METHANOGENIC ARCHAEA AND FUNCTIONAL PATHWAYS SHOW DIFFERENT CORRELATIONS TO THE SEVERITY OF CONSTIPATION IN IBS

Background
Methane production is associated with oroanal transit time (OATT) and constipation in irritable bowel syndrome (IBS) (Algera NGM 2022). However, increasing breath methane and fecal methanogens have been observed with increasing transit time also in healthy individuals (Procházková Gut 2023). In this study we investigated the links between different methanogenic species and pathways with the severity of symptoms in IBS independent of transit time.

Methods
Gut microbiota profiles were obtained for 129 individuals with IBS of all subtypes who reported gastrointestinal symptom severity (GSRS-IBS), stool frequency and form (BSF), psychological distress (HADS), and somatic symptom severity (PHQ-12). OATT was assessed by radiopaque markers. Breath methane was measured during a lactulose nutrient challenge test (LeNeve AJG 2013). Fecal microbiota profiles were obtained using whole-genome sequencing and classification with the UHGG v2 database (Almeida Nat Biotech 2020). Functional pathways were quantified using gut metabolic modules (GMMs) (Vieira-Silva Nat Microbiol 2016). Associations to symptoms and effects of covariates were tested using metadeconfoundR (Forslund Nature 2021).

Results
The proportions of different methanogenic archaea and of pathways for methane production increased with increasing severity of constipation, but were not linked to pain, satiety or bloating. When considering OATT, there was no significant association between constipation and Methanobrevibacter smithii, the most abundant and prevalent human methanogen, or its pathway of methane production from hydrogen and carbon dioxide. However, we observed significant associations, not due to increased OATT, between hard stools and the species Methanobrevibacter oralis and Methanobrevibacter woesei, and for both hard stools and incomplete bowel emptying with methane production from trimethylamine (Figure 1).

Conclusion
The severity of constipation in individuals with IBS is associated with methanogenic archaea and functional pathways that are not dominant in healthy individuals. These results suggest that changes in the gut environment favor low abundant methanogens independent of transit time, that might contribute to the pathophysiology in IBS.