SEP 10, 2020 7:30 AM PDT

Keynote Presentation: Discovery of a gene-microbiome interaction in lung cancer: lessons learned and future directions

C.E. Credits: P.A.C.E. CE Florida CE
Speaker

Abstract

The selective pressure placed on the resident microbiota by local changes in the host environment – DNA damage, chronic inflammation, metabolic shifts, barrier damage, reduced immunosurveillance – might make tumor microenvironment a perfect niche for certain bacterial clades. While bacteria have long been known to play a role in carcinogenesis, only a few have been identified as initiators. In this work we uncover a unique microbiome-gene interaction in lung cancer, between the tumor suppressor gene TP53 and a consortia of bacteria. One taxa in particular, Acidovorax, we discovered was highly abundant in smokers, the primary risk factor for lung cancer. Knowing that mutations in TP53 are prevalent in 70-80% of squamous cell carcinoma (SCC), and confer reduced barrier function, we found that mutations in TP53 were associated with higher Acidovorax in SCC tumors. Further, preliminary data show that Acidovorax temperans administered by nasal instillation accelerates lung tumorigenesis and is detrimental to the survival of a mouse model of adenocarcinoma driven by AdCre-activated Kras and mutant Trp53. Importantly, A. temperans, has the ability to degrade hydrocarbons, such as those found in tobacco smoke, which strongly suggests that microbial metabolism impacts host cellular metabolism and pharmacokinetics. In conducting this research, many lessons were learned, especially in regards to collecting and analyzing low biomass samples. These lessons will be conveyed as critical concepts in human microbiome research and guidelines will be presented for future research studies.

Learning Objectives:

1. Define the main confounders in low-biomass microbiome studies

2. List the key controls you need in human low-biomass studies

3. Name at least two additional methods required to demonstrate ‘proof of life’ beyond sequencing in human microbiome studies


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