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Short-Chain Fatty Acids: Promising Therapeutic Targets for Respiratory Syncytial Virus Infection

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Abstract

The intestinal microbiota is a complex community of organisms present in the human gastrointestinal tract, some of which can produce short-chain fatty acids (SCFAs) through the fermentation of dietary fiber. SCFAs play a major role in mediating the intestinal microbiota’s regulation of host immunity and intestinal homeostasis. Respiratory syncytial virus (RSV) can cause an imbalance between anti-inflammatory and proinflammatory responses in the host. In addition, changes in SCFA levels and the structure of the intestinal microbiota have been observed after RSV infection. Therefore, there may be a link between SCFAs and RSV infection, and SCFAs are expected to be therapeutic targets for RSV infection.

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References

  1. Coultas JA, Smyth R, Openshaw PJ (2019) Respiratory syncytial virus (RSV): a scourge from infancy to old age. Thorax 74(10):986–993. https://doi.org/10.1136/thoraxjnl-2018-212212

    Article  PubMed  Google Scholar 

  2. Burrell R, Saravanos G, Britton PN (2023) Unintended impacts of COVID-19 on the epidemiology and burden of paediatric respiratory infections. Paediatric Respiratory Rev S1526–0542(23)00044–1. Advance online publication. https://doi.org/10.1016/j.prrv.2023.07.004

  3. Rekha K, Venkidasamy B, Samynathan R, Nagella P, Rebezov M, Khayrullin M, Ponomarev E, Bouyahya A, Sarkar T, Shariati MA, Thiruvengadam M, Simal-Gandara J (2024) Short-chain fatty acid: an updated review on signaling, metabolism, and therapeutic effects. Crit Rev Food Sci Nutr 64(9):2461–2489. https://doi.org/10.1080/10408398.2022.2124231

    Article  PubMed  CAS  Google Scholar 

  4. Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT (1987) Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28(10):1221–1227. https://doi.org/10.1136/gut.28.10.1221

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Boets E, Gomand SV, Deroover L, Preston T, Vermeulen K, De Preter V, Hamer HM, Van den Mooter G, De Vuyst L, Courtin CM, Annaert P, Delcour JA, Verbeke KA (2017) Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study. J Physiol 595(2):541–555. https://doi.org/10.1113/JP272613

    Article  PubMed  CAS  Google Scholar 

  6. Topping DL, Clifton PM (2001) Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 81(3):1031–1064. https://doi.org/10.1152/physrev.2001.81.3.1031

    Article  PubMed  CAS  Google Scholar 

  7. Ríos-Covián D, Ruas-Madiedo P, Margolles A, Gueimonde M, de Los Reyes-Gavilán CG, Salazar N (2016) Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol 7:185. https://doi.org/10.3389/fmicb.2016.00185

    Article  PubMed  PubMed Central  Google Scholar 

  8. Flint HJ, Duncan SH, Scott KP, Louis P (2015) Links between diet, gut microbiota composition and gut metabolism. Proc Nutr Soc 74(1):13–22. https://doi.org/10.1017/S0029665114001463

    Article  PubMed  CAS  Google Scholar 

  9. Louis P, Hold GL, Flint HJ (2014) The gut microbiota, bacterial metabolites and colorectal cancer. Nat Rev Microbiol 12(10):661–672. https://doi.org/10.1038/nrmicro3344

    Article  PubMed  CAS  Google Scholar 

  10. van der Hee B, Wells JM (2021) Microbial regulation of host physiology by short-chain fatty acids. Trends Microbiol 29(8):700–712. https://doi.org/10.1016/j.tim.2021.02.001

    Article  PubMed  CAS  Google Scholar 

  11. Reichardt N, Duncan SH, Young P, Belenguer A, McWilliam Leitch C, Scott KP, Flint HJ, Louis P (2014) Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J 8(6):1323–1335. https://doi.org/10.1038/ismej.2014.14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Fusco W, Lorenzo MB, Cintoni M, Porcari S, Rinninella E, Kaitsas F, Lener E, Mele MC, Gasbarrini A, Collado MC, Cammarota G, Ianiro G (2023) Short-chain fatty-acid-producing bacteria: key components of the human gut microbiota. Nutrients 15(9):2211. https://doi.org/10.3390/nu15092211

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Rios-Covian D, Gueimonde M, Duncan SH, Flint HJ, De Los Reyes-Gavilan CG (2015) Enhanced butyrate formation by cross-feeding between Faecalibacterium prausnitzii and Bifidobacterium adolescentis. FEMS Microbiol Lett 362(21):fnv176. https://doi.org/10.1093/femsle/fnv176

    Article  PubMed  CAS  Google Scholar 

  14. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54(9):2325–2340. https://doi.org/10.1194/jlr.R036012

    Article  CAS  Google Scholar 

  15. Sivaprakasam S, Bhutia YD, Yang S, Ganapathy V (2017) Short-Chain Fatty Acid Transporters: Role in Colonic Homeostasis. Compr Physiol 8(1):299–314. https://doi.org/10.1002/cphy.c170014

    Article  PubMed  PubMed Central  Google Scholar 

  16. Maiuolo J, Bulotta RM, Ruga S, Nucera S, Macrì R, Scarano F, Oppedisano F, Carresi C, Gliozzi M, Musolino V, Mollace R, Muscoli C, Mollace V (2024) The postbiotic properties of butyrate in the modulation of the gut microbiota: the potential of its combination with polyphenols and dietary fibers. Int J Mol Sci 25(13):6971. https://doi.org/10.3390/ijms25136971

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Albillos A, de Gottardi A, Rescigno M (2020) The gut-liver axis in liver disease: Pathophysiological basis for therapy. J Hepatol 72(3):558–577. https://doi.org/10.1016/j.jhep.2019.10.003

    Article  PubMed  CAS  Google Scholar 

  18. Portincasa P, Bonfrate L, Vacca M, De Angelis M, Farella I, Lanza E, Khalil M, Wang DQ, Sperandio M, Di Ciaula A (2022) Gut microbiota and short chain fatty acids: implications in glucose homeostasis. Int J Mol Sci 23(3):1105. https://doi.org/10.3390/ijms23031105

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489(7415):220–230. https://doi.org/10.1038/nature11550

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Ley RE, Peterson DA, Gordon JI (2006) Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124(4):837–848. https://doi.org/10.1016/j.cell.2006.02.017

    Article  PubMed  CAS  Google Scholar 

  21. Yang B, Ding M, Chen Y, Han F, Yang C, Zhao J, Malard P, Stanton C, Ross RP, Zhang H, Chen W (2021) Development of gut microbiota and bifidobacterial communities of neonates in the first 6 weeks and their inheritance from mother. Gut microbes 13(1):1–13. https://doi.org/10.1080/19490976.2021.1908100

    Article  PubMed  CAS  Google Scholar 

  22. Wang Z, Liu J, Li F, Luo Y, Ge P, Zhang Y, Wen H, Yang Q, Ma S, Chen H (2022) The gut-lung axis in severe acute Pancreatitis-associated lung injury: the protection by the gut microbiota through short-chain fatty acids. Pharmacol Res 182:106321. https://doi.org/10.1016/j.phrs.2022.106321

    Article  PubMed  CAS  Google Scholar 

  23. Nie Y, Luo F, Lin Q (2018) Dietary nutrition and gut microflora: A promising target for treating diseases. Trends Food Sci Technol 75:72–80

    Article  CAS  Google Scholar 

  24. Yagi K, Asai N, Huffnagle GB, Lukacs NW, Fonseca W (2022) Early-life lung and gut microbiota development and respiratory syncytial virus infection. Front Immunol 13:877771. https://doi.org/10.3389/fimmu.2022.87777

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Yang W, Cong Y (2021) Gut microbiota-derived metabolites in the regulation of host immune responses and immune-related inflammatory diseases. Cell Mol Immunol 18(4):866–877. https://doi.org/10.1038/s41423-021-00661-4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Manson JM, Rauch M, Gilmore MS (2008) The commensal microbiology of the gastrointestinal tract. GI microbiota and regulation of the immune system, 15–28.

