Prior exposure to ciprofloxacin disrupts intestinal homeostasis and predisposes ayu (<i>Plecoglossus altivelis</i>) to subsequent <i>Pseudomonas plecoglossicida</i>-induced infection

Xiang-Yu Wu; Jin-Bo Xiong; Chen-Jie Fei; Ting Dai; Ting-Fang Zhu; Zi-Yue Zhao; Jing Pan; Li Nie; Jiong Chen

doi:10.24272/j.issn.2095-8137.2022.159

Volume 43 Issue 4

Jul. 2022

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Article Navigation > Zoological Research > 2022 > 43(4): 648-665

Xiang-Yu Wu, Jin-Bo Xiong, Chen-Jie Fei, Ting Dai, Ting-Fang Zhu, Zi-Yue Zhao, Jing Pan, Li Nie, Jiong Chen. Prior exposure to ciprofloxacin disrupts intestinal homeostasis and predisposes ayu (Plecoglossus altivelis) to subsequent Pseudomonas plecoglossicida-induced infection. Zoological Research, 2022, 43(4): 648-665. doi: 10.24272/j.issn.2095-8137.2022.159

Citation:

Xiang-Yu Wu, Jin-Bo Xiong, Chen-Jie Fei, Ting Dai, Ting-Fang Zhu, Zi-Yue Zhao, Jing Pan, Li Nie, Jiong Chen. Prior exposure to ciprofloxacin disrupts intestinal homeostasis and predisposes ayu (Plecoglossus altivelis) to subsequent Pseudomonas plecoglossicida-induced infection. Zoological Research, 2022, 43(4): 648-665. doi: 10.24272/j.issn.2095-8137.2022.159

Citation:

Xiang-Yu Wu, Jin-Bo Xiong, Chen-Jie Fei, Ting Dai, Ting-Fang Zhu, Zi-Yue Zhao, Jing Pan, Li Nie, Jiong Chen. Prior exposure to ciprofloxacin disrupts intestinal homeostasis and predisposes ayu (Plecoglossus altivelis) to subsequent Pseudomonas plecoglossicida-induced infection. Zoological Research, 2022, 43(4): 648-665. doi: 10.24272/j.issn.2095-8137.2022.159

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Prior exposure to ciprofloxacin disrupts intestinal homeostasis and predisposes ayu (Plecoglossus altivelis) to subsequent Pseudomonas plecoglossicida-induced infection

doi: 10.24272/j.issn.2095-8137.2022.159

Xiang-Yu Wu^{1, 2, 3, #},
Jin-Bo Xiong^{1, 2, 3, #},
Chen-Jie Fei^{1, 2, 3},
Ting Dai^{1, 2, 3},
Ting-Fang Zhu^{1, 2, 3},
Zi-Yue Zhao^{1, 2, 3},
Jing Pan^{1, 2, 3},
Li Nie^{1, 2, 3
,
,},
Jiong Chen^{1, 2, 3
,
,}

1.
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Ningbo University, Ningbo, Zhejiang 315211, China
2.
Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Meishan Campus, Ningbo University, Ningbo, Zhejiang 315211, China
3.
Collaborative Innovation Center for Zhejiang Marine High-Efficiency and Healthy Aquaculture, School of Marine Sciences, Ningbo University, Ningbo, Zhejiang 315211, China

#Authors contributed equally to this work

Funds: This work was supported by the Key Research and Development Project of Zhejiang Province (2021C02062), National Natural Science Foundation of China (32173004, 31972821), Natural Science Foundation of Zhejiang Province (LZ18C190001), Natural Science Foundation of Ningbo City (202003N4011), and Research Project of State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products (2010DS700124-ZZ2008)

More Information

Corresponding author: E-mail: nieli@nbu.edu.cn; chenjiong@nbu.edu.cn
Received Date: 2022-06-06
Accepted Date: 2022-07-01

