{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:13:50Z","timestamp":1773389630185,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shaanxi Province Agricultural Key Core Technology Research Project","award":["2024NYGG005"],"award-info":[{"award-number":["2024NYGG005"]}]},{"name":"Agricultural Special Fund of Shaanxi Province","award":["XN17"],"award-info":[{"award-number":["XN17"]}]},{"name":"Agricultural Special Fund of Shaanxi Province","award":["2021JM-102"],"award-info":[{"award-number":["2021JM-102"]}]},{"name":"Research and Development of Key Technologies for the Prevention and Control of Major Animal Diseases","award":["K4030220214"],"award-info":[{"award-number":["K4030220214"]}]},{"name":"Study on the Effects of Olaike on Animal Digestive and Absorptive Functions and Immune Levels","award":["K4030220403"],"award-info":[{"award-number":["K4030220403"]}]},{"name":"School-Enterprise Projects","award":["20240052300897"],"award-info":[{"award-number":["20240052300897"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Peptide-based antimicrobial drugs are promising alternatives to antibiotics owing to their broad-spectrum bactericidal activity and unique pathogen membrane disruption mechanism. Our previous study demonstrated that the recombinant antimicrobial protein PIL22-PBD-2 (PIP) inhibits pathogens and repairs intestinal cell damage\n                      <jats:italic>in vitro<\/jats:italic>\n                      , but its\n                      <jats:italic>in vivo<\/jats:italic>\n                      therapeutic potential against bacterial infections remains uncharacterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we developed an oral drug delivery nano-platform composed of PIP and poly(lactic-co-glycolic acid) (PLGA) using the double emulsion solvent evaporation method, and evaluated its therapeutic efficacy in a mouse model of sepsis induced by enterotoxigenic\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      O8 (ETEC O8).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PLGA-PIP nanoparticles were successfully prepared and showed excellent resistance to trypsin degradation as well as good biocompatibility\n                      <jats:italic>in vivo<\/jats:italic>\n                      . In septic mice, treatment with 300 mg\/kg PLGA-PIP significantly alleviated weight loss and clinical symptoms (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), reduced serum biochemical indices and organ indexes (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), and decreased ETEC O8 loads in feces, liver, spleen, and kidneys (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01). PLGA-PIP also mitigated pathological damage in major organs, increased duodenal villus height and VH\/CD ratio (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), upregulated the expression of tight junction proteins (ZO-1, E-cadherin) and endogenous antimicrobial factors (Cryptdin-1, Reg3\u03b3) (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01), and suppressed the expression of pro-inflammatory cytokines IL-6, IL-1\u03b2, and TNF-\u03b1 (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings demonstrate that PLGA-PIP effectively ameliorates ETEC O8-induced sepsis in mice by enhancing intestinal barrier function, reducing pathogen burden, and inhibiting inflammation. Therefore, PLGA-PIP represents a promising oral antibiotic alternative for the treatment of bacterial infections.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1728161","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:26:11Z","timestamp":1773379571000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PLGA nanoparticles loaded with recombinant antimicrobial protein PIP significantly improves the survival state and pathological damage caused by ETEC O8-induced sepsis in mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Xian","family":"Li","sequence":"first","affiliation":[{"name":"Animal Disease Prevention and Control, Healthy Breeding Engineering Technology Research Center, Mianyang Normal University","place":["Mianyang, Sichuan, China"]},{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]},{"name":"Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Yangling, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjie","family":"Li","sequence":"additional","affiliation":[{"name":"Hebei Veyong Pharmaceutical Co., Ltd.","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Qiu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]},{"name":"Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Yangling, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]},{"name":"Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Yangling, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunjiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Hebei