Login Register Cart 0
Generic placeholder image

Current Genomics

Editor-in-Chief

ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Genomic and Metagenomic Insights into the Distribution of Nicotine-degrading Enzymes in Human Microbiota

Author(s): Ying Guan, Zhouhai Zhu, Qiyuan Peng, Meng Li, Xuan Li, Jia-Wei Yang, Yan-Hong Lu, Meng Wang and Bin-Bin Xie*

Volume 25, Issue 3, 2024

Published on: 20 March, 2024

Page: [226 - 235] Pages: 10

DOI: 10.2174/0113892029302230240319042208

Price: $65

Abstract

Introduction: Nicotine degradation is a new strategy to block nicotine-induced pathology. The potential of human microbiota to degrade nicotine has not been explored.

Aims: This study aimed to uncover the genomic potentials of human microbiota to degrade nicotine.

Method: To address this issue, we performed a systematic annotation of Nicotine-Degrading Enzymes (NDEs) from genomes and metagenomes of human microbiota. A total of 26,295 genomes and 1,596 metagenomes for human microbiota were downloaded from public databases and five types of NDEs were annotated with a custom pipeline. We found 959 NdhB, 785 NdhL, 987 NicX, three NicA1, and three NicA2 homologs.

Results: Genomic classification revealed that six phylum-level taxa, including Proteobacteria, Firmicutes, Firmicutes_A, Bacteroidota, Actinobacteriota, and Chloroflexota, can produce NDEs, with Proteobacteria encoding all five types of NDEs studied. Analysis of NicX prevalence revealed differences among body sites. NicX homologs were found in gut and oral samples with a high prevalence but not found in lung samples. NicX was found in samples from both smokers and non-smokers, though the prevalence might be different.

Conclusion: This study represents the first systematic investigation of NDEs from the human microbiota, providing new insights into the physiology and ecological functions of human microbiota and shedding new light on the development of nicotine-degrading probiotics for the treatment of smoking-related diseases.

