Long COVID is characterised by a significant restructure of the gut ecosystem reflecting a shift in homeostatic balance, while short-term montelukast treatment shows minimal impact on the microbial landscape without further destabilising the gut environment.
Key Findings
Results
Long COVID patients showed significant structural reorganisation of the gut microbial community compared to healthy controls, despite largely maintained overall species richness.
Analysis used 16S rRNA gene sequencing (Illumina MiSeq) on stool samples from long COVID patients and healthy controls
Alpha diversity (Shannon index) was largely preserved, indicating species richness was not substantially reduced
Beta diversity (Bray-Curtis dissimilarity) revealed significant differences in community structure between long COVID patients and healthy controls
The authors describe this as 'qualitative dysbiosis' reflecting a shift in homeostatic balance where the core microbial community remains present but its proportions are altered
Results
Long COVID patients were characterised by enrichment of Firmicutes, specifically the genera Agathobacter and Faecalibacterium.
Linear discriminant effect size (LEfSe) analysis was used to identify differentially abundant taxa
Agathobacter and Faecalibacterium genera within the phylum Firmicutes were enriched in the long COVID group
These taxa were identified as key drivers of the architectural shift in microbial community structure in long COVID patients
This finding represents an increase in certain butyrate-producing bacteria in the long COVID group relative to healthy controls
Results
Healthy controls were characterised by higher abundances of phyla Verrucomicrobiota and Actinobacteriota, as well as genera Alistipes and Akkermansia.
LEfSe analysis identified these taxa as discriminating features of the healthy control microbiome
Akkermansia, a genus within Verrucomicrobiota, was notably higher in healthy controls
Alistipes genus was also enriched in healthy controls compared to long COVID patients
These taxa are generally considered markers of a healthy gut environment
Results
Montelukast treatment led to a specific enrichment of the genus Dialister but did not disrupt the overall microbial community structure.
Longitudinal analysis compared montelukast-treated patients versus placebo
The broader community structure remained stable in both treatment and placebo groups over the study period
Enrichment of Dialister was identified as a targeted and potentially transient effect of montelukast treatment
Short-term montelukast treatment was described as having 'minimal impact on the microbial landscape, suggesting treatment does not further destabilise the gut environment'
Methods
This study was designed as a proof-of-concept investigation combining a cross-sectional comparison and a longitudinal analysis.
Cross-sectional component compared gut microbiota between long COVID patients and healthy controls
Longitudinal component followed montelukast-treated patients versus placebo over time
Gut microbiome profiling was conducted using 16S rRNA gene sequencing on the Illumina MiSeq platform
Both alpha diversity (Shannon) and beta diversity (Bray-Curtis) metrics were evaluated, followed by relative abundance and LEfSe analysis
What This Means
This research suggests that people with long COVID have a meaningfully different gut bacterial community compared to healthy individuals, even though they don't necessarily have fewer types of bacteria overall. Instead of a reduction in bacterial diversity, long COVID appears to cause a reshuffling of which bacteria dominate the gut — with certain bacterial groups like Agathobacter and Faecalibacterium becoming more prominent, while bacteria typically associated with gut health, such as Akkermansia, are less abundant. The researchers describe this as a 'qualitative dysbiosis,' meaning the gut ecosystem is reorganised rather than simply depleted.
The study also examined whether montelukast — an anti-inflammatory drug originally used for asthma that is being explored as a potential treatment for long COVID — alters the gut microbiome. The findings suggest that short-term montelukast treatment had only a very limited and specific effect on gut bacteria, causing an increase in one particular bacterial genus (Dialister) without broadly disrupting the microbial community. This is relevant because some medications can cause significant unintended changes to gut bacteria, and the results suggest montelukast does not appear to do so.
This research matters because it adds to the growing evidence that long COVID involves changes to the gut microbiome, which may play a role in the wide range of persistent symptoms patients experience. The relatively modest effect of montelukast on the gut microbiome could be seen as reassuring for those studying it as a repurposed treatment. However, as a proof-of-concept study, larger and longer-term research will be needed to confirm these findings and determine their clinical significance.
Camps-Massa P, Pérez-Mormeneu J, Guevara-Nuñez D, Saiz-Escobedo L, Calatayud L, González-Díaz A, et al.. (2026). Gut microbiome shift in long COVID: impact of disease and montelukast treatment.. Journal of global health. https://doi.org/10.7189/jogh.16.04164