Veyong Pharmaceutical Co., Ltd.","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menglong","family":"Yue","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]},{"name":"Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Yangling, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Congshang","family":"Lei","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]},{"name":"Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Yangling, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Yin","sequence":"additional","affiliation":[{"name":"Animal Disease Prevention and Control, Healthy Breeding Engineering Technology Research Center, Mianyang Normal University","place":["Mianyang, Sichuan, China"]},{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefeng","family":"Qi","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University","place":["Yangling, Shaanxi, China"]},{"name":"Key Laboratory of Ruminant Disease Prevention and Control (West), Ministry of Agriculture and Rural Affairs","place":["Yangling, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiwen","family":"Chen","sequence":"additional","affiliation":[{"name":"Animal Disease Prevention and Control, Healthy Breeding Engineering Technology Research Center, Mianyang Normal University","place":["Mianyang, Sichuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"110171","DOI":"10.1016\/j.vetmic.2024.110171","article-title":"Prevalence and molecular characteristics of intestinal pathogenic Escherichia coli isolated from diarrheal pigs in southern China","volume":"296","author":"Li","year":"2024","journal-title":"Vet Microbiol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/j.aninu.2024.03.006","article-title":"Nutrition strategies to control post-weaning diarrhea of piglets: from the perspective of feeds","volume":"17","author":"Tang","year":"2024","journal-title":"Anim Nutr"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.3389\/fimmu.2019.02333","article-title":"\u03b2-Defensin 129 attenuates bacterial endotoxin-induced inflammation and intestinal epithelial cell apoptosis","volume":"10","author":"Xie","year":"2019","journal-title":"Front Immunol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"671683","DOI":"10.3389\/fmicb.2021.671683","article-title":"Early-life intervention using exogenous fecal microbiota alleviates gut injury and reduce inflammation caused by weaning stress in piglets","volume":"12","author":"Ma","year":"2021","journal-title":"Front Microbiol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e03258-19","DOI":"10.1128\/mBio.03258-19","article-title":"Romo1-derived antimicrobial peptide is a new antimicrobial agent against multidrug-resistant bacteria in a murine model of sepsis","volume":"11","author":"Lee","year":"2020","journal-title":"mBio"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"6687555","DOI":"10.1155\/2021\/6687555","article-title":"TLR4-NLRP3-GSDMD-mediated pyroptosis plays an important role in aggravated liver injury of CD38\u2212\/\u2212 sepsis mice","volume":"2021","author":"Zhang","year":"2021","journal-title":"J Immunol Res"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.3389\/fimmu.2019.01673","article-title":"Porcine beta-defensin 2 provides protection against bacterial infection by a direct bactericidal activity and alleviates inflammation via interference with the TLR4\/NF-\u03baB pathway","volume":"10","author":"Huang","year":"2019","journal-title":"Front Immunol"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"43918","DOI":"10.1021\/acsami.4c06381","article-title":"Versatile fabrication of biocompatible antimicrobial materials enabled by cationic peptide bundles","volume":"16","author":"Liu","year":"2024","journal-title":"ACS Appl Mater Interfaces"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e2105955","DOI":"10.1002\/advs.202105955","article-title":"Designing self-assembling chimeric peptide nanoparticles with high stability for combating piglet bacterial infections","volume":"9","author":"Tan","year":"2022","journal-title":"Adv Sci"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.immuni.2015.07.005","article-title":"Transcription factor Bcl11b controls identity and function of mature type 2 innate lymphoid cells","volume":"43","author":"Califano","year":"2015","journal-title":"Immunity"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.vetmic.2019.02.027","article-title":"Protecting intestinal epithelial cells against deoxynivalenol and E. coli damage by recombinant porcine IL-22","volume":"231","author":"Li","year":"2019","journal-title":"Vet Microbiol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1136\/gutjnl-2018-317232","article-title":"Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice","volume":"68","author":"Hendrikx","year":"2019","journal-title":"Gut"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s13567-024-01428-1","article-title":"Expression