{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:09:08Z","timestamp":1784534948015,"version":"3.55.0"},"reference-count":72,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S\u014dlaria Bi\u014d Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic low-grade aging-associated inflammation, or inflammaging, is a central pillar of age-related decline in quality of life. Inflammaging is partially mediated by impaired intestinal, immune, and microbiome function, and it has been hypothesized that probiotics could be used to promote healthy aging. SBD121, a defined synbiotic containing food-derived microbial strains and prebiotic fibers, has previously been shown to improve grip strength in male rats, an important indicator of healthspan, and is under evaluation in a clinical trial of 143 newly diagnosed rheumatoid arthritis patients (NCT06005220). However, the mechanisms underlying its potential benefits have not been determined. Here, we examined the function of SBD121 in microbial, cellular, and animal models relevant to inflammaging. SBD121 inhibited the growth of potential microbial pathogens, produced immunomodulatory metabolites in vitro, and improved human intestinal cell barrier function under both basal and challenge conditions, while reducing inflammatory chemokine secretion following inflammatory challenge. SBD121 also reduced the secretion of multiple chemokines in lipopolysaccharide-stimulated human intestinal and immune cells. Finally, SBD121 improved survival and locomotor activity in a C. elegans longevity model, providing evidence of benefits to lifespan and healthspan. Together, these data demonstrate that SBD121 exhibits beneficial microbial, epithelial, immune, and longevity effects and support continued investigation of SBD121 as a candidate intervention for healthy aging.<\/jats:p>","DOI":"10.3390\/ijms27146369","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:54:13Z","timestamp":1784534053000},"page":"6369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Defined Synbiotic Produces Immunomodulatory Metabolites, Engages Gut\u2013Immune Pathways Relevant to Inflammaging, and Supports Healthy Aging in a Nematode Model"],"prefix":"10.3390","volume":"27","author":[{"given":"Ryan S.","family":"Green","sequence":"first","affiliation":[{"name":"S\u014dlaria Bi\u014d, Waltham, MA 02453, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Diaz-Infante Morales","sequence":"additional","affiliation":[{"name":"S\u014dlaria Bi\u014d, Waltham, MA 02453, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Schott","sequence":"additional","affiliation":[{"name":"S\u014dlaria Bi\u014d, Waltham, MA 02453, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Charbonneau","sequence":"additional","affiliation":[{"name":"S\u014dlaria Bi\u014d, Waltham, MA 02453, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1536-2941","authenticated-orcid":false,"given":"Alicia E.","family":"Ballok","sequence":"additional","affiliation":[{"name":"S\u014dlaria Bi\u014d, Waltham, MA 02453, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026, May 05). Ageing and Health. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/ageing-and-health."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: A new immune\u2013metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2511046","DOI":"10.4014\/jmb.2511.11046","article-title":"Gut Microbiota, Probiotics, and Aging: Molecular Mechanisms and Implications for Healthy Aging","volume":"36","author":"Kim","year":"2026","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.jacc.2021.12.017","article-title":"Inflammation, Aging, and Cardiovascular Disease: JACC Review Topic of the Week","volume":"79","author":"Liberale","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"526.e9","DOI":"10.1016\/j.amjmed.2005.10.049","article-title":"Inflammatory Markers and Loss of Muscle Mass (Sarcopenia) and Strength","volume":"119","author":"Schaap","year":"2006","journal-title":"Am. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/gerona\/gln038","article-title":"Chronic Inflammation Is Associated with Low Physical Function in Older Adults Across Multiple Comorbidities","volume":"64","author":"Brinkley","year":"2009","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1093\/gerona\/glu127","article-title":"Aging and the Burden of Multimorbidity: Associations With Inflammatory and Anabolic Hormonal Biomarkers","volume":"70","author":"Fabbri","year":"2014","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41392-023-01502-8","article-title":"Inflammation and aging: Signaling pathways and intervention therapies","volume":"8","author":"Li","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1038\/s12276-025-01480-7","article-title":"Hallmarks of cellular senescence: Biology, mechanisms, regulations","volume":"57","author":"Ajoolabady","year":"2025","journal-title":"Exp. Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100113","DOI":"10.1016\/j.mocell.2024.100113","article-title":"The role of p21 in cellular senescence and aging-related diseases","volume":"47","author":"Yan","year":"2024","journal-title":"Mol. Cells"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.18632\/aging.205577","article-title":"Mapping the core senescence phenotype of primary human colon fibroblasts","volume":"16","author":"Hattangady","year":"2024","journal-title":"Aging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"238","DOI":"10.4062\/biomolther.2025.222","article-title":"Immunosenescence in Human Disease: Mechanistic Insights and Therapeutic Opportunities","volume":"34","author":"Kim","year":"2026","journal-title":"Biomol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1016\/j.exger.2013.09.003","article-title":"The Th17\/Treg balance is disturbed during aging","volume":"48","author":"Schmitt","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7547","DOI":"10.4049\/jimmunol.0900519","article-title":"Unlike Th1, Th17 Cells Mediate Sustained Autoimmune Inflammation and Are Highly Resistant to Restimulation-Induced Cell Death","volume":"183","author":"Shi","year":"2009","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/s41419-019-2086-z","article-title":"Keep calm: The intestinal barrier at the interface of peace and war","volume":"10","author":"Thoo","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.chom.2017.03.002","article-title":"Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction","volume":"21","author":"Thevaranjan","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_18","first-page":"275","article-title":"Gut microbiota, intestinal permeability, and systemic inflammation: A narrative review","volume":"19","author":"Petito","year":"2023","journal-title":"Intern. Emerg. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"eadi0672","DOI":"10.1126\/sciimmunol.adi0672","article-title":"A dynamic atlas of immunocyte migration from the gut","volume":"9","author":"Zhu","year":"2024","journal-title":"Sci. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fu, Y., Lyu, J., and Wang, S. (2023). The role of intestinal microbes on intestinal barrier function and host immunity from a metabolite perspective. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1277102"},{"key":"ref_21","first-page":"1","article-title":"Bacterial acetate metabolism and its influence on human epithelia","volume":"8","author":"Hosmer","year":"2024","journal-title":"Emerg. Top. Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Choi, E.J., Jang, Y.Y., Choi, E.J., and Oh, C.J. (2025). The Role of Lactate in Immune Regulation: A Metabolic Rheostat via Transporters, Receptors, and Epigenetic Modifiers. Cells, 14.","DOI":"10.3390\/cells14141096"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, G., Xiong, Y., Li, Z., Yu, Q., Li, S., Xie, J., Zeng, S., Yu, D., Yang, Y., and Yu, J. (2025). Gut microbiota-derived metabolites modulate Treg\/Th17 balance: Novel therapeutic targets in autoimmune diseases. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1710733"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e144156","DOI":"10.1172\/jci.insight.144156","article-title":"Gut-derived acetate promotes B10 cells with antiinflammatory effects","volume":"6","author":"Tan","year":"2021","journal-title":"JCI Insight"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kumar, A., Saranyadevi, S., Thirumalaisamy, S.K., Dapana Durage, T.T., Jaiswal, S.G., Kavitake, D., and Wei, S. (2025). Phenolic acids in fermented foods: Microbial biotransformation, antioxidant mechanisms, and functional health implications. Front. Mol. Biosci., 12.","DOI":"10.3389\/fmolb.2025.1678673"},{"key":"ref_26","unstructured":"Rajamohamed, H., Sameeha, K., Edlin Domini, T., Harun, M., Dheva Kumar, S., and Paul Mathi Vathana, K. (2025). GABA: The Peacekeeper Neurotransmitter\u2014Gut-microbiota Derived Origins and Salivary Biomarker Detection Using Elisa. Ann. Neurosci., 09727531251398979."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hwang, Y.K., and Oh, J.S. (2025). Interaction of the Vagus Nerve and Serotonin in the Gut\u2013Brain Axis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26031160"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"116434","DOI":"10.1016\/j.celrep.2025.116434","article-title":"Identification of human gut bacteria that produce bioactive serotonin and promote colonic innervation","volume":"44","author":"Moretti","year":"2025","journal-title":"Cell Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114839","DOI":"10.1016\/j.fct.2024.114839","article-title":"Food safety assessment and 28-day toxicity study of the synbiotic medical food consortium SBD121","volume":"191","author":"Easson","year":"2024","journal-title":"Food Chem. Toxicol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ibrahim, S.A., Ayivi, R.D., Zimmerman, T., Siddiqui, S.A., Altemimi, A.B., Fidan, H., Esatbeyoglu, T., and Bakhshayesh, R.V. (2021). Lactic Acid Bacteria as Antimicrobial Agents: Food Safety and Microbial Food Spoilage Prevention. Foods, 10.","DOI":"10.3390\/foods10123131"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jgar.2017.08.008","article-title":"Characterisation of two novel bacteriocin-like substances produced by Bacillus amyloliquefaciens ELI149 with broad-spectrum antimicrobial activity","volume":"11","author":"Salazar","year":"2017","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1007\/s42770-021-00559-3","article-title":"Optimization of bioprocess of Schleiferilactobacillus harbinensis Ca12 and its viability in frozen Brazilian berries (A\u00e7ai, Euterpe oleracea Mart.)","volume":"52","author":"Colares","year":"2021","journal-title":"Braz. J. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00203-020-02054-z","article-title":"Conditions of nisin production by Lactococcus lactis subsp. lactis and its main uses as a food preservative","volume":"203","author":"Khelissa","year":"2020","journal-title":"Arch. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1163\/18762891-bja00109","article-title":"Targeted detection of microbes in synbiotic medical foods SBD111 and SBD121 to evaluate gut persistence: A randomised, open label trial","volume":"1","author":"Miller","year":"2026","journal-title":"Benef. Microbes"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00018-017-2671-1","article-title":"Role of gut microbiota in aging-related health decline: Insights from invertebrate models","volume":"75","author":"Clark","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s40005-016-0259-7","article-title":"Probiotic Delivery Systems: A Brief Overview","volume":"46","author":"Kim","year":"2016","journal-title":"J. Pharm. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.micpath.2019.01.037","article-title":"Antimicrobial activity and spectroscopic characterization of surfactin class of lipopeptides from Bacillus amyloliquefaciens SR1","volume":"128","author":"Nanjundan","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"107717","DOI":"10.1016\/j.micpath.2025.107717","article-title":"Age-related oral microbiota dysbiosis and systemic diseases","volume":"205","author":"Deng","year":"2025","journal-title":"Microb. Pathog."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2607076","DOI":"10.1080\/19490976.2025.2607076","article-title":"The role of gut microbiome in aging-associated diseases: Where do we stand now and how technology will transform the future","volume":"18","author":"Aldriwesh","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Sep\u00falveda-Pontigo, A., Ch\u00e1vez-Villacreses, K., Madrid-Mu\u00f1oz, C., Conejeros-Lillo, S., Parra, F., Melo-Gonz\u00e1lez, F., Regaldiz, A., Gonz\u00e1lez, V.P., M\u00e9ndez-P\u00e9rez, I., and Castillo-Godoy, D.P. (2025). Segatella copri Outer-Membrane Vesicles Are Internalized by Human Macrophages and Promote a Pro-Inflammatory Profile. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083630"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Klimesova, K., Zakostelska, Z.J., and Tlaskalova-Hogenova, H. (2018). Oral Bacterial and Fungal Microbiome Impacts Colorectal Carcinogenesis. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00774"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7577","DOI":"10.1007\/s13197-015-1921-1","article-title":"Probiotics, Prebiotics and Synbiotics\u2014A Review","volume":"52","author":"Pandey","year":"2015","journal-title":"J. Food Sci. Technol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kyriacou, M.C., El-Nakhel, C., Pannico, A., Graziani, G., Soteriou, G.A., Giordano, M., Palladino, M., Ritieni, A., De Pascale, S., and Rouphael, Y. (2020). Phenolic constitution, phytochemical and macronutrient content in three species of microgreens as modulated by natural fiber and synthetic substrates. Antioxidants, 9.","DOI":"10.3390\/antiox9030252"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Gilbert, S., Xu, J., Acosta, K., Poulev, A., Lebeis, S., and Lam, E. (2018). Bacterial production of indole related compounds reveals their role in association between duckweeds and endophytes. Front. Chem., 6.","DOI":"10.3389\/fchem.2018.00265"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Yuan, L., van der Mei, H.C., Busscher, H.J., and Peterson, B.W. (2020). Two-Stage Interpretation of Changes in TEER of Intestinal Epithelial Layers Protected by Adhering Bifidobacteria During E. coli Challenges. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.599555"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/B978-1-4377-2206-2.00068-3","article-title":"Small Intestine","volume":"Volume 1\u20132","author":"Abbott","year":"2013","journal-title":"Shackelford\u2019s Surgery of the Alimentary Tract"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/0016-5085(84)90592-4","article-title":"Methods for the determination of epithelial cell kinetic parameters of human colonic epithelium isolated from surgical and biopsy specimens","volume":"86","author":"Cheng","year":"1984","journal-title":"Gastroenterology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/ar.1092070305","article-title":"Cell production in mouse intestinal epithelium measured by stathmokinetic flow cytometry and coulter particle counting","volume":"207","author":"Cheng","year":"1983","journal-title":"Anat. Rec."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3109\/00365521.2014.898326","article-title":"Surface area of the digestive tract\u2014Revisited","volume":"49","author":"Helander","year":"2014","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1007\/s00018-015-1931-1","article-title":"Compartmentalizing intestinal epithelial cell toll-like receptors for immune surveillance","volume":"72","author":"Yu","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kobayashi, N., Takahashi, D., Takano, S., Kimura, S., and Hase, K. (2019). The Roles of Peyer\u2019s Patches and Microfold Cells in the Gut Immune System: Relevance to Autoimmune Diseases. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02345"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/86373","article-title":"Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria","volume":"2","author":"Rescigno","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.imbio.2008.02.001","article-title":"Effects of probiotic bacteria and their genomic DNA on TH1\/TH2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects","volume":"213","author":"Ghadimi","year":"2008","journal-title":"Immunobiology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.3748\/wjg.v16.i28.3529","article-title":"Probiotic Bio-Three induces Th1 and anti-inflammatory effects in PBMC and dendritic cells","volume":"16","author":"Hua","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Lemme-Dumit, J.M., Cazorla, S.I., Perdig\u00f3n, G.D.V., and Maldonado-Galdeano, C. (2021). Probiotic Bacteria and Their Cell Walls Induce Th1-Type Immunity Against Salmonella Typhimurium Challenge. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.660854"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.jaut.2008.04.017","article-title":"Role of Th1 and Th17 cells in organ-specific autoimmunity","volume":"31","author":"Dardalhon","year":"2008","journal-title":"J. Autoimmun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1016\/j.cell.2025.03.043","article-title":"A type 1 immune-stromal cell network mediates disease tolerance against intestinal infection","volume":"188","author":"Westfall","year":"2025","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1080\/09540105.2019.1579785","article-title":"Two strains of probiotic Lactobacillus enhance immune response and promote naive T cell polarization to Th1","volume":"30","author":"Ren","year":"2019","journal-title":"Food Agric. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"107114","DOI":"10.1016\/j.jff.2025.107114","article-title":"A synbiotic medical food improves gut barrier function, reduces immune responses, and inhibits osteoclast activity in models of postmenopausal bone loss aligned with clinical outcomes","volume":"135","author":"Green","year":"2025","journal-title":"J. Funct. Foods"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e14484","DOI":"10.1111\/1751-7915.14484","article-title":"Mutualistic interactions of lactate-producing lactobacilli and lactate-utilizing Veillonella dispar: Lactate and glutamate cross-feeding for the enhanced growth and short-chain fatty acid production","volume":"17","author":"Zhang","year":"2024","journal-title":"Microb. Biotechnol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2944","DOI":"10.1111\/febs.14466","article-title":"A guide to chemokines and their receptors","volume":"285","author":"Hughes","year":"2018","journal-title":"FEBS J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1038\/ni.2391","article-title":"Restraint of inflammatory signaling by interdependent strata of negative regulatory pathways","volume":"13","author":"Murray","year":"2012","journal-title":"Nat. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"aaf1098","DOI":"10.1126\/science.aaf1098","article-title":"Trained immunity: A program of innate immune memory in health and disease","volume":"352","author":"Netea","year":"2016","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.coi.2011.10.004","article-title":"Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium","volume":"24","author":"Ausubel","year":"2012","journal-title":"Curr. Opin. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1002\/jsfa.5633","article-title":"High-throughput micro plate assays for screening flavonoid content and DPPH-scavenging activity in sorghum bran and flour","volume":"92","author":"Herald","year":"2012","journal-title":"J. Sci. Food Agric."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"E344","DOI":"10.1152\/ajpendo.00366.2021","article-title":"Development of a synbiotic that protects against ovariectomy-induced trabecular bone loss","volume":"322","author":"Lawenius","year":"2022","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"BSR20171497","DOI":"10.1042\/BSR20171497","article-title":"Morphofunctional properties of a differentiated Caco2\/HT-29 co-culture as an in vitro model of human intestinal epithelium","volume":"38","author":"Ferraretto","year":"2018","journal-title":"Biosci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1177\/153537020222700817","article-title":"TNF-\u03b1 sensitizes HT-29 colonic epithelial cells to intestinal lactobacilli","volume":"227","author":"McCracken","year":"2002","journal-title":"Exp. Biol. Med."},{"key":"ref_69","unstructured":"PROGEN (2025, January 21). PolymorphPrepTM|1895. Available online: https:\/\/www.progen.com\/polymorphprep\/1895."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kleiveland, C., and Kleiveland, C. (2015). Peripheral Blood Mononuclear Cells. The Impact of Food Bioactives on Health, Springer.","DOI":"10.1007\/978-3-319-16104-4_15"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-9255-9-1","article-title":"LPS induced inflammatory responses in human peripheral blood mononuclear cells is mediated through NOX4 and Gi\u03b1 dependent PI-3kinase signalling","volume":"9","author":"Ngkelo","year":"2012","journal-title":"J. Inflamm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"8.37.1","DOI":"10.1002\/cpns.17","article-title":"The movement tracker: A flexible system for automated movement analysis in invertebrate model organisms","volume":"77","author":"Mouchiroud","year":"2016","journal-title":"Curr. Protoc. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6369\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T07:58:31Z","timestamp":1784534311000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":72,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146369"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146369","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]}}}