., Faris A., Wilkins L., Monga M., Miller A.W. 2022. Delineating the role of urinary metabolome in the lithogenesis of calcium-based kidney stones. Urology Gold Journal.
43. Werneburg G.T., Adler A., Zhang A., Mukherjee S.D., Haywood S., Miller A.W., Klein E.A. 2022. Transperineal prostate biopsy is associated with lower tissue core pathogen burden relative to transrectal biopsy: mechanistic underpinnings for lower infection risk in the transperineal approach. Urology Gold Journal
42. Miller A.W., Tasian G., Penniston K.L., Fitzpatrick K., Agudelo J., Lange D. 2022. The mechanistic role of the intestinal and urinary microbiome in recurrent kidney stone disease. Nature Reviews Urology.
41. Wolfe, A, Liu F., Du J., Zhai Q., Hu J., Miller A.W., Ren T., Feng Y., Jiang P., Hu L., Seng J., Gu C., Yan R., Lv L., Wolfe A.J., Feng N. 2022. The bladder microbiome, metabolome, cytokines, and phenotypes in patients with systemic lupus erythematosus. Microbiology Spectrum
40. Khosravi-Darani, K., Karamad, D. Miller A.W. 2022. Probiotic oxalate- degrading bacteria: new insight of environmental variables and expression of the oxc and frc genes on oxalate degradation activity. Foods.
39. Kachroo N., Monga M., Miller A.W. 2022. Functional profiling of the urinary tract microbiome reveals microbial influences on urolithiasis. Urolithiasis.
38. Kachroo N., Lange D., Penniston K.L., Stern J., Tasian G., Bajic P., Wolfe A.J., Suryavanshi M., Ticinesi A., Meschi T., Monga M., Miller A.W. 2021. Meta-analysis of clinical microbiome studies in urolithiasis reveal age, stone composition, and study location as the predominant factors in urolithiasis-associated microbiome composition. mBio.
37. Agudelo J., Miller A.W. 2021. A perspective on the metabolic potential for microbial contributions to urolithiasis. Kidney360
36. Batagello C., Vicentini F.C., Monga M., Miller A.W., Marchini G.S., Torricelli F., Danilovic A., Coelho R.F, Srougi M., Nahas W.C., Mazzucchi E. 2021. Effect of tranexamic acid in the blood transfusion rate and outcomes of patients with complex kidney stone undergoing percutaneous nephrolithotomy: a randomized, double-blinded, placebo-controlled trial. BJUI.
35. Kachroo N., Lange D., Penniston K.L., Stern J., Tasian G., Bajic P., Wolfe A.J., Suryavanshi M., Ticinesi A., Meschi T., Monga M., Miller A.W. 2021. Standardizing microbiome studies for urolithiasis to minimize experimental biases and allow cross-study comparison. Nature Reviews Urology. *Featured in Urotoday and the 2020 GUKI year in review.
34. Karamad D., Khosravi-Darani K., Hosseini H., Tavasoli S., Miller A.W. 2020. Assessment of the process variables for degradation of oxalate by Lactobacillus acidophilus ATCC 4356 using simulated rumen fluid media and tea. Applied food biotechnology 7(4): 195-205.
33. Sánchez-Tapia M., Miller A.W., Tovar, A.R., Torres N. 2020. The development of metabolic endotoxemia is dependent on the type of sweetener and the presence of saturated fat in the diet. Gut microbes 12(1): 1801301.
32. Han Y., Glueck B., Shapiro D., Miller A.W., Roychowdhury S., Cresci G.A.M. 2020. Dietary synbiotic supplementation protects barrier integrity of hepatocytes and liver sinusoidal endothelium in a mouse model of chronic-binge ethanol exposure. Nutrients 12(2), 373.
31. Karamad D., Khosravia-Darani K., Hosseini H., Tavasoli S., Miller A.W. 2019. Evaluation of Oxalobacter formigenes DSM 4420 biodegradation activity for high oxalate media content: an in vitro model. Biocatalysis and agricultural biotechnology 22, 101378.
30. Lange D.L., Miller A.W., Tasian G. 2019. Antibiotics and Kidney Stones: Perturbation of the Gut-Kidney Axis. American Journal of Kidney Diseases 74(6), pp.724-726.
29. Wilkins L.J., Monga M., Miller A.W. 2019. Defining dysbiosis for a cluster of chronic diseases. Scientific Reports 9(1), 1-10.
28. Miller A.W. 2019. Commentary: Loss of microbial function associated with antibiotics and high fat/high sugar diet. Journal of Infectiology 2(2), 23.
27. Zampini A., Nguyen A., Rose E., Monga M., Miller A.W. 2019. Defining dysbiosis in patients with urolithiasis. Scientific Reports 9(1), 1-13.
26. Miller A.W., Choy D., Penniston K.L., Lange D. 2019. Inhibition of urinary stone disease by a multi-species bacterial network ensures healthy oxalate homeostasis. Kidney International 96(1), 180-188.
25. Miller A.W., Orr T., Monga M., Dearing M.D. 2019. Loss of microbial function associated with antibiotics and high fat/high sugar diet. International Society for Microbial Ecology Journal 13(6), 1379-1390.
24. Miller A.W. 2018. The role of the intestinal microbiome in oxalate homeostasis. In: D. Lange & B. Chew, The Role of Bacteria in Urology, Springer, Vancouver, BC.
23. Kohl K., Oakeson K., Orr T., Miller A.W., Forbey J., Phillips C., Dale C., Weiss R, Dearing M.D. 2018. Metagenomic sequencing provides insights into microbial detoxification in the guts of small mammalian herbivores (Neotoma spp.). FEMS Microbiology Ecology 94(12), fiy184.
