{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:05:36Z","timestamp":1779890736295,"version":"3.53.1"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation Innovation and Development Joint Fund Project of Shandong Province","award":["ZR2021LZY021"],"award-info":[{"award-number":["ZR2021LZY021"]}]},{"name":"Key R&D Program Project (Competitive Platform) of Shandong Province","award":["2025CXPT123"],"award-info":[{"award-number":["2025CXPT123"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Objectives: This study aimed to investigate the therapeutic effects and potential mechanisms of Lonicerae japonicae Flos (Jinyinhua, JYH) against respiratory syncytial virus (RSV)-induced pneumonia by integrating lung tissue metabolomics with gut microbiota analysis. Methods: An RSV-infected mouse model was established through intranasal inoculation. Lung pathological changes, viral RNA levels, lung index, and inflammatory cytokine levels were evaluated. Untargeted metabolomics and 16S rRNA gene amplicon sequencing were performed to characterize JYH-mediated alterations in pulmonary metabolites and the gut microbiota. Spearman correlation analysis was conducted to assess associations between differentially abundant bacterial genera and significantly altered metabolites. Results: JYH alleviated RSV-induced pulmonary histopathological injury, reduced viral RNA levels, decreased lung index and interleukin-6 (IL-6) levels, and increased interferon-\u03b3 (IFN-\u03b3) levels. Metabolomic profiling identified 46 differential metabolites, among which 26 showed a reversal trend following JYH administration. These metabolites were mainly enriched in pathways associated with the synaptic vesicle cycle, lysosomal function, and Forkhead box O (FoxO) signaling. Gut microbiota analysis showed that JYH increased microbial richness and diversity, whereas KEGG-based functional prediction indicated that the differentially abundant taxa were primarily involved in amino acid, carbohydrate, and nucleotide metabolism. Moreover, correlation analysis revealed significant associations between key bacterial genera, including Gemella, Sutterella, and CC_115, and differential metabolites such as pyridoxamine, uridine monophosphate (UMP), and argininosuccinic acid. Conclusions: JYH may protect against RSV-induced pneumonia by restoring pulmonary metabolic homeostasis and modulating gut microbiota composition. These findings provide new insights into metabolite\u2013microbiota interactions underlying the anti-RSV activity of JYH.<\/jats:p>","DOI":"10.3390\/metabo16060360","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:31:56Z","timestamp":1779885116000},"page":"360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrating Metabolomics and Gut Microbiota to Reveal the Therapeutic Effect of Lonicerae japonicae Flos Against Respiratory Syncytial Virus"],"prefix":"10.3390","volume":"16","author":[{"given":"Yanghai","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Liang","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","first-page":"198","article-title":"Biomarkers in Urine and Feces of BALB\/c Mice Infected with RSV Pneumonia Using GC-MS Technology","volume":"33","author":"Meng","year":"2017","journal-title":"J. Nanjing Univ. Tradit. Chin. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107500","DOI":"10.1016\/j.micpath.2025.107500","article-title":"Intestinal microbiota and respiratory system diseases: Relationships with three common respiratory virus infections","volume":"203","author":"Wu","year":"2025","journal-title":"Microb. Pathog."},{"key":"ref_3","first-page":"2671","article-title":"Investigation of the relationships among respiratory syncytial virus infection, T cell immune response and intestinal flora","volume":"27","author":"Zheng","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29368","DOI":"10.1039\/C8RA05640D","article-title":"High-resolution lipidomics reveals dysregulation of lipid metabolism in respiratory syncytial virus pneumonia mice","volume":"8","author":"Shan","year":"2018","journal-title":"RSC Adv."