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Integrated Gut Microbiome and Metabolomics Analysis Reveals Microbial-Metabolic Cross-talk in Allergic Rhinitis

ABSTRACT:

Background: Emerging evidence indicates a link between gut dysbiosis and allergic rhinitis (AR) pathogenesis. Nevertheless, the mechanistic role of gut microbiota in AR progression requires further characterization. To address this, we employed an integrated multi-omics strategy to delineate gut microbial composition and metabolic signatures in AR patients.

Methods: Fecal specimens from 23 AR patients and 15 matched healthy controls (total n = 38) were subjected to 16S rRNA gene sequencing to assess bacterial community structure, alongside untargeted metabolomic profiling of microbial metabolites. Spearman’s rank correlation analysis was applied to evaluate microbiota-metabolite interactions.

Results: AR patients showed reduced gut microbial diversity (ACE index, PD whole tree; p < 0.05) with depletion of SCFA-producing Faecalibacterium and enrichment of Escherichia and Fusobacterium. Metabolomics revealed impaired butyrate metabolism (p = 0.03) and decreased anti-inflammatory metabolites (quercetin, caffeic acid). Spearman correlations linked Faecalibacterium to butyrate (ρ = 0.62, p = 0.002) and Gemella to pro-inflammatory 12,13-DHOME (ρ = −0.58, p = 0.005), implicating microbial-metabolic crosstalk.

Conclusions: Gut dysbiosis in AR drives immune-metabolic imbalance via SCFA depletion and pro-inflammatory mediators, highlighting microbiota-targeted therapies as potential interventions.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS13021 | MetaboLights | 2025-09-22

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13021_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS13021_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13021_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13021_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Project description:Background: Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies. Methods: SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD. Results: Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by TNF-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term. Conclusions: Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.

Project description:Background and Aims: Many inflammatory diseases are associated with microbial dysbiosis, which may considerably alter the production of short-chain fatty acids (SCFAs). SCFAs are produced in the large bowel through bacterial fermentation of dietary fiber and play an important role in maintaining gut homeostasis. SCFAs, particularly acetate and butyrate, show beneficial immunomodulatory effects contributing to the prevention of inflammatory and allergic reactions. Thus, reduced production of SCFAs may impact on the mucosal immune responses critical to fighting pathogens. This study aims to determine the influence of SCFAs on a murine model of colonic bacterial infection. Methods: In the present study, we used acetate- (HAMSA) or butyrate- (HAMSB) yielding diets to deliver high concentrations of individual SCFAs to the large bowel of mice infected with C. rodentium. We assessed the effects of these SCFAs on clinical burden and gut pathogenicity in correlation with changes in bacteria growth, fecal microbiota composition, function and changes in the immunological profile. Results: Here we show in vitro that acetate and butyrate directly inhibited growth of the attaching and effacing (A/E) pathogen C. rodentium in a bacteriostatic manner. This correlated with reduced expression of Tir, a gene responsible for bacterial adherence and pathogenicity. Interestingly, HAMSA-fed mice presented reduced clinical scores during C. rodentium infection associated with high concentrations of fecal acetate. This was linked with compositional and functional changes in the microbiota when examining 16s sequencing and proteomics analysis. The HAMSA mediated is protection involved increased expression IL-22 and Muc-2 in the colon and increased numbers of CD8αα+ TCRγδ T cells in the colonic epithelium. These effects were dependent on GPR43, a metabolite-sensing GPCR that binds acetate. Conclusions: We established a promising new approach to moderate bacterial gut infections by manipulating the gut microbiota and mucosal immune tolerance through diets that yield the SCFA acetate.

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Integrated Gut Microbiome and Metabolomics Analysis Reveals Microbial-Metabolic Cross-talk in Allergic Rhinitis

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