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Article ; Online: The lung-gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes.

Sencio, Valentin / Machado, Marina Gomes / Trottein, François

2021 Volume 14, Issue 2, Page(s) 296–304

Abstract: Bacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host's defense against viral respiratory infections. The gut microbiota's composition and function can ...

Abstract	Bacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host's defense against viral respiratory infections. The gut microbiota's composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota's composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung-gut axis in coronavirus disease 2019.
MeSH term(s)	Animals ; COVID-19/immunology ; Diet ; Dietary Fiber/metabolism ; Dysbiosis/immunology ; Dysbiosis/microbiology ; Gastrointestinal Microbiome ; Humans ; Immunity, Mucosal ; Influenza, Human/immunology ; Lung/immunology ; Probiotics ; Respiratory Syncytial Viruses ; Respiratory Tract Infections
Chemical Substances	Dietary Fiber
Language	English
Publishing date	2021-01-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2411370-0
ISSN	1935-3456 ; 1933-0219
ISSN (online)	1935-3456
ISSN	1933-0219
DOI	10.1038/s41385-020-00361-8
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Article ; Online: Short-Chain Fatty Acids as a Potential Treatment for Infections: a Closer Look at the Lungs.

Machado, Marina Gomes / Sencio, Valentin / Trottein, François

Infection and immunity

2021 Volume 89, Issue 9, Page(s) e0018821

Abstract: Short-chain fatty acids (SCFAs) are the main metabolites produced by the gut microbiota via the fermentation of complex carbohydrates and fibers. Evidence suggests that SCFAs play a role in the control of infections through direct action both on ... ...

Abstract	Short-chain fatty acids (SCFAs) are the main metabolites produced by the gut microbiota via the fermentation of complex carbohydrates and fibers. Evidence suggests that SCFAs play a role in the control of infections through direct action both on microorganisms and on host signaling. This review summarizes the main microbicidal effects of SCFAs and discusses studies highlighting the effect of SCFAs in the virulence and viability of microorganisms. We also describe the diverse and complex modes of action of the SCFAs on the immune system in the face of infections with a specific focus on bacterial and viral respiratory infections. A growing body of evidence suggests that SCFAs protect against lung infections. Finally, we present potential strategies that may be leveraged to exploit the biological properties of SCFAs for increasing effectiveness and optimizing patient benefits.
MeSH term(s)	Animals ; Anti-Infective Agents/immunology ; Anti-Infective Agents/metabolism ; Anti-Infective Agents/therapeutic use ; Fatty Acids, Volatile/immunology ; Fatty Acids, Volatile/metabolism ; Fatty Acids, Volatile/therapeutic use ; Humans ; Infections/drug therapy ; Infections/immunology ; Infections/microbiology ; Lung/drug effects ; Lung/immunology ; Lung/microbiology ; Lung/virology ; Microbial Viability ; Respiratory Tract Infections/drug therapy ; Respiratory Tract Infections/immunology ; Respiratory Tract Infections/microbiology ; Respiratory Tract Infections/virology ; Signal Transduction/immunology ; Virulence
Chemical Substances	Anti-Infective Agents ; Fatty Acids, Volatile
Language	English
Publishing date	2021-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.00188-21
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Article ; Online: Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance.

Ustjanzew, Arsenij / Sencio, Valentin / Trottein, François / Faber, Jörg / Sandhoff, Roger / Paret, Claudia

International journal of molecular sciences

2022 Volume 23, Issue 11

Abstract: Non-conventional T cells, such as γδ T and invariant natural killer T (iNKT) cells, are emerging players in fighting cancer. Alpha-galactosylceramide (α-GalCer) is used as an exogenous ligand to activate iNKT cells. Human cells don't have a direct ... ...

Abstract	Non-conventional T cells, such as γδ T and invariant natural killer T (iNKT) cells, are emerging players in fighting cancer. Alpha-galactosylceramide (α-GalCer) is used as an exogenous ligand to activate iNKT cells. Human cells don't have a direct pathway producing α-GalCer, which, however, can be produced by bacteria. We searched the literature for bacteria strains that are able to produce α-GalCer and used available sequencing data to analyze their presence in human tumor tissues and their association with survival. The modulatory effect of antibiotics on the concentration of α-GalCer was analyzed in mice. The human gut bacteria
MeSH term(s)	Adenocarcinoma/metabolism ; Animals ; Bacteroides ; Colonic Neoplasms/metabolism ; Galactosylceramides ; Immunotherapy ; Mice ; Mice, Inbred C57BL ; Natural Killer T-Cells ; Prevotella
Chemical Substances	Galactosylceramides ; alpha-galactosylceramide
Language	English
Publishing date	2022-05-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23115896
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Article ; Online: Faecalibacterium duncaniae

Chollet, Loïc / Heumel, Séverine / Deruyter, Lucie / Bouilloux, Fabrice / Delval, Lou / Robert, Véronique / Gevaert, Marie-Hélène / Pichavant, Muriel / Sencio, Valentin / Robil, Cyril / Wolowczuk, Isabelle / Sokol, Harry / Auger, Sandrine / Douablin, Alexandre / Langella, Philippe / Chatel, Jean-Marc / Grangette, Corinne / Trottein, François

Frontiers in immunology

2024 Volume 15, Page(s) 1347676

Abstract: The gut-lung axis is critical during viral respiratory infections such as influenza. Gut dysbiosis during infection translates into a massive drop of microbially produced short-chain fatty acids (SCFAs). Among them, butyrate is important during influenza ...

