Impact of food production and food processing chemicals on the growth and transcription of human gastrointestinal bacteria

Abstract

Recent studies have associated several pesticides, food packaging chemicals, and food processing chemicals with changes in microbiome composition and function. These agri-food chemicals are pervasive in modern food consumption, but no systematic approach has been taken to understand the extent of their direct impact at concentrations relevant to dietary exposure in the general population. I asked: what is the impact of agri-food chemicals on the growth and function of gastrointestinal microbiota? I screened 58 representative gastrointestinal bacteria species in the presence of 30 widely used agri-food chemicals at 1μM. I further characterized one observed growth interaction between Bisphenol S (BPS) and Bifidobacterium adolescentis by screening 31 B. adolescentis strains. Comparative genomics analysis of these strains was performed to identify enriched functions. A subset of seven chemicals and eight bacteria from our growth screen were also selected for RNA-seq to assess sub-inhibitory transcriptional response in the absence of growth inhibition. A Salmonella Typhimurium promoter library was screened to better characterized findings from the RNA-seq experiment. I observed 15% of bacteria were impacted by at least one agrochemical and 41% of agri-food chemicals impacted the growth of at least one bacteria. Azo food dyes and bisphenols were overrepresented in growth impacts among all compounds screened. Further screening with BPS and Bifidobacterium found that 52% of screened B. adolescentis were impacted. Comparative genomics analysis correlated the growth impact with functions relating to phage-associated and cell wall proteins. Transcriptomics of 56 different agrochemical-bacterial pairs found notable impacts of azo dyes, even in the absence of growth impacts. These impacts were found to relate to invasion and metabolic functions in random promoter library assays. These results characterize direct agri-food chemicals impacts on microbial growth and function, broaden our understanding of xenobiotic-microbiome interactions, and raise key questions regarding the widespread use of agri-food chemicals.