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Acetate, a metabolite produced by the gut microbiota, serves as a key regulator of macrophage polarization. Evidence demonstrates that a high-calorie diet (HCD) lowers acetate levels, thereby aggravating pulmonary inflammation, but the underlying mechanism remains unclear. Objectives: This study investigated whether HCD-induced exacerbation of pulmonary inflammation in juvenile mice is associated with acetate-mediated macrophage polarization. Methods: The pulmonary inflammation model was established in juvenile mice by lipopolysaccharide (LPS) nebulization, with high-calorie diet (HCD) feeding to reduce systemic acetate levels. After model establishment, serum, lung tissue, colon tissue, and feces were collected from each group. Enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), enzyme-coupled colorimetric assay, Western blotting (WB), and flow cytometry were used to evaluate histopathological changes in the lung and colon, systemic and pulmonary inflammation, acetate levels, and macrophage polarization. Exogenous acetate supplementation was administered to observe its regulatory effect on macrophage polarization, and the downstream signaling pathways were further explored. Results: Results revealed that an HCD significantly reduced acetate levels in both lung and fecal samples from juvenile mice with LPS-induced pulmonary inflammation. HCD increased pro-inflammatory cytokines (IL-1\u03b2, TNF-\u03b1, IL-6) in lung tissue and serum, worsened pulmonary injury, and shifted macrophage polarization toward an M1 phenotype while reducing M2 macrophages. This imbalance was evident in both lung and colon tissues, accompanied by decreased p-AMPK\/AMPK and p-YAP\/YAP ratios in these tissues. Acetate supplementation and treatment with the AMPK activator Acadesine (AICAR; 5-aminoimidazole-4-carboxamide ribonucleoside) mitigated these effects. Conclusions: These findings provide new insights into the association between HCD-induced exacerbation of pulmonary inflammation in juvenile mice and acetate-mediated macrophage polarization, and suggest potential therapeutic strategies. However, given the lack of AMPK inhibition\/knockdown and YAP-specific intervention experiments, the involvement of the AMPK\/YAP signaling pathway should be interpreted as an association rather than a confirmed causal mechanism.<\/jats:p>","DOI":"10.3390\/nu18193196","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:35:59Z","timestamp":1790595359000},"page":"3196","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High-Calorie Diet Aggravates Lipopolysaccharide-Induced Pulmonary Inflammation in Juvenile Mice: Association of Acetate-Mediated Macrophage Polarization with AMPK\/YAP Signaling"],"prefix":"10.3390","volume":"18","author":[{"given":"Futongyu","family":"Sun","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Chinese Medicine Epidemic Disease, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Shuxuan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8357-9027","authenticated-orcid":false,"given":"Chen","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Lina","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yongkuan","family":"Ji","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Qianqian","family":"Li","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250300, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Xiaohong","family":"Gu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"},{"name":"Institute of Chinese Medicine Epidemic Disease, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Tiegang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/s41572-021-00259-0","article-title":"Pneumonia","volume":"7","author":"Torres","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e330","DOI":"10.1016\/S2666-5247(23)00031-9","article-title":"Infection and co-infection patterns of community-acquired pneumonia in patients of different ages in China from 2009 to 2020: A national surveillance study","volume":"4","author":"Liu","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref_3","unstructured":"World Health Organization (2024). Guideline on Management of Pneumonia and Diarrhoea in Children Up to 10 Years of Age."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e212","DOI":"10.1016\/S2214-109X(24)00450-9","article-title":"Prevalence, aetiology, and hospital outcomes of paediatric acute critical illness in resource-constrained settings (Global PARITY): A multicentre, international, point prevalence and prospective cohort study","volume":"13","author":"Kortz","year":"2025","journal-title":"Lancet Glob. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jand.2015.08.010","article-title":"Poor Adherence to US Dietary Guidelines for Children and Adolescents in the National Health and Nutrition Examination Survey Population","volume":"116","author":"Banfield","year":"2016","journal-title":"J. Acad. Nutr. Diet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s11883-023-01171-6","article-title":"Caregiver Influences on Eating Behaviors in Children: An Opportunity for Preventing Obesity","volume":"25","author":"Schratz","year":"2023","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dong, F., Yu, H., Ma, J., Wu, L., Liu, T., Lv, G., Zhen, J., Li, X., Lewith, G., and Gu, X. (2016). Exploring association between gastrointestinal heat retention syndrome and recurrent respiratory tract infections in children: A prospective cohort study. BMC Complement. Altern. Med., 16.","DOI":"10.1186\/s12906-016-1062-8"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e13479","DOI":"10.1111\/aji.13479","article-title":"Effect of a high-calorie diet and constant light exposure on female reproduction, metabolism and immune inflammation: A comparative study of different mouse models","volume":"86","author":"Zhang","year":"2021","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.bbi.2020.04.040","article-title":"The impact of nutrition on COVID-19 susceptibility and long-term consequences","volume":"87","author":"Butler","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"608","DOI":"10.21037\/tp-2024-494","article-title":"Impact of body mass index on clinical outcomes in pediatric patients with mycoplasma pneumoniae pneumonia: A retrospective cohort study","volume":"14","author":"Xuan","year":"2025","journal-title":"Transl. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Khanh Hoang, N., Maegawa, E., Murakami, S., Schaffer, S.W., and Ito, T. (2022). N-Chlorotaurine Reduces the Lung and Systemic Inflammation in LPS-Induced Pneumonia in High Fat Diet-Induced Obese Mice. Metabolites, 12.","DOI":"10.3390\/metabo12040349"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1038\/s41598-020-58632-0","article-title":"Effect of High Calorie Diet on Intestinal Flora in LPS-Induced Pneumonia Rats","volume":"10","author":"Bai","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/JLB.3MA0322-458RR","article-title":"A high-calorie diet aggravates LPS-induced pneumonia by disturbing the gut microbiota and Th17\/Treg balance","volume":"112","author":"Liu","year":"2022","journal-title":"J. Leukoc. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, Y., Zheng, J., Wang, X., Yang, P., and Zhao, D. (2022). Alveolar macrophages and airway hyperresponsiveness associated with respiratory syncytial virus infection. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1012048"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.cell.2020.08.020","article-title":"Patrolling Alveolar Macrophages Conceal Bacteria from the Immune System to Maintain Homeostasis","volume":"183","author":"Neupane","year":"2020","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1038\/s41467-024-48589-3","article-title":"Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation","volume":"15","author":"Zhao","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Abe, C., Bhaswant, M., Miyazawa, T., and Miyazawa, T. (2023). The Potential Use of Exosomes in Anti-Cancer Effect Induced by Polarized Macrophages. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15031024"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Atri, C., Guerfali, F.Z., and Laouini, D. (2018). Role of Human Macrophage Polarization in Inflammation during Infectious Diseases. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061801"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111486","DOI":"10.1016\/j.yexcr.2019.06.031","article-title":"NETs promote ALI\/ARDS inflammation by regulating alveolar macrophage polarization","volume":"382","author":"Song","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.tim.2025.01.008","article-title":"The Lost Kingdom: Commensal protists in the gut microbiota","volume":"33","author":"Gerrick","year":"2025","journal-title":"Trends Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/s42003-024-06815-0","article-title":"The gut microbiota and its metabolite butyrate shape metabolism and antiviral immunity along the gut-lung axis in the chicken","volume":"7","author":"Guillory","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S150","DOI":"10.1513\/AnnalsATS.201503-133AW","article-title":"The Gut-Lung Axis in Respiratory Disease","volume":"12","author":"Marsland","year":"2015","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Schlatterer, K., Peschel, A., and Kretschmer, D. (2021). Short-Chain Fatty Acid and FFAR2 Activation\u2014A New Option for Treating Infections?. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.785833"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.immuni.2018.04.022","article-title":"Dietary Fiber Confers Protection against Flu by Shaping Ly6c- Patrolling Monocyte Hematopoiesis and CD8+ T Cell Metabolism","volume":"48","author":"Trompette","year":"2018","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1186\/s12964-025-02367-w","article-title":"High-fat diet impairs microbial metabolite production and aggravates influenza A infection","volume":"23","author":"Hornung","year":"2025","journal-title":"Cell Commun. Signal. CCS"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lagod, P.P., Qasem, A., and Naser, S.A. (2025). Short Chain Fatty Acids Lower Inflammation and Restore Intestinal Integrity and Function Markers in Mycobacterium paratuberculosis-Infection In Vitro Model. Nutrients, 17.","DOI":"10.3390\/nu17233663"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s40035-026-00542-8","article-title":"Bacteroides coprocola protects dopaminergic neurons in rotenone-induced Parkinson\u2019s disease mouse model by modulating gut microbiota dysbiosis and inhibiting the NLRP3 signaling pathway","volume":"15","author":"Liu","year":"2026","journal-title":"Transl. Neurodegener."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s12602-025-10520-7","article-title":"Butyrate-Producing Mixed Probiotics Alleviate MRSA-Induced Acute Lung Injury in Mice by Promoting M2 Macrophage Polarization","volume":"18","author":"Li","year":"2025","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111619","DOI":"10.1016\/j.biopha.2021.111619","article-title":"Role of microbiota-derived short-chain fatty acids in cancer development and prevention","volume":"139","author":"Mirzaei","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101737","DOI":"10.1016\/j.smim.2023.101737","article-title":"A major mechanism for immunomodulation: Dietary fibres and acid metabolites","volume":"66","author":"Xie","year":"2023","journal-title":"Semin. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Stricker, S., Hain, T., Chao, C.M., and Rudloff, S. (2022). Respiratory and Intestinal Microbiota in Pediatric Lung Diseases-Current Evidence of the Gut-Lung Axis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23126791"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7174","DOI":"10.1039\/C9FO01465A","article-title":"Altered short chain fatty acid profiles induced by dietary fiber intervention regulate AMPK levels and intestinal homeostasis","volume":"10","author":"Li","year":"2019","journal-title":"Food Funct."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s12943-021-01420-9","article-title":"AMPK promotes antitumor immunity by downregulating PD-1 in regulatory T cells via the HMGCR\/p38 signaling pathway","volume":"20","author":"Pokhrel","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1186\/s12967-023-04772-6","article-title":"The role of AMPK in macrophage metabolism, function and polarisation","volume":"21","author":"Cui","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gei\u00df, C., Salas, E., Guevara-Coto, J., R\u00e9gnier-Vigouroux, A., and Mora-Rodr\u00edguez, R.A. (2022). Multistability in Macrophage Activation Pathways and Metabolic Implications. Cells, 11.","DOI":"10.3390\/cells11030404"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kang, L., Yi, J., Lau, C.W., He, L., Chen, Q., Xu, S., Li, J., Xia, Y., Zhang, Y., and Huang, Y. (2023). AMPK-Dependent YAP Inhibition Mediates the Protective Effect of Metformin against Obesity-Associated Endothelial Dysfunction and Inflammation. Antioxidants, 12.","DOI":"10.3390\/antiox12091681"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"110433","DOI":"10.1016\/j.abb.2025.110433","article-title":"AMPK-YAP signaling pathway-mediated mitochondrial dynamics and mitophagy participate in the protective effect of silibinin on HaCaT cells under high glucose conditions","volume":"769","author":"Wang","year":"2025","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.celrep.2019.03.028","article-title":"YAP Aggravates Inflammatory Bowel Disease by Regulating M1\/M2 Macrophage Polarization and Gut Microbial Homeostasis","volume":"27","author":"Zhou","year":"2019","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.1016\/j.celrep.2020.02.013","article-title":"Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production","volume":"30","author":"Sencio","year":"2020","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e0018821","DOI":"10.1128\/IAI.00188-21","article-title":"Short-Chain Fatty Acids as a Potential Treatment for Infections: A Closer Look at the Lungs","volume":"89","author":"Machado","year":"2021","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Li, Q., Liu, H., Bai, C., Jiang, L., Su, C., Qin, X., Liu, T., and Gu, X. (2025). A high-calorie diet exacerbates lipopolysaccharide-induced pneumonia by promoting acetate-mediated macrophage polarization via the HDAC9\/10-HIF-1\u03b1-glycolysis axis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1614768"},{"key":"ref_44","unstructured":"(2022). Laboratory Animals\u2014Microbiological and Parasitological Standards and Monitoring (Standard No. GB 14922-2022)."