« Previous
Graphical Abstract

[1]
Hoffmann, D.; Hoffmann, I. Letters to the Editor - Tobacco smoke components. Beitr. Tabforsch. Int., 1998, 18(1), 49-52.
[http://dx.doi.org/10.2478/cttr-2013-0668]
[2]
Thielen, A.; Klus, H.; Müller, L. Tobacco smoke: Unraveling a controversial subject. Exp. Toxicol. Pathol., 2008, 60(2-3), 141-156.
[http://dx.doi.org/10.1016/j.etp.2008.01.014] [PMID: 18485684]
[3]
Borgerding, M.; Klus, H. Analysis of complex mixtures – Cigarette smoke. Exp. Toxicol. Pathol., 2005, 57(Suppl. 1), 43-73.
[http://dx.doi.org/10.1016/j.etp.2005.05.010] [PMID: 16092717]
[4]
Talhout, R.; Schulz, T.; Florek, E.; Van Benthem, J.; Wester, P.; Opperhuizen, A. Hazardous compounds in tobacco smoke. Int. J. Environ. Res. Public Health, 2011, 8(2), 613-628.
[http://dx.doi.org/10.3390/ijerph8020613] [PMID: 21556207]
[5]
WHO global report on trends in prevalence of tobacco use 2000-2025, 4th ed; World Health Organization: Geneva, 2021.
[6]
Xue, S.; Schlosburg, J.E.; Janda, K.D. A new strategy for smoking cessation: Characterization of a bacterial enzyme for the degradation of nicotine. J. Am. Chem. Soc., 2015, 137(32), 10136-10139.
[http://dx.doi.org/10.1021/jacs.5b06605] [PMID: 26237398]
[7]
Dulchavsky, M.; Clark, C.T.; Bardwell, J.C.A.; Stull, F. A cytochrome c is the natural electron acceptor for nicotine oxidoreductase. Nat. Chem. Biol., 2021, 17(3), 344-350.
[http://dx.doi.org/10.1038/s41589-020-00712-3] [PMID: 33432238]
[8]
Chen, B.; Sun, L.; Zeng, G.; Shen, Z.; Wang, K.; Yin, L.; Xu, F.; Wang, P.; Ding, Y.; Nie, Q.; Wu, Q.; Zhang, Z.; Xia, J.; Lin, J.; Luo, Y.; Cai, J.; Krausz, K.W.; Zheng, R.; Xue, Y.; Zheng, M.H.; Li, Y.; Yu, C.; Gonzalez, F.J.; Jiang, C. Gut bacteria alleviate smoking-related NASH by degrading gut nicotine. Nature, 2022, 610(7932), 562-568.
[http://dx.doi.org/10.1038/s41586-022-05299-4] [PMID: 36261549]
[9]
Zhang, Z.; Mei, X.; He, Z.; Xie, X.; Yang, Y.; Mei, C.; Xue, D.; Hu, T.; Shu, M.; Zhong, W. Nicotine metabolism pathway in bacteria: Mechanism, modification, and application. Appl. Microbiol. Biotechnol., 2022, 106(3), 889-904.
[http://dx.doi.org/10.1007/s00253-022-11763-y] [PMID: 35072735]
[10]
Mu, Y.; Chen, Q.; Parales, R.E.; Lu, Z.; Hong, Q.; He, J.; Qiu, J.; Jiang, J. Bacterial catabolism of nicotine: Catabolic strains, pathways and modules. Environ. Res., 2020, 183, 109258.
[http://dx.doi.org/10.1016/j.envres.2020.109258] [PMID: 32311908]
[11]
Grether-Beck, S.; Igloi, G.L.; Pust, S.; Schilz, E.; Decker, K.; Brandsch, R. Structural analysis and molybdenum-dependent expression of the pAO1-encoded nicotine dehydrogenase genes of Arthrobacter nicotinovorans. Mol. Microbiol., 1994, 13(5), 929-936.
[http://dx.doi.org/10.1111/j.1365-2958.1994.tb00484.x] [PMID: 7815950]
[12]
Baitsch, D.; Sandu, C.; Brandsch, R.; Igloi, G.L. Gene cluster on pAO1 of Arthrobacter nicotinovorans involved in degradation of the plant alkaloid nicotine: Cloning, purification, and characterization of 2,6-dihydroxypyridine 3-hydroxylase. J. Bacteriol., 2001, 183(18), 5262-5267.
[http://dx.doi.org/10.1128/JB.183.18.5262-5267.2001] [PMID: 11514508]
[13]
Tang, H.; Wang, L.; Meng, X.; Ma, L.; Wang, S.; He, X.; Wu, G.; Xu, P. Novel nicotine oxidoreductase-encoding gene involved in nicotine degradation by Pseudomonas putida strain S16. Appl. Environ. Microbiol., 2009, 75(3), 772-778.
