Clostridium butyricum-induced ω-3 fatty acid 18-HEPE elicits anti-influenza virus pneumonia effects through interferon-λ upregulation

Hagihara, Mao; Yamashita, Makoto; Ariyoshi, Tadashi; Eguchi, Shuhei; Minemura, Ayaka; Miura, Daiki; Higashi, Seiya; Oka, Koichiro; Nonogaki, Tsunemasa; Mori, Takeshi; Iwasaki, Kenta; Hirai, Jun; Shibata, Yuichi; Umemura, Takumi; Kato, Hideo; Asai, Nobuhiro; Yamagishi, Yuka; Ota, Akinobu; Takahashi, Motomichi; Mikamo, Hiroshige

doi:10.1016/j.celrep.2022.111755

Cited by 22 publications

(29 citation statements)

References 67 publications

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“…FFAR4 is a receptor for ω-3 long chain fatty acids, and has been experimentally shown to be activated by α-linolenic acid and other ω-3 fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid [ 29 ]. Typically, ω-3 fatty acids are ingested via a normal diet [ 30 ]; however, the intestinal microbiota also bear the ability to metabolize fatty acids into new bioactive forms that can activate FFAR4 [ 31 ]. The activation of FFRA4 by ω-3 fatty acids has been observed to protect against colitis development though actions on both the intestinal epithelium [ 32 ] and the intestinal immune cells [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring Microbial Metabolite Receptors in Inflammatory Bowel Disease: An In Silico Analysis of Their Potential Role in Inflammation and Fibrosis

Spathakis,

Dovrolis,

Filidou

et al. 2024

Pharmaceuticals

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Metabolites produced by dysbiotic intestinal microbiota can influence disease pathophysiology by participating in ligand–receptor interactions. Our aim was to investigate the differential expression of metabolite receptor (MR) genes between inflammatory bowel disease (IBD), healthy individuals (HIs), and disease controls in order to identify possible interactions with inflammatory and fibrotic pathways in the intestine. RNA-sequencing datasets containing 643 Crohn’s disease (CD) patients, 467 ulcerative colitis (UC) patients and 295 HIs, and 4 Campylobacter jejuni-infected individuals were retrieved from the Sequence Read Archive, and differential expression was performed using the RaNA-seq online platform. The identified differentially expressed MR genes were used for correlation analysis with up- and downregulated genes in IBD, as well as functional enrichment analysis using a R based pipeline. Overall, 15 MR genes exhibited dysregulated expression in IBD. In inflamed CD, the hydroxycarboxylic acid receptors 2 and 3 (HCAR2, HCAR3) were upregulated and were associated with the recruitment of innate immune cells, while, in the non-inflamed CD ileum, the cannabinoid receptor 1 (CNR1) and the sphingosine-1-phospate receptor 4 (S1PR4) were downregulated and were involved in the regulation of B-cell activation. In inflamed UC, the upregulated receptors HCAR2 and HCAR3 were more closely associated with the process of TH-17 cell differentiation, while the pregnane X receptor (NR1I2) and the transient receptor potential vanilloid 1 (TRPV1) were downregulated and were involved in epithelial barrier maintenance. Our results elucidate the landscape of metabolite receptor expression in IBD, highlighting associations with disease-related functions that could guide the development of new targeted therapies.

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Section: Discussionmentioning

confidence: 99%

Exploring Microbial Metabolite Receptors in Inflammatory Bowel Disease: An In Silico Analysis of Their Potential Role in Inflammation and Fibrosis