  27. Lordan C, Thapa D, Ross RP, Cotter PD (2020) Potential for enriching next-generation health-promoting gut bacteria through prebiotics and other dietary components. Gut microbes 11(1):1–20. https://doi.org/10.1080/19490976.2019.1613124

    Article  PubMed  Google Scholar 

  28. Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, Harmsen HJM, Faber KN, Hermoso MA (2019) Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol 10:277. https://doi.org/10.3389/fimmu.2019.00277

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Engels C, Ruscheweyh HJ, Beerenwinkel N, Lacroix C, Schwab C (2016) The Common Gut Microbe Eubacterium hallii also Contributes to Intestinal Propionate Formation. Front Microbiol 7:713. https://doi.org/10.3389/fmicb.2016.00713

    Article  PubMed  PubMed Central  Google Scholar 

  30. Singh V, Lee G, Son H, Koh H, Kim ES, Unno T, Shin JH (2023) Butyrate producers, “The Sentinel of Gut”: Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics. Front Microbiol 13:1103836. https://doi.org/10.3389/fmicb.2022.1103836

    Article  PubMed  PubMed Central  Google Scholar 

  31. Horvath TD, Ihekweazu FD, Haidacher SJ, Ruan W, Engevik KA, Fultz R, Hoch KM, Luna RA, Oezguen N, Spinler JK, Haag AM, Versalovic J, Engevik MA (2022) Bacteroides ovatus colonization influences the abundance of intestinal short chain fatty acids and neurotransmitters. Iscience 25(5):104158. https://doi.org/10.1016/j.isci.2022.104158

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Macfarlane S, Macfarlane GT (2003) Regulation of short-chain fatty acid production. Proc Nutr Soc 62(1):67–72. https://doi.org/10.1079/PNS2002207

    Article  PubMed  CAS  Google Scholar 

  33. Shin JH, Tillotson G, MacKenzie TN, Warren CA, Wexler HM, Goldstein EJC (2024) Bacteroides and related species: The keystone taxa of the human gut microbiota. Anaerobe 85:102819. https://doi.org/10.1016/j.anaerobe.2024.102819

    Article  PubMed  CAS  Google Scholar 

  34. Sibanda T, Marole TA, Thomashoff UL, Thantsha MS, Buys EM (2024) Bifidobacterium species viability in dairy-based probiotic foods: challenges and innovative approaches for accurate viability determination and monitoring of probiotic functionality. Front Microbiol 15:1327010. https://doi.org/10.3389/fmicb.2024.1327010

    Article  PubMed  PubMed Central  Google Scholar 

  35. He BL, Xiong Y, Hu TG, Zong MH, Wu H (2023) Bifidobacterium spp. as functional foods: a review of current status, challenges, and strategies. Critical Rev Food Sci Nutrition 63(26):8048–8065. https://doi.org/10.1080/10408398.2022.2054934

    Article  CAS  Google Scholar 

  36. Turroni F, Taverniti V, Ruas-Madiedo P, Duranti S, Guglielmetti S, Lugli GA, Gioiosa L, Palanza P, Margolles A, van Sinderen D, Ventura M (2014) Bifidobacterium bifidum PRL2010 modulates the host innate immune response. Appl Environ Microbiol 80(2):730–740. https://doi.org/10.1128/AEM.03313-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Shang J, Wan F, Zhao L, Meng X, Li B (2020) Potential Immunomodulatory Activity of a Selected Strain Bifidobacterium bifidum H3–R2 as Evidenced in vitro and in Immunosuppressed Mice. Front Microbiol 11:2089. https://doi.org/10.3389/fmicb.2020.02089

    Article  PubMed  PubMed Central  Google Scholar 

  38. Martinez FA, Balciunas EM, Converti A, Cotter PD, de Souza Oliveira RP (2013) Bacteriocin production by Bifidobacterium spp. Rev Biotechnol Adv 31(4):482–488. https://doi.org/10.1016/j.biotechadv.2013.01.010

    Article  CAS  Google Scholar 

  39. Zhao Y, Chen F, Wu W, Sun M, Bilotta AJ, Yao S, Xiao Y, Huang X, Eaves-Pyles TD, Golovko G, Fofanov Y, D’Souza W, Zhao Q, Liu Z, Cong Y (2018) GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3. Mucosal Immunol 11(3):752–762. https://doi.org/10.1038/mi.2017.118

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. van Harten RM, van Woudenbergh E, van Dijk A, Haagsman HP (2018) Cathelicidins: immunomodulatory antimicrobials. Vaccines 6(3):63. https://doi.org/10.3390/vaccines6030063

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Ruppin H, Bar-Meir S, Soergel KH, Wood CM, Schmitt MG Jr (1980) Absorption of short-chain fatty acids by the colon. Gastroenterology 78(6):1500–1507

    Article  PubMed  CAS  Google Scholar 

  42. Walker AW, Duncan SH, McWilliam Leitch EC, Child MW, Flint HJ (2005) pH and peptide supply can radically alter bacterial populations and short-chain fatty acid ratios within microbial communities from the human colon. Appl Environ Microbiol 71(7):3692–3700. https://doi.org/10.1128/AEM.71.7.3692-3700.2005

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Johansson ME, Ambort D, Pelaseyed T, Schütte A, Gustafsson JK, Ermund A, Subramani DB, Holmén-Larsson JM, Thomsson KA, Bergström JH, van der Post S, Rodriguez-Piñeiro AM, Sjövall H, Bäckström M, Hansson GC (2011) Composition and functional role of the mucus layers in the intestine. Cell Mol Life Sci : CMLS 68(22):3635–3641. https://doi.org/10.1007/s00018-011-0822-3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Blaak EE, Canfora EE, Theis S, Frost G, Groen AK, Mithieux G, Nauta A, Scott K, Stahl B, van Harsselaar J, van Tol R, Vaughan EE, Verbeke K (2020) Short chain fatty acids in human gut and metabolic health. Beneficial Microbes 11(5):411–455. https://doi.org/10.3920/BM2020.0057

    Article  PubMed  CAS  Google Scholar 

  45. Jung TH, Park JH, Jeon WM, Han KS (2015) Butyrate modulates bacterial adherence on LS174T human colorectal cells by stimulating mucin secretion and MAPK signaling pathway. Nurs Res Pract 9(4):343–349. https://doi.org/10.4162/nrp.2015.9.4.343

    Article  CAS  Google Scholar 

  46. Louis P, Flint HJ (2017) Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol 19(1):29–41. https://doi.org/10.1111/1462-2920.13589

    Article  PubMed  CAS  Google Scholar 

  47. Liu XF, Shao JH, Liao YT, Wang LN, Jia Y, Dong PJ, Liu ZZ, He DD, Li C, Zhang X (2023) Regulation of short-chain fatty acids in the immune system. Front Immunol 14:1186892. https://doi.org/10.3389/fimmu.2023.1186892

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Bergman EN (1990) Energy contributions of volatile fatty acids from the gastrointestinal tract in various species. Physiol Rev 70(2):567–590. https://doi.org/10.1152/physrev.1990.70.2.567

    Article  PubMed  CAS  Google Scholar 

  49. Roediger WE (1982) Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 83(2):424–429

    Article  PubMed  CAS  Google Scholar 

  50. Zambell KL, Fitch MD, Fleming SE (2003) Acetate and butyrate are the major substrates for de novo lipogenesis in rat colonic epithelial cells. J Nutr 133(11):3509–3515. https://doi.org/10.1093/jn/133.11.3509

    Article  PubMed  CAS  Google Scholar 

  51. Wang RX, Lee JS, Campbell EL, Colgan SP (2020) Microbiota-derived butyrate dynamically regulates intestinal homeostasis through regulation of actin-associated protein synaptopodin. Proc Natl Acad Sci USA 117(21):11648–11657. https://doi.org/10.1073/pnas.1917597117

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Hudson BD, Tikhonova IG, Pandey SK, Ulven T, Milligan G (2012) Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3. J Biol Chem 287(49):41195–41209. https://doi.org/10.1074/jbc.M112.396259

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM (2012) Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 61(2):364–371. https://doi.org/10.2337/db11-1019

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Brown AJ, Jupe S, Briscoe CP (2005) A family of fatty acid binding receptors. DNA Cell Biol 24(1):54–61. https://doi.org/10.1089/dna.2005.24.54

    Article  PubMed  CAS  Google Scholar 

  55. Pingitore A, Chambers ES, Hill T, Maldonado IR, Liu B, Bewick G, Morrison DJ, Preston T, Wallis GA, Tedford C, Castañera González R, Huang GC, Choudhary P, Frost G, Persaud SJ (2017) The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. Diabetes Obes Metab 19(2):257–265. https://doi.org/10.1111/dom.12811

    Article  PubMed  CAS  Google Scholar 

  56. Liu P, Wang Y, Yang G, Zhang Q, Meng L, Xin Y, Jiang X (2021) The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis. Pharmacol Res 165:105420. https://doi.org/10.1016/j.phrs.2021.105420

    Article  PubMed  CAS  Google Scholar 

  57. Ang Z, Er JZ, Ding JL (2015) The short-chain fatty acid receptor GPR43 is transcriptionally regulated by XBP1 in human monocytes. Sci Rep 5:8134. https://doi.org/10.1038/srep08134

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Maslowski KM, Vieira AT, Ng A, Kranich J, Sierro F, Yu D, Schilter HC, Rolph MS, Mackay F, Artis D, Xavier RJ, Teixeira MM, Mackay CR (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461(7268):1282–1286. https://doi.org/10.1038/nature08530