[http://dx.doi.org/10.1128/AEM.02300-08] [PMID: 19060159]
[14]
Tang, H.; Wang, L.; Wang, W.; Yu, H.; Zhang, K.; Yao, Y.; Xu, P. Systematic unraveling of the unsolved pathway of nicotine degradation in Pseudomonas. PLoS Genet., 2013, 9(10), e1003923.
[http://dx.doi.org/10.1371/journal.pgen.1003923] [PMID: 24204321]
[15]
Huang, H.; Yu, W.; Wang, R.; Li, H.; Xie, H.; Wang, S. Genomic and transcriptomic analyses of Agrobacterium tumefaciens S33 reveal the molecular mechanism of a novel hybrid nicotine-degrading pathway. Sci. Rep., 2017, 7(1), 4813.
[http://dx.doi.org/10.1038/s41598-017-05320-1] [PMID: 28684751]
[16]
Gevers, D.; Knight, R.; Petrosino, J.F.; Huang, K.; McGuire, A.L.; Birren, B.W.; Nelson, K.E.; White, O.; Methé, B.A.; Huttenhower, C. The Human Microbiome Project: A community resource for the healthy human microbiome. PLoS Biol., 2012, 10(8), e1001377.
[http://dx.doi.org/10.1371/journal.pbio.1001377] [PMID: 22904687]
[17]
Escapa, I.F.; Chen, T.; Huang, Y.; Gajare, P.; Dewhirst, F.E.; Lemon, K.P. New insights into human nostril microbiome from the expanded human oral microbiome database (eHOMD): A resource for the microbiome of the human aerodigestive tract. mSystems, 2018, 3(6), e00187-18.
[http://dx.doi.org/10.1128/mSystems.00187-18] [PMID: 30534599]
[18]
Kim, CY; Lee, M; Yang, S; Kim, K; Yong, D; Kim, HR; Lee, I Human reference gut microbiome catalog including newly assembled genomes from under-represented Asian metagenomes. Genome Med., 2021, 13(1), 134.
[http://dx.doi.org/10.1186/s13073-021-00950-7]
[19]
Lin, X.; Hu, T.; Chen, J.; Liang, H.; Zhou, J.; Wu, Z.; Ye, C.; Jin, X.; Xu, X.; Zhang, W.; Jing, X.; Yang, T.; Wang, J.; Yang, H.; Kristiansen, K.; Xiao, L.; Zou, Y. The genomic landscape of reference genomes of cultivated human gut bacteria. Nat. Commun., 2023, 14(1), 1663.
[http://dx.doi.org/10.1038/s41467-023-37396-x] [PMID: 36966151]
[20]
Liu, C.; Du, M.X.; Abuduaini, R.; Yu, H.Y.; Li, D.H.; Wang, Y.J.; Zhou, N.; Jiang, M.Z.; Niu, P.X.; Han, S.S.; Chen, H.H.; Shi, W.Y.; Wu, L.; Xin, Y.H.; Ma, J.; Zhou, Y.; Jiang, C.Y.; Liu, H.W.; Liu, S.J. Enlightening the taxonomy darkness of human gut microbiomes with a cultured biobank. Microbiome, 2021, 9(1), 119.
[http://dx.doi.org/10.1186/s40168-021-01064-3] [PMID: 34020714]
[21]
Browne, H.P.; Forster, S.C.; Anonye, B.O.; Kumar, N.; Neville, B.A.; Stares, M.D.; Goulding, D.; Lawley, T.D. Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature, 2016, 533(7604), 543-546.
[http://dx.doi.org/10.1038/nature17645] [PMID: 27144353]
[22]
Richardson, L.; Allen, B.; Baldi, G.; Beracochea, M.; Bileschi, M.L.; Burdett, T.; Burgin, J.; Caballero-Pérez, J.; Cochrane, G.; Colwell, L.J.; Curtis, T.; Escobar-Zepeda, A.; Gurbich, T.A.; Kale, V.; Korobeynikov, A.; Raj, S.; Rogers, A.B.; Sakharova, E.; Sanchez, S.; Wilkinson, D.J.; Finn, R.D. MGnify: The microbiome sequence data analysis resource in 2023. Nucleic Acids Res., 2023, 51(D1), D753-D759.
[http://dx.doi.org/10.1093/nar/gkac1080] [PMID: 36477304]
[23]
Almeida, A.; Nayfach, S.; Boland, M.; Strozzi, F.; Beracochea, M.; Shi, Z.J.; Pollard, K.S.; Sakharova, E.; Parks, D.H.; Hugenholtz, P.; Segata, N.; Kyrpides, N.C.; Finn, R.D. A unified catalog of 204,938 reference genomes from the human gut microbiome. Nat. Biotechnol., 2021, 39(1), 105-114.
