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Glyphosate has limited short-term effects on commensal bacterial community composition in the gut environment due to sufficient aromatic amino acid levels
2018
Nielsen, Lene Nørby | Roager, Henrik M. | Casas, Mònica Escolà | Frandsen, Henrik L. | Gosewinkel, Ulrich | Bester, Kai | Licht, Tine Rask | Hendriksen, Niels Bohse | Bahl, Martin Iain
Recently, concerns have been raised that residues of glyphosate-based herbicides may interfere with the homeostasis of the intestinal bacterial community and thereby affect the health of humans or animals. The biochemical pathway for aromatic amino acid synthesis (Shikimate pathway), which is specifically inhibited by glyphosate, is shared by plants and numerous bacterial species. Several in vitro studies have shown that various groups of intestinal bacteria may be differently affected by glyphosate. Here, we present results from an animal exposure trial combining deep 16S rRNA gene sequencing of the bacterial community with liquid chromatography mass spectrometry (LC-MS) based metabolic profiling of aromatic amino acids and their downstream metabolites. We found that glyphosate as well as the commercial formulation Glyfonova®450 PLUS administered at up to fifty times the established European Acceptable Daily Intake (ADI = 0.5 mg/kg body weight) had very limited effects on bacterial community composition in Sprague Dawley rats during a two-week exposure trial. The effect of glyphosate on prototrophic bacterial growth was highly dependent on the availability of aromatic amino acids, suggesting that the observed limited effect on bacterial composition was due to the presence of sufficient amounts of aromatic amino acids in the intestinal environment. A strong correlation was observed between intestinal concentrations of glyphosate and intestinal pH, which may partly be explained by an observed reduction in acetic acid produced by the gut bacteria. We conclude that sufficient intestinal levels of aromatic amino acids provided by the diet alleviates the need for bacterial synthesis of aromatic amino acids and thus prevents an antimicrobial effect of glyphosate in vivo. It is however possible that the situation is different in cases of human malnutrition or in production animals.
Mostrar más [+] Menos [-]Exposure to the fungicide propamocarb causes gut microbiota dysbiosis and metabolic disorder in mice
2018
Wu, Sisheng | Jin, Cuiyuan | Wang, Yueyi | Fu, Zhengwei | Jin, Yuanxiang
Propamocarb (PM) is a widely used fungicide with property of affecting fatty acid and phospholipid biosynthesis in funguses. In this study, we explored its effects on mice gut microbiota and metabolism by exposing mice to 3, 30, and 300 mg/L PM through drinking water for a duration of 28 days. We observed that the transcription of hepatic genes related to regulate lipid metabolism were perturbed by PM exposure. The microbiota in the cecal contents and feces changed during or after PM exposure at phylum or genus levels. 16S rRNA gene sequencing for the cecal content revealed shifted in overall microbial structure after PM exposure, and operational taxonomic unit (OTU) analysis indicated that 32.2% of OTUs changed by 300 mg/mL PM exposure for 28 days. In addition, based on 1H NMR analysis,a total of 20 fecal metabolites mainly including succinate, short chain fatty acids, bile acids and trimethylamine were found to be significantly influenced by exposure to 300 mg/L PM.,. These metabolites were tightly correlated to host metabolism. Our findings indicated that high doses of PM exposure could disturb mice metabolism through, or partly through, altering the gut microbiota and microbial metabolites.
Mostrar más [+] Menos [-]Dioxin-like PCB 126 increases intestinal inflammation and disrupts gut microbiota and metabolic homeostasis
2018
Petriello, Michael C. | Hoffman, Jessie B. | Vsevolozhskaya, Olga | Morris, Andrew J. | Hennig, Bernhard
The gut microbiome is sensitive to diet and environmental exposures and is involved in the regulation of host metabolism. Additionally, gut inflammation is an independent risk factor for the development of metabolic diseases, specifically atherosclerosis and diabetes. Exposures to dioxin-like pollutants occur primarily via ingestion of contaminated foods and are linked to increased risk of developing cardiometabolic diseases. We aimed to elucidate the detrimental impacts of dioxin-like pollutant exposure on gut microbiota and host gut health and metabolism in a mouse model of cardiometabolic disease. We utilized 16S rRNA sequencing, metabolomics, and regression modeling to examine the impact of PCB 126 on the microbiome and host metabolism and gut health. 16S rRNA sequencing showed that gut microbiota populations shifted at the phylum and genus levels in ways that mimic observations seen in chronic inflammatory diseases. PCB 126 reduced cecum alpha diversity (0.60 fold change; p = 0.001) and significantly increased the Firmicutes to Bacteroidetes ratio (1.63 fold change; p = 0.044). Toxicant exposed mice exhibited quantifiable concentrations of PCB 126 in the colon, upregulation of Cyp1a1 gene expression, and increased markers of intestinal inflammation. Also, a significant correlation between circulating Glucagon-like peptide-1 (GLP-1) and Bifidobacterium was evident and dependent on toxicant exposure. PCB 126 exposure disrupted the gut microbiota and host metabolism and increased intestinal and systemic inflammation. These data imply that the deleterious effects of dioxin-like pollutants may be initiated in the gut, and the modulation of gut microbiota may be a sensitive marker of pollutant exposures.