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Fachi JL, Sécca C, Rodrigues PB, Mato FCP, Di Luccia B, Felipe JS, Pral LP, Rungue M, Rocha VM, Sato FT, Sampaio U, Clerici MTPS, Rodrigues HG, Câmara NOS, Consonni SR, Vieira AT, Oliveira SC, Mackay CR, Layden BT, Bortoluci KR, Vinolo MAR (2020) Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2. J Experimental Med 217(3):jem.20190489. https://doi.org/10.1084/jem.20190489

    Article  CAS  Google Scholar 

  60. Galvão I, Tavares LP, Corrêa RO, Fachi JL, Rocha VM, Rungue M, Garcia CC, Cassali G, Ferreira CM, Martins FS, Oliveira SC, Mackay CR, Teixeira MM, Vinolo MAR, Vieira AT (2018) The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumoniae infection in the lung. Front Immunol 9:142. https://doi.org/10.3389/fimmu.2018.00142

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Schlatterer K, Beck C, Schoppmeier U, Peschel A, Kretschmer D (2021) Acetate sensing by GPR43 alarms neutrophils and protects from severe sepsis. Commun Biol 4(1):928. https://doi.org/10.1038/s42003-021-02427-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Tan J, McKenzie C, Vuillermin PJ, Goverse G, Vinuesa CG, Mebius RE, Macia L, Mackay CR (2016) Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways. Cell Rep 15(12):2809–2824. https://doi.org/10.1016/j.celrep.2016.05.047

    Article  PubMed  CAS  Google Scholar 

  63. He J, Zhang P, Shen L, Niu L, Tan Y, Chen L, Zhao Y, Bai L, Hao X, Li X, Zhang S, Zhu L (2020) Short-chain fatty acids and their association with signalling pathways in inflammation, glucose and lipid metabolism. Int J Mol Sci 21(17):6356. https://doi.org/10.3390/ijms21176356

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Ikeda T, Nishida A, Yamano M, Kimura I (2022) Short-chain fatty acid receptors and gut microbiota as therapeutic targets in metabolic, immune, and neurological diseases. Pharmacol Ther 239:108273. https://doi.org/10.1016/j.pharmthera.2022.108273

    Article  PubMed  CAS  Google Scholar 

  65. Nakajima A, Kaga N, Nakanishi Y, Ohno H, Miyamoto J, Kimura I, Hori S, Sasaki T, Hiramatsu K, Okumura K, Miyake S, Habu S, Watanabe S (2017) Maternal high fiber diet during pregnancy and lactation influences regulatory t cell differentiation in offspring in mice. J Immunol (Baltimore, Md.:1950) 199(10):3516–3524. https://doi.org/10.4049/jimmunol.1700248

    Article  CAS  Google Scholar 

  66. Trompette A, Gollwitzer ES, Yadava K, Sichelstiel AK, Sprenger N, Ngom-Bru C, Blanchard C, Junt T, Nicod LP, Harris NL, Marsland BJ (2014) Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nat Med 20(2):159–166. https://doi.org/10.1038/nm.3444

    Article  PubMed  CAS  Google Scholar 

  67. Eckalbar WL, Erle DJ (2019) Singling out Th2 cells in eosinophilic esophagitis. J Clin Investig 129(5):1830–1832. https://doi.org/10.1172/JCI128479

    Article  PubMed  PubMed Central  Google Scholar 

  68. Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi H, Thangaraju M, Prasad PD, Manicassamy S, Munn DH, Lee JR, Offermanns S, Ganapathy V (2014) Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40(1):128–139. https://doi.org/10.1016/j.immuni.2013.12.007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Guilloteau P, Martin L, Eeckhaut V, Ducatelle R, Zabielski R, Van Immerseel F (2010) From the gut to the peripheral tissues: the multiple effects of butyrate. Nutr Res Rev 23(2):366–384. https://doi.org/10.1017/S0954422410000247

    Article  PubMed  CAS  Google Scholar 

  70. Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, Brunet I, Wan LX, Rey F, Wang T, Firestein SJ, Yanagisawa M, Gordon JI, Eichmann A, Peti-Peterdi J, Caplan MJ (2013) Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci USA 110(11):4410–4415. https://doi.org/10.1073/pnas.1215927110

    Article  PubMed  PubMed Central  Google Scholar 

  71. Dinsart G, Leprovots M, Lefort A, Libert F, Quesnel Y, Veithen A, Vassart G, Huysseune S, Parmentier M, Garcia MI (2024) The olfactory receptor Olfr78 promotes differentiation of enterochromaffin cells in the mouse colon. EMBO Rep 25(1):304–333. https://doi.org/10.1038/s44319-023-00013-5

    Article  PubMed  Google Scholar 

  72. Roduit C, Frei R, Ferstl R, Loeliger S, Westermann P, Rhyner C, Schiavi E, Barcik W, Rodriguez-Perez N, Wawrzyniak M, Chassard C, Lacroix C, Schmausser-Hechfellner E, Depner M, von Mutius E, Braun-Fahrländer C, Karvonen AM, Kirjavainen PV, Pekkanen J, Dalphin JC, PASTURE/EFRAIM study group (2019) High levels of butyrate and propionate in early life are associated with protection against atopy. Allergy 74(4):799–809. https://doi.org/10.1111/all.13660

  73. Yip W, Hughes MR, Li Y, Cait A, Hirst M, Mohn WW, McNagny KM (2021) Butyrate Shapes Immune Cell Fate and Function in Allergic Asthma. Front Immunol 12:628453. https://doi.org/10.3389/fimmu.2021.628453

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Ramaiah MJ, Tangutur AD, Manyam RR (2021) Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy. Life Sci 277:119504. https://doi.org/10.1016/j.lfs.2021.119504

    Article  PubMed  CAS  Google Scholar 

  75. Waldecker M, Kautenburger T, Daumann H, Busch C, Schrenk D (2008) Inhibition of histone-deacetylase activity by short-chain fatty acids and some polyphenol metabolites formed in the colon. J Nutr Biochem 19(9):587–593. https://doi.org/10.1016/j.jnutbio.2007.08.002

    Article  PubMed  CAS  Google Scholar 

  76. Lawlor L, Yang XB (2019) Harnessing the HDAC-histone deacetylase enzymes, inhibitors and how these can be utilised in tissue engineering. Int J Oral Sci 11(2):20. https://doi.org/10.1038/s41368-019-0053-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Martin-Gallausiaux C, Béguet-Crespel F, Marinelli L, Jamet A, Ledue F, Blottière HM, Lapaque N (2018) Butyrate produced by gut commensal bacteria activates TGF-beta1 expression through the transcription factor SP1 in human intestinal epithelial cells. Sci Rep 8(1):9742. https://doi.org/10.1038/s41598-018-28048-y

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Kim CH (2018) Immune regulation by microbiome metabolites. Immunology 154(2):220–229. https://doi.org/10.1111/imm.12930

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Mirzaei R, Afaghi A, Babakhani S, Sohrabi MR, Hosseini-Fard SR, Babolhavaeji K, Khani Ali Akbari S, Yousefimashouf R, Karampoor S (2021) Role of microbiota-derived short-chain fatty acids in cancer development and prevention. Biomed Pharmacother Biomed Pharmacother 139:111619. https://doi.org/10.1016/j.biopha.2021.111619

    Article  PubMed  CAS  Google Scholar 

  80. Ashique S, De Rubis G, Sirohi E, Mishra N, Rihan M, Garg A, Reyes RJ, Manandhar B, Bhatt S, Jha NK, Singh TG, Gupta G, Singh SK, Chellappan DK, Paudel KR, Hansbro PM, Oliver BG, Dua K (2022) Short Chain Fatty Acids: Fundamental mediators of the gut-lung axis and their involvement in pulmonary diseases. Chem Biol Interact 368:110231. https://doi.org/10.1016/j.cbi.2022.110231

    Article  PubMed  CAS  Google Scholar 

  81. Kotlyarov S (2022) Role of short-chain fatty acids produced by gut microbiota in innate lung immunity and pathogenesis of the heterogeneous course of chronic obstructive pulmonary disease. Int J Mol Sci 23(9):4768. https://doi.org/10.3390/ijms23094768

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Li X, Shang S, Wu M, Song Q, Chen D (2024) Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis. Cancer Lett 598:217096. https://doi.org/10.1016/j.canlet.2024.217096

    Article  PubMed  CAS  Google Scholar 

  83. Harding JN, Siefker D, Vu L, You D, DeVincenzo J, Pierre JF, Cormier SA (2020) Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity. BMC Microbiol 20(1):140. https://doi.org/10.1186/s12866-020-01816-5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Cabrera-Rubio R, Calvo C, Alcolea S, Bergia M, Atucha J, Pozo F, Casas I, Arroyas M, Collado MC, García-García ML (2024) Gut and respiratory tract microbiota in children younger than 12 months hospitalized for bronchiolitis compared with healthy children: can we predict the severity and medium-term respiratory outcome? Microbiol Spectrum 12(7):e0255623. https://doi.org/10.1128/spectrum.02556-23