[http://dx.doi.org/10.1038/s41587-020-0603-3] [PMID: 32690973]
[24]
Integrative, H.M.P. The integrative human microbiome project. Nature, 2019, 569(7758), 641-648.
[http://dx.doi.org/10.1038/s41586-019-1238-8]
[25]
Wang, P.; Dong, Y.; Jiao, J.; Zuo, K.; Han, C.; Zhao, L.; Ding, S.; Yang, X.; Chen, M.; Li, J. Cigarette smoking status alters dysbiotic gut microbes in hypertensive patients. J. Clin. Hypertens. (Greenwich), 2021, 23(7), 1431-1446.
[http://dx.doi.org/10.1111/jch.14298] [PMID: 34029428]
[26]
Mas-Lloret, J.; Obón-Santacana, M.; Ibáñez-Sanz, G.; Guinó, E.; Pato, M.L.; Rodriguez-Moranta, F.; Mata, A.; García-Rodríguez, A.; Moreno, V.; Pimenoff, V.N. Gut microbiome diversity detected by high-coverage 16S and shotgun sequencing of paired stool and colon sample. Sci. Data, 2020, 7(1), 92.
[http://dx.doi.org/10.1038/s41597-020-0427-5] [PMID: 32179734]
[27]
Zhang, X.; Zhang, D.; Jia, H.; Feng, Q.; Wang, D.; Liang, D.; Wu, X.; Li, J.; Tang, L.; Li, Y.; Lan, Z.; Chen, B.; Li, Y.; Zhong, H.; Xie, H.; Jie, Z.; Chen, W.; Tang, S.; Xu, X.; Wang, X.; Cai, X.; Liu, S.; Xia, Y.; Li, J.; Qiao, X.; Al-Aama, J.Y.; Chen, H.; Wang, L.; Wu, Q.; Zhang, F.; Zheng, W.; Li, Y.; Zhang, M.; Luo, G.; Xue, W.; Xiao, L.; Li, J.; Chen, W.; Xu, X.; Yin, Y.; Yang, H.; Wang, J.; Kristiansen, K.; Liu, L.; Li, T.; Huang, Q.; Li, Y.; Wang, J. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat. Med., 2015, 21(8), 895-905.
[http://dx.doi.org/10.1038/nm.3914] [PMID: 26214836]
[28]
Ren, L.; Zhang, R.; Rao, J.; Xiao, Y.; Zhang, Z.; Yang, B.; Cao, D.; Zhong, H.; Ning, P.; Shang, Y.; Li, M.; Gao, Z.; Wang, J. Transcriptionally active lung microbiome and its association with bacterial biomass and host inflammatory status. mSystems, 2018, 3(5), e00199-18.
[http://dx.doi.org/10.1128/mSystems.00199-18] [PMID: 30417108]
[29]
Zheng, L.; Sun, R.; Zhu, Y.; Li, Z.; She, X.; Jian, X.; Yu, F.; Deng, X.; Sai, B.; Wang, L.; Zhou, W.; Wu, M.; Li, G.; Tang, J.; Jia, W.; Xiang, J. Lung microbiome alterations in NSCLC patients. Sci. Rep., 2021, 11(1), 11736.
[http://dx.doi.org/10.1038/s41598-021-91195-2] [PMID: 34083661]
[30]
Feigelman, R.; Kahlert, C.R.; Baty, F.; Rassouli, F.; Kleiner, R.L.; Kohler, P.; Brutsche, M.H.; von Mering, C. Sputum DNA sequencing in cystic fibrosis: Non-invasive access to the lung microbiome and to pathogen details. Microbiome, 2017, 5(1), 20.
[http://dx.doi.org/10.1186/s40168-017-0234-1] [PMID: 28187782]
[31]
Ma, Y.; Zhang, Y.; Jiang, H.; Xiang, S.; Zhao, Y.; Xiao, M.; Du, F.; Ji, H.; Kaboli, P.J.; Wu, X.; Li, M.; Wen, Q.; Shen, J.; Yang, Z.; Li, J.; Xiao, Z. Metagenome analysis of intestinal bacteria in healthy people, patients with inflammatory bowel disease and colorectal cancer. Front. Cell. Infect. Microbiol., 2021, 11, 599734.
[http://dx.doi.org/10.3389/fcimb.2021.599734] [PMID: 33738265]
[32]
Bolger, A.M.; Lohse, M.; Usadel, B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics, 2014, 30(15), 2114-2120.
[http://dx.doi.org/10.1093/bioinformatics/btu170] [PMID: 24695404]
[33]
Li, D.; Luo, R.; Liu, C.M.; Leung, C.M.; Ting, H.F.; Sadakane, K.; Yamashita, H.; Lam, T.W. MEGAHIT v1.0: A fast and scalable metagenome assembler driven by advanced methodologies and community practices. Methods, 2016, 102, 3-11.
