Toxic and health impacts of aflatoxin b1 and green tea polyphenols on the gut microbiome in rats
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Commensal microorganisms are critical to host physiology and health. Extensive evidence has shown that they could modulate the kinetics and dynamics of xenobiotics in host system. It is largely unknown, however, how xenobiotics modulate commensal microbiota and impact the overall health. With a repeated dosing regimen, utilizing 16S rRNA gene survey and metagenomic analysis, this dissertation elaborates the dose-response relationship between the gut microbiome of rat models with two natural xenobiotics, aflatoxin B1 (AFB1) and green tea polyphenol (GTP) respectively. We found that male young F344 rats orally exposed to different concentrations of AFB1 (0, 5, 25, and 75 µg/kg respectively) for 4 weeks significantly decreased phylogenetic diversity, but increased the evenness, of the gut microbiota in a dose-dependent manner. In addition to a dose-dependent shift in the community structure, some beneficial lactic acid bacteria were significantly depleted. In contrast, administering 0, 0.5% and 1.5% (g/ml) of GTP in water to female middle-aged Sprague-Dawley rats for 6 months significantly decreased both the phylogenetic diversity and evenness of the gut microbiota and induced a dose-dependent shift of community structure. Bacteroidetes and Oscillospira, previously linked to lean phenotype, were enriched; and Peptostreptococcaceae, previously linked to colorectal cancer, were depleted. Correspondingly, among many microbial genes impacted by GTP, genes related to energy production and conversion were consistently enriched with increasing doses. These results demonstrate that AFB1 and GTP induced compositional and functional changes in the gut microbiome, which could be critical to the overall health of the experimental rats. In addition, a standard protocol for preparing DNA libraries for microbiome studies and analyzing next-generation sequencing data for the microbiome has been established. Further studies are warranted to explore the phenotypical modification of the gut microbiota to confirm the specific functions and pathways that were modified, and to elucidate the interactions between other types of xenobiotics and the commensal microbiota and their potential roles in modulating health.