of recombination antimicrobial protein PIL22-PBD-2 in Pichia pastoris and verification of its biological function in vitro","volume":"56","author":"Li","year":"2025","journal-title":"Vet Res"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"3417","DOI":"10.7150\/thno.53105","article-title":"Colon tissue-accumulating mesoporous carbon nanoparticles loaded with Musca domestica cecropin for ulcerative colitis therapy","volume":"11","author":"Zhang","year":"2021","journal-title":"Theranostics"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"16674","DOI":"10.1021\/acsnano.4c01640","article-title":"Enhanced prostate-specific membrane antigen targeting by precision control of DNA scaffolded nanoparticle ligand presentation","volume":"18","author":"Jana","year":"2024","journal-title":"ACS Nano"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"122603","DOI":"10.1016\/j.biomaterials.2024.122603","article-title":"Regulating tumor innervation by nanodrugs potentiates cancer immunochemotherapy and relieve chemotherapy-induced neuropathic pain","volume":"309","author":"Zuo","year":"2024","journal-title":"Biomaterials"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"122697","DOI":"10.1016\/j.biomaterials.2024.122697","article-title":"Dictating the spatial-temporal delivery of molecular adjuvant and antigen for the enhanced vaccination","volume":"311","author":"Yan","year":"2024","journal-title":"Biomaterials"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"101658","DOI":"10.1016\/j.arr.2022.101658","article-title":"Brain drug delivery and neurodegenerative diseases: polymeric PLGA-based nanoparticles as a forefront platform","volume":"79","author":"Pinto","year":"2022","journal-title":"Ageing Res Rev"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.2147\/ijn.S445269","article-title":"Microstructure formation and characterization of long-acting injectable microspheres: the gateway to fully controlled drug release pattern","volume":"19","author":"Wang","year":"2024","journal-title":"Int J Nanomedicine"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.jconrel.2012.01.043","article-title":"PLGA-based nanoparticles: an overview of biomedical applications","volume":"161","author":"Danhier","year":"2012","journal-title":"J Control Release"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2416","DOI":"10.1016\/j.apsb.2021.04.001","article-title":"Oral delivery of proteins and peptides: challenges, status quo and future perspectives","volume":"11","author":"Zhu","year":"2021","journal-title":"Acta Pharm Sin B"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"121677","DOI":"10.1016\/j.biomaterials.2022.121677","article-title":"Enhancement of anticancer immunity by immunomodulation of apoptotic tumor cells using annexin A5 protein-labeled nanocarrier system","volume":"288","author":"Lee","year":"2022","journal-title":"Biomaterials"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"811616","DOI":"10.3389\/fimmu.2021.811616","article-title":"Oral Administration of Nanopeptide CMCS-20H conspicuously boosts immunity and precautionary effect against bacterial infection in fish","volume":"12","author":"Huo","year":"2021","journal-title":"Front Immunol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"10088","DOI":"10.1021\/acsnano.3c12487","article-title":"Targeted and self-adjuvated nanoglycovaccine candidate for cancer immunotherapy","volume":"18","author":"Freitas","year":"2024","journal-title":"ACS Nano"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"644887","DOI":"10.3389\/fmicb.2021.644887","article-title":"The antimicrobial peptide mastoparan X protects against enterohemorrhagic Escherichia coli O157:H7 infection, inhibits inflammation, and enhances the intestinal epithelial barrier","volume":"12","author":"Zhao","year":"2021","journal-title":"Front Microbiol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1292\/jvms.21-0157","article-title":"Dietary carbohydrate effects on histological features of ileal mucosa in White Leghorn chicken","volume":"83","author":"Salahuddin","year":"2021","journal-title":"J Vet Med Sci"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"912207","DOI":"10.3389\/fnut.2022.912207","article-title":"In vitro digestion characteristics of hydrolyzed infant formula and its effects on the growth and development in mice","volume":"9","author":"Feng","year":"2022","journal-title":"Front Nutr"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"5252","DOI":"10.1038\/s41467-019-13118-0","article-title":"Characterization of antibiotic resistance genes in the species of the rumen microbiota","volume":"10","author":"Sabino","year":"2019","journal-title":"Nat