{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:06:32Z","timestamp":1790726792044,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32201994"],"award-info":[{"award-number":["32201994"]}]},{"name":"National Natural Science Foundation of China","award":["RD06"],"award-info":[{"award-number":["RD06"]}]},{"name":"Coree Beijing Co., Ltd","award":["32201994"],"award-info":[{"award-number":["32201994"]}]},{"name":"Coree Beijing Co., Ltd","award":["RD06"],"award-info":[{"award-number":["RD06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Heyndrickxia coagulans (formerly Bacillus coagulans) has been increasingly utilized as an immunomodulatory probiotics. Oral administration of H. coagulans HOM5301 significantly boosted both innate and adaptive immunity in mice, particularly by increasing the phagocytic capacity of monocytes\/macrophages. Lipoteichoic acid (LTA), a major microbe-associated molecular pattern (MAMP) in Gram-positive bacteria, exhibits differential immunomodulatory effects due to its structural heterogeneity. We extracted, purified, and characterized LTA from H. coagulans HOM5301. The results showed that HOM5301 LTA consists of a glycerophosphate backbone. Its molecular weight is in the range of 10\u201316 kDa. HOM5301 LTA induced greater productions of nitric oxide, TNF\u03b1, and IL-6 in RAW 264.7 macrophages compared to Staphylococcus aureus LTA. Comparative transcriptome and proteome analyses identified the differentially expressed genes and proteins triggered by HOM5301 LTA. KEGG analyses revealed that HOM5301 LTA transcriptionally and translationally activated macrophages through two immune-related pathways: cytokine\u2013cytokine receptor interaction and phagosome formation. Protein\u2013protein interaction network analysis indicated that the pro-inflammatory response elicited by HOM5301 LTA was TLR2-dependent, possibly requiring the coreceptor CD14, and is mediated via the MAPK and NF-kappaB pathways. Our results demonstrate that LTA is an important MAMP of H. coagulans HOM5301 that boosts immune responses, suggesting that HOM5301 LTA may be a promising immunoadjuvant.<\/jats:p>","DOI":"10.3390\/nu16173014","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T06:18:35Z","timestamp":1725603515000},"page":"3014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Lipoteichoic Acid from Heyndrickxia coagulans HOM5301 Modulates the Immune Response of RAW 264.7 Macrophages"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9819-9091","authenticated-orcid":false,"given":"Shiqi","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"},{"name":"Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing 101312, China"},{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Healthy, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinglan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing 101312, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ding","sequence":"additional","affiliation":[{"name":"Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing 101312, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing 101312, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suwon","family":"Lee","sequence":"additional","affiliation":[{"name":"Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing 101312, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing 101312, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongyoon","family":"Lim","sequence":"additional","affiliation":[{"name":"Food & Biotech R&D Center, Coree Beijing Co., Ltd., Beijing 101312, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8620-4631","authenticated-orcid":false,"given":"Nan","family":"Shang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Healthy, China Agricultural University, Beijing 100083, China"},{"name":"College of Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liang, J., Li, C., Chen, Z., Guo, F., Dou, J., Wang, T., and Xu, Z.S. (2024). Progress of research and application of Heyndrickxia coagulans (Bacillus coagulans) as probiotic bacteria. Front. Cell Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1415790"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108567","DOI":"10.1016\/j.foodres.2019.108567","article-title":"Bacillus coagulans GBI-30, 6068 decreases upper respiratory and gastrointestinal tract symptoms in healthy Mexican scholar-aged children by modulating immune-related proteins","volume":"125","author":"Mosqueda","year":"2019","journal-title":"Food Res. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1519\/JSC.0000000000003265","article-title":"The effect of 2 weeks of inactivated probiotic Bacillus coagulans on endocrine, inflammatory, and performance responses during self-defense training in soldiers","volume":"33","author":"Hoffman","year":"2019","journal-title":"J. Strength Cond. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.29219\/fnr.v62.1218","article-title":"Bacillus coagulans MTCC 5856 for the management of major depression with irritable bowel syndrome: A randomised, double-blind, placebo controlled, multi-centre, pilot clinical study","volume":"62","author":"Majeed","year":"2018","journal-title":"Food Nutr. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2172-11-15","article-title":"GanedenBC30 cell wall and metabolites: Anti-inflammatory and immune modulating effects in vitro","volume":"11","author":"Jensen","year":"2010","journal-title":"BMC Immunol."},{"key":"ref_6","first-page":"5463290","article-title":"Bacillus coagulans TL3 inhibits LPS-induced caecum damage in rat by regulating the TLR4\/MyD88\/NF-kappaB and Nrf2 signal pathways and modulating intestinal microflora","volume":"2022","author":"Wang","year":"2022","journal-title":"Oxid Med. Cell Longev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Liu, Y., Wang, J., and Wu, C. (2021). Modulation of gut microbiota and immune system by probiotics, pre-biotics, and post-biotics. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.634897"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1177\/09680519050110061001","article-title":"Structure\/function relationships of lipoteichoic acids","volume":"11","author":"Morath","year":"2005","journal-title":"J. Endotoxin Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Friedrich, A.D., Leoni, J., Paz, M.L., and Gonzalez Maglio, D.H. (2022). Lipoteichoic acid from Lacticaseibacillus rhamnosus GG modulates dendritic cells and T cells in the gut. Nutrients, 14.","DOI":"10.3390\/nu14030723"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104360","DOI":"10.1016\/j.micpath.2020.104360","article-title":"Differential role of lipoteichoic acids isolated from Staphylococcus aureus and Lactobacillus plantarum on the aggravation and alleviation of atopic dermatitis","volume":"147","author":"Kim","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1007\/s12272-016-0804-y","article-title":"Lipoteichoic acids as a major virulence factor causing inflammatory responses via Toll-like receptor 2","volume":"39","author":"Kang","year":"2016","journal-title":"Arch. Pharm. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Matsuzaki, C., Shiraishi, T., Chiou, T.Y., Nakashima, Y., Higashimura, Y., Yokota, S.I., Yamamoto, K., and Takahashi, T. (2022). Role of lipoteichoic acid from the genus Apilactobacillus in inducing a strong IgA response. Appl. Environ. Microbiol., 88.","DOI":"10.1128\/aem.00190-22"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lu, Q., Guo, Y., Yang, G., Cui, L., Wu, Z., Zeng, X., Pan, D., and Cai, Z. (2022). Structure and anti-inflammation potential of lipoteichoic acids isolated from Lactobacillus strains. Foods, 11.","DOI":"10.3390\/foods11111610"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ijbiomac.2019.12.227","article-title":"Bifidobacteria cell wall-derived exo-polysaccharides, lipoteichoic acids, peptidoglycans, polar lipids and proteins\u2014Their chemical structure and biological attributes","volume":"147","author":"Pyclik","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105694","DOI":"10.1016\/j.jff.2023.105694","article-title":"In vitro and in vivo evaluation of efficacy and safety of Weizmannia coagulans HOM5301 for boosting immunity","volume":"107","author":"Zhang","year":"2023","journal-title":"J. Funct. Foods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1111\/1751-7915.13769","article-title":"Lipoteichoic acid from Bifidobacterium animalis subsp. lactis BPL1: A novel postbiotic that reduces fat deposition via IGF-1 pathway","volume":"15","author":"Balaguer","year":"2022","journal-title":"Microb. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/1475-2859-11-161","article-title":"Lipoteichoic acid is an important microbe-associated molecular pattern of Lactobacillus rhamnosus GG","volume":"11","author":"Claes","year":"2012","journal-title":"Microb. Cell Fact."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.carbpol.2018.10.041","article-title":"A polysaccharide extracted from Astragalus membranaceus residue improves cognitive dysfunction by altering gut microbiota in diabetic mice","volume":"205","author":"Liu","year":"2019","journal-title":"Carbohyd. Polym."