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sun, Y., Liu, H., Jiang, J., Hu, L., Ma, Q., Li, S., Liu, T., and Gu, X. (2025). High-Calorie Diets Exacerbate Lipopolysaccharide-Induced Pneumonia by Promoting Propionate-Mediated Neutrophil Extracellular Traps. Nutrients, 17.","DOI":"10.3390\/nu17132242"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.bja.2021.02.035","article-title":"Spinal astrocyte aldehyde dehydrogenase-2 mediates ethanol metabolism and analgesia in mice","volume":"127","author":"Jin","year":"2021","journal-title":"Br. J. Anaesth."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.cmet.2018.12.019","article-title":"ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition","volume":"29","author":"Lu","year":"2019","journal-title":"Cell Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/s41467-017-00953-2","article-title":"Blood vessel control of macrophage maturation promotes arteriogenesis in ischemia","volume":"8","author":"Krishnasamy","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/s41596-021-00644-9","article-title":"IBEX: An iterative immunolabeling and chemical bleaching method for high-content imaging of diverse tissues","volume":"17","author":"Radtke","year":"2022","journal-title":"Nat. Protoc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41586-022-05513-3","article-title":"Close relatives of MERS-CoV in bats use ACE2 as their functional receptors","volume":"612","author":"Xiong","year":"2022","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Wang, Z., Yu, J., Liu, Y., Gong, J., Hu, Z., and Liu, Z. (2025). Role of the microbiota\u2013gut\u2013lung axis in the pathogenesis of pulmonary disease in children and novel therapeutic strategies. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1636876"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nrgastro.2017.34","article-title":"Gut microbiota: Neonatal gut microbiota induces lung immunity against pneumonia","volume":"14","author":"Tamburini","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.chom.2020.07.004","article-title":"Early Life Microbiota and Respiratory Tract Infections","volume":"28","author":"Binkowska","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1164\/rccm.201810-1993OC","article-title":"Loss of Microbial Topography between Oral and Nasopharyngeal Microbiota and Development of Respiratory Infections Early in Life","volume":"200","author":"Man","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1007\/s00431-023-05037-6","article-title":"Characteristics of the oropharyngeal microbiota among infants with pneumonia and their effects on immune response and subsequent respiratory morbidity","volume":"182","author":"Hong","year":"2023","journal-title":"Eur. J. Pediatr."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Tian, Z., Deng, T., Gui, X., Wang, L., Yan, Q., and Wang, L. (2023). Mechanisms of Lung and Intestinal Microbiota and Innate Immune Changes Caused by Pathogenic Enterococcus Faecalis Promoting the Development of Pediatric Pneumonia. Microorganisms, 11.","DOI":"10.3390\/microorganisms11092203"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/s41590-025-02227-2","article-title":"The role of gut microbial metabolites in the T cell lifecycle","volume":"26","author":"Tran","year":"2025","journal-title":"Nat. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature18846","article-title":"Diet-microbiota interactions as moderators of human metabolism","volume":"535","author":"Sonnenburg","year":"2016","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15767","DOI":"10.1021\/acs.chemrev.0c01321","article-title":"A Journey from Structure to Function of Bacterial Lipopolysaccharides","volume":"122","author":"Duda","year":"2022","journal-title":"Chem. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.immuni.2019.05.023","article-title":"Gut Mycobiota in Immunity and Inflammatory Disease","volume":"50","author":"Li","year":"2019","journal-title":"Immunity"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"110231","DOI":"10.1016\/j.cbi.2022.110231","article-title":"Short Chain Fatty Acids: Fundamental mediators of the gut-lung axis and their involvement in pulmonary diseases","volume":"368","author":"Ashique","year":"2022","journal-title":"Chem.-Biol. Interact."