With the extensive production and use of various chemicals, emerging pollutants including environmental endocrine disrupting chemicals, perfluoro chemicals, antibiotics, and microplastics have been continuously entering the environment, and spread to water through multiple pathways. The pollution of these emerging pollutants raised continuous concerns for the safety of drinking water, threating the ecological environment and human health. In combination with international research progress, we discussed in detail about pollution, source, and risk assessment of emerging pollutants in drinking water. We further suggested and prospected the challenge of environmental management of emerging pollutants. This review could promote the public's understanding of emerging pollutants, and provide theoretical support for risk prevention and treatment of emerging pollutants in drinking water.
Discharged wastewater treatment plant (WWTP) effluents can contaminate receiving water bodies with human feces and alter the abundance of antibiotic resistance genes (ARGs). In this study, we examined the co-occurrence of ARGs, human fecal pollution indicator crAssphage, and antibiotics in human feces and a series of connected receiving water bodies affected by human feces, including water from different treatment units of a WWTP, river, lake, and tap waters. Results showed that crAssphage was detected in 68.2 % of the studied water bodies, confirming widespread human fecal contamination. Both ARG and crAssphage abundances exhibited a distance-decay effect from the emission source to the receiving environment. Interestingly, the detected ARG abundance in the water bodies was significantly correlated with crAssphage abundance but not with the residual antibiotic concentration, demonstrating that the presence of ARG could largely be explained by the extent of fecal pollution, with no clear signs of antibiotic selection. In addition, 14 ARGs co-shared by human feces and water bodies were significantly correlated with crAssphage. Furthermore, a close evolutionary relationship was observed between the blaTEM-1 gene from human feces and aquatic environments. These results imply a potential ARG exchange between human feces and receiving water bodies. Overall, this study provides important insights into the distribution and sources of ARGs in water bodies affected by human fecal contamination.
Background: ALKBH5 belongs to the ALKB family consists of a Fe (II) and a-ketoglutarate-dependent dioxygenase. ALKBH5 directly catalyzes the oxidative demethylation of m6A-methylated adenosine. ALKBH5 involves in tumorigenesis and tumor progression, and is often dysregulated in a wide range of cancers, including colorectal cancer. Emerging evidence indicates that the expression of ALKBH5 is associated with the abundance of infiltrating immune cells in the microenvironment. However, how ALKBH5 affects immune cell infiltration in the microenvironment in colorectal cancer (CRC) has not been reported. The aim of this study was to identify how the expression of ALKBH5 affects the biological behaviors of CRC cell lines and regulates the effects on infiltrating CD8(+) T cells in CRC microenvironment with its specific mechanism.Methods: Firstly, the transcriptional expression profiles of CRC were downloaded from TCGA database and integrated via R software (4.1.2). Between CRC and normal colorectal tissues, ALKBH5 mRNA expressions were compared (Wilcoxon rank-sum). We further identified the expression levels of ALKBH5 in CRC tissues and cell lines through quantitative PCR, western blot, and immunohistochemistry. Then, how ALKBH5 affects the biological behaviors of CRC cells were confirmed by gain- and loss-of-function analysis. Furthermore, the relationship between ALKBH5 level and 22 tumor-infiltrating immune cells was examined through CIBERSORT in R software. Furthermore, we explored the correlation between ALKBH5 expression and tumor-infiltrated CD8(+), CD4(+) and regulatory T cells by utilizing the TIMER database. Finally, the association between chemokines and CD8(+) T cells infiltration in CRC was analyzed using GEPIA online database. qRT-PCR, WB and IHC were used to further determine the effect of ALKBH5 on NF-?B-CCL5 signaling axis and CD8(+) T cells infiltration.Results: Clinically, ALKBH5 expression was downregulated in CRC and low levels of ALKBH5 expression were correlated with poor overall survival (OS). Functionally, overexpression of ALKBH5 reduced the proliferation, migration and invasion of CRC cells, and vice versa. Overexpression of ALKBH5 suppresses NF-?B pathway, thus reduces CCL5 expression and promotes CD8(+) T cells infiltration in CRC microenvironment.Conclusions: ALKBH5 is poorly expressed in CRC, and overexpression of ALKBH5 attenuates CRC malignant progression by inhibiting CRC cell proliferation, migration, invasion and promoting CD8(+) T cells infiltration in the tumor microenvironment through NF-?B-CCL5 axis.
Antibiotics ingested in the human gut may create selective pressure to change the composition of the gut microbiota, which could adversely effect the immune system of the host. However, the occurrence and distribution of antibiotics in the human gut remains unclear. A total population of 180 individuals, across three Chinses regions with different economic development levels, including children, adults, and elders, were sampled in 2017. A total of 19 representative antibiotics, including both clinical and veterinary antibiotics, were investigated in human faeces. While clinical use and prescriptions were the main exposure pathways for children, environmental media were the exposure pathway to adults. In addition, significant differences (P < 0.05) in antibiotic residues in human faeces were observed amongst various economic development levels, where human faeces from underdeveloped areas were mostly associated with higher levels of antibiotics. This study first to investigate the occurrence and distribution of typical antibiotics in the faeces of a Chinese population and thereby provide a reference for the intensive study of the effects and mechanisms of antibiotics on human gut microbiota.
