Metagenomic and Metabolomic Analysis of the Toxic Effects of Trichloroacetamide-Induced Gut Microbiome and Urine Metabolome Perturbations in Mice

Disinfection byproducts (DBPs) in drinking water have been linked to various diseases, including colon, colorectal, rectal, and bladder cancer. Trichloroacetamide (TCAcAm) is an emerging nitrogenous DBP, and our previous study found that TCAcAm could induce some changes associated with host–gut microbiota co-metabolism. In this study, we used an integrated approach combining metagenomics, based on high-throughput sequencing, and metabolomics, based on nuclear magnetic resonance (NMR), to evaluate the toxic effects of TCAcAm exposure on the gut microbiome and urine metabolome. High-throughput sequencing revealed that the gut microbiome’s composition and function were significantly altered after TCAcAm exposure for 90 days in Mus musculus mice. In addition, metabolomic analysis showed that a number of gut microbiota-related metabolites were dramatically perturbed in the urine of the mice. These results may provide novel insight into evaluating the health risk of environmental pollutants as well as revealing the potential mechanism of TCAcAm’s toxic effects

Correlations of Gut Microbial Community Shift with Hepatic Damage and Growth Inhibition of <i>Carassius auratus</i> Induced by Pentachlorophenol Exposure

Goldfish (<i>Carassius auratus</i>) were exposed to 0–100 μg/L pentachlorophenol (PCP) for 28 days to investigate the correlations of fish gut microbial community shift with the induced toxicological effects. PCP exposure caused accumulation of PCP in the fish intestinal tract in a time- and dose-dependent manner, while hepatic PCP reached the maximal level after a 21 day exposure. Under the relatively higher PCP stress, the fish body weight and liver weight were reduced and hepatic CAT and SOD activities were inhibited, demonstrating negative correlations with the PCP levels in liver and gut content (<i>R</i> < −0.5 and <i>P</i> < 0.05 each). Pyrosequencing of the 16S rRNA gene indicated that PCP exposure increased the abundance of Bacteroidetes in the fish gut. Within the Bacteroidetes phylum, the <i>Bacteroides</i> genus had the highest abundance, which was significantly correlated with PCP exposure dosage and duration (<i>R</i> > 0.5 and <i>P</i> < 0.05 each). Bioinformatic analysis revealed that <i>Bacteroides</i> showed quantitatively negative correlations with <i>Chryseobacterium</i>, <i>Microbacterium</i>, <i>Arthrobacter</i>, and <i>Legionella</i> in the fish gut, and the Bacteroidetes abundance, <i>Bacteroides</i> abundance, and Firmicutes/Bacteroidetes ratio played crucial roles in the reduction of body weight and liver weight under PCP stress. The results may extend our knowledge regarding the roles of gut microbiota in ecotoxicology

Principal coordinate analysis of 11 PWWTP and STP sludge samples based on the percentages of ARG subtypes.

Principal coordinate analysis of 11 PWWTP and STP sludge samples based on the percentages of ARG subtypes.</p

The abundance and diversity of MGEs in PWWTP sludge.

<p>The abundance and diversity of MGEs in PWWTP sludge.</p

Redundancy analysis of the correlation between the percentages of 36 dominant genera with the percentages of eight ARG types in PWWTP sludge.

<p>Arrows represent the seven genera significantly correlated with ARGs distribution (<i>p</i><0.05).</p

Percentage of the predominant ARG subtypes (≥1% in at least one sludge sample) in PWWTP and STP sludge.

<p>Percentage of the predominant ARG subtypes (≥1% in at least one sludge sample) in PWWTP and STP sludge.</p

Abundance of ARGs in the PWWTP and STP sludge samples.

<p>(A) Total abundance of ARGs in the PWWTP and STP sludge. (B) Percentage of the ARG types in the PWWTP and STP sludge. (C) Percentage of resistance mechanisms in the PWWTP and STP sludge.</p

Bacterial community in the PWWTP sludge samples.

<p>(A) Percentages of different phyla in the PWWTP sludge. “Others (1%)” refers to the phyla with abundance <1% in all samples. (B) Percentages of top 10 genera in the PWWTP sludge samples. The asterisks indicate the significant difference with <i>p</i>-value<0.05 between anaerobic and aerobic sludge samples.</p

Treatment processes in the two PWWTPs and the shared ARGs.

<p>(A) The flow charts and sampling sites of the treatment processes in two PWWTPs. The black points in oxidation ditch represent the sampling sites. HA: Hydrolytic Acidification; CASS: Cyclic Activated Sludge System; UBF: Up-flow Blanket Filter; (B) Number of shared ARG subtypes by adjacent treatment systems in two PWWTPs. (C) Percentage of the shared ARGs in the total ARGs.</p