Chronic exposure to low concentrations of lead induces metabolic disorder and dysbiosis of the gut microbiota in mice

Xia, Jizhou; Jin, Cuiyuan; Pan, Zihong; Sun, Liwei; Fu, Zhengwei; Jin, Yuanxiang

doi:10.1016/j.scitotenv.2018.03.053

Cited by 140 publications

(50 citation statements)

References 60 publications

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“…Consistent with the results of previous studies, increased levels of SOD and MDA were observed in the zebrafish embryos treated with chromium (Cr) for 96 h in a concentration-dependent manner (3, 10, and 30 µM) [37]. In addition, the mRNA expression of the gene encoding SOD increased after eight-week exposure to Pb salts [2]. We suggest that the elevation of SOD in the zebrafishes' brains after chronic PbCl 2 exposure at a low concentration is a compensatory response of acclimation.…”

Section: Discussionsupporting

confidence: 90%

“…To validate the effect of chronic lead exposure, a variety of animal models have been studied, from a nematode [34], an aquatic model [35], to a rodent model [2]. Lead toxicity is more severe in aquatic animals than in rodents.…”

Section: Discussionmentioning

confidence: 99%

“…However, lead can directly enter aquatic environments from urban sources, including households and waste management and sewage treatment plants. Several studies have reported that lead can cause adverse effects even at a low concentration [1,2]. Dissolved lead concentrations in freshwater and saltwater with chronic effects neurological disorders) expression, increased apoptosis, and altered locomotor behavior in zebrafish embryos and larvae [23].…”

Section: Introductionmentioning

confidence: 99%

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Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Thi

Audira

et al. 2020

IJMS

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Lead and lead-derived compounds have been extensively utilized in industry, and their chronic toxicity towards aquatic animals has not been thoroughly addressed at a behavioral level. In this study, we assessed the risk of exposure to lead at a waterborne environmental concentration in adult zebrafish by behavioral and biochemical analyses. Nine tests, including three-dimension (3D) locomotion, novel tank exploration, mirror biting, predator avoidance, social interaction, shoaling, circadian rhythm locomotor activity, color preference, and a short-term memory test, were performed to assess the behavior of adult zebrafish after the exposure to 50 ppb PbCl 2 for one month. The brain tissues were dissected and subjected to biochemical assays to measure the relative expression of stress biomarkers and neurotransmitters to elucidate the underlying mechanisms for behavioral alterations. The results of the behavioral tests showed that chronic exposure to lead could elevate the stress and anxiety levels characterized by elevated freezing and reduced exploratory behaviors. The chronic exposure to PbCl 2 at a low concentration also induced a sharp reduction of aggressiveness and short-term memory. However, no significant change was found in predator avoidance, social interaction, shoaling, or color preference. The biochemical assays showed elevated cortisol and reduced serotonin and melatonin levels in the brain, thus, altering the behavior of the PbCl 2 -exposed zebrafish. In general, this study determined the potential ecotoxicity of long-term lead exposure in adult zebrafish through multiple behavioral assessments. The significant findings were that even at a low concentration, long-term exposure to lead could impair the memory and cause a decrease in the aggressiveness and exploratory activities of zebrafish, which may reduce their survival fitness.(EC10/NOEC-usually more than 14 days) on fish range from 18 to 1559 µg/L and 44 to 437 µg/L, respectively [3,4].More evidence has shown the detrimental impacts of lead on human health, especially at a neurobehavioral level. The neurotoxicity of chronic exposure to low concentrations of lead can impair cognitive performance in childhood through to adulthood [5][6][7][8][9]. Some studies demonstrated the correlation between the exposure to lead at low concentrations and attention-deficit/hyperactivity disorder (ADHD) in children [10]. The development of the central nervous system can be disrupted when children are exposed to low concentrations of lead for a long period of time (blood lead level below 10 mg/dL) [11]. Therefore, lead toxicity has become a serious issue for human health and environmental protection [6]. According to previous studies, the effect of lead on the nervous system includes the disruption of key molecules during neuronal migration and differentiation, interference with synapse formation mediated by a reduction in neuronal sialic acid production and premature differentiation of glial cells, interference with neurotransmitter release, and disruption of the...