Mostrar más [+] Menos [-]PCBs–high-fat diet interactions as mediators of gut microbiota dysbiosis and abdominal fat accumulation in female mice
2018
Chi, Yulang | Lin, Yi | Zhu, Huimin | Huang, Qiansheng | Ye, Guozhu | Dong, Sijun
Polychlorinated biphenyls (PCBs), one type of lipophilic pollutant, are ubiquitous in daily life. PCBs exposure has been implicated in the alterations of gut microbial community which is profoundly associated with diverse metabolic disorders, including obesity. High-fat diet (H) is a dietary pattern characterized by a high percentage of fat. According to the theory that similarities can be easily solvable in each other, PCBs and H exposures are inevitably and objectively coexistent in a real living environment, prompting great concerns about their individual and combined effects on hosts. However, the effects of PCBs-H interactions on gut microbiota and obesity are still incompletely understood. In the present study, the effects of PCBs and/or H on the gut microbiota alteration and obesity risk in mice were examined and the interactions between PCBs and H were investigated. Obtained results showed that PCBs and/or H exposure induced prominent variations in the gut microbiota composition and diversity. Exposure to PCBs also resulted in higher body fat percentage, greater size of abdominal subcutaneous adipocytes and increased expression of proinflammatory cytokines including TNF-α, iNOS and IL-6. Such PCBs-induced changes could be further enhanced upon the co-exposure of H, implying that obese individuals may be vulnerable to PCBs exposure. Taken together, the present study is helpful for a better understanding of the gut microbiota variation influenced by PCBs and/or H exposure, and furthermore, provides a novel insight into the mechanism of PCBs-H interactions on host adiposity.
Mostrar más [+] Menos [-]Gut as a target for cadmium toxicity
2018
Tinkov, Alexey A. | Gritsenko, Viktor A. | Skalnaya, Margarita G. | Cherkasov, Sergey V. | Aaseth, Jan | Skalny, Anatoly V.
The primary objective of the present study was to review the impact of Cd exposure on gut microbiota and intestinal physiology, as well as to estimate whether gut may be considered as the target for Cd toxicity. The review is based on literature search in available databases. The existing data demonstrate that the impact of Cd on gut physiology is two-sided. First, Cd exposure induces a significant alteration of bacterial populations and their relative abundance in gut (increased Bacteroidetes-to-Firmicutes ratio), accompanied by increased lipopolysaccharide (LPS) production, reflecting changed metabolic activity of the intestinal microbiome. Second, in intestinal wall Cd exposure induces inflammatory response and cell damage including disruption of tight junctions, ultimately leading to increased gut permeability. Together with increased LPS production, impaired barrier function causes endotoxinemia and systemic inflammation. Hypothetically, Cd-induced increase gut permeability may also result in increased bacterial translocation. On the one hand, bacteriolysis may be associated with aggravation of endotoxemia. At the same time, together with Cd-induced impairment of macrophage inflammatory response, increased bacterial translocation may result in increased susceptibility to infections. Such a supposition is generally in agreement with the finding of higher susceptibility of Cd-exposed mice to infections. The changed microbiome metabolic activity and LPS-induced systemic inflammation may have a significant impact on target organs. The efficiency of probiotics in at least partial prevention of the local (intestinal) and systemic toxic effects of cadmium confirms the role of altered gut physiology in Cd toxicity. Therefore, probiotic treatment may be considered as the one of the strategies for prevention of Cd toxicity in parallel with chelation, antioxidant, and anti-inflammatory therapy.