    Article  CAS  Google Scholar 

  85. Groves HT, Cuthbertson L, James P, Moffatt MF, Cox MJ, Tregoning JS (2018) Respiratory disease following viral lung infection alters the murine gut microbiota. Front Immunol 9:182. https://doi.org/10.3389/fimmu.2018.00182

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Groves HT, Higham SL, Moffatt MF, Cox MJ, Tregoning JS (2020) Respiratory viral infection alters the gut microbiota by inducing inappetence. mBio 11(1):e03236-19. https://doi.org/10.1128/mBio.03236-19

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Ji JJ, Sun QM, Nie DY, Wang Q, Zhang H, Qin FF, Wang QS, Lu SF, Pang GM, Lu ZG (2021) Probiotics protect against RSV infection by modulating the microbiota-alveolar-macrophage axis. Acta Pharmacol Sin 42(10):1630–1641. https://doi.org/10.1038/s41401-020-00573-5

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Hasegawa K, Linnemann RW, Mansbach JM, Ajami NJ, Espinola JA, Petrosino JF, Piedra PA, Stevenson MD, Sullivan AF, Thompson AD, Camargo CA Jr (2016) The fecal microbiota profile and bronchiolitis in infants. Pediatrics 138(1):e20160218. https://doi.org/10.1542/peds.2016-0218

    Article  PubMed  PubMed Central  Google Scholar 

  89. Alba C, Aparicio M, González-Martínez F, González-Sánchez MI, Pérez-Moreno J, Toledo Del Castillo B, Rodríguez JM, Rodríguez-Fernández R, Fernández L (2021) Nasal and fecal microbiota and immunoprofiling of infants with and without RSV bronchiolitis. Front Microbiol 12:667832. https://doi.org/10.3389/fmicb.2021.667832

    Article  PubMed  PubMed Central  Google Scholar 

  90. Russell MM, Leimanis-Laurens ML, Bu S, Kinney GA, Teoh ST, McKee RL, Ferguson K, Winters JW, Lunt SY, Prokop JW, Rajasekaran S, Comstock SS (2022) Loss of health promoting bacteria in the gastrointestinal microbiome of PICU infants with bronchiolitis: a single-center feasibility study. Children (Basel, Switzerland) 9(1):114. https://doi.org/10.3390/children9010114

    Article  PubMed  Google Scholar 

  91. Antunes KH, Stein RT, Franceschina C, da Silva EF, de Freitas DN, Silveira J, Mocellin M, Leitão L, Fachi JL, Pral LP, Gonzalez A, Oliveira S, Duarte L, Cassão G, Gonçalves JIB, Reis TM, Abbadi BL, Dornelles M, Sperotto NDM, Rigo M, de Souza APD (2022) Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis. EBioMedicine 77:103891. https://doi.org/10.1016/j.ebiom.2022.103891

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Bao L, Deng W, Huang B, Gao H, Liu J, Ren L, Wei Q, Yu P, Xu Y, Qi F, Qu Y, Li F, Lv Q, Wang W, Xue J, Gong S, Liu M, Wang G, Wang S, Song Z, Qin C (2020) The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature 583(7818):830–833. https://doi.org/10.1038/s41586-020-2312-y

    Article  PubMed  CAS  Google Scholar 

  93. Anker MS, Landmesser U, von Haehling S, Butler J, Coats AJS, Anker SD (2021) Weight loss, malnutrition, and cachexia in COVID-19: facts and numbers. J Cachexia Sarcopenia Muscle 12(1):9–13. https://doi.org/10.1002/jcsm.12674

    Article  PubMed  Google Scholar 

  94. Liu J, Huang Y, Liu N, Qiu H, Zhang X, Liu X, He M, Chen M, Huang S (2024) The imbalance of pulmonary Th17/Treg cells in BALB/c suckling mice infected with respiratory syncytial virus-mediated intestinal immune damage and gut microbiota changes. Microbiol Spectrum 12(6):e0328323. https://doi.org/10.1128/spectrum.03283-23

    Article  CAS  Google Scholar 

  95. Yang X, Liu X, Nie Y, Zhan F, Zhu B (2023) Oxidative stress and ROS-mediated cellular events in RSV infection: potential protective roles of antioxidants. Virology J 20(1):224. https://doi.org/10.1186/s12985-023-02194-w

    Article  Google Scholar 

  96. Restori KH, Srinivasa BT, Ward BJ, Fixman ED (2018) Neonatal immunity, respiratory virus infections, and the development of asthma. Front Immunol 9:1249. https://doi.org/10.3389/fimmu.2018.01249

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Ruterbusch M, Pruner KB, Shehata L, Pepper M (2020) In Vivo CD4+ T Cell Differentiation and Function: Revisiting the Th1/Th2 Paradigm. Annu Rev Immunol 38:705–725. https://doi.org/10.1146/annurev-immunol-103019-085803

    Article  PubMed  CAS  Google Scholar 

  98. Carpenter AC, Bosselut R (2010) Decision checkpoints in the thymus. Nat Immunol 11(8):666–673. https://doi.org/10.1038/ni.1887I

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Stockinger B, Omenetti S (2017) The dichotomous nature of T helper 17 cells. Nat Rev Immunol 17(9):535–544. https://doi.org/10.1038/nri.2017.50

    Article  PubMed  CAS  Google Scholar 

  100. Fulton RB, Weiss KA, Pewe LL, Harty JT, Varga SM (2013) Aged mice exhibit a severely diminished CD8 T cell response following respiratory syncytial virus infection. J Virol 87(23):12694–12700. https://doi.org/10.1128/JVI.02282-12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  101. Ruckwardt TJ, Bonaparte KL, Nason MC, Graham BS (2009) Regulatory T cells promote early influx of CD8+ T cells in the lungs of respiratory syncytial virus-infected mice and diminish immunodominance disparities. J Virol 83(7):3019–3028. https://doi.org/10.1128/JVI.00036-09

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Rutigliano JA, Ruckwardt TJ, Martin JE, Graham BS (2007) Relative dominance of epitope-specific CD8+ T cell responses in an F1 hybrid mouse model of respiratory syncytial virus infection. Virology 362(2):314–319. https://doi.org/10.1016/j.virol.2006.12.023

    Article  PubMed  CAS  Google Scholar 

  103. Schmidt ME, Varga SM (2020) Cytokines and CD8 T cell immunity during respiratory syncytial virus infection. Cytokine 133:154481. https://doi.org/10.1016/j.cyto.2018.07.012

    Article  PubMed  CAS  Google Scholar 

  104. Morabito KM, Erez N, Graham BS, Ruckwardt TJ (2016) Phenotype and hierarchy of two transgenic T cell lines targeting the respiratory syncytial virus KdM282-90 epitope is transfer dose-dependent. PLoS ONE 11(1):e0146781. https://doi.org/10.1371/journal.pone.0146781

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Cannon MJ, Openshaw PJ, Askonas BA (1988) Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. J Exp Med 168(3):1163–1168. https://doi.org/10.1084/jem.168.3.1163

    Article  PubMed  CAS  Google Scholar 

  106. Legg JP, Hussain IR, Warner JA, Johnston SL, Warner JO (2003) Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med 168(6):633–639. https://doi.org/10.1164/rccm.200210-1148OC

    Article  PubMed  Google Scholar 

  107. Roe MF, Bloxham DM, Cowburn AS, O’Donnell DR (2011) Changes in helper lymphocyte chemokine receptor expression and elevation of IP-10 during acute respiratory syncytial virus infection in infants. Pediatric Allergy Immunol: Off Publication Eur Soc Pediatric Allergy Immunol 22(2):229–234. https://doi.org/10.1111/j.1399-3038.2010.01032.x

    Article  Google Scholar 

  108. Becker Y (2006) Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy–a review. Virus Genes 33(2):235–252. https://doi.org/10.1007/s11262-006-0064-x

    Article  PubMed  CAS  Google Scholar 

  109. Qin L, Qiu KZ, Hu CP, Wu GJ, Wang LL, Tan YR (2019) Bronchial epithelial cells promote the differentiation of Th2 lymphocytes in airway microenvironment through jagged/Notch-1 signaling after RSV infection. Int Arch Allergy Immunol 179(1):43–52. https://doi.org/10.1159/000495581

    Article  PubMed  CAS  Google Scholar 

  110. Li B, Wu FL, Feng XB, Sun DK, Cui QQ, Zhao ZX (2012) Changes and the clinical significance of CD4⁺ CD25⁺ regulatory T cells and Th17 cells in peripheral blood of infants with respiratory syncytial virus bronchiolitis. Chinese J Cell Mol Immunol 28(4):426–8