[http://dx.doi.org/10.1016/j.ymeth.2016.02.020] [PMID: 27012178]
[34]
Zhu, W.; Lomsadze, A.; Borodovsky, M. Ab initio gene identification in metagenomic sequences. Nucleic Acids Res., 2010, 38(12), e132.
[http://dx.doi.org/10.1093/nar/gkq275] [PMID: 20403810]
[35]
Buchfink, B.; Reuter, K.; Drost, H.G. Sensitive protein alignments at tree-of-life scale using DIAMOND. Nat. Methods, 2021, 18(4), 366-368.
[http://dx.doi.org/10.1038/s41592-021-01101-x] [PMID: 33828273]
[36]
Nakamura, T.; Yamada, K.D.; Tomii, K.; Katoh, K. Parallelization of MAFFT for large-scale multiple sequence alignments. Bioinformatics, 2018, 34(14), 2490-2492.
[http://dx.doi.org/10.1093/bioinformatics/bty121] [PMID: 29506019]
[37]
Price, M.N.; Dehal, P.S.; Arkin, A.P. FastTree 2--approximately maximum-likelihood trees for large alignments. PLoS One, 2010, 5(3), e9490.
[http://dx.doi.org/10.1371/journal.pone.0009490] [PMID: 20224823]
[38]
Chaumeil, P.A.; Mussig, A.J.; Hugenholtz, P.; Parks, D.H. GTDB-Tk: A toolkit to classify genomes with the Genome Taxonomy Database. Bioinformatics, 2020, 36(6), 1925-1927.
[http://dx.doi.org/10.1093/bioinformatics/btz848] [PMID: 31730192]
[39]
Parks, D.H.; Chuvochina, M.; Rinke, C.; Mussig, A.J.; Chaumeil, P.A.; Hugenholtz, P. GTDB: An ongoing census of bacterial and archaeal diversity through a phylogenetically consistent, rank normalized and complete genome-based taxonomy. Nucleic Acids Res., 2022, 50(D1), D785-D794.
[http://dx.doi.org/10.1093/nar/gkab776] [PMID: 34520557]
[40]
Hall, T.A. BioEdit: A user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp. Ser., 1999, 41, 95-98.
[41]
Tamura, K.; Stecher, G.; Kumar, S. MEGA11: Molecular evolutionary genetics analysis version 11. Mol. Biol. Evol., 2021, 38(7), 3022-3027.
[http://dx.doi.org/10.1093/molbev/msab120] [PMID: 33892491]
[42]
Jumper, J.; Evans, R.; Pritzel, A.; Green, T.; Figurnov, M.; Ronneberger, O.; Tunyasuvunakool, K.; Bates, R.; Žídek, A.; Potapenko, A.; Bridgland, A.; Meyer, C.; Kohl, S.A.A.; Ballard, A.J.; Cowie, A.; Romera-Paredes, B.; Nikolov, S.; Jain, R.; Adler, J.; Back, T.; Petersen, S.; Reiman, D.; Clancy, E.; Zielinski, M.; Steinegger, M.; Pacholska, M.; Berghammer, T.; Bodenstein, S.; Silver, D.; Vinyals, O.; Senior, A.W.; Kavukcuoglu, K.; Kohli, P.; Hassabis, D. Highly accurate protein structure prediction with AlphaFold. Nature, 2021, 596(7873), 583-589.
[http://dx.doi.org/10.1038/s41586-021-03819-2] [PMID: 34265844]
[43]
Liu, J.; Ma, G.; Chen, T.; Hou, Y.; Yang, S.; Zhang, K.Q.; Yang, J. Nicotine-degrading microorganisms and their potential applications. Appl. Microbiol. Biotechnol., 2015, 99(9), 3775-3785.
[http://dx.doi.org/10.1007/s00253-015-6525-1] [PMID: 25805341]
[44]
EFSA Panel on Dietetic Products. Scientific Opinion on the safety of ‘heat-treated milk products fermented with Bacteroides xylanisolvens DSM 23964’ as a novel food. EFSA J., 2015, 13(1), 3956.
[http://dx.doi.org/10.2903/j.efsa.2015.3956]
[45]
Liu, X.; Mao, B.; Gu, J.; Wu, J.; Cui, S.; Wang, G.; Zhao, J.; Zhang, H.; Chen, W. Blautia —a new functional genus with potential probiotic properties? Gut Microbes, 2021, 13(1), 1875796.
[http://dx.doi.org/10.1080/19490976.2021.1875796] [PMID: 33525961]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy