The scientific community is closely monitoring the replacement of antibiotics with doses of ZnO in weaned piglets. Since 2022, the use of zinc in medical doses has been banned in the European Union. Therefore, pig farmers are looking for other solutions. Some studies have suggested that zinc nanoparticles might replace ZnO for the prevention of diarrhea in weaning piglets. Like ZnO, zinc nanoparticles are effective against pathogenic microorganisms, e.g., Enterobacteriaceae family in vitro and in vivo. However, the effect on probiotic Lactobacillaceae appears to differ for ZnO and zinc nanoparticles. While ZnO increases their numbers, zinc nanoparticles act in the opposite way. These phenomena have been also confirmed by in vitro studies that reported a strong antimicrobial effect of zinc nanoparticles against Lactobacillales order. Contradictory evidence makes this topic still controversial, however. In addition, zinc nanoparticles vary in their morphology and properties based on the method of their synthesis. This makes it difficult to understand the effect of zinc nanoparticles on the intestinal microbiome. This review is aimed at clarifying many circumstances that may affect the action of nanoparticles on the weaning piglets' microbiome, including a comprehensive overview of the zinc nanoparticles in vitro effects on bacterial species occurring in the digestive tract of weaned piglets.

Department of Animal Morphology Physiology and Genetics Mendel University in Brno Brno Czechia

Department of Animal Nutrition and Forage Production Mendel University in Brno Brno Czechia

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Swain PS, Rao SBN, Rajendran D, Dominic G, Selvaraju S. Nano zinc, an alternative to conventional zinc as animal feed supplement: a review. Anim Nutr. (2016) 2:134–41. 10.1016/j.aninu.2016.06.003 PubMed DOI PMC

Huang SW, Wang L, Liu LM, Hou YX, Li L. Nanotechnology in agriculture, livestock, and aquaculture in China. A review. Agron Sust Dev. (2015) 35:369–400. 10.1007/s13593-014-0274-x DOI

Shen JH, Chen Y, Wang Z, Zhou AG, He M, Mao L, et al. . Coated zinc oxide improves intestinal immunity function and regulates microbiota composition in weaned piglets. Br J Nutr. (2014) 111:2123–34. 10.1017/S0007114514000300 PubMed DOI

Turan NB, Erkan HS, Engin GO, Bilgili MS. Nanoparticles in the aquatic environment: usage, properties, transformation and toxicity-a review. Process Saf Environ Protect. (2019) 130:238–49. 10.1016/j.psep.2019.08.014 DOI

Wang W, Van Noten N, Degroote J, Romeo A, Vermeir P, Michiels J. Effect of zinc oxide sources and dosages on gut microbiota and integrity of weaned piglets. J Anim Physiol Anim Nutr. (2019) 103:231–41. 10.1111/jpn.12999 PubMed DOI

Palansooriya KN, Shaheen SM, Chen SS, Tsang DCW, Hashimoto Y, Hou DY, et al. . Soil amendments for immobilization of potentially toxic elements in contaminated soils: a critical review. Environ Int. (2020) 134:105046. 10.1016/j.envint.2019.105046 PubMed DOI

Maares M, Haase H. A guide to human zinc absorption: general overview and recent advances of in vitro intestinal models. Nutrients. (2020) 12:762. 10.3390/nu12030762 PubMed DOI PMC

Xia T, Lai WQ, Han MM, Han M, Ma X, Zhang LY. Dietary Zno nanoparticles alters intestinal microbiota and inflammation response in weaned piglets. Oncotarget. (2017) 8:64878–91. 10.18632/oncotarget.17612 PubMed DOI PMC

Commission Recommendation of 18 October 2011 on the Definition of Nanomaterial (2011/696/Eu) (2011) . Available online at: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32011H0696 (accessed March 22, 2022).

Sirelkhatim A, Mahmud S, Seeni A, Kaus NHM, Ann LC, Bakhori SKM, et al. . Review on zinc oxide nanoparticles: antibacterial activity and toxicity mechanism. Nano Micro Lett. (2015) 7:219–42. 10.1007/s40820-015-0040-x PubMed DOI PMC

Chauhan A .S., Kaul, M. Engineering of “critical nanoscale design parameters” (CNDPs) in PAMAM dendrimer nanoparticles for drug delivery applications. J Nanopart Res. (2018) 20:226. 10.1007/s11051-018-4318-z DOI

Case CL, Carlson MS. Effect of feeding organic and inorganic sources of additional zinc on growth performance and zinc balance in nursery pigs. J Anim Sci. (2002) 80:1917–24. 10.2527/2002.8071917x PubMed DOI

Brugger D, Hanauer M, Ortner J, Windisch WM. The response of zinc transporter gene expression of selected tissues in a pig model of subclinical zinc deficiency. J Nutr Biochem. (2021) 90:108576. 10.1016/j.jnutbio.2020.108576 PubMed DOI

Zhao CY, Tan SX, Xiao XY, Qiu XS, Pan JQ, Tang ZX. Effects of dietary zinc oxide nanoparticles on growth performance and antioxidative status in broilers. Biol Trace Element Res. (2014) 160:361–7. 10.1007/s12011-014-0052-2 PubMed DOI

Parashuramulu S, Nagalakshmi D, Rao DS, Kumar MK, Swain PS. Effect of zinc supplementation on antioxidant status and immune response in buffalo calves. Anim Nutr Feed Technol. (2015) 15:179–88. 10.5958/0974-181X.2015.00020.7 DOI

Gammoh NZ, Rink L. Zinc in infection and inflammation. Nutrients. (2017) 9:624. 10.3390/nu9060624 PubMed DOI PMC

Hasegawa H, Suzuki K, Nakaji S, Sugawara K. Effects of zinc on the reactive oxygen species generating capacity of human neutrophils and on the serum opsonic activity in vitro. Luminescence. (2000) 15:321–7. 10.1002/1522-7243(200009/10)15:5<321::AID-BIO605>3.0.CO;2-O PubMed DOI

Lee SR. Critical role of zinc as either an antioxidant or a prooxidant in cellular systems. Oxid Med Cell Long. (2018) 2018:9156285. 10.1155/2018/9156285 PubMed DOI PMC

MacDonald RS. The role of zinc in growth and cell proliferation. J Nutr. (2000) 130:1500S−8. 10.1093/jn/130.5.1500S PubMed DOI

Pace NJ, Weerapana E. A competitive chemical-proteomic platform to identify zinc-binding cysteines. Acs Chem Biol. (2014) 9:258–65. 10.1021/cb400622q PubMed DOI

Prasad AS. Zinc: an antioxidant and anti-inflammatory agent: role of zinc in degenerative disorders of aging. J Trace Elements Medi Biol. (2014) 28:364–71. 10.1016/j.jtemb.2014.07.019 PubMed DOI

Broom LJ, Monteiro A, Pinon A. Recent advances in understanding the influence of zinc, copper, and manganese on the gastrointestinal environment of pigs and poultry. Animals. (2021) 11:1276. 10.3390/ani11051276 PubMed DOI PMC

Cuajungco MP, Ramirez MS, Tolmasky ME. Zinc: multidimensional effects on living organisms. Biomedicines. (2021) 9:208. 10.3390/biomedicines9020208 PubMed DOI PMC

Kambe T, Tsuji T, Hashimoto A, Itsumura N. The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Physiol Rev. (2015) 95:749–84. 10.1152/physrev.00035.2014 PubMed DOI

Pereira AM, Maia MRG, Fonseca AJM, Cabrita ARJ. Zinc in dog nutrition, health and disease: a review. Animals. (2021) 11:978. 10.3390/ani11040978 PubMed DOI PMC

Kimura T, Kambe T. The functions of metallothionein and Zip and Znt transporters: an overview and perspective. Int J Mol Sci. (2016) 17:336. 10.3390/ijms17030336 PubMed DOI PMC

Li YX, Xia ST, Jiang XH, Feng C, Gong SM, Ma J, et al. . Gut microbiota and diarrhea: an updated review. Front Cell Infect Microbiol. (2021) 11:625210. 10.3389/fcimb.2021.625210 PubMed DOI PMC

Davin R, Manzanilla EG, Klasing KC, Perez JF. Effect of weaning and in-feed high doses of zinc oxide on zinc levels in different body compartments of piglets. J Anim Physiol Anim Nutr. (2013) 97:6–12. 10.1111/jpn.12046 PubMed DOI

Huang SX, McFall M, Cegielski AC, Kirkwood RN. Effect of dietary zinc supplementation on Escherichia coli septicemia in weaned pigs. Swine Health Prod. (1999) 7:109–11.

Isaacson R, Kim HB. The intestinal microbiome of the pig. Anim Health Res Rev. (2012) 13:100–9. 10.1017/S1466252312000084 PubMed DOI

Burrough ER, De Mille C, Gabler NK. Zinc overload in weaned pigs: tissue accumulation, pathology, and growth impacts. J Vet Diagn Invest. (2019) 31:537–45. 10.1177/1040638719852144 PubMed DOI PMC

Bonetti A, Tugnoli B, Piva A, Grilli E. Towards zero zinc oxide: feeding strategies to manage post-weaning diarrhea in piglets. Animals. (2021) 11:642. 10.3390/ani11030642 PubMed DOI PMC

Ghassan AA, Mijan N, Taufiq-Yap YH. Nanomaterials: An overview of nanorods synthesis and optimization. In: Ghamsari MS, Dhara S, editors. Nanorods and Nanocomposites. London: IntechOpen; (2019). p. 11–34. 10.5772/intechopen.84550 DOI

Sabir S, Arshad M, Chaudhari SK. Zinc oxide nanoparticles for revolutionizing agriculture: synthesis and applications. Sci World J.(2014) 2014:925494. 10.1155/2014/925494 PubMed DOI PMC

Moghaddam AB, Moniri M, Azizi S, Rahim RA, Bin Ariff A, Saad WZ, et al. . Biosynthesis of Zno nanoparticles by a new Pichia kudriavzevii yeast strain and evaluation of their antimicrobial and antioxidant activities. Molecules. (2017) 22:872. 10.3390/molecules22060872 PubMed DOI PMC

Kundu D, Hazra C, Chatterjee A, Chaudhari A, Mishra S. Extracellular biosynthesis of zinc oxide nanoparticles using rhodococcus pyridinivorans Nt2: multifunctional textile finishing, biosafety evaluation and in vitro drug delivery in colon carcinoma. J Photochem Photobiol B Biol. (2014) 140:194–204. 10.1016/j.jphotobiol.2014.08.001 PubMed DOI

Shamsuzzaman Mashrai A, Khanam H, Aljawfi RN. Biological synthesis of zno nanoparticles using C. albicans and Studying their catalytic performance in the synthesis of steroidal pyrazolines. Arabian J Chem. (2017) 10:S1530–S. 10.1016/j.arabjc.2013.05.004 DOI

Salem SS, Fouda MMG, Fouda A, Awad MA, Al-Olayan EM, Allam AA, et al. . Antibacterial, cytotoxicity and larvicidal activity of green synthesized selenium nanoparticles using Penicillium corylophilum. J Clust Sci. (2021) 32:351–61. 10.1007/s10876-020-01794-8 DOI

Nam L. Nanoparticles: synthesis and applications. Mater Biomed Eng Elsevier. (2019) 2019:211–40. 10.1016/B978-0-08-102814-8.00008-1 DOI

Susan Azizi N, Jaya Gade, Anil Kashyap, Anupama Kashyap, Damini Vishwakarma. A critical analysis of the biogenic synthesis of transition metal nanoparticles along with its application and stability. Eur J Mol Clin Med. (2021) 7:6368–97.

Basnet P, Chanu TI, Samanta D, Chatterjee S. A review on bio-synthesized zinc oxide nanoparticles using plant extracts as reductants and stabilizing agents. J Photochem Photobiol B Biol. (2018) 183:201–21. 10.1016/j.jphotobiol.2018.04.036 PubMed DOI

Keerthana S, Kumar A. Potential risks and benefits of zinc oxide nanoparticles: a systematic review. Crit Rev Toxicol. (2020) 50:47–71. 10.1080/10408444.2020.1726282 PubMed DOI

Moatamed ER, Hussein AA, El-desoky MM, El Khayat Z. Comparative study of zinc oxide nanoparticles and its bulk form on liver function of wistar rat. Toxicol Indus Health. (2019) 35:074823371987897. 10.1177/0748233719878970 PubMed DOI

Li YF, Chen CY. Fate and toxicity of metallic and metal-containing nanoparticles for biomedical applications. Small. (2011) 7:2965–80. 10.1002/smll.201101059 PubMed DOI

Warheit DB, Webb TR, Sayes CM, Colvin VL, Reed KL. Pulmonary instillation studies with nanoscale Tio2 rods and dots in rats: toxicity is not dependent upon particle size and surface area. Toxicol Sci. (2006) 91:227–36. 10.1093/toxsci/kfj140 PubMed DOI

Golbamaki N, Rasulev B, Cassano A, Robinson RLM, Benfenati E, Leszczynski J, et al. . Genotoxicity of metal oxide nanomaterials: review of recent data and discussion of possible mechanisms. Nanoscale. (2015) 7:2154–98. 10.1039/C4NR06670G PubMed DOI

McClements DJ, Xiao H. Is nano safe in foods? establishing the factors impacting the gastrointestinal fate and toxicity of organic and inorganic food-grade nanoparticles. Npj Sci Food. (2017) 1:6. 10.1038/s41538-017-0005-1 PubMed DOI PMC

Frohlich EE, Frohlich E. Cytotoxicity of nanoparticles contained in food on intestinal cells and the gut microbiota. Int J Mol Sci. (2016) 17:509. 10.3390/ijms17040509 PubMed DOI PMC

Jeon YR, Yu J, Choi SJ. Fate Determination of Zno in commercial foods and human intestinal cells. Int J Mol Sci. (2020) 21:433. 10.3390/ijms21020433 PubMed DOI PMC

Barua S, Mitragotri S. Challenges associated with penetration of nanoparticles across cell and tissue barriers: a review of current status and future prospects. Nano Today. (2014) 9:223–43. 10.1016/j.nantod.2014.04.008 PubMed DOI PMC

Tay CY, Setyawati MI, Xie JP, Parak WJ, Leong DT. Back to basics: exploiting the innate physico-chemical characteristics of nanomaterials for biomedical applications. Adv Funct Mater. (2014) 24:5936–55. 10.1002/adfm.201401664 DOI

Choi SJ, Choy JH. Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction. Int J Nanomed. (2014) 9:261–9. 10.2147/IJN.S57920 PubMed DOI PMC

Nishikawa M, Hasegawa S, Yamashita F, Takakura Y, Hashida M. Electrical charge on protein regulates its absorption from the rat small intestine. Am J Physiol Gastroint Liver Physiol. (2002) 282:G711–9. 10.1152/ajpgi.00358.2001 PubMed DOI

Yu J, Choi S-J. Particle size and biological fate of Zno do not cause acute toxicity, but affect toxicokinetics and gene expression profiles in the rat livers after oral administration. Int J Mol Sci. (2021) 22:1698. 10.3390/ijms22041698 PubMed DOI PMC

Longmire M, Choyke PL, Kobayashi H. Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine. (2008) 3:703–17. 10.2217/17435889.3.5.703 PubMed DOI PMC

da Silva BL, Caetano BL, Chiari-Andreo BG, Pietro R, Chiavacci LA. Increased antibacterial activity of zno nanoparticles: influence of size and surface modification. Colloids Surfaces B Biointerfaces. (2019) 177:440–7. 10.1016/j.colsurfb.2019.02.013 PubMed DOI

Siddiqi KS, Ur Rahman A, Tajuddin, Husen A. Properties of zinc oxide nanoparticles and their activity against microbes. Nanoscale Res Lett. (2018) 13:1–141. 10.1186/s11671-018-2532-3 PubMed DOI PMC

Yu ZJ, Li Q, Wang J, Yu YL, Wang Y, Zhou QH, et al. . Reactive oxygen species-related nanoparticle toxicity in the biomedical field. Nanoscale Res Lett. (2020) 15:115. 10.1186/s11671-020-03344-7 PubMed DOI PMC

Padmavathy N, Vijayaraghavan R. Enhanced bioactivity of zno nanoparticles-an antimicrobial study. Sci Technol Adv Mater. (2008) 9:035004. 10.1088/1468-6996/9/3/035004 PubMed DOI PMC

Saliani M, Jalal R, Goharshadi EK. Effects of Ph and temperature on antibacterial activity of zinc oxide nanofluid against Escherichia coli O157: H7 and Staphylococcus aureus. Jundishapur J Microbiol. (2015) 8:e17115. 10.5812/jjm.17115 PubMed DOI PMC

Rajagopal M, Walker S. Envelope structures of gram-positive bacteria. Curr Top Microbiol Immunol. (2017) 404:1–44. 10.1007/82_2015_5021 PubMed DOI PMC

Feris K, Otto C, Tinker J, Wingett D, Punnoose A, Thurber A, et al. . electrostatic interactions affect nanoparticle-mediated toxicity to gram-negative bacterium pseudomonas aeruginosa Pao1. Langmuir. (2010) 26:4429–36. 10.1021/la903491z PubMed DOI

Shinde VV, Dalavi DS, Mali SS, Hong CK, Kim JH, Patil PS. surfactant free microwave assisted synthesis of Zno microspheres: study of their antibacterial activity. Appl Surface Sci. (2014) 307:495–502. 10.1016/j.apsusc.2014.04.064 DOI

Al-Shabib N, Husain F, Ahmed F, Khan RA, Ahmad I, Alsharaeh E, et al. . Biogenic synthesis of Zinc oxide nanostructures from Nigella sativa seed: prospective role as food packaging material inhibiting broad-spectrum quorum sensing and biofilm. Sci Rep. (2016) 6:36761. 10.1038/srep36761 PubMed DOI PMC

Barreto MSR, Andrade CT, da Silva LCRP, Cabral LM, Flosi Paschoalin VM, Del Aguila EM. In vitro physiological and antibacterial characterization of zno nanoparticle composites in simulated porcine gastric and enteric fluids. BMC Vet Res. (2017) 13:181. 10.1186/s12917-017-1101-9 PubMed DOI PMC

Aleaghil SA, Fattahy E, Baei B, Saghali M, Bagheri H, Javid N, et al. . Antibacterial activity of zinc oxide nanoparticles on Staphylococcus aureus. Int J Adv Biotechnol Res. (2016) 7:1569–75. 10.38094/jlbsr1332 PubMed DOI

Bhattacharyya P, Agarwal B, Goswami M, Maiti D, Baruah S, Tribedi P. Zinc oxide nanoparticle inhibits the biofilm formation of Streptococcus pneumoniae. Antonie Van Leeuwenhoek Int J Gen Mol Microbiol. (2018) 111:89–99. 10.1007/s10482-017-0930-7 PubMed DOI

Husain FM, Hasan I, Qais FA, Khan RA, Alam P, Alsalme A. Fabrication of zinc oxide-xanthan gum nanocomposite via green route: attenuation of quorum sensing regulated virulence functions and mitigation of biofilm in gram-negative bacterial pathogens. Coatings. (2020) 10:1190. 10.3390/coatings10121190 DOI

Ali SS, Sonbol FI, Sun JZ, Hussein MA, Hafez AEE, Abdelkarim EA, et al. . Molecular characterization of virulence and drug resistance genes-producing Escherichia coli isolated from chicken meat: metal oxide nanoparticles as novel antibacterial agents. Microbial Pathogenesis. (2020) 143:104164. 10.1016/j.micpath.2020.104164 PubMed DOI

Graves JL, Tajkarimi M, Cunningham Q, Campbell A, Nonga H, Harrison SH, et al. . Rapid evolution of silver nanoparticle resistance in Escherichia coli. Front Genet. (2015) 6:42. 10.3389/fgene.2015.00042 PubMed DOI PMC

Martinez-Rodriguez NL, Tavarez S, Gonzalez-Sanchez ZI. In vitro toxicity assessment of zinc and nickel ferrite nanoparticles in human erythrocytes and peripheral blood mononuclear cell. Toxicol In Vitro. (2019) 57:54–61. 10.1016/j.tiv.2019.02.011 PubMed DOI

Tiwari V, Mishra N, Gadani K, Solanki PS, Shah NA, Tiwari M. (2018). Mechanism of anti-bacterial activity of zinc oxide nanoparticle against carbapenem-resistant Acinetobacter baumannii. Front Microbiol. (2018) 9:1218. 10.3389/fmicb.2018.01218 PubMed DOI PMC

Ghebretatios M, Schaly S, Prakash S. Nanoparticles in the food industry and their impact on human gut microbiome and diseases. Int J Mol Sci. (2021) 22:1942. 10.3390/ijms22041942 PubMed DOI PMC

Lallo da Silva B, Abuçafy MP, Berbel Manaia E, Oshiro Junior JA, Chiari-Andréo BG, Pietro RCR, et al. . Relationship between structure and antimicrobial activity of zinc oxide nanoparticles: an overview. Int J Nanomed. (2019) 14:9395–410. 10.2147/IJN.S216204 PubMed DOI PMC

Chen PY, Wang H, He M, Chen BB, Yang B, Hu B. Size-dependent cytotoxicity study of Zno nanoparticles in Hepg2 cells. Ecotoxicol Environ Saf. (2019) 171:337–46. 10.1016/j.ecoenv.2018.12.096 PubMed DOI

Bandeira M, Giovanela M, Roesch-Ely M, Devine DM, Crespo JD. Green synthesis of zinc oxide nanoparticles: a review of the synthesis methodology and mechanism of formation. Sust Chem Pharmacy. (2020) 15:100223. 10.1016/j.scp.2020.100223 DOI

Bekele B, Degefa A, Tesgera F, Jule LT, Shanmugam R, Dwarampudi LP, et al. . Green versus chemical precipitation methods of preparing zinc oxide nanoparticles and investigation of antimicrobial properties. J Nanomater. (2021) 2021:10. 10.1155/2021/9210817 DOI

Patino-Portela MC, Arciniegas-Grijalba PA, Mosquera-Sanchez LP, Sierra BEG, Munoz-Florez JE, Erazo-Castillo LA, et al. . Effect of method of synthesis on antifungal ability of Zno nanoparticles: chemical route vs green route. Adv Nano Res. (2021) 10:191–210. 10.12989/anr.2020.10.2.191 DOI

Hayat S, Ashraf A, Zubair M, Aslam B, Siddique MH, Khurshid M, et al. . Biofabrication of Zno nanoparticles using acacia arabica leaf extract and their antibiofilm and antioxidant potential against foodborne pathogens. PLoS ONE. (2022) 17:e0259190. 10.1371/journal.pone.0259190 PubMed DOI PMC

Barbero F, Russo L, Vitali M, Piella J, Salvo I, Borrajo ML, et al. . Formation of the protein corona: the interface between nanoparticles and the immune system. Semin Immunol. (2017) 34:52–60. 10.1016/j.smim.2017.10.001 PubMed DOI

Devi SA, Harshiny M, Udaykumar S, Gopinath P, Matheswaran M. Strategy of metal iron doping and green-mediated Zno nanoparticles: dissolubility, antibacterial and cytotoxic traits. Toxicol Res. (2017) 6:854–65. 10.1039/C7TX00093F PubMed DOI PMC

Campbell JM, Crenshaw JD, Polo J. The biological stress of early weaned piglets. J Anim Sci Biotechnol. (2013) 4:19. 10.1186/2049-1891-4-19 PubMed DOI PMC

Panah FM, Lauridsen C, Hojberg O, Nielsen TS. Etiology of colitis-complex diarrhea in growing pigs: a review. Animals. (2021) 11:2151. 10.3390/ani11072151 PubMed DOI PMC

Yang H, Xiong X, Wang X, Li T, Yin Y. Effects of weaning on intestinal crypt epithelial cells in piglets. Sci Rep. (2016) 6:36939. 10.1038/srep36939 PubMed DOI PMC

Xiong X, Tan B, Song M, Ji P, Kim K, Yin YL, et al. . Nutritional intervention for the intestinal development and health of weaned pigs. Front Vet Sci. (2019) 6:46. 10.3389/fvets.2019.00046 PubMed DOI PMC

Lalles JP, Bosi P, Smidt H, Stokes CR. Nutritional management of gut health in pigs around weaning. Proc Nutr Soc. (2007) 66:260–8. 10.1017/S0029665107005484 PubMed DOI

Rhouma M, Fairbrother JM, Beaudry F, Letellier A. Post weaning diarrhea in pigs: risk factors and non-colistin-based control strategies. Acta Vet Scand. (2017) 59:31. 10.1186/s13028-017-0299-7 PubMed DOI PMC

Yang H, Huang XC, Fang SM, He MZ, Zhao YZ, Wu ZF, et al. . Unraveling the fecal microbiota and metagenomic functional capacity associated with feed efficiency in pigs. Front Microbiol. (2017) 8:1555. 10.3389/fmicb.2017.01555 PubMed DOI PMC

Molist F, van Oostrum M, Perez JF, Mateos GG, Nyachoti CM, van der Aar PJ. Relevance of functional properties of dietary fibre in diets for weanling pigs. Anim Feed Sci Technol. (2014) 189:1–10. 10.1016/j.anifeedsci.2013.12.013 DOI

Petri D, Hill JE, Van Kessel AG. Microbial succession in the gastrointestinal tract (Git) of the preweaned pig. Livestock Sci. (2010) 133:107–9. 10.1016/j.livsci.2010.06.037 DOI

Guevarra RB, Hong SH, Cho JH, Kim BR, Shin J, Lee JH, et al. . The dynamics of the piglet gut microbiome during the weaning transition in association with health and nutrition. J Anim Sci Biotechnol. (2018) 9:54. 10.1186/s40104-018-0269-6 PubMed DOI PMC

Gaskins HR, Collier CT, Anderson DB. Antibiotics as growth promotants: mode of action. Anim Biotechnol. (2002) 13:29–42. 10.1081/ABIO-120005768 PubMed DOI

Wylensek D, Hitch TCA, Riedel T, Afrizal A, Kumar N, Wortmann E, et al. . A collection of bacterial isolates from the pig intestine reveals functional and taxonomic diversity. Nat Commun. (2020) 11:6389. 10.1038/s41467-020-19929-w PubMed DOI PMC

Luise D, Le Sciellour M, Buchet A, Resmond R, Clement C, Rossignol MN, et al. . The fecal microbiota of piglets during weaning transition and its association with piglet growth across various farm environments. PLoS ONE. (2021) 16:e0250655. 10.1371/journal.pone.0250655 PubMed DOI PMC

Saladrigas-García M, D'Angelo M, Ko HL, Nolis P, Ramayo-Caldas Y, Folch JM, et al. . Understanding host-microbiota interactions in the commercial piglet around weaning. Sci Rep. (2021) 11:23488. 10.1038/s41598-021-02754-6 PubMed DOI PMC

Rutledge PJ, Challis GL. Discovery of microbial natural products by activation of silent biosynthetic gene clusters. Nat Rev Microbiol. (2015) 13:509–23. 10.1038/nrmicro3496 PubMed DOI

Maltecca C, Bergamaschi M, Tiezzi F. The interaction between microbiome and pig efficiency: A review. J Anim Breed Genet. (2020) 137: 4–13. 10.1111/jbg.12443 PubMed DOI

Patil Y, Gooneratne R, Ju XH. Interactions between host and gut microbiota in domestic pigs: a review. Gut Microbes. (2020) 11:310–34. 10.1080/19490976.2019.1690363 PubMed DOI PMC

Pluske JR, Turpin DL, Kim JC. Gastrointestinal tract (gut) health in the young pig. Anim Nutr. (2018) 4:187–96. 10.1016/j.aninu.2017.12.004 PubMed DOI PMC

Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host-microbial relationships in the intestine. Science. (2001) 291:881–4. 10.1126/science.291.5505.881 PubMed DOI

Wei XY, Tsai TC, Howe S, Zhao JC. Weaning induced gut dysfunction and nutritional interventions in nursery pigs: a partial review. Animals. (2021) 11:1279. 10.3390/ani11051279 PubMed DOI PMC

Ren W, Yan HL, Yu B, Walsh MC, Yu J, Zheng P, et al. . Prevotella-rich enterotype may benefit gut health in finishing pigs fed diet with a high amylose-to-amylopectin ratio. Anim Nutr. (2021) 7:400–11. 10.1016/j.aninu.2020.08.007 PubMed DOI PMC

Amat S, Lantz H, Munyaka PM, Willing BP. Prevotella in pigs: the positive and negative associations with production and health. Microorganisms. (2020) 8:1584. 10.3390/microorganisms8101584 PubMed DOI PMC

Dong B, Lin X, Jing X, Hu T, Zhou J, Chen J, et al. . A bacterial genome and culture collection of gut microbial in weanling piglet. Microbiol Spectr. (2022) 10:e02417–21. 10.1128/spectrum.02417-21 PubMed DOI PMC

Ruiz VLA, Bersano JG, Carvalho AF, Catroxo MHB, Chiebao DP, Gregori F, et al. . Case–control study of pathogens involved in piglet diarrhea. BMC Res Notes. (2016) 9:22. 10.1186/s13104-015-1751-2 PubMed DOI PMC

Dubreuil JD. Enterotoxigenic Escherichia coli targeting intestinal epithelial tight junctions: an effective way to alter the barrier integrity. Microbial Pathogenesis. (2017) 113:129–34. 10.1016/j.micpath.2017.10.037 PubMed DOI

Dubreuil JD, Isaacson RE, Schifferli DM. Animal enterotoxigenic Escherichia coli. EcoSal Plus. (2016) 7:10. 10.1128/ecosalplus.ESP-0006-2016 PubMed DOI PMC

Nosho K, Sukawa Y, Adachi Y, Ito M, Mitsuhashi K, Kurihara H, et al. . Association of fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. World J Gastroenterol. (2016) 22:557–66. 10.3748/wjg.v22.i2.557 PubMed DOI PMC

Wei Y, Li Y, Jia J, Jiang Y, Zhao B, Zhang Q, et al. . Aggravated hepatotoxicity occurs in aged mice but not in young mice after oral exposure to zinc oxide nanoparticles. Nanoimpact. (2016) 3–4:1–11. 10.1016/j.impact.2016.09.003 DOI

Arguello H, Estelle J, Zaldivar-Lopez S, Jimenez-Marin A, Carvajal A, Lopez-Bascon MA, et al. . Early Salmonella typhimurium infection in pigs disrupts microbiome composition and functionality principally at the Ileum Mucosa. Sci Rep. (2018) 8:7788. 10.1038/s41598-018-26083-3 PubMed DOI PMC

Dou S, Gadonna-Widehem P, Rome V, Hamoudi D, Rhazi L, Lakhal L, et al. . Characterisation of early-life fecal microbiota in susceptible and healthy pigs to post-weaning diarrhoea. PLoS ONE. (2017) 12:e0169851. 10.1371/journal.pone.0169851 PubMed DOI PMC

Gryaznova MV, Dvoretskaya YD, Syromyatnikov MY, Shabunin SV, Parshin PA, Mikhaylov EV, et al. . Changes in the microbiome profile in different parts of the intestine in piglets with diarrhea. Animals. (2022) 12:320. 10.3390/ani12030320 PubMed DOI PMC

Starke IC, Pieper R, Neumann K, Zentek J, Vahjen W. The impact of high dietary zinc oxide on the development of the intestinal microbiota in weaned piglets. Fems Microbiol Ecol. (2014) 87:416–27. 10.1111/1574-6941.12233 PubMed DOI

Yu T, Zhu C, Chen SC, Gao L, Lv H, Feng RW, et al. . dietary high zinc oxide modulates the microbiome of ileum and colon in weaned piglets. Front Microbiol. (2017) 8:825. 10.3389/fmicb.2017.00825 PubMed DOI PMC

Pei X, Xiao ZP, Liu LJ, Wang G, Tao WJ, Wang MQ, et al. . Effects of dietary zinc oxide nanoparticles supplementation on growth performance, zinc status, intestinal morphology, microflora population, and immune response in weaned pigs. J Sci Food Agric. (2019) 99:1366–74. 10.1002/jsfa.9312 PubMed DOI

Skalny AV, Aschner M, Lei XG, Gritsenko VA, Santamaria A, Alekseenko SI, et al. . Gut microbiota as a mediator of essential and toxic effects of zinc in the intestines and other tissues. Int J Mol Sci. (2021) 22:13074. 10.3390/ijms222313074 PubMed DOI PMC

Hojberg O, Canibe N, Poulsen HD, Hedemann MS, Jensen BB. Influence of dietary zinc oxide and copper sulfate on the gastrointestinal ecosystem in newly weaned piglets. Appl Environ Microbiol. (2005) 71:2267–77. 10.1128/AEM.71.5.2267-2277.2005 PubMed DOI PMC

Pieper R, Dadi TH, Pieper L, Vahjen W, Franke A, Reinert K, et al. . Concentration and chemical form of dietary zinc shape the porcine colon microbiome, its functional capacity and antibiotic resistance gene repertoire. ISME J. (2020) 14:2783–93. 10.1038/s41396-020-0730-3 PubMed DOI PMC

Oh HJ, Park YJ, Cho JH, Song MH, Gu BH, Yun W, et al. . Changes in diarrhea score, nutrient digestibility, zinc utilization, intestinal immune profiles, and fecal microbiome in weaned piglets by different forms of zinc. Animals. (2021) 11:1356. 10.3390/ani11051356 PubMed DOI PMC

Megahed A, Zeineldin M, Evans K, Maradiaga N, Blair B, Aldridge B, et al. . Impacts of environmental complexity on respiratory and gut microbiome community structure and diversity in growing pigs. Sci Rep. (2019) 9:13773. 10.1038/s41598-019-50187-z PubMed DOI PMC

Xu C, Xie J, Ho D, Wang C, Kohler N, Walsh EG, et al. . Au-Fe3o4 dumbbell nanoparticles as dual-functional probes. Angewandte Chemie Int Ed. (2008) 47:173–6. 10.1002/anie.200704392 PubMed DOI PMC

Young WN, Moon CD, Thomas DG, Cave NJ, Bermingham EN. Pre- and Post-weaning diet alters the faecal metagenome in the cat with differences vitamin and carbohydrate metabolism gene abundances. Sci Rep. (2016) 6:34668. 10.1038/srep34668 PubMed DOI PMC

Oh SM, Kim MJ, Hosseindoust A, Kim KY, Choi YH, Ham HB, et al. . Hot melt extruded-based nano zinc as an alternative to the pharmacological dose of Zno in weanling piglets. Asian Austral J Anim Sci. (2020) 33:992–1001. 10.5713/ajas.19.0140 PubMed DOI PMC

Zheng L, Hu Y, He X, Zhao Y, Xu H. Isolation of swine-derived lactobacillus plantarum and its synergistic antimicrobial and health-promoting properties with Zno nanoparticles. J Appl Microbiol. (2020) 128:1764–75. 10.1111/jam.14605 PubMed DOI

Kociova S, Dolezelikova K, Horky P, Skalickova S, Baholet D, Bozdechova L, et al. . Zinc phosphate-based nanoparticles as alternatives to zinc oxide in diet of weaned piglets. J Anim Sci Biotechnol. (2020) 11:59. 10.1186/s40104-020-00458-x PubMed DOI PMC

Milani NC, Sbardella M, Ikeda NY, Arno A, Mascarenhas BC, Miyada VS. Dietary zinc oxide nanoparticles as growth promoter for weanling pigs. Anim Feed Sci Technol. (2017) 227:13–23. 10.1016/j.anifeedsci.2017.03.001 DOI

Martin L, Lodemann U, Bondzio A, Gefeller E-M, Vahjen W, Aschenbach JR, et al. . A high amount of dietary zinc changes the expression of zinc transporters and metallothionein in jejunal epithelial cells in vitro and in vivo but does not prevent zinc accumulation in jejunal tissue of piglets. J Nutr. (2013) 143:1205–10. 10.3945/jn.113.177881 PubMed DOI

Mohd Yusof H, Mohamad R, Zaidan UH, Rahman NAA. Sustainable microbial cell nanofactory for zinc oxide nanoparticles production by zinc-tolerant probiotic lactobacillus plantarum strain Ta4. Microbial Cell Factories. (2020) 19:10. 10.3390/app10196973 PubMed DOI PMC

Zheng L, Duarte ME, Sevarolli Loftus A, Kim SW. Intestinal health of pigs upon weaning: challenges and nutritional intervention. Front Vet Sci. (2021) 8:628258. 10.3389/fvets.2021.628258 PubMed DOI PMC

Khan MF, Hameedullah M, Ansari AH, Ahmad E, Lohani MB, Khan RH, et al. . Flower-shaped Zno nanoparticles synthesized by a novel approach at near-room temperatures with antibacterial and antifungal properties. Int J Nanomed. (2014) 9:853–64. 10.2147/IJN.S47351 PubMed DOI PMC

Crespo-Piazuelo D, Gardiner GE, Ranjitkar S, Bouwhuis MA, Ham R, Phelan JP, et al. . Maternal supplementation with Bacillus altitudinisspores improves porcine offspring growth performance and carcass weight. Br J Nutr. (2022) 127:403–20. 10.1017/S0007114521001203 PubMed DOI

Ifeanyichukwu UL, Fayemi OE, Ateba CN. Green synthesis of zinc oxide nanoparticles from pomegranate (Punica granatum) Extracts and characterization of their antibacterial activity. Molecules. (2020) 25:4521. 10.3390/molecules25194521 PubMed DOI PMC

Tong DG, Wu P, Su PK, Wang DQ, Tian HY. Preparation of zinc oxide nanospheres by solution plasma process and their optical property, photocatalytic and antibacterial activities. Mater Lett. (2012) 70:94–7. 10.1016/j.matlet.2011.11.114 DOI

Sivakamavalli J, Pandiselvi K, Park K, Kwak IS. Garcinia cambogia assisted synthesis of Zno nanoparticles coupled with chitosan for antibacterial, antibiofilm, cytotoxic, anticancer and ecotoxicity assessment. J Cluster Sci. 1:1–16. 10.1007/s10876-021-02032-5 DOI

Al Sharie AH, El-Elimat T, Darweesh RS, Swedan S, Shubair Z, Al-Qiam R, et al. . Green synthesis of zinc oxide nanoflowers using Hypericum triquetrifolium extract: characterization, antibacterial activity and cytotoxicity against lung cancer A549 cells. Appl Organometallic Chem. (2020) 34:e5667. 10.1002/aoc.5667 DOI

Liang SXT, Wong LS, Lim YM, Lee PF, Djearamane S. Effects of zinc oxide nanoparticles on Streptococcus pyogenes. South Afr J Chem Eng. (2020) 34:63–71. 10.1016/j.sajce.2020.05.009 DOI

Mirhosseini F, Amiri M, Daneshkazemi A, Zandi H, Javadi ZS. Antimicrobial effect of different sizes of nano zinc oxide on oral microorganisms. Front Dentistry. (2019) 16:105–12. 10.18502/fid.v16i2.1361 PubMed DOI PMC

Narayanan PM, Wilson WS, Abraham AT, Sevanan M. Synthesis, characterization, and antimicrobial activity of zinc oxide nanoparticles against human pathogens. Bionanoscience. (2012) 2:329–35. 10.1007/s12668-012-0061-6 DOI

Rahaiee S, Ranjbar M, Azizi H, Govahi M, Zare M. Green synthesis, characterization, and biological activities of saffron leaf extract-mediated zinc oxide nanoparticles: a sustainable approach to reuse an agricultural waste. Appl Organometallic Chem. (2020) 34:e5705. 10.1002/aoc.5705 DOI

Yusof HM, Rahman NA, Mohamad R, Zaidan UH, Samsudin AA. Antibacterial potential of biosynthesized zinc oxide nanoparticles against poultry-associated foodborne pathogens: an in vitro study. Animals. (2021) 11:2093. 10.3390/ani11072093 PubMed DOI PMC

Jayabalan J, Mani G, Krishnan N, Pernabas J, Devadoss JM, Jang HT. green biogenic synthesis of zinc oxide nanoparticles using pseudomonas putida culture and its in vitro antibacterial and anti-biofilm activity. Biocatal Agric Biotechnol. (2019) 21:101327. 10.1016/j.bcab.2019.101327 DOI

Hsueh YH, Ke WJ, Hsieh CT, Lin KS, Tzou DY, Chiang CL. Zno nanoparticles affect bacillus subtilis cell growth and biofilm formation. PLoS ONE. (2015) 10:e0128457. 10.1371/journal.pone.0128457 PubMed DOI PMC

Wang M, Li Y, Yang J, Shi R, Xiong L, Sun Q. Effects of food-grade inorganic nanoparticles on the probiotic properties of Lactobacillus plantarum and Lactobacillus fermentum. LWT. (2021) 139:110540. 10.1016/j.lwt.2020.110540 DOI

Javed R, Rais F, Fatima H, Haq Iu, Kaleem M, Naz SS, et al. . Chitosan encapsulated zno nanocomposites: fabrication, characterization, and functionalization of bio-dental approaches. Mater Sci Eng C. (2020) 116:111184. 10.1016/j.msec.2020.111184 PubMed DOI

Sheik Mydeen S, Raj Kumar R, Kottaisamy M, Vasantha VS. Biosynthesis of Zno nanoparticles through extract from prosopis juliflora plant leaf: antibacterial activities and a new approach by rust-induced photocatalysis. J Saudi Chem Soc. (2020) 24:393–406. 10.1016/j.jscs.2020.03.003 DOI

Jyoti A, Agarwal M, Tomar RS. Synergistic effect of zinc oxide nanoparticles and guava leaf extract for enhanced antimicrobial activity against enterotoxigenic Escherichia coli. J Biochem Technol. (2020) 11:17–23.

Joghee S, Ganeshan P, Vincent A, Hong SI. Ecofriendly biosynthesis of zinc oxide and magnesium oxide particles from medicinal plant Pisonia grandis R.Br. leaf extract and their antimicrobial activity. Bionanoscience. (2019) 9:141–54. 10.1007/s12668-018-0573-9 DOI

Fröber K, Bergs C, Pich A, Conrads G. Biofunctionalized Zinc Peroxide Nanoparticles Inhibit Peri-Implantitis Associated Anaerobes and Aggregatibacter Actinomycetemcomitans Ph-Dependent. Anaerobe. (2020) 62:102153. 10.1016/j.anaerobe.2020.102153 PubMed DOI

Abdelsattar AS, Farouk WM, Gouda SM, Safwat A, Hakim TA, El-Shibiny A. Utilization of Ocimum basilicum extracts for zinc oxide nanoparticles synthesis and their antibacterial activity after a novel combination with phage. Mater Lett. (2022) 309:131344. 10.1016/j.matlet.2021.131344 DOI

Rajeswaran S, Thirugnanasambandan SS, Subramaniyan SR, Kandasamy S, Vilwanathan R. Synthesis of eco-friendly facile nano-sized zinc oxide particles using aqueous extract of Cymodocea serrulata and its potential biological applications. Appl Phys Mater Sci Process. (2019) 125:105. 10.1007/s00339-019-2404-4 DOI

Singh M, Lee KE, Vinayagam R, Kang SG. Antioxidant and antibacterial profiling of pomegranate-pericarp extract functionalized-zinc oxide nanocomposite. Biotechnol Bioprocess Eng. (2021) 26:728–37. 10.1007/s12257-021-0211-1 PubMed DOI PMC

El-Zayat MM, Eraqi MM, Alrefai H, El-Khateeb AY, Ibrahim MA, Aljohani HM, et al. . The antimicrobial, antioxidant, and anticancer activity of greenly synthesized selenium and zinc composite nanoparticles using Ephedra Aphylla extract. Biomolecules. (2021) 11:470. 10.3390/biom11030470 PubMed DOI PMC

Jin T, Sun D, Su JY, Zhang H, Sue HJ. Antimicrobial efficacy of zinc oxide quantum dots against listeria monocytogenes, Salmonella enteritidis, and Escherichia coli O157:H7. J Food Sci. (2009) 74:M46–52. 10.1111/j.1750-3841.2008.01013.x PubMed DOI

Rajasekaran P, Santra S. Hydrothermally treated chitosan hydrogel loaded with copper and zinc particles as a potential micronutrient-based antimicrobial feed additive. Front Vet Sci. (2015) 2:62. 10.3389/fvets.2015.00062 PubMed DOI PMC

Osaili TM, Albiss BA, Al-Nabulsi AA, Alromi RF, Olaimat A, Al-Holy M, et al. . Effects of metal oxide nanoparticles with plant extract on viability of foodborne pathogens. J Food Saf. (2019) 39:e12681. 10.1111/jfs.12681 DOI

Xie YP, He YP, Irwin PL, Jin T, Shi XM. Antibacterial activity and mechanism of action of zinc oxide nanoparticles against Campylobacter jejuni. Appl Environ Microbiol. (2011) 77:2325–31. 10.1128/AEM.02149-10 PubMed DOI PMC

Saxena V, Pandey LM. Synthesis, characterization and antibacterial activity of aluminum doped zinc oxide. In: International Conference on Nanotechnology - Ideas, Innovations and Initiatives (ICN3I). Roorkee: (2019). p. 1388–1400. 10.1016/j.matpr.2019.06.605 DOI

Barma MD, Muthupandiyan I, Samuel SR, Amaechi BT. Inhibition of Streptococcus mutans, antioxidant property and cytotoxicity of novel nano-zinc oxide varnish. Arch Oral Biol. (2021) 126:105132. 10.1016/j.archoralbio.2021.105132 PubMed DOI

Mohapatra SS, Limayem, A,. Chitosan oligomer zinc oxide nanoparticle compositions for treating drug resistant bacteria biofilm. USF Patents. 1172. (2020). Available online at: https://digitalcommons.usf.edu/usf_patents/1172 (accessed March 03, 2022).

Vidhya E, Vijayakumar S, Prathipkumar S, Praseetha PK. Green way biosynthesis: characterization, antimicrobial and anticancer activity of zno nanoparticles. Gene Rep. (2020) 20:100688. 10.1016/j.genrep.2020.100688 DOI

Suba S, Vijayakumar S, Vidhya E, Punitha VN, Nilavukkarasi M. Microbial mediated synthesis of Zno nanoparticles derived from Lactobacillus spp.: characterizations, antimicrobial and biocompatibility efficiencies. Sensors Int. (2021) 2:100104. 10.1016/j.sintl.2021.100104 DOI

Yiamsawas D, Boonpavanitchakul K, Kangwansupamonkon W. Synthesis and characterization of Zno nanostructures with antimicrobial properties. In: 2008 International Conference on Nanoscience and Nanotechnology. Melbourne, VIC: IEEE; (2008). p. 33–6. 10.1109/ICONN.2008.4639264 DOI

Khan I, Jehanzeb M, Nadeem R, Nadhman A, Sadiq Azam IU, Ahmad F. Green synthesis, characterization and biological evaluation of zinc nanoparticles from flower extract of Brassica oleracea Italica. Pak J Bot. (2021) 53:281–6. 10.30848/PJB2021-1(40) DOI

Ahmad P, Alyemeni MN, Al-Huqail AA, Alqahtani MA, Wijaya L, Ashraf M, et al. . Zinc oxide nanoparticles application alleviates arsenic (as) toxicity in soybean plants by restricting the uptake of as and modulating key biochemical attributes, antioxidant enzymes, ascorbate-glutathione cycle and glyoxalase system. Plants. (2020) 9:825. 10.3390/plants9070825 PubMed DOI PMC

Song YM, Kim MH, Kim HN, Jang I, Han JH, Fontamillas GA, et al. . Effects of dietary supplementation of lipid-coated zinc oxide on intestinal mucosal morphology and expression of the genes associated with growth and immune function in weanling pigs. Asian Austral J Anim Sci. (2018) 31:403–9. 10.5713/ajas.17.0718 PubMed DOI PMC

Li J, Zhang Q, Xu M, Wu C, Li P. Antimicrobial efficacy and cell adhesion inhibition of in situ synthesized zno nanoparticles/polyvinyl alcohol nanofibrous membranes. Adv Condensed Matter Phys. (2016) 2016:6394124. 10.1155/2016/6394124 DOI

Eymard-Vernain E, Luche S, Rabilloud T, Lelong C. Zno and Tio(2)nanoparticles alter the ability Ofbacillus Subtilisto fight against a stress. PLoS ONE. (2020) 15:e0240510. 10.1371/journal.pone.0240510 PubMed DOI PMC

Yoo A, Lin M, Mustapha A. Zinc oxide and silver nanoparticle effects on intestinal bacteria. Materials. (2021) 14:2489. 10.3390/ma14102489 PubMed DOI PMC