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3 Characterizing Interactions Between the Human Microbiome and Environmental Chemicals
Pages 34-48

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From page 34...
... Early obser- metabolism of environmental chemicals genervations regarding the fate of the antibacterial pro- ally lags behind knowledge of how the microbidrug1 Prontosil cemented the need to improve our ome modulates drugs. Still, there is compelling understanding of how microorganisms metabolize evidence on gut microbiome involvement in the chemicals and how these processes might affect the metabolic transformation of environmental chemihost, favorably or unfavorably (Spink et al.
From page 35...
... This chapter ex Conceptually, each interaction can have favor- plores the mechanisms highlighted in Figure 3-1 able or unfavorable influences on chemical expo- and concludes with a discussion of interindividual sure, and the role of the interactions in modifying variability and microbiome metabolism of envisusceptibility to toxicity in connection with envi- ronmental chemicals. ronmentally relevant exposures remains uncertain.
From page 36...
... It is well established that micro- port that environmental chemicals can alter microbiomes of specific composition can have distinct biome composition, the use of high doses that are causal effects on host biology. If exposure to an of questionable relevance to human environmental environmental chemical or any other factor leads exposures is a common limitation of the literato alterations in microbiome composition, the al- ture (Claus et al.
From page 37...
... Increasing evidence strategy for determining direct and indirect effects suggests that there are intimate bidirectional inon the host is to compare the host phenotypic re- teractions between the microbiota and epithelial sponse to the environmental factor in the presence cells wherein the composition and activity of the and absence of a microbiome. For example, admin- gut microbiota, for example, modulate the strucistration of a high-dose broad-spectrum antibiotic ture and function of the intestinal epithelium and cocktail in mouse models caused host responses vice versa (Ulluwishewa et al.
From page 38...
... Various probiotic is largely limited to the gut microbiome, which treatments and microbiome manipulations have probably has less complex pathways than envialtered expression of tight-junction proteins con- ronmental microbiomes because the gut is primarcurrently with changes in intestinal permeability ily an anaerobic environment and has less micro(Turner 2009)
From page 39...
... Studies that used sim- different from that of the parent compounds, and ulated in vitro human gut microbiomes reported this has yet to be resolved. It is noteworthy that 32-NF physiologically based pharmacokinetic (PBPK)
From page 40...
... Microbial β-glucuronidases in the gut can thione S-transferases and N-acetyltransferases in cleave the glucuronide conjugate and promote human gut microbiomes, and this finding suggests enterohepatic recirculation of a parent drug mol- a potential for such enzymatic activities (Das et al. ecule.
From page 41...
... Layered on top of developmental events are Recent analyses based on comprehensive studgenetic influences that are the focus of pharma- ies that used RNAseq profiling of the intestinal cogenomicists and their study of people who are epithelium and liver show that the gut microbiota poor, intermediate, extensive, and ultrarapid me- indeed contributes to the development and regutabolizers identified through genetic screens (Ma lation of genes involved in chemical metabolism and Lu 2011)
From page 42...
... . That process from the Human Microbiome Project have begun is critical for regulating bile acid secretion in the to identify microbial gene homologues for major liver and uptake in the ileum that the microbiota families of chemical metabolism enzymes (Saad tightly controls in such a way as to favor optimal et al.
From page 43...
... modulate the pharmacokinetics and metabolism of environmental chemicals generally lags behind REFERENCES that of drugs, there is compelling evidence of gut microbiome involvement in the metabolic trans- Bakke, J.E., J.A. Gustafsson, and B.E.
From page 44...
... 2015. Intestinal transport and testinal microbiota-farnesoid X receptor axis modulates metabolism of bile acids.
From page 45...
... 2013. Xeno biotics shape the physiology and gene expression of the active human gut microbiome.
From page 46...
... 2013. Gut microbiota regulates bile acid me chtenstein, A
From page 47...
... 2016. The microbial pharmacists within us: versible alterations in the mouse distal gut microbiome.
From page 48...
... Anaerobic metabolism of 1-amino-2-naphthol bile acids and gut microbiota and its impact on farnesoid based azo dyes (Sudan dyes) by human intestinal micro X receptor signaling.


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