Commun"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1039\/d4np00002a","article-title":"Medium-sized peptides from microbial sources with potential for antibacterial drug development","volume":"41","author":"Chen","year":"2024","journal-title":"Nat Prod Rep"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"508","DOI":"10.3390\/antibiotics13060508","article-title":"Efficacy of short novel antimicrobial peptides in a mouse model of Staphylococcus pseudintermedius skin infection","volume":"13","author":"Ouyang","year":"2024","journal-title":"Antibiotics"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"395707","DOI":"10.1088\/1361-6528\/ad5b66","article-title":"Construction of recombinant Omp25 or EipB protein loaded PLGA nanovaccines for brucellosis protection","volume":"35","author":"Akmayan","year":"2024","journal-title":"Nanotechnology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"129951","DOI":"10.1016\/j.foodchem.2021.129951","article-title":"Antimicrobial peptides purified from hydrolysates of kanihua (Chenopodium pallidicaule Aellen) seed protein fractions","volume":"360","author":"Moscoso-Mujica","year":"2021","journal-title":"Food Chem"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.jconrel.2020.07.011","article-title":"Pharmacokinetics of inhaled nanotherapeutics for pulmonary delivery","volume":"326","author":"Shen","year":"2020","journal-title":"J Control Release"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2467187","DOI":"10.1080\/19490976.2025.2467187","article-title":"Salmonella utilizes L-arabinose to silence virulence gene expression for accelerated pathogen growth within the host","volume":"17","author":"Yu","year":"2025","journal-title":"Gut Microbes"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"651488","DOI":"10.3389\/fmicb.2021.651488","article-title":"Re-evaluation of a neonatal mouse model of infection with enterotoxigenic Escherichia coli","volume":"12","author":"Carroll","year":"2021","journal-title":"Front Microbiol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"508","DOI":"10.3390\/vaccines12050508","article-title":"Further evaluation of enterohemorrhagic Escherichia coli gold nanoparticle vaccines utilizing Citrobacter rodentium as the model organism","volume":"12","author":"Bowser","year":"2024","journal-title":"Vaccine"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"Ehec-0022-2013","DOI":"10.1128\/microbiolspec.EHEC-0022-2013","article-title":"Animal models of enterohemorrhagic Escherichia coli infection","volume":"2","author":"Ritchie","year":"2014","journal-title":"Microbiol Spectr"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s13567-024-01321-x","article-title":"Effect of oral administration of microcin Y on growth performance, intestinal barrier function and gut microbiota of chicks challenged with Salmonella Pullorum","volume":"55","author":"Li","year":"2024","journal-title":"Vet Res"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"4280","DOI":"10.3748\/wjg.14.4280","article-title":"Role of cytokines in inflammatory bowel disease","volume":"14","author":"Sanchez-Munoz","year":"2008","journal-title":"World J Gastroenterol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1017\/s0007114512006083","article-title":"Dietary supplementation of young broiler chickens with Capsicum and turmeric oleoresins increases resistance to necrotic enteritis","volume":"110","author":"Lee","year":"2013","journal-title":"Br J Nutr"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s10620-018-5309-8","article-title":"Homoectoine protects against colitis by preventing a claudin switch in epithelial tight junctions","volume":"64","author":"Castro-Ochoa","year":"2019","journal-title":"Dig Dis Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"127615","DOI":"10.1016\/j.ijbiomac.2023.127615","article-title":"Polysaccharide from Sparassis latifolia alleviates intestinal barrier dysfunction in mice exposed to lead","volume":"253","author":"Cheng","year":"2023","journal-title":"Int J Biol Macromol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.phymed.2018.09.228","article-title":"Comparison of anti-inflammatory effects of berberine, and its natural oxidative and reduced derivatives from Rhizoma Coptidis in vitro and in vivo","volume":"52","author":"Li","year":"2019","journal-title":"Phytomedicine"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1728161\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:26:13Z","timestamp":1773379573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1728161\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,13]]},"references-count":43,"alternative-id":["10.3389\/fvets.2026.1728161"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2026.1728161","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,13]]},"article-number":"1728161"}}