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/s41385-019-0160-6","article-title":"Microbes, metabolites, and the gut-lung axis","volume":"12","author":"Dang","year":"2019","journal-title":"Mucosal Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Machado, M.G., Patente, T.A., Rouill\u00e9, Y., Heumel, S., Melo, E.M., Deruyter, L., Pourcet, B., Sencio, V., Teixeira, M.M., and Trottein, F. (2022). Acetate Improves the Killing of Streptococcus pneumoniae by Alveolar Macrophages via NLRP3 Inflammasome and Glycolysis-HIF-1\u03b1 Axis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.773261"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s42255-025-01442-3","article-title":"AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis","volume":"8","author":"Smith","year":"2026","journal-title":"Nat. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"AMPK: A nutrient and energy sensor that maintains energy homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1194\/jlr.R036012","article-title":"The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism","volume":"54","author":"Groen","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Facchin, S., Calgaro, M., and Savarino, E.V. (2025). Rethinking Short-Chain Fatty Acids: A Closer Look at Propionate in Inflammation, Metabolism, and Mucosal Homeostasis. Cells, 14.","DOI":"10.3390\/cells14151130"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2598957","DOI":"10.1080\/19490976.2025.2598957","article-title":"GPR41 deficiency alters the gut microbiota-bile acid axis, reduces ileal expression of Npc1l1, and attenuates hypercholesterolemia in male mice","volume":"17","author":"Hutchison","year":"2025","journal-title":"Gut Microbes"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1042\/CS20240787","article-title":"Cross-talk between microbiota-gut-brain axis and blood pressure regulation","volume":"139","author":"Welathanthree","year":"2025","journal-title":"Clin. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1126\/science.adz1398","article-title":"A cellular basis for heightened gut sensitivity in females","volume":"390","author":"Venkataraman","year":"2025","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Lin, H.V., Frassetto, A., Kowalik, E.J., Nawrocki, A.R., Lu, M.M., Kosinski, J.R., Hubert, J.A., Szeto, D., Yao, X., and Forrest, G. (2012). Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035240"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/s43587-025-00869-3","article-title":"Activation of AMPK by GLP-1R agonists mitigates Alzheimer-related phenotypes in transgenic mice","volume":"5","author":"Zhang","year":"2025","journal-title":"Nat. Aging"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.apsb.2024.10.010","article-title":"Akkermansia muciniphila-derived acetate activates the hepatic AMPK\/SIRT1\/PGC-1\u03b1 axis to alleviate ferroptosis in metabolic-associated fatty liver disease","volume":"15","author":"Zhuge","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"119088","DOI":"10.1016\/j.atherosclerosis.2024.119088","article-title":"Orally administrated acetate inhibits atherosclerosis progression through AMPK activation via GPR43 in plaque macrophages","volume":"401","author":"Wada","year":"2025","journal-title":"Atherosclerosis"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Isolauri, E., and Laitinen, K. (2025). Resilience to Global Health Challenges Through Nutritional Gut Microbiome Modulation. Nutrients, 17.","DOI":"10.3390\/nu17030396"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","article-title":"Macrophage Polarization","volume":"79","author":"Murray","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1161\/CIRCRESAHA.116.309194","article-title":"Abandoning M1\/M2 for a Network Model of Macrophage Function","volume":"119","author":"Nahrendorf","year":"2016","journal-title":"Circ. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1042\/CS20220531","article-title":"M1\/M2 macrophages and their overlaps\u2014Myth or reality?","volume":"137","author":"Strizova","year":"2023","journal-title":"Clin. Sci."},{"key":"ref_79","first-page":"497841","article-title":"Animal models of cardiovascular diseases","volume":"2011","author":"Zaragoza","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1093\/infdis\/jir657","article-title":"Sex-based differences in susceptibility to respiratory and systemic pneumococcal disease in mice","volume":"204","author":"Kadioglu","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Mishra, P., Esfahani, E.K., Fernyhough, P., and Albensi, B.C. (2025). Estradiol Prevents Amyloid Beta-Induced Mitochondrial Dysfunction and Neurotoxicity in Alzheimer\u2019s Disease via AMPK-Dependent Suppression of NF-\u03baB Signaling. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136203"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3196\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:52:09Z","timestamp":1790596329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/19\/3196"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":81,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["nu18193196"],"URL":"https:\/\/doi.org\/10.3390\/nu18193196","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]}}}