Human gut microbiota is the reservoir of antibiotic resistance genes (ARGs) and it plays an important role to human health. The abuse of antibiotics is still severe at present, which further aggravates the spread of ARGs. Bacterial resistance seriously affects human health, food safety and ecological safety, and pathogens carrying ARGs pose a great threat to clinical treatment. In combination with the research progress in China and abroad, this paper discussed in detail about gut resistome from the aspects including the composition, origin, propagation and evolution. In addition, the research methods of human gut resistome and the future prospect were summarized. This study could promote the public’s understanding of gut resistome and provide theoretical support for rational use of antibiotics.
The usages of antibiotics in treating the pathogenic infections could alter the gut microbiome and associated resistome, causing long term adverse impact on human health. In this study, mice were treated with human-simulated regimen 25.0 mg kg(-1) of amoxicillin for seven days, and their gut microbiota and resistome were characterized using the 16S rRNA amplicons sequencing and the high-throughput qPCR, respectively. Meanwhile, the flora restorations after individual applications of inulin, Bifidobacterium longum (B. longum), and fecal microbiota transplantation (FMT) were analyzed for up to 35 days. The results revealed the prolonged negative impact of single course AMX exposure on mice gut microbiota and resistome. To be specific, pathobionts of Klebsiella and Escherichia-Shigella were significantly enriched, while prebiotics of Bifidobacterium and Lactobacillus were dramatically depleted. Furthermore, beta-lactam resistance genes and efflux resistance genes were obviously enriched after amoxicillin exposure. Compared to B. longum, FMT and inulin were demonstrated to preferably restore the gut microbiota via reconstituting microbial community and stimulating specific prebiotic respectively. Such variation of microbiome caused their distinct alleviations on resistome alteration. Inulin earned the greatest elimination on AMX induced ARG abundance and diversity enrichment. FMT and B. longum caused remove of particular ARGs such as ndm-1, blaPER. Network analysis revealed that most of the ARGs were prone to be harbored by Firmicutes and Proteobacteria. In general, gut resistome shift was partly associated with the changing bacterial community structures and transposase and integron. Taken together, these results demonstrated the profound disruption of gut microbiota and resistome after single-course amoxicillin treatment and different restoration by inulin, B. longum and FMT. (C) 2020 Elsevier Ltd. All rights reserved.
Antibiotics treatment could cause the dysbiosis of human intestinal microbiota and antibiotic resistome. Fecal microbiota transplantation (FMT) has been an efficacious treatment to restore the dysbiosis of intestinal microbiota in a variety of intestinal diseases. However, to data, the effect of the combinatorial antibiotic treatment on microbiota, antibiotic resistome and the FMT for restoration affected by combinatorial antibiotic exposure in the human intestinal microbiota remain unclear. In this study, we systematically investigated the effect of the colistin and amoxicillin combinatorial exposure in the simulator of the human intestinal microbial ecosystem (SHIME) and found that this combinatorial exposure significantly altered (p < 0.05) the human intestinal microbiota and antibiotic resistome. The shift of bacterial community and antibiotic resistome could incompletely recovery to baseline by FMT treatment after combinatorial antibiotic exposure. Additionally, the variance of antibiotic resistome was dominantly driven by the bacterial community (41.18%-68.03%) after the combinatorial antibiotic exposure. Overall, this study first to investigate the influence of the colistin and amoxicillin combinatorial exposure on the intestinal microbiota and antibiotic resistome, and assess the FMT recovery in the simulated human intestinal microbiota, which may potentially provide a correct administration of antibiotics and application of FMT in the clinic.
Human gut microbiota is an important reservoir of antibiotic resistance genes (ARGs). Although dysbacteriosis after the antibiotic course has been previously observed in the patient guts, a comprehensive comparison of gut resistomes, microbiota and antibiotic residues in healthy individuals and patients undergoing antibiotic administration is little. Using high-throughput qPCR, 16S rRNA gene amplicon sequencing and UPLC-MS/MS, we systematically examined the antibiotic resistome, gut microbiota, and antibiotic residues in fecal samples from both Chinese healthy individuals and patients receiving antibiotic therapy. Compared with healthy individuals, patients' guts harbored lower diverse gut resistome and microbiota, but higher concentrations of antibiotics and ARGs. Antibiotic concentration in human guts was positively correlated with ARG total abundance, but was negatively related to the diversity of both ARGs and bacterial communities, which demonstrated that antibiotic administration could shape the antibiotic resistomes and bacterial communities in the patient guts. Gene cfxA was evaluated as a potential biomarker to distinguish the patients receiving antibiotic therapy from the healthy individuals in China since its wide detection and significant enrichment in the guts of the patients. The detection of some veterinary antibiotics in human guts illustrated the potential transmission of antibiotic from the external environment to human via the food chain. The obtained results could help to better understand the influence of antibiotic therapy in shaping antibiotic reistomes and bacterial communities in Chinese individuals.