Spathakis,

Dovrolis,

Filidou

et al. 2024

Pharmaceuticals

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“…The continuous (7-day) administration of F. duncaniae was indeed associated with a greater IFN-Λ concentration in BALF and this was significant after IAV infection. It is noteworthy that Bifidobacterium longum and Clostridium butyricum were shown to inhibit IAV replication through IFN-Λ( 81 , 82 ). Mechanistically, gut microbiome-induced ω-3 fatty acid 18-hydroxy eicosapentaenoic acid promoted IFN-Λ production by lung epithelial cells ( 82 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is noteworthy that Bifidobacterium longum and Clostridium butyricum were shown to inhibit IAV replication through IFN-Λ( 81 , 82 ). Mechanistically, gut microbiome-induced ω-3 fatty acid 18-hydroxy eicosapentaenoic acid promoted IFN-Λ production by lung epithelial cells ( 82 ). Although the mechanisms in our settings remained to be investigated, the present study is (to the best of our knowledge) the first to have shown that the commensal F. duncaniae exerts antiviral effects.…”

Section: Discussionmentioning

confidence: 99%

Faecalibacterium duncaniae as a novel next generation probiotic against influenza

Chollet,

Heumel,

Deruyter

et al. 2024

Front. Immunol.

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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 Faecalibacterium duncaniae (formerly referred to as F. prausnitzii) is an emerging probiotic with several health-promoting characteristics. To investigate the potential effects of F. duncaniae on influenza outcomes, mice were gavaged with live F. duncaniae (A2-165 or I-4574 strains) five days before infection. Supplementation of F. duncaniae was associated with less severe disease, a lower pulmonary viral load, and lower levels of lung inflammation. F. duncaniae supplementation impacted on gut dysbiosis induced by infection, as assessed by 16S rRNA sequencing. Interestingly, F. duncaniae administration was associated with a recovery in levels of SCFAs (including butyrate) in infected animals. The live form of F. duncaniae was more potent that the pasteurized form in improving influenza outcomes. Lastly, F. duncaniae partially protected against secondary (systemic) bacterial infection. We conclude that F. duncaniae might serve as a novel next generation probiotic against acute viral respiratory diseases.

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“…In one example, IL-22 KO mice was utilized to verify the involvement of IL-22 expression in the process of dissecting the mechanism of fiber-mediated nourishment microbiota in gut affecting metabolic syndrome ( Zou et al, 2018 ). In another example, IRF-1 and IRF-7 knockout mice were used to verify whether 18-hydroxyeicosapentaenoic acid produced by gut microbiota Clostridium butyricum promoted lung function through G protein-coupled receptor (GPR) 120 and IFN regulatory factor (IRF)-1/-7 activation ( Hagihara et al, 2022 ).…”

Section: Whole-body Genetic Tools For Deciphering Host-specific Genes...mentioning

confidence: 99%

Recent advances in host-focused molecular tools for investigating host-gut microbiome interactions

Wang,

Gong,

Xiao

et al. 2024

Front. Microbiol.

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Microbial communities in the human gut play a significant role in regulating host gene expression, influencing a variety of biological processes. To understand the molecular mechanisms underlying host-microbe interactions, tools that can dissect signaling networks are required. In this review, we discuss recent advances in molecular tools used to study this interplay, with a focus on those that explore how the microbiome regulates host gene expression. These tools include CRISPR-based whole-body genetic tools for deciphering host-specific genes involved in the interaction process, Cre-loxP based tissue/cell-specific gene editing approaches, and in vitro models of host-derived organoids. Overall, the application of these molecular tools is revolutionizing our understanding of how host-microbiome interactions contribute to health and disease, paving the way for improved therapies and interventions that target microbial influences on the host.

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Clostridium butyricum-induced ω-3 fatty acid 18-HEPE elicits anti-influenza virus pneumonia effects through interferon-λ upregulation

Cited by 22 publications

References 67 publications

Exploring Microbial Metabolite Receptors in Inflammatory Bowel Disease: An In Silico Analysis of Their Potential Role in Inflammation and Fibrosis

Exploring Microbial Metabolite Receptors in Inflammatory Bowel Disease: An In Silico Analysis of Their Potential Role in Inflammation and Fibrosis

Faecalibacterium duncaniae as a novel next generation probiotic against influenza

Recent advances in host-focused molecular tools for investigating host-gut microbiome interactions

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