Abstract	The gut-lung axis is critical during viral respiratory infections such as influenza. Gut dysbiosis during infection translates into a massive drop of microbially produced short-chain fatty acids (SCFAs). Among them, butyrate is important during influenza suggesting that microbiome-based therapeutics targeting butyrate might hold promises. The butyrate-producing bacterium
MeSH term(s)	Mice ; Animals ; Humans ; Influenza, Human ; Dysbiosis/microbiology ; RNA, Ribosomal, 16S/genetics ; Fatty Acids, Volatile ; Butyrates ; Faecalibacterium/genetics ; Probiotics
Chemical Substances	RNA, Ribosomal, 16S ; Fatty Acids, Volatile ; Butyrates
Language	English
Publishing date	2024-03-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1347676
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Article ; Online: Interaction between Bacteria and the Immune System for Cancer Immunotherapy

Arsenij Ustjanzew / Valentin Sencio / François Trottein / Jörg Faber / Roger Sandhoff / Claudia Paret

International Journal of Molecular Sciences, Vol 23, Iss 5896, p

The α-GalCer Alliance

2022 Volume 5896

Abstract	Non-conventional T cells, such as γδ T and invariant natural killer T (iNKT) cells, are emerging players in fighting cancer. Alpha-galactosylceramide (α-GalCer) is used as an exogenous ligand to activate iNKT cells. Human cells don’t have a direct pathway producing α-GalCer, which, however, can be produced by bacteria. We searched the literature for bacteria strains that are able to produce α-GalCer and used available sequencing data to analyze their presence in human tumor tissues and their association with survival. The modulatory effect of antibiotics on the concentration of α-GalCer was analyzed in mice. The human gut bacteria Bacteroides fragilis , Bacteroides vulgatus, and Prevotella copri produce α-GalCer structures that are able to activate iNKT cells. In mice, α-GalCer was depleted upon treatment with vancomycin. The three species were detected in colon adenocarcinoma (COAD) and rectum adenocarcinoma tissues, and Prevotella copri was also detected in bone tumors and glioblastoma tissues. Bacteroides vulgatus in COAD tissues correlated with better survival. In conclusion, α-GalCer-producing bacteria are part of the human gut microbiome and can infiltrate tumor tissues. These results suggest a new mechanism of interaction between bacteria and immune cells: α-GalCer produced by bacteria may activate non-conventional T cells in tumor tissues, where they can exert a direct or indirect anti-tumor activity.
Keywords	microbiome ; microbiota ; immunotherapy ; alpha-galactosylceramide ; iNKT ; colorectal cancer ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: SARS-CoV-2 infection induces persistent adipose tissue damage in aged golden Syrian hamsters.

Bogard, Gemma / Barthelemy, Johanna / Hantute-Ghesquier, Aline / Sencio, Valentin / Brito-Rodrigues, Patricia / Séron, Karin / Robil, Cyril / Flourens, Anne / Pinet, Florence / Eberlé, Delphine / Trottein, François / Duterque-Coquillaud, Martine / Wolowczuk, Isabelle

Cell death & disease

2023 Volume 14, Issue 2, Page(s) 75

Abstract: Coronavirus disease 2019 (COVID-19, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)) is primarily a respiratory illness. However, various extrapulmonary manifestations have been reported in patients with severe forms of COVID-19. ... ...

