Our lab has been focusing on incorporating mining from multi-omics data into population studies to understand the etiological role of the gut microbiome in human diseases, including cancer. We will apply state-of-the-art multi-omic’ approaches including genomic, metagenomic, and metabolomic profiling to define the mechanisms by which microbes regulate intestinal oncogenesis, immune responses, and malignancies. We also support the metagenomic platform in the Center for Microbes, Development and Health (CMDH) by generating and sharing methodologies and data with the CMDH scientific and clinical communities.

The dysbiosis of gut microbiome could influence multiple human diseases uniquely through a combination of metabolism and small molecule products, immunomodulation, and direct interaction with a tumorigenic or protective microenvironment. Our previous work has identified that the structure and functions of the gut microbiome could help to predict individuals with colorectal adenomas (polyps with a risk of becoming cancer) or colorectal cancer risk. Thus, understanding how gut microbes may contribute to cancer development is crucial for microbiome targeting prevention and treatment for precision cancer care.

Our research projects have three objectives:

1）Epidemiological risk factors correlate of the cancer microbiome

We are integrating metagenome profiling with machine learning approaches to unveil the influence of lifestyle and environmental factors on the microbiome in large scale investigations of human populations. We expect to have far-reaching implications in the field of hypothesis-driven microbiome discovery, forward from the correlative studies based on large-scale population cohorts.

2）Dynamics of gut microbiome in tumor microenvironment

Several cancer risk-associated microbes have been identified, however, the influence of these microorganisms on the tumor microenvironment is poorly understood. We will combine approaches for direct visualization of host-microbe interactions in the tumor microenvironment and functional validation in vivo model systems.

3）The role of microbiome in cancer therapeutic response

We are developing computational algorithm and statistical modeling to investigate how the tumor microbiome influence the impact of or shaped in cancer patients receiving novel cancer therapy. These will provide multiple opportunities for potential translation into the clinic through the development of novel diagnostics and therapeutics that target microbes to improve cancer treatment efficacy, and ultimately facilitate the personalized medicine in public health.

Selected Publications

1. Yan Y, Drew DA, Markowitz A, Lloyd-Price J, Abu-Ali G, Nguyen LH, Tran C, Chung DC, Gilpin KK, Meixell D, Parziale M, Schuck M, Patel Z, Richter JM, Kelsey PB, Garrett WS, Chan AT, Stadler ZK, Huttenhower C. Structure of the mucosal and stool microbiome in Lynch syndrome. Cell Host & Microbes. 2020. PMID: 32240601.

2. Yan Y, Nguyen LH, Franzosa EA, Huttenhower C. Strain-level epidemiology of the human microbiome. Genome Medicine. 2020. PMID: 27098841.

3. Yan Y, Klinkhamer PGL, Van Veen JA, Kuramae EE. Environmental filtering: A case of bacterial community assembly in soil. Soil Biology and Biochemistry. 2019. Volume 136, 107531.

4. Yan Y, Kuramae EE, de Hollander M, Klinkhamer PGL, Van Veen JA. Functional traits dominate the diversity-related selection of bacterial communities in the rhizosphere. ISME J. 2017. PMID: 27482928.

5. Yan Y, Kuramae EE, de Hollander M, Klinkhamer PGL, Van Veen JA. Revisiting the dilution procedure used to manipulate microbial biodiversity in terrestrial systems. Applied Environmental Microbiology. 2015. PMID: 25888175.

6. Wang Y, Yan Y, Thompson K, Bae S, Shen JX, Vlamakis H, Hartman EM, Huttenhower C. Characterizing microbial community viability from built environment using propidium monoazide. Microbiome. 2021. PMID: 33478576.

7. Wang DD, Nguyen LH, Li YP, Yan Y, Ma WJ, Rinott E, Ivey K, Shai I, Willett WC, Hu FB, Eric B. Rimm EB, Stampfer MJ, Chan AT, Huttenhower C. The gut microbiome modifies the protective effects of a Mediterranean diet against cardiometabolic disease risk. Nature Medicine. 2021. PMID: 33574608.

8. Spencer C. et.al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science. 2021. PMID: 34941392.

9. Young C, Wood HM, Seshadri RA, Nang PV, Vaccaro C, Melendez LC, Bose M, Doi MV, Pi？ero TA, Valladares CT, Arguero J, Balaguer AF, Thompson KN, Yan Y, Huttenhower C, Quirke P. The colorectal cancer (CRC)-associated faecal microbiome of developing countries resembles that of developed countries. Genome Medicine. 2021. PMID: 33593386.

10. Young C, Wood HM, Seshadri RA, Nang PV, Vaccaro C, Melendez LC, Bose M, Doi MV, Pi？ero TA, Valladares CT, Arguero J, Balaguer AF, Thompson KN, Yan Y, Huttenhower C, Quirke P. Microbiome analysis of over 2000 NHS Bowel Cancer Screening Programme (NHSBCSP) samples shows the potential to improve screening accuracy. Clinical Cancer Research. 2021. PMID: 33658300.

11. Sikavi DR, Nguyen LH, Haruki K, Ugai T, Ma WJ, Wang DD, Thompson K, Yan Y, Branck T, Wilkinson J, Akimoto N, Zhong R, Lau MC, Mima K, Kosumi K, Morikawa T, Rimm EB, Garrett WS, Izard J, Cao Y, Song MY, Huttenhower C, Ogino SJ, Chan AT. The sulfur microbial diet and risk of colorectal cancer by molecular subtypes and intratumoral microbial species in adult men. 2021. Clinical and Translational Gastroenterology. PMID: 34333506.

12. Zhang YC, Thompson K, Branck T, Yan Y, Nguyen LH, Franzosa EA, Huttenhower C. Metatranscriptomics for the human microbiome and microbial community functional profiling. 2021. Annual Review of Biomedical Data Science. PMID: 34465175.

13. Nguyen LH, Ma W, Wang DD, Cao Y, Mallick H, Gerbaba TK, Lloyd-Price J, Abu-Ali G, Hall AB, Sikavi D, Drew DA, Mehta RS, Arze C, Joshi AD, Yan Y, Branck T, DuLong C, Ivey KL, Ogino S, Rimm EB, Song M, Garrett WS, Izard J, Huttenhower C, Chan AT. Association Between Sulfur-Metabolizing Bacterial Communities in Stool and Risk of Distal Colorectal Cancer in Men. Gastroenterology. 2020. PMID: 31972239.