Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection

Antunes, Krist Helen; Singanayagam, Aran; Williams, Lily M.; Faiez, Tasnim Syakirah; Farı́as, Ana; Jackson, Millie M.; Faizi, Fatima K.; Aniscenko, Julia; Kebadze, Tatiana; Veerati, Punnam Chander; Wood, Lisa G.; Bartlett, Nathan W.; Souza, Ana Paula Duarte de; Johnston, Sebastian L.

doi:10.1016/j.jaci.2022.09.026

Cited by 21 publications

(16 citation statements)

References 38 publications

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“…SCFAs might have an important role in this setting. Indeed, recent research findings indicate that acetate reduces the viral load via an influence on type I IFN ( 25 – 27 , 83 , 84 ). The corresponding results for butyrate are subject to debate.…”

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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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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“…In the case of human rhinovirus infection in mice, treatment with acetate ameliorated the virus-induced pro-inflammatory responses and reduced the IL-6 expression. In addition, treatment of butyrate modulates the expression of the IFN-β and IFN-ϒ gene in human bronchial and alveolar epithelial cell lines . SCFAs impart the anti-inflammatory function due to its inhibitory effects on the immune cell chemotaxis and adhesion, activation of anti-inflammatory cytokines’ levels and acceleration of programmed cell death .…”

Section: Immunomodulatory Effects Of the Scfas In Lungsmentioning

confidence: 99%

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis─A Potential Therapeutic Intervention to Improve Lung Health

Verma,

Bhagchandani,

Rai

et al. 2024

ACS Omega

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The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut−lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut−lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.

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“…Recent in vivo pre-clinical data also indicate protection against rhinovirus-induced respiratory tract infections (i.e., the most common trigger of asthma exacerbations) following intranasal administration of short-chain fatty acids. However, this study does not focus on obesity-driven airway inflammation [ 92 ].…”

Section: Relevant Sectionsmentioning

confidence: 99%

Application of Metabolomics in Obesity-Related Childhood Asthma Subtyping: A Narrative Scoping Review

et al. 2023

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Obesity-related asthma is a heterogeneous childhood asthma phenotype with rising prevalence. Observational studies identify early-life obesity or weight gain as risk factors for childhood asthma development. The reverse association is also described, children with asthma have a higher risk of being obese. Obese children with asthma have poor symptom control and an increased number of asthma attacks compared to non-obese children with asthma. Clinical trials have also identified that a proportion of obese children with asthma do not respond as well to usual treatment (e.g., inhaled corticosteroids). The heterogeneity of obesity-related asthma phenotypes may be attributable to different underlying pathogenetic mechanisms. Although few childhood obesity-related asthma endotypes have been described, our knowledge in this field is incomplete. An evolving analytical profiling technique, metabolomics, has the potential to link individuals’ genetic backgrounds and environmental exposures (e.g., diet) to disease endotypes. This will ultimately help define clinically relevant obesity-related childhood asthma subtypes that respond better to targeted treatment. However, there are challenges related to this approach. The current narrative scoping review summarizes the evidence for metabolomics contributing to asthma subtyping in obese children, highlights the challenges associated with the implementation of this approach, and identifies gaps in research.

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Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection

Cited by 21 publications

References 38 publications

Faecalibacterium duncaniae as a novel next generation probiotic against influenza

Faecalibacterium duncaniae as a novel next generation probiotic against influenza

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis─A Potential Therapeutic Intervention to Improve Lung Health

Application of Metabolomics in Obesity-Related Childhood Asthma Subtyping: A Narrative Scoping Review

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