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Teoh, S.T., Leimanis-Laurens, M.L., Comstock, S.S., Winters, J.W., Vandenbosch, N.L., Prokop, J.W., Bachmann, A.S., Lunt, S.Y., and Rajasekaran, S. (2022). Combined Plasma and Urinary Metabolomics Uncover Metabolic Perturbations Associated with Severe Respiratory Syncytial Viral Infection and Future Development of Asthma in Infant Patients. Metabolites, 12.","DOI":"10.3390\/metabo12020178"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117278","DOI":"10.1016\/j.jep.2023.117278","article-title":"Traditional uses, botany, phytochemistry, and pharmacology of Lonicerae japonicae flos and Lonicerae flos: A systematic comparative review","volume":"322","author":"Li","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_7","first-page":"331","article-title":"Research progress on the extraction, composition analysis and pharmacological effects of volatile oil of Lonicera japonica","volume":"40","author":"Zheng","year":"2025","journal-title":"West China J. Pharm. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Liang, Y., Liu, M., Wang, Y., Liu, L., and Gao, Y. (2023). Analyzing the Material Basis of Anti-RSV Efficacy of Lonicerae japonicae Flos Based on the PK-PD Model. Molecules, 28.","DOI":"10.3390\/molecules28186437"},{"key":"ref_9","first-page":"1061","article-title":"Study on Fingerprint and in vitro Antiviral Activity of Lonicera japonica Polysaccharide","volume":"31","author":"Ding","year":"2020","journal-title":"China Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"45723","DOI":"10.1038\/srep45723","article-title":"Antiviral activity of chlorogenic acid against influenza A (H1N1\/H3N2) virus and its inhibition of neuraminidase","volume":"7","author":"Ding","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_11","first-page":"769","article-title":"Integrate network pharmacology to explore the anti-RSV pneumonia mechanism of Lonicera Japonica Thunb. based upon UPLC-Q-Exactive-Orbitrap-MS","volume":"41","author":"Li","year":"2021","journal-title":"Chin. J. Hosp. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3724\/SP.J.1123.2020.06013","article-title":"Liquid chromatography-mass spectrometry-based metabolomics study of the efficacy of Chinese medicine asthma-relieving decoction on respiratory syncytial virus infection","volume":"39","author":"Ouyang","year":"2021","journal-title":"Chin. J. Chromatogr."},{"key":"ref_13","first-page":"1585","article-title":"Antiviral Effects of Jinxin Oral Liquid Against Respiratory Syncytial Virus Infection in Vitro Based on Gas Chromatography-Mass Spectrometer Metabolomics","volume":"43","author":"Meng","year":"2016","journal-title":"Liaoning J. Tradit. Chin. Med."},{"key":"ref_14","first-page":"4408","article-title":"Regulation of Jinxin Oral Liquid on metabolites in spleen of mice with RSV pneumonia based on GC-MS","volume":"47","author":"Meng","year":"2016","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"ref_15","first-page":"125","article-title":"Progress in the study of the inhibitory effect of glutathione on viruses and its interaction with molecules in vivo","volume":"18","author":"Wang","year":"2021","journal-title":"Health Med. Res. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/apm.13095","article-title":"Serum metabolomic profiling reveals important difference between infants with and without subsequent recurrent wheezing in later childhood after RSV bronchiolitis","volume":"129","author":"Zhang","year":"2021","journal-title":"APMIS Acta Pathol. Microbiol. Immunol. Scand."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0166-2236(00)01724-0","article-title":"Generating diversity at GABAergic synapses","volume":"24","author":"Cherubini","year":"2001","journal-title":"Trends Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0166-2236(99)01445-9","article-title":"Weinberg, Shaping excitation at glutamatergic synapses","volume":"22","author":"Conti","year":"1999","journal-title":"Trends Neurosci."},{"key":"ref_19","first-page":"981","article-title":"Clinical characteristics and serum cytokine profile of children with acute exacerbation of bronchial asthma induced by respiratory syncytial virus infection","volume":"19","author":"Li","year":"2021","journal-title":"Clin. Educ. Gen. Pract."},{"key":"ref_20","first-page":"3067","article-title":"Analysis of influencing factors of recurrent wheezing in children with respiratory syncytial virus bronchiolitis","volume":"36","author":"Sheng","year":"2021","journal-title":"Matern. Child Health Care China"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/iid3.366","article-title":"Transcriptomic analysis reveals novel mechanisms of SARS-CoV-2 infection in human lung cells","volume":"8","author":"Yang","year":"2020","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_22","first-page":"2258","article-title":"Metabolomics on Pudilan Xiaoyan Oral Liquid in treatment of Influenza A\/H1N1-induced pneumonia based on GC-MS","volume":"49","author":"Qian","year":"2018","journal-title":"Chin. Tradit. Herb. Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1053\/j.gastro.2010.08.049","article-title":"A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes","volume":"139","author":"Willing","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Garc\u00eda L\u00f3pez, E., and Mart\u00edn-Galiano, A.J. (2020). The Versatility of Opportunistic Infections Caused by Gemella Isolates Is Supported by the Carriage of Virulence Factors From Multiple Origins. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.00524"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1111\/all.13449","article-title":"Oral microbiota maturation during the first 7 years of life in relation to allergy development","volume":"73","author":"Dzidic","year":"2018","journal-title":"Allergy"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13824","DOI":"10.1038\/s41598-019-50217-w","article-title":"Microbiome-Transcriptome Interactions Related to Severity of Respiratory Syncytial Virus Infection","volume":"9","author":"Sonawane","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"L250","DOI":"10.1152\/ajplung.00265.2014","article-title":"Moraxella catarrhalis induces an immune response in the murine lung that is independent of human CEACAM5 expression and long-term smoke exposure","volume":"309","author":"Gutbier","year":"2015","journal-title":"Am. J. Physiol.-Lung Cell. Mol. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1159\/000067473","article-title":"Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro","volume":"67","author":"Riise","year":"2000","journal-title":"Respiration"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Latorre, J.D., Adhikari, B., Park, S.H., Teague, K.D., Graham, L.E., Mahaffey, B.D., Baxter, M.F.A., Hernandez-Velasco, X., Kwon, Y.M., and Ricke, S.C. (2018). Evaluation of the Epithelial Barrier Function and Ileal Microbiome in an Established Necrotic Enteritis Challenge Model in Broiler Chickens. Front. Vet. Sci., 5.","DOI":"10.3389\/fvets.2018.00199"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1093\/bioinformatics\/bts342","article-title":"Associating microbiome composition with environmental covariates using generalized UniFrac distances","volume":"28","author":"Chen","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.anaerobe.2014.08.010","article-title":"Butyricicoccus pullicaecorum, a butyrate producer with probiotic potential, is intrinsically tolerant to stomach and small intestine conditions","volume":"30","author":"Geirnaert","year":"2014","journal-title":"Anaerobe"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.fct.2014.06.024","article-title":"Safety assessment of the butyrate-producing Butyricicoccus pullicaecorum strain 25-3(T), a potential probiotic for patients with inflammatory bowel disease, based on oral toxicity tests and whole genome sequencing","volume":"72","author":"Steppe","year":"2014","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1136\/gutjnl-2012-303611","article-title":"Butyricicoccus pullicaecorum in inflammatory bowel disease","volume":"62","author":"Eeckhaut","year":"2013","journal-title":"Gut"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Eeckhaut, V., Wang, J., Van Parys, A., Haesebrouck, F., Joossens, M., Falony, G., Raes, J., Ducatelle, R., and Van Immerseel, F. (2016). The Probiotic Butyricicoccus pullicaecorum Reduces Feed Conversion and Protects from Potentially Harmful Intestinal Microorganisms and Necrotic Enteritis in Broilers. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01416"},{"key":"ref_35","first-page":"5192","article-title":"Characteristics of intestinal flora in patients with primary Sj\u00f6gren\u2019s syndrome with deficiency of both qi and yin","volume":"35","author":"Zhou","year":"2020","journal-title":"China J. Tradit. Chin. Med. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2217\/fmb-2020-0101","article-title":"Insights into gut microbiome and its functional pathways in asthma patients through high-throughput sequencing","volume":"16","author":"Huang","year":"2021","journal-title":"Future Microbiol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/6\/360\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:22:17Z","timestamp":1779888137000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/16\/6\/360"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["metabo16060360"],"URL":"https:\/\/doi.org\/10.3390\/metabo16060360","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]}}}