Abstract	Coronavirus disease 2019 (COVID-19, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2)) is primarily a respiratory illness. However, various extrapulmonary manifestations have been reported in patients with severe forms of COVID-19. Notably, SARS-CoV-2 was shown to directly trigger white adipose tissue (WAT) dysfunction, which in turn drives insulin resistance, dyslipidemia, and other adverse outcomes in patients with COVID-19. Although advanced age is the greatest risk factor for COVID-19 severity, published data on the impact of SARS-CoV-2 infection on WAT in aged individuals are scarce. Here, we characterized the response of subcutaneous and visceral WAT depots to SARS-CoV-2 infection in young adult and aged golden hamsters. In both age groups, infection was associated with a decrease in adipocyte size in the two WAT depots; this effect was partly due to changes in tissue's lipid metabolism and persisted for longer in aged hamsters than in young-adult hamsters. In contrast, only the subcutaneous WAT depot contained crown-like structures (CLSs) in which dead adipocytes were surrounded by SARS-CoV-2-infected macrophages, some of them forming syncytial multinucleated cells. Importantly, older age predisposed to a unique manifestation of viral disease in the subcutaneous WAT depot during SARS-CoV-2 infection; the persistence of very large CLSs was indicative of an age-associated defect in the clearance of dead adipocytes by macrophages. Moreover, we uncovered age-related differences in plasma lipid profiles during SARS-CoV-2 infection. These data suggest that the WAT's abnormal response to SARS-CoV-2 infection may contribute to the greater severity of COVID-19 observed in elderly patients.
MeSH term(s)	Animals ; Cricetinae ; Adipose Tissue, White/pathology ; COVID-19/pathology ; Disease Models, Animal ; Mesocricetus ; SARS-CoV-2
Language	English
Publishing date	2023-02-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-023-05574-w
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Article ; Online: Shotgun metagenomics and systemic targeted metabolomics highlight indole-3-propionic acid as a protective gut microbial metabolite against influenza infection.

Heumel, Séverine / de Rezende Rodovalho, Vinícius / Urien, Charlotte / Specque, Florian / Brito Rodrigues, Patrícia / Robil, Cyril / Delval, Lou / Sencio, Valentin / Descat, Amandine / Deruyter, Lucie / Ferreira, Stéphanie / Gomes Machado, Marina / Barthelemy, Adeline / Angulo, Fabiola Silva / Haas, Joel T / Goosens, Jean François / Wolowczuk, Isabelle / Grangette, Corinne / Rouillé, Yves /

Grimaud, Ghjuvan / Lenski, Marie / Hennart, Benjamin / Ramirez Vinolo, Marco Aurélio / Trottein, François

Gut microbes

2024 Volume 16, Issue 1, Page(s) 2325067

Abstract: The gut-to-lung axis is critical during respiratory infections, including influenza A virus (IAV) infection. In the present study, we used high-resolution shotgun metagenomics and targeted metabolomic analysis to characterize influenza-associated changes ...

Abstract	The gut-to-lung axis is critical during respiratory infections, including influenza A virus (IAV) infection. In the present study, we used high-resolution shotgun metagenomics and targeted metabolomic analysis to characterize influenza-associated changes in the composition and metabolism of the mouse gut microbiota. We observed several taxonomic-level changes on day (D)7 post-infection, including a marked reduction in the abundance of members of the
MeSH term(s)	Humans ; Animals ; Mice ; Propionates ; Influenza, Human ; Gastrointestinal Microbiome ; Tryptophan ; Actinobacteria ; Inflammation ; Polyamines
Chemical Substances	propionic acid (JHU490RVYR) ; Propionates ; Tryptophan (8DUH1N11BX) ; Polyamines
Language	English
Publishing date	2024-03-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2575755-6
ISSN	1949-0984 ; 1949-0984
ISSN (online)	1949-0984
ISSN	1949-0984
DOI	10.1080/19490976.2024.2325067
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Article ; Online: Description of a Newly Isolated

Verstraeten, Sophie / Sencio, Valentin / Raise, Audrey / Huillet, Eugénie / Layec, Séverine / Deruyter, Lucie / Heumel, Séverine / Auger, Sandrine / Robert, Véronique / Langella, Philippe / Beney, Laurent / Trottein, François / Thomas, Muriel

Nutrients

2022 Volume 14, Issue 7

Abstract: The expanding knowledge on the systemic influence of the human microbiome suggests that fecal samples are underexploited sources of new beneficial strains for extra-intestinal health. We have recently shown that acetate, a main circulating microbiota- ... ...

Abstract	The expanding knowledge on the systemic influence of the human microbiome suggests that fecal samples are underexploited sources of new beneficial strains for extra-intestinal health. We have recently shown that acetate, a main circulating microbiota-derived molecule, reduces the deleterious effects of pulmonary
MeSH term(s)	Animals ; Clostridiales/classification ; Clostridiales/isolation & purification ; Disease Models, Animal ; Humans ; Influenza, Human/complications ; Interleukin-8 ; Mice ; Orthomyxoviridae Infections/complications ; Pneumococcal Infections/microbiology ; Pneumococcal Infections/prevention & control ; Salmonella Infections, Animal/microbiology ; Salmonella Infections, Animal/prevention & control ; Salmonella typhimurium ; Streptococcus pneumoniae
Chemical Substances	Interleukin-8
Language	English
Publishing date	2022-04-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu14071478
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Article ; Online: Tirap controls Mycobacterium tuberculosis phagosomal acidification.