Mostrar más [+] Menos [-]Systematic characterization and proposed pathway of tetracycline degradation in solid waste treatment by Hermetia illucens with intestinal microbiota
2018
Cai, Minmin | Ma, Shiteng | Hu, Ruiqi | Tomberlin, Jeffery K. | Yu, Chan | Huang, Yongping | Zhan, Shuai | Li, Wu | Zheng, Longyu | Yu, Ziniu | Zhang, Jibin
Antibiotics can effectively protect livestock from pathogen infection, but residual antibiotics in manure bring risks to ecosystems and public health. Here, we demonstrated that black soldier fly larvae (BSFL) could provide an environmentally friendly manure treatment based on their ability to effectively and rapidly degrade tetracycline (TC). Investigation of the biological mechanisms and degradation pathways of TC by BSFL indicated that nearly 97% of TC was degraded within 12 days in a non-sterile BSFL treatment system, which is up to 1.6-fold faster than that achieved by normal composting. Our results showed that rapid TC-degradation was largely carried out by the intestinal microbiota of the larvae, which doubled the TC-degradation rates compared to those achieved in sterile BSFL systems. This conclusion was further supported by highly-efficient TC-biodegradation both in vivo and in vitro by four larval intestinal isolates. Moreover, detailed microbiome analysis indicated that intestinal bacterial and fungal communities were modified along with significantly increased tet gene copy number in the gut, providing the means to tolerate and degrade TC. Through analysis of TC degradation in vitro, four possible biodegradation products, two hydrolysis products and three conceivable inactivation products were identified, which suggested TC degradation reactions including hydrolysis, oxygenation, deamination, demethylation, ring-cleavage, modification, etc. In conclusion, our studies suggested an estimation of the fate of TC antibiotics in manure treatment by BSFL colonized by gut microbes. These results may provide a strategy for accelerating the degradation of antibiotics by adjusting the intestinal microbiota of BSFL.
Mostrar más [+] Menos [-]Dysbiosis of gut microbiota by chronic coexposure to titanium dioxide nanoparticles and bisphenol A: Implications for host health in zebrafish
2018
Chen, Lianguo | Guo, Yongyong | Hu, Chenyan | Lam, Paul K.S. | Lam, James C.W. | Zhou, Bingsheng
Gut microbiota is of critical relevance to host health. However, toxicological understanding of environmental pollutants on gut microbiota is limited, not to mention their combined effects. In the present study, adult zebrafish (Danio rerio) were exposed to titanium dioxide nanoparticles (nano-TiO₂; 100 μg/L), bisphenol A (BPA; 0, 2, and 20 μg/L) or their binary mixtures for three months. Sequencing of 16S rRNA amplicons found that nano-TiO₂ and BPA coexposure shifted the intestinal microbial community, interacting in an antagonistic manner when the BPA concentration was low but in a synergistic manner at a higher BPA concentration. Sex- and concentration-dependent responses to the coexposure regime were also observed for zebrafish growth and intestinal health (e.g. neurotransmission, epithelial barrier permeability, inflammation, and oxidative stress). Correlation analysis showed that oxidative stress after nano-TiO₂ and BPA coexposure was tightly associated with the imbalanced ratio of pathogenic Lawsonia and normal metabolic Hyphomicrobium, where higher abundance of Lawsonia but lower abundance of Hyphomicrobium were induced concurrently. A positive relationship was observed between zebrafish body weight and the abundance of Bacteroides in the gut, which was also closely associated with the genera of Anaerococcus, Finegoldia, and Peptoniphilus. This study revealed, for the first time, the combined effects of nano-TiO₂ and BPA coexposure on the dynamics of the gut microbiome, which proved to have toxicological implications for zebrafish host health.
