Food Chemicals Disrupt Human Gut Microbiota Activity And Impact Intestinal Homeostasis As Revealed By In Vitro Systems

Clémence Defois, Jérémy Ratel, Ghislain Garrait, Sylvain Denis, Olivier Le Goff, Jérémie Talvas, Pascale Mosoni, Erwan Engel, Pierre Peyret, Clémence Defois, Jérémy Ratel, Ghislain Garrait, Sylvain Denis, Olivier Le Goff, Jérémie Talvas, Pascale Mosoni, Erwan Engel, Pierre Peyret

Abstract

Growing evidence indicates that the human gut microbiota interacts with xenobiotics, including persistent organic pollutants and foodborne chemicals. The toxicological relevance of the gut microbiota-pollutant interplay is of great concern since chemicals may disrupt gut microbiota functions, with a potential impairment of host homeostasis. Herein we report within batch fermentation systems the impact of food contaminants (polycyclic aromatic hydrocarbons, polychlorobiphenyls, brominated flame retardants, dioxins, pesticides and heterocyclic amines) on the human gut microbiota by metatranscriptome and volatolome i.e. "volatile organic compounds" analyses. Inflammatory host cell response caused by microbial metabolites following the pollutants-gut microbiota interaction, was evaluated on intestinal epithelial TC7 cells. Changes in the volatolome pattern analyzed via solid-phase microextraction coupled to gas chromatography-mass spectrometry mainly resulted in an imbalance in sulfur, phenolic and ester compounds. An increase in microbial gene expression related to lipid metabolism processes as well as the plasma membrane, periplasmic space, protein kinase activity and receptor activity was observed following dioxin, brominated flame retardant and heterocyclic amine exposure. Conversely, all food contaminants tested induced a decreased in microbial transcript levels related to ribosome, translation and nucleic acid binding. Finally, we demonstrated that gut microbiota metabolites resulting from pollutant disturbances may promote the establishment of a pro-inflammatory state in the gut, as stated with the release of cytokine IL-8 by intestinal epithelial cells.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Transcript levels related to microbial GO slim terms that were up and downregulated after the 24 hr of pollutant exposure. Analysis was performed on the pooled rRNA-depleted RNA arising from five technical replicates. Variations are expressed as the Z-Score. Lines represent GO slim terms, columns represent pollutant samples.
Figure 2
Figure 2
Transcript levels related to microbial GO slim terms that were up and downregulated after the 24 hr of pollutant exposure. Variations are expressed as the log2 of the pollutant and the vehicle CPM abundance ratio (y-axis). Analysis was performed on the pooled rRNA-depleted RNA arising from five technical replicates. GO slim terms are represented on the x-axis. GO: gene ontology.
Figure 3
Figure 3
Differentially expressed microbial genes after the 24 hr of pollutant exposure. (A) Number of differentially expressed genes. (B) Mean abundances in CPM of the differentially expressed genes. Analysis was performed on the pooled rRNA-depleted RNA arising from five technical replicates. Only genes with at least a 3-fold change are represented, and values were derived from a comparison between the pollutant and the vehicle condition.
Figure 4
Figure 4
Microbial genes specifically induced by pollutants after the 24 hr of exposure. (A) Number of pollutant-specific genes shared between each couple of pollutants. (B) Representation of the core pollutant-specific genes. Analysis was performed on the pooled rRNA-depleted RNA arising from five technical replicates.
Figure 5
Figure 5
Percentage of necrotic and apoptotic TC7 cells after 4 hr of FDS and microbiota-free medium exposure. Values are the mean of the three replicates ± SEM. Significant variations were assessed using the Mann-Whitney test (p-value 

Figure 6

IL-8 release in the TC7…

Figure 6

IL-8 release in the TC7 cell culture supernatants. TC7 cells were exposed to…

Figure 6
IL-8 release in the TC7 cell culture supernatants. TC7 cells were exposed to FDS and microbiota-free medium for 4 hr. Values represent the mean of three replicates ± SEM. Significant variations were assessed using the Mann-Whitney test (p-value 
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Figure 6
Figure 6
IL-8 release in the TC7 cell culture supernatants. TC7 cells were exposed to FDS and microbiota-free medium for 4 hr. Values represent the mean of three replicates ± SEM. Significant variations were assessed using the Mann-Whitney test (p-value 

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