Medicine and Health Sciences Commons^™

Association Between Sulfur-Metabolizing Bacterial Communities In Stool And Risk Of Distal Colorectal Cancer In Men, Long H. Nguyen, Wenjie Ma, Dong D. Wang, Yin Cao, Himel Mallick, Teklu K. Gerbaba, Jason Lloyd-Price, Galeb Abu-Ali, A. Brantley Hall, Daniel Sikavi, David A. Drew, Raaj S. Mehta, Cesar Arze, Amit D. Joshi, Yan Yan, Tobyn Branck, Casey Dulong, Kerry L. Ivey, Shuji Ogino, Eric B. Rimm, Mingyang Song, Wendy S. Garrett, Jacques Izard, Cutis Huttenhower, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Background & Aims: Sulfur-metabolizing microbes, which convert dietary sources of sulfur into genotoxic hydrogen sulfide (H₂S), have been associated with development of colorectal cancer (CRC). We identified a dietary pattern associated with sulfur-metabolizing bacteria in stool and then investigated its association with risk of incident CRC using data from a large prospective study of men.

Methods: We collected data from 51,529 men enrolled in the Health Professionals Follow-up Study since 1986 to determine the association between sulfur-metabolizing bacteria in stool and risk of CRC over 26 years of follow-up. First, in a subcohort of 307 healthy men, we …

A Mouse Model Of Human Tlr4 D299g/T399i Snps Reveals Mechanisms Of Altered Lps And Pathogen Responses, Katharina Richard, Kurt H. Piepenbrink, Kari Ann Shirey, Archana Gopalakrishnan, Shreeram Nallar, Daniel J. Prantner, Darren J. Perkins, Wendy Lai, Alexandra Vik, Vladimir Y. Toshchakov, Chiguang Feng, Rachel Fanaroff, Andrei E. Medvedev, Jorge C.G. Blanco, Stefanie N. Vogel

Department of Food Science and Technology: Faculty Publications

Two cosegregating single-nucleotide polymorphisms (SNPs) in human TLR4, an A896G transition at SNP rs4986790 (D299G) and a C1196T transition at SNP rs4986791 (T399I), have been associated with LPS hyporesponsiveness and differential susceptibility to many infectious or inflammatory diseases. However, many studies failed to confirm these associations, and transfection experiments resulted in conflicting conclusions about the impact of these SNPs on TLR4 signaling. Using advanced protein modeling from crystallographic data of human and murine TLR4, we identified homologous substitutions of these SNPs in murine Tlr4, engineered a knock-in strain expressing the D298G and N397I TLR4 SNPs homozygously, and characterized in vivo …