Mostrar más [+] Menos [-]Polystyrene microplastics induce microbiota dysbiosis and inflammation in the gut of adult zebrafish
2018
Jin, Yuanxiang | Xia, Jizhou | Pan, Zihong | Yang, Jiajing | Wang, Wenchao | Fu, Zhengwei
Microplastic (MP) are environmental pollutants and have the potential to cause varying degrees of aquatic toxicity. In this study, the effects on gut microbiota of adult male zebrafish exposed for 14 days to 100 and 1000 μg/L of two sizes of polystyrene MP were evaluated. Both 0.5 and 50 μm-diameter spherical polystyrene MP increased the volume of mucus in the gut at a concentration of 1000 μg/L (about 1.456 × 10¹⁰ particles/L for 0.5 μm and 1.456 × 10⁴ particles/L for 50 μm). At the phylum level, the abundance of Bacteroidetes and Proteobacteria decreased significantly and the abundance of Firmicutes increased significantly in the gut after 14-day exposure to 1000 μg/L of both sizes of polystyrene MP. In addition, high throughput sequencing of the 16S rRNA gene V3-V4 region revealed a significant change in the richness and diversity of microbiota in the gut of polystyrene MP-exposed zebrafish. A more in depth analysis, at the genus level, revealed that a total of 29 gut microbes identified by operational taxonomic unit (OTU) analysis were significantly changed in both 0.5 and 50 μm-diameter polystyrene MP-treated groups. Moreover, it was observed that 0.5 μm polystyrene MP not only increased mRNA levels of IL1α, IL1β and IFN but also their protein levels in the gut, indicating that inflammation occurred after polystyrene MP exposure. Our findings suggest that polystyrene MP could induce microbiota dysbiosis and inflammation in the gut of adult zebrafish.
Mostrar más [+] Menos [-]Inhalational exposure to particulate matter air pollution alters the composition of the gut microbiome
2018
Mutlu, Ece A. | Comba, Işın Y. | Cho, Takugo | Engen, Phillip A. | Yazıcı, Cemal | Soberanes, Saul | Hamanaka, Robert B. | Niğdelioğlu, Recep | Meliton, Angelo Y. | Ghio, Andrew J. | Budinger, G.R Scott | Mutlu, Gökhan M.
Recent studies suggest an association between particulate matter (PM) air pollution and gastrointestinal (GI) disease. In addition to direct deposition, PM can be indirectly deposited in oropharynx via mucociliary clearance and upon swallowing of saliva and mucus. Within the GI tract, PM may alter the GI epithelium and gut microbiome. Our goal was to determine the effect of PM on gut microbiota in a murine model of PM exposure via inhalation. C57BL/6 mice were exposed via inhalation to either concentrated ambient particles or filtered air for 8-h per day, 5-days a week, for a total of 3-weeks. At exposure's end, GI tract tissues and feces were harvested, and gut microbiota was analyzed. Alpha-diversity was modestly altered with increased richness in PM-exposed mice compared to air-exposed mice in some parts of the GI tract. Most importantly, PM-induced alterations in the microbiota were very apparent in beta-diversity comparisons throughout the GI tract and appeared to increase from the proximal to distal parts. Changes in some genera suggest that distinct bacteria may have the capacity to bloom with PM exposure. Exposure to PM alters the microbiota throughout the GI tract which maybe a potential mechanism that explains PM induced inflammation in the GI tract.
Mostrar más [+] Menos [-]Environmental concentrations of antibiotics impair zebrafish gut health
2018
Zhou, Li | Limbu, Samwel Mchele | Shen, Meilin | Zhai, Wanying | Qiao, Fang | He, Anyuan | Du, Zhen-Yu | Zhang, Meiling
Antibiotics have been widely used in human and veterinary medicine to both treat and prevent disease. Due to their high water solubility and low bioavailability, many antibiotic residues have been found in aquatic environments. Fish are an indispensable link between the environmental pollution and human health. However, the chronic effects of environmental concentrations of antibiotics in fish have not been thoroughly investigated. Sulfamethoxazole (SMX) and oxytetracycline (OTC) are frequently detected in aquatic environments. In this study, zebrafish were exposed to SMX (260 ng/L) and OTC (420 ng/L) for a six-week period. Results indicated that exposure to antibiotics did not influence weight gain of fish but increased the metabolic rate and caused higher mortality when treated fish were challenged with Aeromonas hydrophila. Furthermore, exposure to antibiotics in water resulted in a significant decrease in intestinal goblet cell numbers, alkaline phosphatase (AKP), acid phosphatase (ACP) activities, and the anti-oxidant response while there was a significant increase in expression of inflammatory factors. Antibiotic exposure also disturbed the intestinal microbiota in the OTC-exposed group. Our results indicated that environmental antibiotic concentrations can impair the gut health of zebrafish. The potential health risk of antibiotic residues in water should be evaluated in the future.
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