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wu, S., Liu, H., Li, S., Sun, H., He, X., Huang, Y., and Long, H. (2021). Transcriptome analysis reveals possible immunomodulatory activity mechanism of Chlorella sp. exopolysaccharides on RAW264.7 macrophages. Mar. Drugs., 19.","DOI":"10.3390\/md19040217"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.bbrc.2011.03.107","article-title":"Multi-spectrometric analyses of lipoteichoic acids isolated from Lactobacillus plantarum","volume":"407","author":"Jang","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Yoshida, S., Kawai, H., Soe, Y., Eain, H.S., Sanou, S., Takabatake, K., Takeshita, Y., Hisatomi, M., Nagatsuka, H., and Asaumi, J. (2024). Efficacy of cisplatin-CXCR4 antagonist combination therapy in oral cancer. Cancers, 16.","DOI":"10.3390\/cancers16132326"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1038\/nprot.2016.095","article-title":"Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown","volume":"11","author":"Pertea","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1002\/imt2.12","article-title":"Majorbio Cloud: A one-stop, comprehensive bioinformatic platform for multiomics analyses","volume":"1","author":"Ren","year":"2022","journal-title":"Imeta"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1002\/pmic.201400392","article-title":"Visualization of proteomics data using R and bioconductor","volume":"15","author":"Gatto","year":"2015","journal-title":"Proteomics"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Han, J., Zhao, X., Zhao, X., Li, P., and Gu, Q. (2023). Insight into the structure, biosynthesis, isolation method and biological function of teichoic acid in different gram-positive microorganisms: A review. Int. J. Biol. Macromol., 253.","DOI":"10.1016\/j.ijbiomac.2023.126825"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10321","DOI":"10.1073\/pnas.0504084102","article-title":"Enhanced antiinflammatory capacity of a Lactobacillus plantarum mutant synthesizing modified teichoic acids","volume":"102","author":"Grangette","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1128\/JB.01155-13","article-title":"Lipoteichoic acids, phosphate-containing polymers in the envelope of gram-positive bacteria","volume":"196","author":"Schneewind","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s12602-022-09949-x","article-title":"Levilactobacillus brevis KU15151 inhibits Staphylococcus aureus lipoteichoic acid-induced inflammation in RAW 264.7 macrophages","volume":"14","author":"Kim","year":"2022","journal-title":"Probiotics Antimicro."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.intimp.2008.10.014","article-title":"Differential immunostimulatory effects of Gram-positive bacteria due to their lipoteichoic acids","volume":"9","author":"Ryu","year":"2009","journal-title":"Int. Immunopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41581-022-00633-5","article-title":"Trained immunity\u2014Basic concepts and contributions to immunopathology","volume":"19","author":"Ochando","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cortes-Perez, N.G., de Moreno de LeBlanc, A., Gomez-Gutierrez, J.G., LeBlanc, J.G., and Bermudez-Humaran, L.G. (2021). Probiotics and trained immunity. Biomolecules, 11.","DOI":"10.3390\/biom11101402"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1111\/j.1600-0854.2012.01377.x","article-title":"Phagosome as the organelle linking innate and adaptive immunity","volume":"13","author":"Kagan","year":"2012","journal-title":"Traffic"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41423-021-00780-y","article-title":"Impact of intracellular innate immune receptors on immunometabolism","volume":"19","author":"Chou","year":"2022","journal-title":"Cell Mol. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1189\/jlb.0907656","article-title":"Cellular trafficking of lipoteichoic acid and Toll-like receptor 2 in relation to signaling: Role of CD14 and CD36","volume":"84","author":"Nilsen","year":"2008","journal-title":"J. Leukoc. Biol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/17\/3014\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:49:43Z","timestamp":1760111383000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/17\/3014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":37,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["nu16173014"],"URL":"https:\/\/doi.org\/10.3390\/nu16173014","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,6]]}}}