Published Online: 2022-07-04

Publish Date: 2022-07-18

Abstract

Abstract

With the rapid development of intensive farming, the aquaculture industry uses a great many antibiotics for the prevention and treatment of bacterial diseases. Despite their therapeutic functions, the overuse and accumulation of antibiotics also pose a threat to aquaculture organisms. In the present study, ayu (Plecoglossus altivelis) was used as a fish model to study the impacts of ciprofloxacin (CIP) overuse on intestinal homeostasis and immune response during subsequent Pseudomonas plecoglossicida infection. Based on 16S rRNA gene amplification and Illumina sequencing, we found that CIP pre-exposure caused significant variation in intestinal microbiota, including increased species richness, altered microbiota composition and interaction networks, and increased metabolic dysfunction. Furthermore, immunohistochemical analysis indicated that CIP pre-exposure resulted in severe mucosal layer damage, goblet cell reduction, and epithelial cell necrosis of the intestinal barrier in infected ayu. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that disruption of intestinal homeostasis impaired systemic anti-infection immune responses in the intestine, gill, spleen, and head kidney, while inhibiting IL-1β, TNF-α, and IL-10 expression and promoting TGF-β expression. Our findings indicated that CIP administration can directly affect intestinal microbiota composition and intestinal integrity in ayu fish. This perturbation of intestinal homeostasis is likely responsible for the lower survival rate of hosts following subsequent infection as the capacity to mount an effective immune response is compromised. This study also provides preliminary clues for understanding the effects of antibiotic overuse on higher vertebrates through trophic transfer.
- Ciprofloxacin,
- Microbiota,
- Intestinal barrier,
- Immune responses,
- Ayu

#Authors contributed equally to this work

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References(97)

References

[1]	Andriyanto S, Aryati Y, Sumiati T, Lusiastuti AM, Nurhidayat, Kurniawan K, et al. 2022. The potential roles of gut microbiome in modulating the immune response of Asian Redtail catfish (Hemibagrus nemurus) vaccinated with Aeromonas hydrophila. HAYATI Journal of Biosciences, 29(3): 266−278.
[2]	Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, et al. 2013. T_reg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature, 500(7461): 232−236. doi: 10.1038/nature12331
[3]	Baker-Austin C, Oliver JD, Alam M, Ali A, Waldor MK, Qadri F, et al. 2018. Vibrio spp. infections. Nature Reviews Disease Primers, 4(1): 1−19.
[4]	Banerjee S, Walder F, Büchi L, Meyer M, Held AY, Gattinger A, et al. 2019. Agricultural intensification reduces microbial network complexity and the abundance of keystone taxa in roots. The ISME Journal, 13(7): 1722−1736. doi: 10.1038/s41396-019-0383-2
[5]	Bastian M, Heymann S, Jacomy M. 2009. Gephi: an open source software for exploring and manipulating networks. In: Proceedings of the 3rd International AAAI Conference on Web and Social Media. San Jose: AIAA, 361−362.
[6]	Belkaid Y, Hand TW. 2014. Role of the microbiota in immunity and inflammation. Cell, 157(1): 121−141. doi: 10.1016/j.cell.2014.03.011
[7]	Bhavani S, Kaviarasu D, Uma A, Saravanan S, Gopalakannan A. 2022. Antibiotic Use in Aquaculture and Their Impact on the Aquatic Environment. Biotica Research Today, 4(3): 167−172.
[8]	Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, et al. 2019. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nature Biotechnology, 37(8): 852−857. doi: 10.1038/s41587-019-0209-9
[9]	Booth A, Aga DS, Wester AL. 2020. Retrospective analysis of the global antibiotic residues that exceed the predicted no effect concentration for antimicrobial resistance in various environmental matrices. Environment International, 141: 105796. doi: 10.1016/j.envint.2020.105796
[10]	Caporaso JG, Bittinger K, Bushman FD, Desantis TZ, Andersen GL, Knight R. 2010. PyNAST: a flexible tool for aligning sequences to a template alignment. Bioinformatics, 26(2): 266−267. doi: 10.1093/bioinformatics/btp636
[11]	Carlson JM, Leonard AB, Hyde ER, Petrosino JF, Primm TP. 2017. Microbiome disruption and recovery in the fish Gambusia affinis following exposure to broad-spectrum antibiotic. Infection and Drug Resistance, 10: 143−154. doi: 10.2147/IDR.S129055
[12]	Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT, Schmidt TM, et al. 2008. Decreased diversity of the fecal microbiome in recurrent Clostridium difficile—associated diarrhea. The Journal of Infectious Diseases, 197(3): 435−438. doi: 10.1086/525047
[13]	Csardi G, Nepusz T. 2006. The igraph software package for complex network research. InterJournal, Complex Systems, 1695(5): 1−9.
[14]	Dai WF, Sheng ZL, Chen J, Xiong JB. 2020. Shrimp disease progression increases the gut bacterial network complexity and abundances of keystone taxa. Aquaculture, 517: 734802. doi: 10.1016/j.aquaculture.2019.734802
[15]	Duan H, Yu LL, Tian FW, Zhai QX, Fan LP, Chen W. 2022. Antibiotic-induced gut dysbiosis and barrier disruption and the potential protective strategies. Critical Reviews in Food Science and Nutrition, 62(6): 1427−1452. doi: 10.1080/10408398.2020.1843396
[16]	Early GJ, Seifried SE. 2012. Risk factors for community-associated Staphylococcus aureus skin infection in children of Maui. Hawai'i Journal of Medicine & Public Health, 71(8): 218−223.
[17]	Ebert I, Bachmann J, Kühnen U, Küster A, Kussatz C, Maletzki D, et al. 2011. Toxicity of the fluoroquinolone antibiotics enrofloxacin and ciprofloxacin to photoautotrophic aquatic organisms. Environmental Toxicology and Chemistry, 30(12): 2786−2792. doi: 10.1002/etc.678
[18]	Edgar RC. 2010. Search and clustering orders of magnitude faster than BLAST. Bioinformatics, 26(19): 2460−2461. doi: 10.1093/bioinformatics/btq461
[19]	Edgar RC, Haas BJ, Clemente JC, Quince C, Knight R. 2011. UCHIME improves sensitivity and speed of chimera detection. Bioinformatics, 27(16): 2194−2200. doi: 10.1093/bioinformatics/btr381
[20]	Effler P, Ieong MC, Kimura A, Nakata M, Burr R, Cremer E, et al. 2001. Sporadic Campylobacter jejuni infections in Hawaii: associations with prior antibiotic use and commercially prepared chicken. The Journal of Infectious Diseases, 183(7): 1152−1155. doi: 10.1086/319292
[21]	El-Noby GA, Hassanin M, El-Hady M, Aboshabana S. 2021. Streptococcus: a review article on an emerging pathogen of farmed fishes. Egyptian Journal of Aquatic Biology and Fisheries, 25(1): 123−139. doi: 10.21608/ejabf.2021.138469
[22]	Fick J, Söderström H, Lindberg RH, Phan C, Tysklind M, Larsson DGJ. 2009. Contamination of surface, ground, and drinking water from pharmaceutical production. Environmental Toxicology and Chemistry, 28(12): 2522−2527. doi: 10.1897/09-073.1
[23]	Gao PF, Ma C, Sun Z, Wang LF, Huang S, Su XQ, et al. 2017. Feed-additive probiotics accelerate yet antibiotics delay intestinal microbiota maturation in broiler chicken. Microbiome, 5(1): 91. doi: 10.1186/s40168-017-0315-1
[24]	Girardi C, Greve J, Lamshöft M, Fetzer I, Miltner A, Schäffer A, et al. 2011. Biodegradation of ciprofloxacin in water and soil and its effects on the microbial communities. Journal of Hazardous Materials, 198: 22−30. doi: 10.1016/j.jhazmat.2011.10.004
[25]	Gradel KO, Dethlefsen C, Ejlertsen T, Schønheyder HC, Nielsen H. 2008. Increased prescription rate of antibiotics prior to non-typhoid Salmonella infections: a one-year nested case-control study. Scandinavian Journal of Infectious Diseases, 40(8): 635−641. doi: 10.1080/00365540801961248
[26]	Guan YJ, Jia J, Wu L, Xue X, Zhang G, Wang ZZ. 2018. Analysis of bacterial community characteristics, abundance of antibiotics and antibiotic resistance genes along a pollution gradient of Ba River in Xi’an, China. Frontiers in Microbiology, 9: 3191. doi: 10.3389/fmicb.2018.03191
[27]	Gupta S, Fernandes J, Kiron V. 2019. Antibiotic-induced perturbations are manifested in the dominant intestinal bacterial phyla of Atlantic salmon. Microorganisms, 7(8): 233. doi: 10.3390/microorganisms7080233
[28]	Hagan T, Cortese M, Rouphael N, Boudreau C, Linde C, Maddur MS, et al. 2019. Antibiotics-driven gut microbiome perturbation alters immunity to vaccines in humans. Cell, 178(6): 1313−1328.e13. doi: 10.1016/j.cell.2019.08.010
[29]	Harrell Jr FE, Harrell Jr MFE. 2019. Package ‘hmisc’. In: CRAN2018. 235−236.
[30]	He XT, Deng MC, Wang Q, Yang YT, Yang YF, Nie XP. 2016. Residues and health risk assessment of quinolones and sulfonamides in cultured fish from Pearl River Delta, China. Aquaculture, 458: 38−46. doi: 10.1016/j.aquaculture.2016.02.006
[31]	Huang LX, Zhao LM, Su YQ, Yan QP. 2018. Genome sequence of Pseudomonas plecoglossicida strain NZBD9. Genome Announcements, 6(4): e01412−17.
[32]	Huang ZJ, Zeng SZ, Xiong JB, Hou DW, Zhou RJ, Xing CG, et al. 2020. Microecological Koch’s postulates reveal that intestinal microbiota dysbiosis contributes to shrimp white feces syndrome. Microbiome, 8(1): 32. doi: 10.1186/s40168-020-00802-3
[33]	Ilhan ZE, Łaniewski P, Tonachio A, Herbst-Kralovetz MM. 2020. Members of Prevotella genus distinctively modulate innate immune and barrier functions in a human three-dimensional endometrial epithelial cell model. The Journal of Infectious Diseases, 222(12): 2082−2092. doi: 10.1093/infdis/jiaa324
[34]	Jalili V, Afgan E, Gu Q, Clements D, Blankenberg D, Goecks J, et al. 2020. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2020 update. Nucleic Acids Research, 48(W1): W395−W402. doi: 10.1093/nar/gkaa434
[35]	Ji SK, Jiang T, Yan H, Guo CY, Liu JJ, Su HW, et al. 2018. Ecological restoration of antibiotic-disturbed gastrointestinal microbiota in foregut and hindgut of cows. Frontiers in Cellular and Infection Microbiology, 8: 79. doi: 10.3389/fcimb.2018.00079
[36]	Jiang HY, Zhang DD, Xiao SC, Geng C, Zhang X. 2013. Occurrence and sources of antibiotics and their metabolites in river water, WWTPs, and swine wastewater in Jiulongjiang River basin, South China. Environmental Science and Pollution Research, 20(12): 9075−9083. doi: 10.1007/s11356-013-1924-2
[37]	Kayani MUR, Yu K, Qiu Y, Shen Y, Gao C, Feng R, et al. 2021. Environmental concentrations of antibiotics alter the zebrafish gut microbiome structure and potential functions. Environmental Pollution, 278: 116760. doi: 10.1016/j.envpol.2021.116760
[38]	Kelly KR, Brooks BW. 2018. Global aquatic hazard assessment of ciprofloxacin: exceedances of antibiotic resistance development and ecotoxicological thresholds. Progress in Molecular Biology and Translational Science, 159: 59−77.
[39]	Klein EY, Van Boeckel TP, Martinez EM, Pant S, Gandra S, Levin SA, et al. 2018. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proceedings of the National Academy of Sciences of the United States of America, 115(15): E3463−E3470.
[40]	Krawczyk B, Wityk P, Gałęcka M, Michalik M. 2021. The many faces of Enterococcus spp. —Commensal, probiotic and opportunistic pathogen. Microorganisms, 9(9): 1900. doi: 10.3390/microorganisms9091900
[41]	Kümmerer K, Al-Ahmad A, Mersch-Sundermann V. 2000. Biodegradability of some antibiotics, elimination of the genotoxicity and affection of wastewater bacteria in a simple test. Chemosphere, 40(7): 701−710. doi: 10.1016/S0045-6535(99)00439-7
[42]	Lakshmanan AP, Al Za’abi M, Ali BH, Terranegra A. 2021. The influence of the prebiotic gum acacia on the intestinal microbiome composition in rats with experimental chronic kidney disease. Biomedicine & Pharmacotherapy, 133: 110992.
[43]	Langille MGI, Zaneveld J, Caporaso JG, Mcdonald D, Knights D, Reyes JA, et al. 2013. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nature Biotechnology, 31(9): 814−821. doi: 10.1038/nbt.2676
[44]	Li CH, Chen J, Nie L, Chen J. 2020a. MOSPD2 is a receptor mediating the LEAP-2 effect on monocytes/macrophages in a teleost, Boleophthalmus pectinirostris. Zoological Research, 41(6): 644−655. doi: 10.24272/j.issn.2095-8137.2020.211
[45]	Li HZ, Li N, Wang JJ, Li H, Huang X, Guo L, et al. 2020b. Dysbiosis of gut microbiome affecting small intestine morphology and immune balance: a rhesus macaque model. Zoological Research, 41(1): 20−31. doi: 10.24272/j.issn.2095-8137.2020.004
[46]	Limbu SM, Zhou L, Sun SX, Zhang ML, Du ZY. 2018. Chronic exposure to low environmental concentrations and legal aquaculture doses of antibiotics cause systemic adverse effects in Nile tilapia and provoke differential human health risk. Environment International, 115: 205−219. doi: 10.1016/j.envint.2018.03.034
[47]	Lin YH, Tai CC, Brož V, Tang CK, Chen P, Wu CP, et al. 2020. Adenosine receptor modulates permissiveness of baculovirus (budded virus) infection via regulation of energy metabolism in Bombyx mori. Frontiers in Immunology, 11: 763.
[48]	Liu X, Steele JC, Meng XZ. 2017. Usage, residue, and human health risk of antibiotics in Chinese aquaculture: a review. Environmental Pollution, 223: 161−169. doi: 10.1016/j.envpol.2017.01.003
[49]	Lu JQ, Zhang XC, Qiu QF, Chen J, Xiong JB. 2020. Identifying potential polymicrobial pathogens: moving beyond differential abundance to driver taxa. Microbial Ecology, 80(2): 447−458. doi: 10.1007/s00248-020-01511-y
[50]	MacDonald TM, Beardon PHG, McGilchrist MM, Duncan ID, McKendrick AD, Mcdevitt DG. 1993. The risks of symptomatic vaginal candidiasis after oral antibiotic therapy. QJM:An International Journal of Medicine, 86(7): 419−424.
[51]	Magoč T, Salzberg SL. 2011. FLASH: fast length adjustment of short reads to improve genome assemblies. Bioinformatics, 27(21): 2957−2963. doi: 10.1093/bioinformatics/btr507
[52]	Malik U, Armstrong D, Ashworth M, Dregan A, L’esperance V, Mcdonnell L, et al. 2018. Association between prior antibiotic therapy and subsequent risk of community-acquired infections: a systematic review. Journal of Antimicrobial Chemotherapy, 73(2): 287−296. doi: 10.1093/jac/dkx374
[53]	Marker LM, Hammer AS, Andresen L, Isaack P, Clausen T, Byskov K, et al. 2017. Short-term effect of oral amoxicillin treatment on the gut microbial community composition in farm mink (Neovison vison). FEMS Microbiology Ecology, 93(7): fix092.
[54]	Martin-Gallausiaux C, Béguet-Crespel F, Marinelli L, Jamet A, Ledue F, Blottière HM, et al. 2018. Butyrate produced by gut commensal bacteria activates TGF-beta1 expression through the transcription factor SP1 in human intestinal epithelial cells. Scientific Reports, 8(1): 9742. doi: 10.1038/s41598-018-28048-y
[55]	McCabe RP, Secrist H, Botney M, Egan M, Peters MG. 1993. Cytokine mRNA expression in intestine from normal and inflammatory bowel disease patients. Clinical Immunology and Immunopathology, 66(1): 52−58. doi: 10.1006/clin.1993.1007
[56]	McVernon J, Andrews N, Slack M, Moxon R, Ramsay M. 2008. Host and environmental factors associated with Hib in England, 1998–2002. Archives of Disease in Childhood, 93(8): 670−675. doi: 10.1136/adc.2006.097501
[57]	Mu CL, Yang YX, Yu KF, Yu M, Zhang CJ, Su Y, et al. 2017. Alteration of metabolomic markers of amino-acid metabolism in piglets with in-feed antibiotics. Amino Acids, 49(4): 771−781. doi: 10.1007/s00726-017-2379-4
[58]	Neal RK, Brij OS, Slack BCR, Hawkey JC, Logan RFA. 1994. Recent treatment with H₂ antagonists and antibiotics and gastric surgery as risk factors for Salmonella infection. BMJ, 308(6922): 176. doi: 10.1136/bmj.308.6922.176
[59]	Nie L, Zhou QJ, Qiao Y, Chen J. 2017. Interplay between the gut microbiota and immune responses of ayu (Plecoglossus altivelis) during Vibrio anguillarum infection. Fish & Shellfish Immunology, 68: 479−487.
[60]	Nouws JFM, Grondel JL, Schutte AR, Laurensen J. 1988. Pharmacokinetics of ciprofloxacin in carp, African catfish and rainbow trout. Veterinary Quarterly, 10(3): 211−216. doi: 10.1080/01652176.1988.9694173
[61]	Oksanen J, Blanchet FG, Kindt R, Legendre P, Minchin PR, O’hara R, et al. 2013. Package ‘vegan’. Community Ecology Package, Version, 2(9): 1−295.
[62]	Pavia AT, Shipman LD, Wells JG, Puhr ND, Smith JD, McKinley TW, et al. 1990. Epidemiologic evidence that prior antimicrobial exposure decreases resistance to infection by antimicrobial-sensitive Salmonella. The Journal of Infectious Diseases, 161(2): 255−260.
[63]	Peterson LW, Artis D. 2014. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nature Reviews Immunology, 14(3): 141−153. doi: 10.1038/nri3608
[64]	Pindling S, Azulai D, Zheng B, Dahan D, Perron GG. 2018. Dysbiosis and early mortality in zebrafish larvae exposed to subclinical concentrations of streptomycin. FEMS Microbiology Letters, 365(18): fny188.
[65]	Ribeiro R, Nicoli JR, Santos G, Lima-Santos J. 2021. Impact of vitamin deficiency on microbiota composition and immunomodulation: relevance to autistic spectrum disorders. Nutritional Neuroscience, 24(8): 601−613. doi: 10.1080/1028415X.2019.1660485
[66]	Rooks MG, Garrett WS. 2016. Gut microbiota, metabolites and host immunity. Nature Reviews Immunology, 16(6): 341−352. doi: 10.1038/nri.2016.42
[67]	Roubaud-Baudron C, Ruiz VE, Swan Jr AM, Vallance BA, Ozkul C, Pei ZH, et al. 2019. Long-term effects of early-life antibiotic exposure on resistance to subsequent bacterial infection. mBio, 10(6): e02820−19.
[68]	Santolini M, Barabási AL. 2018. Predicting perturbation patterns from the topology of biological networks. Proceedings of the National Academy of Sciences of the United States of America, 115(27): E6375−E6383.
[69]	Schubert AM, Sinani H, Schloss PD. 2015. Antibiotic-induced alterations of the murine gut Microbiota and subsequent effects on colonization resistance against Clostridium difficile. mBio, 6(4): e00974.
[70]	Sekirov I, Tam NM, Jogova M, Robertson ML, Li YL, Lupp C, et al. 2008. Antibiotic-induced perturbations of the intestinal microbiota alter host susceptibility to enteric infection. Infection and Immunity, 76(10): 4726−4736. doi: 10.1128/IAI.00319-08
[71]	Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. 2003. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Research, 13(11): 2498−2504. doi: 10.1101/gr.1239303
[72]	Shen HY, Zhou Y, Zhou QJ, Li MY, Chen J. 2020. Mudskipper interleukin-34 modulates the functions of monocytes/macrophages via the colony-stimulating factor-1 receptor 1. Zoological Research, 41(2): 123−137. doi: 10.24272/j.issn.2095-8137.2020.026
[73]	Shi SJ, Nuccio EE, Shi ZJ, He ZL, Zhou JZ, Firestone MK. 2016. The interconnected rhizosphere: high network complexity dominates rhizosphere assemblages. Ecology Letters, 19(8): 926−936. doi: 10.1111/ele.12630
[74]	Shin NR, Whon TW, Bae JW. 2015. Proteobacteria: microbial signature of dysbiosis in gut microbiota. Trends in Biotechnology, 33(9): 496−503. doi: 10.1016/j.tibtech.2015.06.011
[75]	Soderholm AT, Pedicord VA. 2019. Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity. Immunology, 158(4): 267−280. doi: 10.1111/imm.13117
[76]	Spinillo A, Capuzzo E, Acciano S, De Santolo A, Zara F. 1999. Effect of antibiotic use on the prevalence of symptomatic vulvovaginal candidiasis. American Journal of Obstetrics and Gynecology, 180(1): 14−17. doi: 10.1016/S0002-9378(99)70141-9
[77]	Stojanov S, Berlec A, Štrukelj B. 2020. The influence of probiotics on the firmicutes/bacteroidetes ratio in the treatment of obesity and inflammatory bowel disease. Microorganisms, 8(11): 1715. doi: 10.3390/microorganisms8111715
[78]	Sun MM, Wu W, Liu ZJ, Cong YZ. 2017. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. Journal of Gastroenterology, 52(1): 1−8. doi: 10.1007/s00535-016-1242-9
[79]	Takiishi T, Fenero CIM, Câmara NOS. 2017. Intestinal barrier and gut microbiota: Shaping our immune responses throughout life. Tissue Barriers, 5(4): e1373208. doi: 10.1080/21688370.2017.1373208
[80]	Thoo L, Noti M, Krebs P. 2019. Keep calm: the intestinal barrier at the interface of peace and war. Cell Death & , Disease, 10(11): 849.
[81]	Thukral AK. 2017. A review on measurement of Alpha diversity in biology. Agricultural Research Journal, 54(1): 1−10. doi: 10.5958/2395-146X.2017.00001.1
[82]	Tran KC, Tran MP, Van Phan T, Dalsgaard A. 2018. Quality of antimicrobial products used in white leg shrimp (Litopenaeus vannamei) aquaculture in Northern Vietnam. Aquaculture, 482: 167−175. doi: 10.1016/j.aquaculture.2017.09.038
[83]	Ubeda C, Pamer EG. 2012. Antibiotics, microbiota, and immune defense. Trends in Immunology, 33(9): 459−466. doi: 10.1016/j.it.2012.05.003
[84]	Wang AR, Ran C, Ringø E, Zhou ZG. 2018. Progress in fish gastrointestinal microbiota research. Reviews in Aquaculture, 10(3): 626−640. doi: 10.1111/raq.12191
[85]	Wang EL, Yuan ZH, Wang KY, Gao DY, Liu ZJ, Liles MR. 2019. Consumption of florfenicol-medicated feed alters the composition of the channel catfish intestinal microbiota including enriching the relative abundance of opportunistic pathogens. Aquaculture, 501: 111−118. doi: 10.1016/j.aquaculture.2018.11.019
[86]	Wang H, Qiu TX, Lu JF, Liu HW, Hu L, Liu L, et al. 2021. Potential aquatic environmental risks of trifloxystrobin: Enhancement of virus susceptibility in zebrafish through initiation of autophagy. Zoological Research, 42(3): 339−349. doi: 10.24272/j.issn.2095-8137.2021.056
[87]	Wang Q, Garrity GM, Tiedje JM, Cole JR. 2007. Naïve Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Applied and Environmental Microbiology, 73(16): 5261−5267. doi: 10.1128/AEM.00062-07
[88]	Wang X, Lu Y, Wang L, Li S, Che J, Xu Y. 2015. Development of antibiotic alternatives on prophylactic and therapeutic treatment for bacterial diseases. Feed and Husbandry, 4: 18−22.
[89]	Wang XH, Hu MH, Gu HX, Zhang LB, Shang YY, Wang T, et al. 2020. Short-term exposure to norfloxacin induces oxidative stress, neurotoxicity and microbiota alteration in juvenile large yellow croaker Pseudosciaena crocea. Environmental Pollution, 267: 115397.
[90]	Weiss S, Van Treuren W, Lozupone C, Faust K, Friedman J, Deng Y, et al. 2016. Correlation detection strategies in microbial data sets vary widely in sensitivity and precision. The ISME Journal, 10(7): 1669−1681. doi: 10.1038/ismej.2015.235
[91]	Xiong JB, Nie L, Chen J. 2019. Current understanding on the roles of gut microbiota in fish disease and immunity. Zoological Research, 40(2): 70−76. doi: 10.24272/j.issn.2095-8137.2018.069
[92]	Xu JP, Schwartz K, Bartoces M, Monsur J, Severson RK, Sobel JD. 2008. Effect of antibiotics on vulvovaginal candidiasis: a MetroNet study. The Journal of the American Board of Family Medicine, 21(4): 261−268. doi: 10.3122/jabfm.2008.04.070169
[93]	Xue X, Jia J, Yue XY, Guan YJ, Zhu L, Wang ZZ. 2021. River contamination shapes the microbiome and antibiotic resistance in sharpbelly (Hemiculter leucisculus). Environmental Pollution, 268: 115796. doi: 10.1016/j.envpol.2020.115796
[94]	Yang HT, Zou SS, Zhai LJ, Wang Y, Zhang FM, An LG, et al. 2017. Pathogen invasion changes the intestinal microbiota composition and induces innate immune responses in the zebrafish intestine. Fish & Shellfish Immunology, 71: 35−42.
[95]	Zhang XR, Zhang JC, Han QF, Wang XL, Wang SG, Yuan XZ, et al. 2021. Antibiotics in mariculture organisms of different growth stages: tissue-specific bioaccumulation and influencing factors. Environmental Pollution, 288: 117715. doi: 10.1016/j.envpol.2021.117715
[96]	Zhao XL, Li P, Zhang SQ, He SW, Xing SY, Cao ZH, et al. 2021. Effects of environmental norfloxacin concentrations on the intestinal health and function of juvenile common carp and potential risk to humans. Environmental Pollution, 287: 117612. doi: 10.1016/j.envpol.2021.117612
[97]	Zimmermann P, Curtis N. 2019. The effect of antibiotics on the composition of the intestinal microbiota-a systematic review. Journal of Infection, 79(6): 471−489. doi: 10.1016/j.jinf.2019.10.008