The Gut Microbiota and Its Metabolite Butyrate Shape Metabolism and Antiviral Immunity Along the Gut-lung Axis in the Chicken

Overview

Journal Commun Biol

Specialty Biology

Date 2024 Sep 19

PMID 39300162

Authors

Vincent Saint-Martin

Vanaique Guillory

Melanie Chollot

Isabelle Fleurot

Emmanuel Kut

Ferdinand Roesch

Ignacio Caballero

Emmanuelle Helloin

Emilie Chambellon

Brian Ferguson

Philippe Velge

Florent Kempf

Sascha Trapp

Rodrigo Guabiraba

Affiliations

Soon will be listed here.

Abstract

The gut microbiota exerts profound influence on poultry immunity and metabolism through mechanisms that yet need to be elucidated. Here we used conventional and germ-free chickens to explore the influence of the gut microbiota on transcriptomic and metabolic signatures along the gut-lung axis in poultry. Our results demonstrated a differential regulation of certain metabolites and genes associated with innate immunity and metabolism in peripheral tissues of germ-free birds. Furthermore, we evidenced the gut microbiota's capacity to regulate mucosal immunity in the chicken lung during avian influenza virus infection. Finally, by fine-analysing the antiviral pathways triggered by the short-chain fatty acid (SCFA) butyrate in chicken respiratory epithelial cells, we found that it regulates interferon-stimulated genes (ISGs), notably OASL, via the transcription factor Sp1. These findings emphasize the pivotal role of the gut microbiota and its metabolites in shaping homeostasis and immunity in poultry, offering crucial insights into the mechanisms governing the communication between the gut and lungs in birds.

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References

He J, Li D, Zhou J, Zhu Y, Yu B . SP1-mediated upregulation of lncRNA LMCD1-AS1 functions a ceRNA for miR-106b-5p to facilitate osteosarcoma progression. Biochem Biophys Res Commun. 2020; 526(3):670-677. DOI: 10.1016/j.bbrc.2020.03.151. View

Mahe F, Rognes T, Quince C, de Vargas C, Dunthorn M . Swarm: robust and fast clustering method for amplicon-based studies. PeerJ. 2014; 2:e593. PMC: 4178461. DOI: 10.7717/peerj.593. View

Morrison D, Preston T . Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016; 7(3):189-200. PMC: 4939913. DOI: 10.1080/19490976.2015.1134082. View

Koskela K, Kohonen P, Salminen H, Uchida T, Buerstedde J, Lassila O . Identification of a novel cytokine-like transcript differentially expressed in avian gammadelta T cells. Immunogenetics. 2004; 55(12):845-54. DOI: 10.1007/s00251-004-0643-8. View

Sergeant M, Constantinidou C, Cogan T, Bedford M, Penn C, Pallen M . Extensive microbial and functional diversity within the chicken cecal microbiome. PLoS One. 2014; 9(3):e91941. PMC: 3962364. DOI: 10.1371/journal.pone.0091941. View

Rhee S, Pothoulakis C, Mayer E . Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol. 2009; 6(5):306-14. PMC: 3817714. DOI: 10.1038/nrgastro.2009.35. View

Del Vesco A, Jang H, Monson M, Lamont S . Role of the chicken oligoadenylate synthase-like gene during in vitro Newcastle disease virus infection. Poult Sci. 2021; 100(5):101067. PMC: 8005822. DOI: 10.1016/j.psj.2021.101067. View

Saint-Martin V, Quere P, Trapp S, Guabiraba R . Uncovering the core principles of the gut-lung axis to enhance innate immunity in the chicken. Front Immunol. 2022; 13:956670. PMC: 9577073. DOI: 10.3389/fimmu.2022.956670. View

Tolnay A, Baskin C, Tumpey T, Sabourin P, Sabourin C, Long J . Extrapulmonary tissue responses in cynomolgus macaques (Macaca fascicularis) infected with highly pathogenic avian influenza A (H5N1) virus. Arch Virol. 2010; 155(6):905-14. PMC: 2892232. DOI: 10.1007/s00705-010-0662-8. View

10.

Jiang Y, Liu H, Liu W, Tong H, Chen C, Lin F . Endothelial Aquaporin-1 (AQP1) Expression Is Regulated by Transcription Factor Mef2c. Mol Cells. 2016; 39(4):292-8. PMC: 4844935. DOI: 10.14348/molcells.2016.2223. View

11.

Chang P, Hao L, Offermanns S, Medzhitov R . The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A. 2014; 111(6):2247-52. PMC: 3926023. DOI: 10.1073/pnas.1322269111. View

12.

Wirusanti N, Baldridge M, Harris V . Microbiota regulation of viral infections through interferon signaling. Trends Microbiol. 2022; 30(8):778-792. PMC: 9344482. DOI: 10.1016/j.tim.2022.01.007. View

13.

Broom L, Kogut M . The role of the gut microbiome in shaping the immune system of chickens. Vet Immunol Immunopathol. 2019; 204:44-51. DOI: 10.1016/j.vetimm.2018.10.002. View

14.

Fachi J, de Souza Felipe J, Pral L, da Silva B, Correa R, de Andrade M . Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism. Cell Rep. 2019; 27(3):750-761.e7. DOI: 10.1016/j.celrep.2019.03.054. View

15.

Rooks M, Garrett W . Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016; 16(6):341-52. PMC: 5541232. DOI: 10.1038/nri.2016.42. View

16.

Sutton K, Costa T, Alber A, Bryson K, Borowska D, Balic A . Visualisation and characterisation of mononuclear phagocytes in the chicken respiratory tract using CSF1R-transgenic chickens. Vet Res. 2018; 49(1):104. PMC: 6389226. DOI: 10.1186/s13567-018-0598-7. View

17.

Zang W, Zheng X . Structure and functions of cellular redox sensor HSCARG/NMRAL1, a linkage among redox status, innate immunity, DNA damage response, and cancer. Free Radic Biol Med. 2020; 160:768-774. PMC: 7497778. DOI: 10.1016/j.freeradbiomed.2020.09.016. View

18.

Furuse M, Okumura J . Nutritional and physiological characteristics in germ-free chickens. Comp Biochem Physiol A Physiol. 1994; 109(3):547-56. View

19.

Bradley K, Finsterbusch K, Schnepf D, Crotta S, Llorian M, Davidson S . Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection. Cell Rep. 2019; 28(1):245-256.e4. DOI: 10.1016/j.celrep.2019.05.105. View

20.

Rampini S, Bloemberg G, Keller P, Buchler A, Dollenmaier G, Speck R . Broad-range 16S rRNA gene polymerase chain reaction for diagnosis of culture-negative bacterial infections. Clin Infect Dis. 2011; 53(12):1245-51. DOI: 10.1093/cid/cir692. View