    Google Scholar 

  111. Qin L, Hu CP, Feng JT, Xia Q (2011) Activation of lymphocytes induced by bronchial epithelial cells with prolonged RSV infection. PLoS ONE 6(12):e27113. https://doi.org/10.1371/journal.pone.0027113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Fulton RB, Meyerholz DK, Varga SM (2010) Foxp3+ CD4 regulatory T cells limit pulmonary immunopathology by modulating the CD8 T cell response during respiratory syncytial virus infection. J Immunol (Baltimore, Md.:1950) 185(4):2382–2392. https://doi.org/10.4049/jimmunol.1000423

    Article  CAS  Google Scholar 

  113. Shalev I, Schmelzle M, Robson SC, Levy G (2011) Making sense of regulatory T cell suppressive function. Semin Immunol 23(4):282–292. https://doi.org/10.1016/j.smim.2011.04.003

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Durant LR, Makris S, Voorburg CM, Loebbermann J, Johansson C, Openshaw PJ (2013) Regulatory T cells prevent Th2 immune responses and pulmonary eosinophilia during respiratory syncytial virus infection in mice. J Virol 87(20):10946–10954. https://doi.org/10.1128/JVI.01295-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Mukherjee S, Lindell DM, Berlin AA, Morris SB, Shanley TP, Hershenson MB, Lukacs NW (2011) IL-17-induced pulmonary pathogenesis during respiratory viral infection and exacerbation of allergic disease. Am J Pathol 179(1):248–258. https://doi.org/10.1016/j.ajpath.2011.03.003

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Bystrom J, Al-Adhoubi N, Al-Bogami M, Jawad AS, Mageed RA (2013) Th17 lymphocytes in respiratory syncytial virus infection. Viruses 5(3):777–791. https://doi.org/10.3390/v5030777

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Sun M, Wu W, Chen L, Yang W, Huang X, Ma C, Chen F, Xiao Y, Zhao Y, Ma C, Yao S, Carpio VH, Dann SM, Zhao Q, Liu Z, Cong Y (2018) Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nat Commun 9(1):3555. https://doi.org/10.1038/s41467-018-05901-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  118. Luo A, Leach ST, Barres R, Hesson LB, Grimm MC, Simar D (2017) The microbiota and epigenetic regulation of T helper 17/regulatory T cells: in search of a balanced immune system. Front Immunol 8:417. https://doi.org/10.3389/fimmu.2017.00417

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Rangan P, Mondino A (2022) Microbial short-chain fatty acids: a strategy to tune adoptive T cell therapy. J Immunother Cancer 10(7):e004147. https://doi.org/10.1136/jitc-2021-004147

    Article  PubMed  PubMed Central  Google Scholar 

  120. Bachem A, Makhlouf C, Binger KJ, de Souza DP, Tull D, Hochheiser K, Whitney PG, Fernandez-Ruiz D, Dähling S, Kastenmüller W, Jönsson J, Gressier E, Lew AM, Perdomo C, Kupz A, Figgett W, Mackay F, Oleshansky M, Russ BE, Parish IA, Bedoui S (2019) Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8+ T cells. Immunity 51(2):285-297.e5. https://doi.org/10.1016/j.immuni.2019.06.002

    Article  PubMed  CAS  Google Scholar 

  121. Qiu J, Villa M, Sanin DE, Buck MD, O’Sullivan D, Ching R, Matsushita M, Grzes KM, Winkler F, Chang CH, Curtis JD, Kyle RL, Van Teijlingen Bakker N, Corrado M, Haessler F, Alfei F, Edwards-Hicks J, Maggi LB Jr, Zehn D, Egawa T, Pearce EL (2019) Acetate promotes T cell effector function during glucose restriction. Cell Rep 27(7):2063-2074.e5. https://doi.org/10.1016/j.celrep.2019.04.022

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Trompette A, Gollwitzer ES, Pattaroni C, Lopez-Mejia IC, Riva E, Pernot J, Ubags N, Fajas L, Nicod LP, Marsland BJ (2018) Dietary fiber confers protection against flu by shaping Ly6c- patrolling monocyte hematopoiesis and CD8+ T cell metabolism. Immunity 48(5):992-1005.e8. https://doi.org/10.1016/j.immuni.2018.04.022

    Article  PubMed  CAS  Google Scholar 

  123. Wang Q, Fang Z, Li L, Wang H, Zhu J, Zhang P, Lee YK, Zhao J, Zhang H, Lu W, Chen W (2022) Lactobacillus mucosae exerted different antiviral effects on respiratory syncytial virus infection in mice. Front Microbiol 13:1001313. https://doi.org/10.3389/fmicb.2022.1001313

    Article  PubMed  PubMed Central  Google Scholar 

  124. Cancro MP, Tomayko MM (2021) Memory B cells and plasma cells: the differentiative continuum of humoral immunity. Immunol Rev 303(1):72–82. https://doi.org/10.1111/imr.13016

    Article  PubMed  CAS  Google Scholar 

  125. Catalán D, Mansilla MA, Ferrier A, Soto L, Oleinika K, Aguillón JC, Aravena O (2021) Immunosuppressive Mechanisms of Regulatory B Cells. Front Immunol 12:611795. https://doi.org/10.3389/fimmu.2021.611795

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Zhivaki D, Lemoine S, Lim A, Morva A, Vidalain PO, Schandene L, Casartelli N, Rameix-Welti MA, Hervé PL, Dériaud E, Beitz B, Ripaux-Lefevre M, Miatello J, Lemercier B, Lorin V, Descamps D, Fix J, Eléouët JF, Riffault S, Schwartz O, Lo-Man R (2017) Respiratory syncytial virus infects regulatory b cells in human neonates via chemokine receptor CX3CR1 and promotes lung disease severity. Immunity 46(2):301–314. https://doi.org/10.1016/j.immuni.2017.01.010

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Russell CD, Unger SA, Walton M, Schwarze J (2017) The Human immune response to respiratory syncytial virus infection. Clin Microbiol Rev 30(2):481–502. https://doi.org/10.1128/CMR.00090-16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Rosser EC, Piper CJM, Matei DE, Blair PA, Rendeiro AF, Orford M, Alber DG, Krausgruber T, Catalan D, Klein N, Manson JJ, Drozdov I, Bock C, Wedderburn LR, Eaton S, Mauri C (2020) Microbiota-derived metabolites suppress arthritis by amplifying aryl-hydrocarbon receptor activation in regulatory B cells. Cell Metab 31(4):837-851.e10. https://doi.org/10.1016/j.cmet.2020.03.003

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Kim M, Qie Y, Park J, Kim CH (2016) Gut microbial metabolites fuel host antibody responses. Cell Host Microbe 20(2):202–214. https://doi.org/10.1016/j.chom.2016.07.001

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Sanchez HN, Moroney JB, Gan H, Shen T, Im JL, Li T, Taylor JR, Zan H, Casali P (2020) B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids. Nat Commun 11(1):60. https://doi.org/10.1038/s41467-019-13603-6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  131. Balan S, Saxena M, Bhardwaj N (2019) Dendritic cell subsets and locations. Int Rev Cell Mol Biol 348:1–68. https://doi.org/10.1016/bs.ircmb.2019.07.004

    Article  PubMed  CAS  Google Scholar 

  132. Tognarelli EI, Bueno SM, González PA (2019) Immune-modulation by the human respiratory syncytial virus: focus on dendritic cells. Front Immunol 10:810. https://doi.org/10.3389/fimmu.2019.00810

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  133. Le Nouën C, Hillyer P, Levenson E, Martens C, Rabin RL, Collins PL, Buchholz UJ (2019) Lack of activation marker induction and chemokine receptor switch in human neonatal myeloid dendritic cells in response to human respiratory syncytial virus. J Virol 93(22):e01216-e1219. https://doi.org/10.1128/JVI.01216-19

    Article  PubMed  PubMed Central  Google Scholar 

  134. Malinczak CA, Rasky AJ, Fonseca W, Schaller MA, Allen RM, Ptaschinski C, Morris S, Lukacs NW (2020) Upregulation of H3K27 demethylase KDM6 during respiratory syncytial virus infection enhances proinflammatory responses and immunopathology. J Immunol (Baltimore, Md.:1950) 204(1):159–168. https://doi.org/10.4049/jimmunol.1900741

    Article  CAS  Google Scholar 

  135. Mire MM, Elesela S, Morris S, Corfas G, Rasky A, Lukacs NW (2024) Respiratory virus-induced PARP1 alters DC metabolism and antiviral immunity inducing pulmonary immunopathology. Viruses 16(6):910. https://doi.org/10.3390/v16060910

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Eisenbarth SC (2019) Dendritic cell subsets in T cell programming: location dictates function. Nat Rev Immunol 19(2):89–103. https://doi.org/10.1038/s41577-018-0088-1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Jie Z, Dinwiddie DL, Senft AP, Harrod KS (2011) Regulation of STAT signaling in mouse bone marrow derived dendritic cells by respiratory syncytial virus. Virus Res 156(1–2):127–133. https://doi.org/10.1016/j.virusres.2011.01.007

