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In this study, we obtained a novel crude exopolysaccharide (EPS) postbiotic from Bacillus subtilis H4. We systematically optimized the EPS production strategy using single-factor analysis, Plackett\u2013Burman design, the path of steepest ascent method, and response surface methodology. The optimized EPS yield was significantly improved, with a maximum yield of 15.01 g\/L under the addition of 4.12% soy peptone, 8.99% sucrose, and 0.06% MnSO4. We found that EPS is a neutral, heterogeneous polysaccharide with a pyranose ring, with a molecular weight of 44,304.913 kDa and a melting point of 218 \u00b0C. It consists of glucose, galactose, arabinose, glucosamine, and mannose at a molar ratio of 58.85:19.81:14.75:10.89:6.58. EPS exhibits strong antioxidant capacities, scavenging ABTS and DPPH radicals with IC50 values of 1 and 6 mg\/mL, respectively. Moreover, it shows notable anti-inflammatory properties, dramatically inhibiting the lipopolysaccharide (LPS)-induced elevation of nitric oxide (NO) levels and over-activation of the TLR4-NF-\u03baB signaling pathway. These findings highlight the potential of EPS as a multifunctional bioactive compound, offering great promise for its application in the food, clinical, and feed industries.<\/jats:p>","DOI":"10.3390\/molecules30102089","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T07:41:47Z","timestamp":1746690107000},"page":"2089","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Efficient Production Strategy of a Novel Postbiotic Produced by Bacillus subtilis and Its Antioxidant and Anti-Inflammatory Effects"],"prefix":"10.3390","volume":"30","author":[{"given":"Jing","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2158-2865","authenticated-orcid":false,"given":"Junyong","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaheer","family":"Abbas","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucui","family":"Tong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Fang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichen","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haosen","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayong","family":"Si","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xubiao","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41575-021-00440-6","article-title":"The international scientific association of probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics","volume":"18","author":"Salminen","year":"2021","journal-title":"Nat. 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