Lung Acetate Levels Decline in Correlation With Increased Type 2 Allergic Markers in a House Dust Mite Allergic Mouse Model

ABSTRACT Aims Microbial dysbiosis is an important feature in allergic asthma. Short‐chain fatty acids (SCFA) produced by the intestinal microbiome play a role in the gut‐lung axis. Little is known about how the gut SCFA levels reflect SCFA levels in other tissues and how these link to the allergic a...

Full description

Saved in:
Bibliographic Details
Main Authors: Roos E. M. Verstegen, Rolf W. Sparidans, Atanaska I. Kostadinova, Johan Garssen, Gert Folkerts, Rudi W. Hendriks, Linette E. M. Willemsen
Format: Article
Language:English
Published: Wiley 2025-08-01
Series:Clinical and Translational Allergy
Subjects:
Online Access:https://doi.org/10.1002/clt2.70082
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849224642744549376
author Roos E. M. Verstegen
Rolf W. Sparidans
Atanaska I. Kostadinova
Johan Garssen
Gert Folkerts
Rudi W. Hendriks
Linette E. M. Willemsen
author_facet Roos E. M. Verstegen
Rolf W. Sparidans
Atanaska I. Kostadinova
Johan Garssen
Gert Folkerts
Rudi W. Hendriks
Linette E. M. Willemsen
author_sort Roos E. M. Verstegen
collection DOAJ
description ABSTRACT Aims Microbial dysbiosis is an important feature in allergic asthma. Short‐chain fatty acids (SCFA) produced by the intestinal microbiome play a role in the gut‐lung axis. Little is known about how the gut SCFA levels reflect SCFA levels in other tissues and how these link to the allergic asthma inflammatory status. Materials and Methods Male BALB/c mice were intranasally exposed to house dust mite (HDM) to induce allergic airway inflammation. Acetate, propionate, and butyrate levels were determined in caecum content, serum and lungs of control and HDM‐allergic mice using liquid chromatography‐mass spectrometry. Faecal microbiome composition was determined by DNA sequencing. Results Mean acetate:propionate:butyrate ratios were 75:15:10 in caecum content, 98:1.5:0.5 in serum, and 38:61:1 in the lung. SCFA levels did not correlate across compartments and propionate was relatively high in the lungs. The faecal microbiome of allergic mice differed from control, with increased Desulfovibrionaceae abundance. The lung acetate proportion was lower in allergic mice compared to control. In allergic mice, declining lung acetate levels correlated with increased HDM‐specific IgE in serum and IL‐13 release by ex vivo HDM‐restimulated lung cells. Ex vivo acetate supplementation did not inhibit HDM‐restimulated lung cell IL‐13 production, while butyrate and propionate did. Conclusions Overall, HDM‐driven murine allergic airway inflammation induced changes in the faecal microbiome and reduced acetate in serum and lung tissue. Hereby, lung acetate levels correlated negatively with sensitisation and type‐2 inflammation, but acetate itself did not suppress ex vivo HDM‐induced cytokine release. Our findings provide new insights on the systemic effects of HDM‐allergic inflammation along the gut‐lung axis.
format Article
id doaj-art-554e89bd15cf458289fac5d83264e1d6
institution Kabale University
issn 2045-7022
language English
publishDate 2025-08-01
publisher Wiley
record_format Article
series Clinical and Translational Allergy
spelling doaj-art-554e89bd15cf458289fac5d83264e1d62025-08-25T07:24:41ZengWileyClinical and Translational Allergy2045-70222025-08-01158n/an/a10.1002/clt2.70082Lung Acetate Levels Decline in Correlation With Increased Type 2 Allergic Markers in a House Dust Mite Allergic Mouse ModelRoos E. M. Verstegen0Rolf W. Sparidans1Atanaska I. Kostadinova2Johan Garssen3Gert Folkerts4Rudi W. Hendriks5Linette E. M. Willemsen6Division of Pharmacology Faculty of Science Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht the NetherlandsDivision of Pharmacology Faculty of Science Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht the NetherlandsDanone Research & Innovation Utrecht the NetherlandsDivision of Pharmacology Faculty of Science Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht the NetherlandsDivision of Pharmacology Faculty of Science Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht the NetherlandsDepartment of Pulmonary Medicine