Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice
Growing evidence indicates that exposure to high levels of nitrite for a prolonged time has adverse health effects. Although gut microbiota is responsible for the transformation of nitrite in the gut, the evidence concerning whether gut microbiota mediates the toxicity of nitrite is still lacking. T...
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Elsevier
2022-02-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322000641 |
| _version_ | 1819294649248907264 |
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| author | Jing Xu Mingzhu Wang Qiuping Liu Xiaoying Lin Kefeng Pu Zhixing He |
| author_facet | Jing Xu Mingzhu Wang Qiuping Liu Xiaoying Lin Kefeng Pu Zhixing He |
| author_sort | Jing Xu |
| collection | DOAJ |
| description | Growing evidence indicates that exposure to high levels of nitrite for a prolonged time has adverse health effects. Although gut microbiota is responsible for the transformation of nitrite in the gut, the evidence concerning whether gut microbiota mediates the toxicity of nitrite is still lacking. The present study addressed the long-term effects of dietary nitrite on male C57BL/6 mice and employed fecal microbiota transplantation (FMT) to reveal whether gut microbiota mediated the effects of nitrite. Furthermore, the effect of azoxymethane (AOM) on gut microbiota was detected for mice drinking normal or nitrite-containing water. High nitrite had toxic effects on C57BL/6 mice. Meanwhile, high nitrite induced skin lesions in mice, accompanied with increased serum ALT, colon IL-6, TNF-α, and MDA levels, together with decreased serum Cr, colon sIgA, and T-AOC levels. After fecal microbiota was transplanted into the normal mice, the nitrite-regulated gut microbiota could also induce skin lesions, coupled with reduced serum Cr, and increased colon MDA. The high dose of nitrite caused the upregulations of Alistipes, Prevotella, and Ruminococcus, which could be transplanted into normal mice through FMT. Inversely, gut microbiota from normal mice reduced the effects of nitrite on serum ALT and Cr, together with colon sIgA and MDA. Gut microbiota from normal mice could also upregulate metabolic genes and downregulate stress genes in the nitrite-treated mice. It might due to the upregulation of Akkermansia and Parabacteroides caused by FMT from normal water-treated mice to nitrite-treated mice. In addition, AOM exhibited to be more toxic to the colon in the nitrite-treated mice in comparison with normal water-treated mice, and it might be due to the expression of Hspa1a and Hspa1b in the colon. Interestingly, gut microbiota was more influenced by AOM in the normal water-treated mice than the nitrite-treated mice. Overall, these data demonstrated that gut microbiota mediated the toxicity of a high concentration of dietary nitrite. |
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| format | Article |
| id | doaj.art-692758a647ae43248ef217175f258a35 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-24T04:29:40Z |
| publishDate | 2022-02-01 |
| publisher | Elsevier |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-692758a647ae43248ef217175f258a352022-12-21T17:15:28ZengElsevierEcotoxicology and Environmental Safety0147-65132022-02-01231113224Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 miceJing Xu0Mingzhu Wang1Qiuping Liu2Xiaoying Lin3Kefeng Pu4Zhixing He5Department of Radiation Oncology, The Second Affiliated Hospital and Cancer Institute, Zhejiang University School of Medicine, Hangzhou 310009, ChinaInstitute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaInstitute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaInstitute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaNano-Bio-Chem Centre, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China; Correspondence to: Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.Institute of Basic Research in Clinical Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China; Corresponding author.Growing evidence indicates that exposure to high levels of nitrite for a prolonged time has adverse health effects. Although gut microbiota is responsible for the transformation of nitrite in the gut, the evidence concerning whether gut microbiota mediates the toxicity of nitrite is still lacking. The present study addressed the long-term effects of dietary nitrite on male C57BL/6 mice and employed fecal microbiota transplantation (FMT) to reveal whether gut microbiota mediated the effects of nitrite. Furthermore, the effect of azoxymethane (AOM) on gut microbiota was detected for mice drinking normal or nitrite-containing water. High nitrite had toxic effects on C57BL/6 mice. Meanwhile, high nitrite induced skin lesions in mice, accompanied with increased serum ALT, colon IL-6, TNF-α, and MDA levels, together with decreased serum Cr, colon sIgA, and T-AOC levels. After fecal microbiota was transplanted into the normal mice, the nitrite-regulated gut microbiota could also induce skin lesions, coupled with reduced serum Cr, and increased colon MDA. The high dose of nitrite caused the upregulations of Alistipes, Prevotella, and Ruminococcus, which could be transplanted into normal mice through FMT. Inversely, gut microbiota from normal mice reduced the effects of nitrite on serum ALT and Cr, together with colon sIgA and MDA. Gut microbiota from normal mice could also upregulate metabolic genes and downregulate stress genes in the nitrite-treated mice. It might due to the upregulation of Akkermansia and Parabacteroides caused by FMT from normal water-treated mice to nitrite-treated mice. In addition, AOM exhibited to be more toxic to the colon in the nitrite-treated mice in comparison with normal water-treated mice, and it might be due to the expression of Hspa1a and Hspa1b in the colon. Interestingly, gut microbiota was more influenced by AOM in the normal water-treated mice than the nitrite-treated mice. Overall, these data demonstrated that gut microbiota mediated the toxicity of a high concentration of dietary nitrite.http://www.sciencedirect.com/science/article/pii/S0147651322000641NitriteGut microbiotaFecal microbiota transplantationToxicityAzoxymethane |
| spellingShingle | Jing Xu Mingzhu Wang Qiuping Liu Xiaoying Lin Kefeng Pu Zhixing He Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice Ecotoxicology and Environmental Safety Nitrite Gut microbiota Fecal microbiota transplantation Toxicity Azoxymethane |
| title | Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice |
| title_full | Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice |
| title_fullStr | Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice |
| title_full_unstemmed | Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice |
| title_short | Gut microbiota mediated the toxicity of high concentration of dietary nitrite in C57BL/6 mice |
| title_sort | gut microbiota mediated the toxicity of high concentration of dietary nitrite in c57bl 6 mice |
| topic | Nitrite Gut microbiota Fecal microbiota transplantation Toxicity Azoxymethane |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322000641 |
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