Belhaouane, Imène / Pochet, Amine / Chatagnon, Jonathan / Hoffmann, Eik / Queval, Christophe J / Deboosère, Nathalie / Boidin-Wichlacz, Céline / Majlessi, Laleh / Sencio, Valentin / Heumel, Séverine / Vandeputte, Alexandre / Werkmeister, Elisabeth / Fievez, Laurence / Bureau, Fabrice / Rouillé, Yves / Trottein, François / Chamaillard, Mathias / Brodin, Priscille / Machelart, Arnaud

PLoS pathogens

2023 Volume 19, Issue 3, Page(s) e1011192

Abstract: Progression of tuberculosis is tightly linked to a disordered immune balance, resulting in inability of the host to restrict intracellular bacterial replication and its subsequent dissemination. The immune response is mainly characterized by an ... ...

Abstract	Progression of tuberculosis is tightly linked to a disordered immune balance, resulting in inability of the host to restrict intracellular bacterial replication and its subsequent dissemination. The immune response is mainly characterized by an orchestrated recruitment of inflammatory cells secreting cytokines. This response results from the activation of innate immunity receptors that trigger downstream intracellular signaling pathways involving adaptor proteins such as the TIR-containing adaptor protein (Tirap). In humans, resistance to tuberculosis is associated with a loss-of-function in Tirap. Here, we explore how genetic deficiency in Tirap impacts resistance to Mycobacterium tuberculosis (Mtb) infection in a mouse model and ex vivo. Interestingly, compared to wild type littermates, Tirap heterozygous mice were more resistant to Mtb infection. Upon investigation at the cellular level, we observed that mycobacteria were not able to replicate in Tirap-deficient macrophages compared to wild type counterparts. We next showed that Mtb infection induced Tirap expression which prevented phagosomal acidification and rupture. We further demonstrate that the Tirap-mediated anti-tuberculosis effect occurs through a Cish-dependent signaling pathway. Our findings provide new molecular evidence about how Mtb manipulates innate immune signaling to enable intracellular replication and survival of the pathogen, thus paving the way for host-directed approaches to treat tuberculosis.
MeSH term(s)	Humans ; Mice ; Animals ; Mycobacterium tuberculosis ; Receptors, Interleukin-1/genetics ; Receptors, Interleukin-1/metabolism ; Signal Transduction ; Tuberculosis ; Adaptor Proteins, Signal Transducing/metabolism ; Hydrogen-Ion Concentration ; Membrane Glycoproteins/metabolism
Chemical Substances	Receptors, Interleukin-1 ; Adaptor Proteins, Signal Transducing ; TIRAP protein, human ; Membrane Glycoproteins ; TIRAP protein, mouse
Language	English
Publishing date	2023-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011192
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Article ; Online: Acetate Improves the Killing of

Machado, Marina Gomes / Patente, Thiago Andrade / Rouillé, Yves / Heumel, Severine / Melo, Eliza Mathias / Deruyter, Lucie / Pourcet, Benoit / Sencio, Valentin / Teixeira, Mauro Martins / Trottein, François

Frontiers in immunology

2022 Volume 13, Page(s) 773261

Abstract: Short-chain fatty acids (SCFAs) are metabolites produced mainly by the gut microbiota with a known role in immune regulation. Acetate, the major SCFA, is described to disseminate to distal organs such as lungs where it can arm sentinel cells, including ... ...

Abstract	Short-chain fatty acids (SCFAs) are metabolites produced mainly by the gut microbiota with a known role in immune regulation. Acetate, the major SCFA, is described to disseminate to distal organs such as lungs where it can arm sentinel cells, including alveolar macrophages, to fight against bacterial intruders. In the current study, we explored mechanisms through which acetate boosts macrophages to enhance their bactericidal activity. RNA sequencing analyses show that acetate triggers a transcriptomic program in macrophages evoking changes in metabolic process and immune effector outputs, including nitric oxide (NO) production. In addition, acetate enhances the killing activity of macrophages towards
MeSH term(s)	Acetates/pharmacology ; Animals ; Biomarkers ; Cytotoxicity, Immunologic/drug effects ; Disease Models, Animal ; Disease Susceptibility ; Gene Knockdown Techniques ; Glycolysis ; Host-Pathogen Interactions/immunology ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Inflammasomes/metabolism ; Interleukin-1beta/metabolism ; Macrophages, Alveolar/physiology ; Mice ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Nitric Oxide/metabolism ; Oxygen Consumption ; Pneumococcal Infections/etiology ; Pneumococcal Infections/metabolism ; RNA, Small Interfering/genetics ; Streptococcus pneumoniae/immunology
Chemical Substances	Acetates ; Biomarkers ; Hif1a protein, mouse ; Hypoxia-Inducible Factor 1, alpha Subunit ; Inflammasomes ; Interleukin-1beta ; NLR Family, Pyrin Domain-Containing 3 Protein ; RNA, Small Interfering ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2022-01-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.773261
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