Erasmus MC, University Medical Center Rotterdam Rotterdam the NetherlandsDivision of Pharmacology Faculty of Science Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht the NetherlandsABSTRACT Aims Microbial dysbiosis is an important feature in allergic asthma. Short‐chain fatty acids (SCFA) produced by the intestinal microbiome play a role in the gut‐lung axis. Little is known about how the gut SCFA levels reflect SCFA levels in other tissues and how these link to the allergic asthma inflammatory status. Materials and Methods Male BALB/c mice were intranasally exposed to house dust mite (HDM) to induce allergic airway inflammation. Acetate, propionate, and butyrate levels were determined in caecum content, serum and lungs of control and HDM‐allergic mice using liquid chromatography‐mass spectrometry. Faecal microbiome composition was determined by DNA sequencing. Results Mean acetate:propionate:butyrate ratios were 75:15:10 in caecum content, 98:1.5:0.5 in serum, and 38:61:1 in the lung. SCFA levels did not correlate across compartments and propionate was relatively high in the lungs. The faecal microbiome of allergic mice differed from control, with increased Desulfovibrionaceae abundance. The lung acetate proportion was lower in allergic mice compared to control. In allergic mice, declining lung acetate levels correlated with increased HDM‐specific IgE in serum and IL‐13 release by ex vivo HDM‐restimulated lung cells. Ex vivo acetate supplementation did not inhibit HDM‐restimulated lung cell IL‐13 production, while butyrate and propionate did. Conclusions Overall, HDM‐driven murine allergic airway inflammation induced changes in the faecal microbiome and reduced acetate in serum and lung tissue. Hereby, lung acetate levels correlated negatively with sensitisation and type‐2 inflammation, but acetate itself did not suppress ex vivo HDM‐induced cytokine release. Our findings provide new insights on the systemic effects of HDM‐allergic inflammation along the gut‐lung axis.https://doi.org/10.1002/clt2.70082asthmamicrobiomeshort chain fatty acids
spellingShingle Roos E. M. Verstegen
Rolf W. Sparidans
Atanaska I. Kostadinova
Johan Garssen
Gert Folkerts
Rudi W. Hendriks
Linette E. M. Willemsen
Lung Acetate Levels Decline in Correlation With Increased Type 2 Allergic Markers in a House Dust Mite Allergic Mouse Model
Clinical and Translational Allergy
asthma
microbiome
short chain fatty acids
title Lung Acetate Levels Decline in Correlation With Increased Type 2 Allergic Markers in a House Dust Mite Allergic Mouse Model
title_full Lung Acetate Levels Decline in Correlation With Increased Type 2 Allergic Markers in a House Dust Mite Allergic Mouse Model
title_fullStr Lung Acetate Levels Decline in Correlation With Increased Type 2 Allergic Markers in a House Dust Mite Allergic Mouse Model
title_full_unstemmed Lung Acetate Levels Decline in Correlation With Increased Type 2 Allergic Markers in a House Dust Mite Allergic Mouse Model
title_short Lung Acetate Levels Decline in Correlation With Increased Type 2 Allergic Markers in a House Dust Mite Allergic Mouse Model
title_sort lung acetate levels decline in correlation with increased type 2 allergic markers in a house dust mite allergic mouse model
topic asthma
microbiome
short chain fatty acids
url https://doi.org/10.1002/clt2.70082
work_keys_str_mv AT roosemverstegen lungacetatelevelsdeclineincorrelationwithincreasedtype2allergicmarkersinahousedustmiteallergicmousemodel
AT rolfwsparidans lungacetatelevelsdeclineincorrelationwithincreasedtype2allergicmarkersinahousedustmiteallergicmousemodel
AT atanaskaikostadinova lungacetatelevelsdeclineincorrelationwithincreasedtype2allergicmarkersinahousedustmiteallergicmousemodel
AT johangarssen lungacetatelevelsdeclineincorrelationwithincreasedtype2allergicmarkersinahousedustmiteallergicmousemodel
AT gertfolkerts lungacetatelevelsdeclineincorrelationwithincreasedtype2allergicmarkersinahousedustmiteallergicmousemodel
AT rudiwhendriks lungacetatelevelsdeclineincorrelationwithincreasedtype2allergicmarkersinahousedustmiteallergicmousemodel
AT linetteemwillemsen lungacetatelevelsdeclineincorrelationwithincreasedtype2allergicmarkersinahousedustmiteallergicmousemodel