Evidence mapPaperPMID 40745568Full record

ArticleCell communication and signaling : CCS2025

High-fat diet impairs microbial metabolite production and aggravates influenza A infection.

Franziska Hornung, Harini K SureshKumar, Laura Klement, Yasmina Reisser, Christoph Wernike, Vivien Nischang, Paul M Jordan, Oliver Werz, Carsten Hoffmann, Bettina Löffler and 1 more

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Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Franziska HornungInstitute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, Jena, Germany.
Harini K SureshKumarInstitute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, Jena, Germany.
Laura KlementInstitute of Molecular Cell biology, CMB- Center for Molecular Biomedicine, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
Yasmina ReisserInstitute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, Jena, Germany.
Christoph WernikeInstitute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, Jena, Germany.
Vivien NischangDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany.
Paul M JordanDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany.
Oliver WerzDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany.
Carsten HoffmannInstitute of Molecular Cell biology, CMB- Center for Molecular Biomedicine, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
Bettina LöfflerInstitute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, Jena, Germany.
Stefanie Deinhardt-EmmerInstitute of Medical Microbiology, Jena University Hospital, Am Klinikum 1, Jena, Germany. stefanie.deinhardt-emmer@med.uni-jena.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlterations 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).

methodsWe 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.

resultsOur 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.

conclusionHFD 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.

Indexed as

Diet, High-FatGastrointestinal MicrobiomeInfluenza A virusInfluenza, HumanOrthomyxoviridae InfectionsAcetatesAnimalsFatty Acids, VolatileHumansLungMaleMiceMice, Inbred C57BLAcetatesFatty Acids, VolatileAcetateFFAR2Gut-lung-axisHigh-fat dietInfluenza A virusInterferon responseMicrobial metabolitesShort-chain fatty acids

Identifiers

PMID40745568
PMCPMC12312391

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.