    Article  PubMed  CAS  Google Scholar 

  138. Hijano DR, Vu LD, Kauvar LM, Tripp RA, Polack FP, Cormier SA (2019) Role of type i interferon (IFN) in the respiratory syncytial virus (RSV) immune response and disease severity. Front Immunol 10:566. https://doi.org/10.3389/fimmu.2019.00566

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  139. Ioannidis I, McNally B, Willette M, Peeples ME, Chaussabel D, Durbin JE, Ramilo O, Mejias A, Flaño E (2012) Plasticity and virus specificity of the airway epithelial cell immune response during respiratory virus infection. J Virol 86(10):5422–5436. https://doi.org/10.1128/JVI.06757-11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Farazuddin M, Acker G, Zourob J, O’Konek JJ, Wong PT, Morris S, Rasky AJ, Kim CH, Lukacs NW, Baker JR Jr (2024) Inhibiting retinoic acid signaling in dendritic cells suppresses respiratory syncytial virus infection through enhanced antiviral immunity. iScience 27(7):110103. https://doi.org/10.1016/j.isci.2024.110103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Cormier SA, Shrestha B, Saravia J, Lee GI, Shen L, DeVincenzo JP, Kim YI, You D (2014) Limited type I interferons and plasmacytoid dendritic cells during neonatal respiratory syncytial virus infection permit immunopathogenesis upon reinfection. J Virol 88(16):9350–9360. https://doi.org/10.1128/JVI.00818-14

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Yang K, Hou Y, Zhang Y, Liang H, Sharma A, Zheng W, Wang L, Torres R, Tatebe K, Chmura SJ, Pitroda SP, Gilbert JA, Fu YX, Weichselbaum RR (2021) Suppression of local type I interferon by gut microbiota-derived butyrate impairs antitumor effects of ionizing radiation. J Exp Med 218(3):e20201915. https://doi.org/10.1084/jem.20201915

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  143. Yin L, Liu X, Yao Y, Yuan M, Luo Y, Zhang G, Pu J, Liu P (2024) Gut microbiota-derived butyrate promotes coronavirus TGEV infection through impairing RIG-I-triggered local type I interferon responses via class I HDAC inhibition. J Virol 98(2):e0137723. https://doi.org/10.1128/jvi.01377-23

    Article  PubMed  CAS  Google Scholar 

  144. Chemudupati M, Kenney AD, Smith AC, Fillinger RJ, Zhang L, Zani A, Liu SL, Anderson MZ, Sharma A, Yount JS (2020) Butyrate reprograms expression of specific interferon-stimulated genes. J Virol 94(16):e00326-e420. https://doi.org/10.1128/JVI.00326-20

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  145. Antunes KH, Fachi JL, de Paula R, da Silva EF, Pral LP, Dos Santos AÁ, Dias GBM, Vargas JE, Puga R, Mayer FQ, Maito F, Zárate-Bladés CR, Ajami NJ, Sant’Ana MR, Candreva T, Rodrigues HG, Schmiele M, Silva Clerici MTP, Proença-Modena JL, Vieira AT, de Souza APD (2019) Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response. Nature Commun 10(1):3273. https://doi.org/10.1038/s41467-019-11152-6

    Article  CAS  Google Scholar 

  146. Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, Miyake T, Matsushita K, Okazaki T, Saitoh T, Honma K, Matsuyama T, Yui K, Tsujimura T, Standley DM, Nakanishi K, Nakai K, Akira S (2010) The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol 11(10):936–944. https://doi.org/10.1038/ni.1920

    Article  PubMed  CAS  Google Scholar 

  147. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25(12):677–686. https://doi.org/10.1016/j.it.2004.09.015

    Article  PubMed  CAS  Google Scholar 

  148. Wang Y, Zheng J, Wang X, Yang P, Zhao D (2022) Alveolar macrophages and airway hyperresponsiveness associated with respiratory syncytial virus infection. Front Immunol 13:1012048. https://doi.org/10.3389/fimmu.2022.1012048

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  149. Clua P, Tomokiyo M, Raya Tonetti F, Islam MA, García Castillo V, Marcial G, Salva S, Alvarez S, Takahashi H, Kurata S, Kitazawa H, Villena J (2020) The role of alveolar macrophages in the improved protection against respiratory syncytial virus and pneumococcal superinfection induced by the peptidoglycan of Lactobacillus rhamnosus CRL1505. Cells 9(7):1653. https://doi.org/10.3390/cells9071653

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  150. Duan H, Wang L, Huangfu M, Li H (2023) The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: mechanisms and therapeutic potentials. Biomed Pharmacother Biomed Pharmacother 165:115276. https://doi.org/10.1016/j.biopha.2023.115276

    Article  PubMed  CAS  Google Scholar 

  151. Xia M, Harb H, Saffari A, Sioutas C, Chatila TA (2018) A Jagged 1-Notch 4 molecular switch mediates airway inflammation induced by ultrafine particles. J Allergy Clin Immunol 142(4):1243-1256.e17. https://doi.org/10.1016/j.jaci.2018.03.009

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Liu H, Xi Q, Tan S, Qu Y, Meng Q, Zhang Y, Cheng Y, Wu G (2023) The metabolite butyrate produced by gut microbiota inhibits cachexia-associated skeletal muscle atrophy by regulating intestinal barrier function and macrophage polarization. Int Immunopharmacol 124(Pt B):111001. https://doi.org/10.1016/j.intimp.2023.111001

    Article  PubMed  CAS  Google Scholar 

  153. Huang C, Du W, Ni Y, Lan G, Shi G (2022) The effect of short-chain fatty acids on M2 macrophages polarization in vitro and in vivo. Clin Exp Immunol 207(1):53–64. https://doi.org/10.1093/cei/uxab028

    Article  PubMed  Google Scholar 

  154. Moreira AP, Cavassani KA, Hullinger R, Rosada RS, Fong DJ, Murray L, Hesson DP, Hogaboam CM (2010) Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore-induced allergic airway disease. J Allergy Clin Immunol 126(4):712-721.e7. https://doi.org/10.1016/j.jaci.2010.06.010

    Article  PubMed  CAS  Google Scholar 

  155. Wang G, Liu J, Zhang Y, Xie J, Chen S, Shi Y, Shi F, Zhu SJ (2023) Ginsenoside Rg3 enriches SCFA-producing commensal bacteria to confer protection against enteric viral infection via the cGAS-STING-type I IFN axis. ISME J 17(12):2426–2440. https://doi.org/10.1038/s41396-023-01541-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  156. Johansson C, Kirsebom FCM (2021) Neutrophils in respiratory viral infections. Mucosal Immunol 14(4):815–827. https://doi.org/10.1038/s41385-021-00397-4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  157. McNamara PS, Ritson P, Selby A, Hart CA, Smyth RL (2003) Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis. Arch Dis Child 88(10):922–926. https://doi.org/10.1136/adc.88.10.922

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Stoppelenburg AJ, Salimi V, Hennus M, Plantinga M, Huis in’t Veld R, Walk J, Meerding J, Coenjaerts F, Bont L, Boes M (2013) Local IL-17A potentiates early neutrophil recruitment to the respiratory tract during severe RSV infection. PloS One 8(10):e78461. https://doi.org/10.1371/journal.pone.0078461

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  159. Kirsebom FCM, Kausar F, Nuriev R, Makris S, Johansson C (2019) Neutrophil recruitment and activation are differentially dependent on MyD88/TRIF and MAVS signaling during RSV infection. Mucosal Immunol 12(5):1244–1255. https://doi.org/10.1038/s41385-019-0190-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  160. Robinson E, Herbert JA, Palor M, Ren L, Larken I, Patel A, Moulding D, Cortina-Borja M, Smyth RL, Smith CM (2023) Trans-epithelial migration is essential for neutrophil activation during RSV infection. J Leukoc Biol 113(4):354–364. https://doi.org/10.1093/jleuko/qiad011

    Article  PubMed  Google Scholar 

  161. Stokes KL, Currier MG, Sakamoto K, Lee S, Collins PL, Plemper RK, Moore ML (2013) The respiratory syncytial virus fusion protein and neutrophils mediate the airway mucin response to pathogenic respiratory syncytial virus infection. J Virol 87(18):10070–10082. https://doi.org/10.1128/JVI.01347-13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  162. Sande CJ, Njunge JM, Mwongeli Ngoi J, Mutunga MN, Chege T, Gicheru ET, Gardiner EM, Gwela A, Green CA, Drysdale SB, Berkley JA, Nokes DJ, Pollard AJ (2019) Airway response to respiratory syncytial virus has incidental antibacterial effects. Nat Commun 10(1):2218. https://doi.org/10.1038/s41467-019-10222-z