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Thi

Audira

et al. 2020

IJMS

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ Metals such as As, Cd, and Cu, as well as excessive amounts of Zn, have been proven to reduce community diversity in previous studies 23,33,34 . Although no effect on α-diversity has been found, Pb was shown to change complexity (β-diversity) in an animal study 35 . However, the results of single exposure in the present study were different from those of previous studies.…”

Section: Discussionmentioning

confidence: 77%

Long-term metal exposure changes gut microbiota of residents surrounding a mining and smelting area

Shao

Zhu

2020

Sci Rep

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In this epidemiologic study, 16 S rRNA sequencing was used to investigate the changes of diversity and composition profile of gut microbiota resulting from long-term exposure to multiple metals, including arsenic (As), cadmium (Cd), cuprum (Cu), lead (Pb), and zinc (Zn). Due to long-term exposure to various metals, the relative abundances of Lachnospiraceae, Eubacterium eligens, Ruminococcaceae UGG-014, Erysipelotrichaceae UCG-003, Tyzzerella 3, Bacteroides, Slackia, italics, and Roseburia were found to become much higher, whereas the abundance of Prevotella 9 presented an opposite trend. Additionally, differences between males and female groups were found, such as the greater richness and evenness of bacteria for men subjected to long-term metal exposure in polluted areas. The changes of men's microbiomes were more significant as a result of higher daily intake, mining and smelting activity, and living habits. This research presents a new theoretical basis for the correlation between long-term metal exposure and gut health for people living in contaminated areas. Recently, the entire gut microecosystem has begun to be regarded as an essential organ in the human body 1. The intestinal microbiome plays an important role, and the microorganisms contained in the microbiome are vast in number, consisting of populations of up to 100 trillion 2. The intestinal microbiome has been proven to be profoundly responsible for maintaining human health, such as energy metabolism, environmental adaptation, immune adjustment, and even brain functions 3-5. In addition, some related metabolic diseases (obesity, cirrhosis, hypertension, etc.) have been associated with the changed structure of the microbiome 6-8. The daily diet is the most critical factor in maintaining the symbiotic relationship between intestinal flora and the host throughout the host's life 9. An epidemiologic study has confirmed that gut microbiota can respond to various dietary styles. Rural children who consumed low-sugar, high-fiber diets were found to have higher microbial richness and biodiversity compared with European children 10. Healey et al. have also found inter-individual variability in gut microbiota response to dietary interventions 11. Some other influencing factors include age, sex, and exercise, as well as prebiotic and probiotic agents 12-14. 16 S ribosomal RNA (rRNA) gene sequence analysis has been widely used to identify bacterial species and perform taxonomy, and massively parallel sequencing (MPS) is also commonly utilized 15. There are nine "hypervariable regions" (V1-V9) in the sequence that can show considerable sequence diversity and are regarded as diagnostic assays for different bacteria 16. Dethlefsen et al. 17 determined the pervasive effects of antibiotics on gut microbiota by tag pyrosequencing of the 16 S rRNA V3 region. By pyrosequencing over 40,000 16 S rRNA gene V4 region amplicons per subject, links between health conditions and intestinal microbiota in elderly Irish subjects were reported 18. Additionally, the V3-V4 regions o...

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“…According to previous studies, continuous exposure to Pb is a risk factor in nephrotoxicity and reproductive, behavioral dysfunctions, and even changed the gut microbiota . Considered the main detoxification organ, the liver is responsible for the absorption, degradation, and metabolism of exogenous chemicals including heavy metals.…”

Section: Introductionmentioning

confidence: 99%

Chronic exposure to low doses of Pb induces hepatotoxicity at the physiological, biochemical, and transcriptomic levels of mice

Luo

Shen

Zhou

et al. 2019

Environmental Toxicology

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Lead (Pb), a non-essential heavy metal, is a major global environmental contaminant with serious toxicological consequences. In the present study, the effects on hepatotoxicity of mice with chronic exposure to low doses of Pb were evaluated. While oral exposure to 0.03 or 0.1 mg/L Pb for 15 weeks in male adult mice had no significant effect on body weights, Pb exposure resulted in liver histopathological effects and increase of hepatic activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). In addition, hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) significantly accumulated after treatment. Conversely, glutathione (GSH) decreased significantly in both 0.03 and 0.1 mg/L Pb-treated groups. Moreover, the hepatic activities of superoxide dismutase 1 (SOD) and catalase (CAT) increased significantly following treatment with 0.1 mg/L Pb for 15 weeks, concomitant with increases in transcriptions of hepatic Sod, Cat, and Gpx. Furthermore, transcriptions of hepatic metallothionein (MT), zinc transporter 5 (Znt5) and copper transporter 1 (Ctr1), and subsequent protein levels were also increased in liver of mice when exposed to 0.1 mg/L Pb for 15 weeks. In addition, the transcriptome data showed that Pb has substantial influence on several pathways, including PPAR signaling pathways, AMPK signaling pathways, fatty acid metabolism, and drug metabolism. Our data suggested that chronic Pb exposure could induce hepatotoxicity at the physiological, biochemical, and transcriptomic levels in mice. K E Y W O R D Shepatotoxicity, oxidative stress, gene expression, Pb

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Chronic exposure to low concentrations of lead induces metabolic disorder and dysbiosis of the gut microbiota in mice

Cited by 140 publications

References 60 publications

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

Long-term metal exposure changes gut microbiota of residents surrounding a mining and smelting area

Chronic exposure to low doses of Pb induces hepatotoxicity at the physiological, biochemical, and transcriptomic levels of mice

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