22. Batagello C.A., Monga M, Miller A.W. 2018. Calcium oxalate urolithiasis: A case of missing microbes? J Endourology 32(11), 995-1005.
21. Kang Z., Liu X., Lu J., Zhao J., Liu Z., Sun H., Wu N., Liu H., Hu Z., Miller A., Su B., Li X. 2018. Gut epithelium LKB1 negatively regulates intestinal inflammation and tumorigenesis by suppressing colitogenic microbiota. Journal of Immunology 200(5), 1889-1900.
20. Miller A.W., Dale C., Dearing M.D. 2017. Microbiota diversification and crash induced by dietary oxalate in the mammalian herbivore, Neotoma albigula. mSphere 2(5), e00428-17.
19. Liu W., Liu X., Li Y., Zhao J., Liu Z., Hu Z., Su B., Cookson M., Miller A., Li X., Kang Z. 2017. LRRK2 promotes the activation of NLRC4 inflammasome during S. typhimurium infection. Journal of Immunology 214(10), 3051-3066.
18. Miller A.W., Dale C., Dearing M.D. 2017. The Induction of Oxalate Metabolism in vivo is More Effective with Functional Microbial Communities than with Functional Microbial Species. mSystems 2(5).
17. Ridenhour B.J., Brooker, S.L., Williams, J.E., Van Leuven J.T., Miller A.W., Dearing M.D., Remien C.H. 2017. Modeling time-series data from microbial communities. Journal of International Society for Microbial Ecology 11(11), 2526-2537.
16. Miller A.W., Oakeson K.F., Dale C., Dearing M.D. 2016. Microbial community transplant results in increased and long-term oxalate degradation. Microbial Ecology 72(2), 470-478.
15. Miller A.W., Oakeson K.F., Dale C., Dearing M.D. 2016. The effect of dietary oxalate on the gut microbiota of the mammalian herbivore Neotoma albigula. Applied and Environmental Microbiology 82(9), 2669-2675.
14. Oakeson K.F., Miller A.W., Dale C., Dearing M.D. 2016. Draft genome sequence of an oxalate-degrading strain of Clostridium sporogenes from the white-throated woodrat (Neotoma albigula). Genome announcements 4(3): e00392-16.
13. Kohl K.D., Miller A.W., Dearing M.D. 2014. Evolutionary irony: evidence that ‘defensive’ plant spines act as a proximate cue to attract a mammalian herbivore. Oikos 124(7): 835-841.
12. Kohl K.D., Miller A.W., Marvin J., Mackie R., Dearing M.D. 2014. Herbivorous rodents (Neotoma spp.) an abundant and active foregut microbiota. Environmental Microbiology 16(9): 2869-2878.
11. Miller A.W., Kohl K.D., Dearing M.D. 2014. Microenvironments of the gut harbor distinct consortia of oxalate-degrading bacteria. Applied and Environmental Microbiology 80(5): 1595-1601. *Featured in spotlight section of journal.
10. Richardson L.L., Miller A.W., Blackwelder P., Al-Sayegh H. 2014. Black band disease. In: C. Woodley (ed) Diseases of coral, Wiley-Blackwell, Hoboken, NJ.
9. Miller A.W., Dearing M.D. 2013. The metabolic and ecological interactions that regulate the balance of oxalate in the gut. Pathogens 2(4): 636-652.
8. Miller A.W., Richardson L.L. 2013. Emerging coral disease: A climate driven process? Marine Ecology 36(3), 278-291.
7. Malenke J.R., Milash B., Miller A.W., Dearing M.D. 2013. Transcriptome sequencing and microarray development for the woodrat (Neotoma spp.): custom genetic tools for exploring herbivore ecology. Molecular Ecology Resources 13(4): 674-687.
6. Miller A.W., Blackwelder P., Al-Sayegh H., Richardson L.L. 2012. Insights into migration and development of coral black band disease based on fine- structure analysis. Revista de Biologia Tropical 60: 21-27.
5. Gantar M., Kaczmarsky L.T., Stanić D., Miller A.W., Richardson L.L. 2011. Antibacterial activity of marine and black band disease cyanobacteria against coral-associated bacteria. Marine Drugs 9(10): 2089-2105.
4. Miller A.W., Richardson L.L. 2011. Fine-structure analysis of black band disease infected coral and coral exposed to the BBD toxins microcystin and sulfide. Journal of Invertebrate Pathology 109(1): 27-33.
3. Miller A.W., Richardson L.L. 2011. A meta-analysis of 16S rRNA gene clone libraries from the polymicrobial black band disease of corals. FEMS Microbiology Ecology 75(2): 231-241.
2. Miller A.W., Blackwelder P., Al-Sayegh H., Richardson L.L. 2011. Ultrastructural characterization of black band disease infecting corals of the Montastraea annularis spp. complex. Diseases of Aquatic Organisms 93: 179-190.
1. Richardson L.L., Miller A.W., Broderick E., Kaczmarsky L.T., Gantar M., Stanić D., Sekar R. 2009. Sulfide, microcystin, and the etiology of black band disease. Diseases of Aquatic Organisms. 87(1-2):79-90.
Careers
Research News
Low levels of bacteria like E. coli and Lactobacillus in our urine come from communities in our kidneys, where they promote or prevent kidney stone formation.
Two Cleveland Clinic-led studies challenge the definition of device-associated infections and show that bacteria can grow on medical devices even in “uninfected” patients.
Urinary tract microbiota varied based on antibiotic use, family history of USD and sex—factors that have been associated with USD, but not linked to the urinary tract microbiome.