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  163. Kirsebom F, Michalaki C, Agueda-Oyarzabal M, Johansson C (2020) Neutrophils do not impact viral load or the peak of disease severity during RSV infection. Sci Rep 10(1):1110. https://doi.org/10.1038/s41598-020-57969-w

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  164. Mejias A, Dimo B, Suarez NM, Garcia C, Suarez-Arrabal MC, Jartti T, Blankenship D, Jordan-Villegas A, Ardura MI, Xu Z, Banchereau J, Chaussabel D, Ramilo O (2013) Whole blood gene expression profiles to assess pathogenesis and disease severity in infants with respiratory syncytial virus infection. PLoS Med 10(11):e1001549. https://doi.org/10.1371/journal.pmed.1001549

    Article  PubMed  PubMed Central  Google Scholar 

  165. Juliana A, Zonneveld R, Plötz FB, van Meurs M, Wilschut J (2020) Neutrophil-endothelial interactions in respiratory syncytial virus bronchiolitis: An understudied aspect with a potential for prediction of severity of disease. J Clin Virol : Off Publication of the Pan Am Society Clin Virology 123:104258. https://doi.org/10.1016/j.jcv.2019.104258

    Article  CAS  Google Scholar 

  166. Tian Z, Zhang Y, Zheng Z, Zhang M, Zhang T, Jin J, Zhang X, Yao G, Kong D, Zhang C, Wang Z, Zhang Q (2022) Gut microbiome dysbiosis contributes to abdominal aortic aneurysm by promoting neutrophil extracellular trap formation. Cell Host Microbe 30(10):1450-1463.e8. https://doi.org/10.1016/j.chom.2022.09.004

    Article  PubMed  CAS  Google Scholar 

  167. Li G, Lin J, Zhang C, Gao H, Lu H, Gao X, Zhu R, Li Z, Li M, Liu Z (2021) Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease. Gut microbes 13(1):1968257. https://doi.org/10.1080/19490976.2021.1968257

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  168. Shen S, Prame Kumar K, Wen SW, Shim R, Wanrooy BJ, Stanley D, Moore RJ, Van TTH, Robert R, Hickey MJ, Wong CHY (2021) Deficiency of dietary fiber modulates gut microbiota composition, neutrophil recruitment and worsens experimental colitis. Front Immunol 12:619366. https://doi.org/10.3389/fimmu.2021.619366

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  169. Lei Y, Tang L, Liu S, Hu S, Wu L, Liu Y, Yang M, Huang S, Tang X, Tang T, Zhao X, Vlodavsky I, Zeng S, Tang B, Yang S (2021) Parabacteroides produces acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration. Microbiome 9(1):115. https://doi.org/10.1186/s40168-021-01065-2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  170. Carrillo-Salinas FJ, Parthasarathy S, Moreno de Lara L, Borchers A, Ochsenbauer C, Panda A, Rodriguez-Garcia M (2022) Short-chain fatty acids impair neutrophil antiviral function in an age-dependent manner. Cells 11(16):2515. https://doi.org/10.3390/cells11162515

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  171. Yan Q, Jia S, Li D, Yang J (2023) The role and mechanism of action of microbiota-derived short-chain fatty acids in neutrophils: from the activation to becoming potential biomarkers. Biomed Pharmacother Biomed Pharmacother 169:115821. https://doi.org/10.1016/j.biopha.2023.115821

    Article  PubMed  CAS  Google Scholar 

  172. Vareille M, Kieninger E, Edwards MR, Regamey N (2011) The airway epithelium: soldier in the fight against respiratory viruses. Clin Microbiol Rev 24(1):210–229. https://doi.org/10.1128/CMR.00014-10

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  173. Aird WC (2007) Phenotypic heterogeneity of the endothelium: I Structure, function, and mechanisms. Circulation Res 100(2):158–173. https://doi.org/10.1161/01.RES.0000255691.76142.4a

    Article  PubMed  CAS  Google Scholar 

  174. Vlahopoulos S, Wang K, Xue Y, Zheng X, Boldogh I, Pan L (2021) Endothelial dysfunction through oxidatively generated epigenetic mark in respiratory viral infections. Cells 10(11):3067. https://doi.org/10.3390/cells10113067

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Glaser L, Coulter PJ, Shields M, Touzelet O, Power UF, Broadbent L (2019) Airway epithelial derived cytokines and chemokines and their role in the immune response to respiratory syncytial virus infection. Pathogens (Basel, Switzerland) 8(3):106. https://doi.org/10.3390/pathogens8030106

    Article  PubMed  CAS  Google Scholar 

  176. Habibi MS, Thwaites RS, Chang M, Jozwik A, Paras A, Kirsebom F, Varese A, Owen A, Cuthbertson L, James P, Tunstall T, Nickle D, Hansel TT, Moffatt MF, Johansson C, Chiu C, Openshaw PJM (2020) Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection. Science (New York, N.Y.) 370(6513):eaba9301. https://doi.org/10.1126/science.aba9301

    Article  PubMed  CAS  Google Scholar 

  177. Singh D, McCann KL, Imani F (2007) MAPK and heat shock protein 27 activation are associated with respiratory syncytial virus induction of human bronchial epithelial monolayer disruption. Am J Phys Lung Cell Mol Physiol 293(2):L436–L445. https://doi.org/10.1152/ajplung.00097.2007

    Article  CAS  Google Scholar 

  178. Kilani MM, Mohammed KA, Nasreen N, Hardwick JA, Kaplan MH, Tepper RS, Antony VB (2004) Respiratory syncytial virus causes increased bronchial epithelial permeability. Chest 126(1):186–191. https://doi.org/10.1378/chest.126.1.186

    Article  PubMed  Google Scholar 

  179. Hu L, Sun L, Yang C, Zhang DW, Wei YY, Yang MM, Wu HM, Fei GH (2024) Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions. J Transl Med 22(1):570. https://doi.org/10.1186/s12967-024-05376-4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  180. Saint-Martin V, Guillory V, Chollot M, Fleurot I, Kut E, Roesch F, Caballero I, Helloin E, Chambellon E, Ferguson B, Velge P, Kempf F, Trapp S, Guabiraba R (2024) The gut microbiota and its metabolite butyrate shape metabolism and antiviral immunity along the gut-lung axis in the chicken. Commun Biol 7(1):1185. https://doi.org/10.1038/s42003-024-06815-0

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  181. Richards LB, Li M, Folkerts G, Henricks PAJ, Garssen J, van Esch BCAM (2020) Butyrate and propionate restore the cytokine and house dust mite compromised barrier function of human bronchial airway epithelial cells. Int J Mol Sci 22(1):65. https://doi.org/10.3390/ijms22010065

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  182. Xiao C, Puddicombe SM, Field S, Haywood J, Broughton-Head V, Puxeddu I, Haitchi HM, Vernon-Wilson E, Sammut D, Bedke N, Cremin C, Sones J, Djukanović R, Howarth PH, Collins JE, Holgate ST, Monk P, Davies DE (2011) Defective epithelial barrier function in asthma. J Allergy Clinical Immunol 128(3):549. https://doi.org/10.1016/j.jaci.2011.05.038

    Article  CAS  Google Scholar 

  183. Li M, van Esch BCAM, Henricks PAJ, Garssen J, Folkerts G (2018) Time and concentration dependent effects of short chain fatty acids on lipopolysaccharide- or tumor necrosis factor α-induced endothelial activation. Front Pharmacol 9:233. https://doi.org/10.3389/fphar.2018.00233

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  184. Pluznick J (2014) A novel SCFA receptor, the microbiota, and blood pressure regulation. Gut Microbes 5(2):202–207. https://doi.org/10.4161/gmic.27492

    Article  PubMed  Google Scholar 

  185. Lee DY, Lee CI, Lin TE, Lim SH, Zhou J, Tseng YC, Chien S, Chiu JJ (2012) Role of histone deacetylases in transcription factor regulation and cell cycle modulation in endothelial cells in response to disturbed flow. Proc Natl Acad Sci USA 109(6):1967–1972. https://doi.org/10.1073/pnas.1121214109

    Article  PubMed  PubMed Central  Google Scholar 

  186. Maldonado Galdeano C, Cazorla SI, Lemme Dumit JM, Vélez E, Perdigón G (2019) Beneficial effects of probiotic consumption on the immune system. Ann Nutr Metab 74(2):115–124. https://doi.org/10.1159/000496426

    Article  PubMed  CAS  Google Scholar 

  187. Hevia A, Delgado S, Sánchez B, Margolles A (2015) Molecular players involved in the interaction between beneficial bacteria and the immune system. Front Microbiol 6:1285. https://doi.org/10.3389/fmicb.2015.01285

    Article  PubMed  PubMed Central  Google Scholar 

  188. Liu Y, Wang J, Wu C (2022) Modulation of gut microbiota and immune system by probiotics, pre-biotics, and post-biotics. Front Nutr 8:634897. https://doi.org/10.3389/fnut.2021.634897

