Antiseptic chlorhexidine in activated sludge: Biosorption, antimicrobial susceptibility, and alteration of community structure.

Chlorhexidine (CHX) is a broad-spectrum antimicrobial, which may pose environmental health risks. This study examined the removal potential and the mechanisms regulating the fate of CHX in activated sludge (AS). Bioreactors inoculated with AS removed 74 ±â€¯8% and 81 ±â€¯6% of CHX at steady state while receiving 0.5 and 1 mg/L CHX, respectively. Analysis of the removal pathways showed that biosorption, rather than biological breakdown or other abiotic losses, largely (>70%) regulated the removal of CHX. 16S rRNA gene-based analysis revealed that CHX selected for Luteolibacter (4.3-10.1-fold change) and Runella (6.2-14.1-fold change) with potential multi-drug resistance mechanisms (e.g., efflux pumps). In contrast, it significantly reduced core members (Comamonadaceae and Flavobacteriaceae) of AS, playing a key role in contaminant removal and floc formation directly associated with the performance of WWTPs (e.g., wastewater effluent quality). Antimicrobial susceptibility testing showed that 0.4-1.3 mg/L of CHX can be sublethal to AS. Our work provided new insights into the fate of CHX in urban waste streams and the potential toxicity and effects on the structure and function of AS, which has practical implications for the management of biological WWTPs treating CHX.

Graphene oxide exposure alters gut microbial community composition and metabolism in an in vitro human model.

Graphene oxide (GO) nanomaterials have unique physicochemical properties that make them highly promising for biomedical, environmental, and agricultural applications. There is growing interest in the use of GO and extensive in vitro and in vivo studies have been conducted to assess its nanotoxicity. Although it is known that GO can alter the composition of the gut microbiota in mice and zebrafish, studies on the potential impacts of GO on the human gut microbiome are largely lacking. This study addresses an important knowledge gap by investigating the impact of GO exposure- at low (25 mg/L) and high (250 mg/L) doses under both fed (nutrient rich) and fasted (nutrient deplete) conditions- on the gut microbial communitys' structure and function, using an in vitro model. This model includes simulated oral, gastric, small intestinal phase digestion of GO followed by incubation in a colon bioreactor. 16S rRNA amplicon sequencing revealed that GO exposure resulted in a restructuring of community composition. 25 mg/L GO induced a marked decrease in the Bacteroidota phylum and increased the ratio of Firmicutes to Bacteroidota (F/B). Untargeted metabolomics on the supernatants indicated that 25 mg/L GO impaired microbial utilization and metabolism of substrates (amino acids, carbohydrate metabolites) and reduced production of beneficial microbial metabolites such as 5-hydroxyindole-3-acetic acid and GABA. Exposure to 250 mg/L GO resulted in community composition and metabolome profiles that were very similar to the controls that lacked both GO and digestive enzymes. Differential abundance analyses revealed that 3 genera from the phylum Bacteroidota (Bacteroides, Dysgonomonas, and Parabacteroides) were more abundant after 250 mg/L GO exposure, irrespective of feed state. Integrative correlation network analysis indicated that the phylum Bacteroidota showed strong positive correlations to multiple microbial metabolites including GABA and 3-indoleacetic acid, are much larger number of correlations compared to other phyla. These results show that GO exposure has a significant impact on gut microbial community composition and metabolism at both low and high GO concentrations.

Gut microbial metabolite p-cresol alters biotransformation of bisphenol A: Enzyme competition or gene induction?

Recent studies on pharmaceuticals have revealed the direct and indirect mechanisms that link human gut microbiome to xenobiotic biotransformation. Though environmental contaminants compose a vital portion of xenobiotics and share overlapping biotransformation pathways with gut microbial metabolites, the possible interplay between gut microbiome and biotransformation of environmental contaminants remains obscure. This study utilized bisphenol A (BPA) and p-cresol as model compounds to explore whether gut microbial metabolites could affect environmental phenol metabolism on both in vitro and in vivo models. We have observed some distinct biotransformation behavior, where in vivo mouse examination using 171 & 1972 µg/kg bw p-cresol injection exhibited enhancing effect on BPA metabolism, but p-cresol was found as a strong inhibitor from 10/5 µM in a non-competitive pattern for BPA biotransformation in in vitro models of liver S9 fractions and HepG2 cell line, respectively. A further investigation revealed that the expression of biotransformation enzyme genes including Ugt1a1, Ugt2b1, or Sult1a1 of p-cresol treated mice were dynamically induced. In silico docking approach was also utilized to explore the non-competitive inhibition mechanism by estimating the binding affinity of key enzyme SULT 1A1. Overall, our results provided a novel insight into the biotransformation interaction between gut microbiome and environmental contaminants.

Long-term oxytetracycline exposure potentially alters brain thyroid hormone and serotonin homeostasis in zebrafish.

The impact of oxytetracycline (OTC) exposure in water on the fish still remains unclear. We hypothesized OTC exposure could alter fish gut microbiome and affect thyroid hormone and serotonin homeostasis in the brain via "chemical-gut-brain" axis. Here, ∼2-month-old juvenile zebrafish (Danio rerio) was exposed to two concentrations of OTC (1 and 100 µg/L) for one month until adulthood. Thyroxine-associated gene analysis in the brain revealed that deiodinase 2 (DIO2), deiodinase 3 (DIO3), and thyroid hormone receptor beta (THRß) expression was significantly decreased. Quantification of thyroid hormones showed a decrease in triiodothyronine (T3) under OTC treatment, which agrees with reduced activity of DIO2. For the serotonin (5-HT) synthesis, the expression of tryptophan hydroxylase (TPH2) was 41 % and 9.3 % of the control group for 1 and 100 µg/L OTC exposed groups; respectively. The intestinal 16S rRNA analysis revealed an increased abundance of Fusobacteria and Proteobacteria, while Actinobacteria was decreased significantly. The altered microbial balance between Proteobacteria and Firmicutes have been previously reported to affect nutrient uptakes such as zinc, which can potentially reduce the activity of DIO2. In summary, this study suggests that long-term OTC exposure not only alters gut microbiome but also changes thyroid hormone and serotonin homeostasis.

Low-dose tetracycline exposure alters gut bacterial metabolism and host-immune response: "Personalized" effect?

The human gut microbiome (GM) in healthy people is chronically exposed to tetracycline (TET) via environmental exposure and dietary uptake. However, limited information is available on its effect on the GM metabolome and effect on the host, especially at the dietary exposure level. Here, we investigated how TET at both sub-pharmaceutical and dietary exposure levels affects the metabolome and the secretome-induced host immune response by studying several representative gut bacteria. Interestingly, the metabolome showed a highly species-specific pattern with a distinct dose-response relationship. B. fragilis was highly sensitive to TET and vitamin, nucleotide, and amino acid metabolism pathways were the most vulnerable metabolic pathways at dietary exposure level. For key metabolite short chain fatty acids, TET significantly induced the synthesis of butyrate in B. fragilis, rather than C. sporogenes and E. coli. Furthermore, TET induced the release of lipopolysaccharides (LPS) in E. coli and enhanced the immune response; however, there was no obvious effect on B. fragilis. Interestingly, the overall immune response modulation with TET exposure relied on the ratio between E. coli and B. fragilis, possibly due to the neutralization of active LPS from E. coli by the LPS from B. fragilis. Overall, our results showed that the effect of TET from environmental exposure on the host health would be highly dependent on the GM composition, especially for the gut bacterial metabolome and secretome induced immune response.