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Updated: Sep 13, 2025
Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice
Published on: June 27, 2020
High-fat diet impairs microbial metabolite production and aggravates influenza A infection
Franziska Hornung1, Harini K SureshKumar1, Laura Klement2
1Institute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, Jena, Germany.
Background:
Alterations in the gut microbiom can significantly impact various regions in the human body, including the pulmonary tract. This study investigates alterations in the gut microbiome during a high-fat diet (HFD), particularly short-chain fatty acids (SCFAs), and how these metabolites affect lung infection caused by Influenza A virus (IAV).
Methods:
We used a HFD-mouse model to evaluate gut microbiota composition, SCFA levels, and pulmonary outcomes following IAV infection. Microbial changes were analyzed via taxonomic and functional profiling and SCFA levels were measured from non-obese and obese serum donors. Ultimately, acetate's effects were tested ex vivo in human precision-cut lung slices (PCLS) and in vitro in pulmonary epithelial cells. Mechanistic studies investigated the involvement of the SCFA receptor free fatty acid receptor 2 (FFAR2) and intracellular antiviral pathways.
Results:
Our data indicates an increased Firmicutes/Bacteroidetes ratio of the gut microbiome and an altered carbohydrate metabolism, leading to reduced SCFA production. Infected HFD mice showed increased IAV titers and sustained microbial alterations. Interestingly, acetate demonstrated antiviral effects in both the human PCLS model and pulmonary cells with an reduced viral replication. These effects depended on FFAR2, which also acts as an IAV co-receptor, as acetate treatment led to FFAR2 internalization and influenced host cell metabolism in our in vitro data.
Conclusion:
HFD alters the SCFA production, reducing acetate levels in the gut microbiome. This reduction may lead to higher viral loads and worsened disease in HFD mice infected with IAV. Our findings indicate that acetate has antiviral effects during IAV infection in both a human ex vivo lung model and pulmonary epithelial cells. Here, acetate prevents viral entry and affects the cellular metabolic state and antiviral response. Understanding these mechanisms could provide new targets for preventing and treating viral infections in individuals with diet-related health issues.
Insights
A high-fat diet (HFD) disrupts the gut microbiome, reducing beneficial short-chain fatty acids (SCFAs) like acetate. This can worsen influenza A virus (IAV) lung infections, but acetate shows potential as an antiviral treatment.
Area of Science:
- Microbiology
- Immunology
- Metabolism
Background:
- Gut microbiome alterations impact pulmonary health.
- High-fat diets (HFD) induce significant changes in gut microbiota and metabolite production.
- Short-chain fatty acids (SCFAs) are key microbial metabolites with systemic effects.
Purpose of the Study:
- Investigate the impact of HFD on gut microbiome composition and SCFA production.
- Determine how these changes affect susceptibility to Influenza A virus (IAV) infection.
- Elucidate the direct antiviral effects of SCFAs, particularly acetate, on IAV in lung tissues.
Main Methods:
- Utilized a HFD-mouse model to assess gut microbiota, SCFA levels, and pulmonary IAV infection outcomes.
- Analyzed microbial taxonomic and functional profiles and measured SCFA levels in serum.
- Tested acetate's antiviral effects ex vivo in human precision-cut lung slices (PCLS) and in vitro in pulmonary epithelial cells, investigating the role of FFAR2.
Main Results:
- HFD increased the Firmicutes/Bacteroidetes ratio and reduced SCFA production, correlating with higher IAV titers in mice.
- Acetate demonstrated significant antiviral effects, reducing viral replication in both human PCLS and pulmonary cells.
- Acetate's antiviral mechanism involves the SCFA receptor FFAR2, influencing viral entry and host cell metabolism.
Conclusions:
- HFD-induced reduction in gut acetate levels may exacerbate IAV lung infections.
- Acetate exhibits direct antiviral properties against IAV by inhibiting viral entry and modulating host cell responses.
- Targeting acetate metabolism and FFAR2 signaling presents a potential therapeutic strategy for viral infections in diet-related conditions.