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  189. Rawi MH, Zaman SA, Pa’ee KF, Leong SS, Sarbini SR (2020) Prebiotics metabolism by gut-isolated probiotics. J Food Sci Technol 57(8):2786–2799. https://doi.org/10.1007/s13197-020-04244-5

    Article  PubMed  PubMed Central  Google Scholar 

  190. Garaiova I, Paduchová Z, Nagyová Z, Wang D, Michael DR, Plummer SF, Marchesi JR, Ďuračková Z, Muchová J (2021) Probiotics with vitamin C for the prevention of upper respiratory tract symptoms in children aged 3–10 years: randomised controlled trial. Beneficial Microbes 12(5):431–440. https://doi.org/10.3920/BM2020.0185

    Article  PubMed  CAS  Google Scholar 

  191. Kumpu M, Kekkonen RA, Kautiainen H, Järvenpää S, Kristo A, Huovinen P, Pitkäranta A, Korpela R, Hatakka K (2012) Milk containing probiotic Lactobacillus rhamnosus GG and respiratory illness in children: a randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr 66(9):1020–1023. https://doi.org/10.1038/ejcn.2012.62

    Article  PubMed  CAS  Google Scholar 

  192. Luoto R, Ruuskanen O, Waris M, Kalliomäki M, Salminen S, Isolauri E (2014) Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial. J Allergy Clin Immunol 133(2):405–413. https://doi.org/10.1016/j.jaci.2013.08.020

    Article  PubMed  Google Scholar 

  193. De Boeck I, van den Broek MFL, Allonsius CN, Spacova I, Wittouck S, Martens K, Wuyts S, Cauwenberghs E, Jokicevic K, Vandenheuvel D, Eilers T, Lemarcq M, De Rudder C, Thys S, Timmermans JP, Vroegop AV, Verplaetse A, Van de Wiele T, Kiekens F, Hellings PW, Lebeer S (2020) Lactobacilli Have a Niche in the Human Nose. Cell Rep 31(8):107674. https://doi.org/10.1016/j.celrep.2020.107674

    Article  PubMed  CAS  Google Scholar 

  194. De Rudder C, Garcia-Tímermans C, De Boeck I, Lebeer S, Van de Wiele T, Calatayud Arroyo M (2020) Lacticaseibacillus casei AMBR2 modulates the epithelial barrier function and immune response in a donor-derived nasal microbiota manner. Sci Rep 10(1):16939. https://doi.org/10.1038/s41598-020-73857-9

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  195. Martens K, De Boeck I, Jokicevic K, Kiekens F, Farré R, Vanderveken OM, Seys SF, Lebeer S, Hellings PW, Steelant B (2021) Lacticaseibacillus casei AMBR2 restores airway epithelial integrity in chronic rhinosinusitis with nasal polyps. Allergy, Asthma Immunol Res 13(4):560–575. https://doi.org/10.4168/aair.2021.13.4.560

    Article  PubMed  CAS  Google Scholar 

  196. Tomosada Y, Chiba E, Zelaya H, Takahashi T, Tsukida K, Kitazawa H, Alvarez S, Villena J (2013) Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection. BMC Immunol 14:40. https://doi.org/10.1186/1471-2172-14-40

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  197. Garcia-Castillo V, Tomokiyo M, Raya Tonetti F, Islam MA, Takahashi H, Kitazawa H, Villena J (2020) Alveolar macrophages are key players in the modulation of the respiratory antiviral immunity induced by orally administered Lacticaseibacillus rhamnosus CRL1505. Front Immunol 11:568636. https://doi.org/10.3389/fimmu.2020.568636

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  198. Spacova I, De Boeck I, Cauwenberghs E, Delanghe L, Bron PA, Henkens T, Simons A, Gamgami I, Persoons L, Claes I, van den Broek MFL, Schols D, Delputte P, Coenen S, Verhoeven V, Lebeer S (2023) Development of a live biotherapeutic throat spray with lactobacilli targeting respiratory viral infections. Microb Biotechnol 16(1):99–115. https://doi.org/10.1111/1751-7915.14189

    Article  PubMed  CAS  Google Scholar 

  199. Weiss G, Rasmussen S, Zeuthen LH, Nielsen BN, Jarmer H, Jespersen L, Frøkiaer H (2010) Lactobacillus acidophilus induces virus immune defence genes in murine dendritic cells by a Toll-like receptor-2-dependent mechanism. Immunology 131(2):268–281. https://doi.org/10.1111/j.1365-2567.2010.03301.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  200. Kwon HK, Lee CG, So JS, Chae CS, Hwang JS, Sahoo A, Nam JH, Rhee JH, Hwang KC, Im SH (2010) Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders. Proc Natl Acad Sci USA 107(5):2159–2164. https://doi.org/10.1073/pnas.0904055107

    Article  PubMed  PubMed Central  Google Scholar 

  201. Fonseca W, Malinczak CA, Fujimura K, Li D, McCauley K, Li J, Best SKK, Zhu D, Rasky AJ, Johnson CC, Bermick J, Zoratti EM, Ownby D, Lynch SV, Lukacs NW, Ptaschinski C (2021) Maternal gut microbiome regulates immunity to RSV infection in offspring. J Exp Med 218(11):e20210235. https://doi.org/10.1084/jem.20210235

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  202. Tonon KM, Chutipongtanate S, Morrow AL, Newburg DS (2024) human milk oligosaccharides and respiratory syncytial virus infection in infants. Adv Nutrition (Bethesda, Md.) 15(6):100218. https://doi.org/10.1016/j.advnut.2024.100218

    Article  CAS  Google Scholar 

  203. Villena J, Chiba E, Tomosada Y, Salva S, Marranzino G, Kitazawa H, Alvarez S (2012) Orally administered Lactobacillus rhamnosus modulates the respiratory immune response triggered by the viral pathogen-associated molecular pattern poly(I:C). BMC Immunol 13:53. https://doi.org/10.1186/1471-2172-13-53

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  204. Tran DM, Tran TT, Phung TTB, Bui HT, Nguyen PTT, Vu TT, Ngo NTP, Nguyen MT, Nguyen AH, Nguyen ATV (2022) Nasal-spraying Bacillus spores as an effective symptomatic treatment for children with acute respiratory syncytial virus infection. Sci Rep 12(1):12402. https://doi.org/10.1038/s41598-022-16136-zIF

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  205. Dyer KD, Drummond RA, Rice TA, Percopo CM, Brenner TA, Barisas DA, Karpe KA, Moore ML, Rosenberg HF (2015) Priming of the respiratory tract with immunobiotic Lactobacillus plantarum limits infection of alveolar macrophages with recombinant pneumonia virus of mice (rK2-PVM). J Virol 90(2):979–991. https://doi.org/10.1128/JVI.02279-15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  206. Kang MS, Park GY (2022) In vitro inactivation of respiratory viruses and rotavirus by the oral probiotic strain Weissella cibaria CMS1. Probiotics Antimicrobial Proteins 14(4):760–766. https://doi.org/10.1007/s12602-022-09947-z

    Article  PubMed  CAS  Google Scholar 

  207. Eguchi K, Fujitani N, Nakagawa H, Miyazaki T (2019) Prevention of respiratory syncytial virus infection with probiotic lactic acid bacterium Lactobacillus gasseri SBT2055. Sci Rep 9(1):4812. https://doi.org/10.1038/s41598-019-39602-7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  208. Bezemer GFG, Diks MAP, Mortaz E, van Ark I, van Bergenhenegouwen J, Kraneveld AD, Folkerts G, Garssen J (2024) A synbiotic mixture of Bifidobacterium breve M16-V, oligosaccharides and pectin, enhances short chain fatty acid production and improves lung health in a preclinical model for pulmonary neutrophilia. Front Nutr 11:1371064. https://doi.org/10.3389/fnut.2024.1371064

    Article  PubMed  PubMed Central  Google Scholar 

  209. Schijf MA, Kruijsen D, Bastiaans J, Coenjaerts FE, Garssen J, van Bleek GM, van’t Land B (2012) Specific dietary oligosaccharides increase Th1 responses in a mouse respiratory syncytial virus infection model. J Virology 86(21):11472–11482. https://doi.org/10.1128/JVI.06708-11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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  1. School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, China

    Mingxin Liang & Weiyi Wu

  2. School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan, China

    Qinqin Dong

  3. Department of Pediatrics, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, 610072, Sichuan, China

    Mingxin Liang, Qinqin Dong, Weiyi Wu & Juan Fan

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Liang, M., Dong, Q., Wu, W. et al. Short-Chain Fatty Acids: Promising Therapeutic Targets for Respiratory Syncytial Virus Infection. Clinic Rev Allerg Immunol 68, 8 (2025). https://doi.org/10.1007/s12016-024-09018-x

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