Comprehensive microbial and clinical profiling of functional constipation: A stratified comparative study of age and constipation subtype

Abstract

BACKGROUND

Gut microbiota dysbiosis plays a central role in the pathogenesis of functional constipation (FC), but clinical treatment has shown uneven efficacy through methods of regulating intestinal flora. Most existing studies have concentrated on overall case-control comparisons, with limited stratification by age or constipation subtype. Knowledge of how these factors shape gut microbiota composition remains inadequate, constraining the development of effective personalized microbiota-based interventions.

AIM

To characterize gut microbiota profiles by age and constipation subtype and identify factors associated with microbial composition in FC.

METHODS

Ninety-two patients with FC completed questionnaires and underwent anorectal manometry and gastrointestinal transit tests; stool samples were collected for 16S rRNA gene sequencing. Stool samples alone were collected from 34 healthy controls. Patients with FC were categorized into age groups (young, middle-aged, and older) and classified into normal-transit constipation, slow-transit constipation (STC), defecatory disorder (DD), and mixed constipation subtypes. Gut microbial compositions across age groups and constipation subtypes were compared, and their correlations with clinical parameters were investigated.

RESULTS

The young group demonstrated significantly higher anal resting and squeeze pressures than the middle-aged and the older groups. Microbial richness and diversity were substantially lower in the older group than in middle-aged and young groups. Gut microbiota in the young group was predominantly enriched in taxa increasing sphincter tone and inhibiting intestinal peristalsis; the older group featured abundances of short-chain fatty acid-producing, beneficial taxa. The middle-aged group showed an enrichment of pro-inflammatory and pathogenic bacteria. Microbial richness and diversity were higher in STC than in the DD group. Moreover, STC group was enriched in taxa associated with slower peristalsis; DD group showed enrichment of motility-promoting taxa.

CONCLUSION

Significant differences in microbial composition and function were observed across age groups and constipation subtypes in FC, suggesting underlying pathophysiological heterogeneity and providing a basis for precision diagnosis and treatment.

Keywords: Gut microbiota; Functional constipation; Gastrointestinal disorder; Microbial diversity; Age-related differences

Core Tip: This study highlights the distinct gut microbiota profiles associated with age and constipation subtypes in patients with functional constipation (FC). Using 16S rRNA sequencing, we found significant age-related differences in microbial diversity and composition, with older adults exhibiting reduced richness and beneficial taxa. Constipation subtypes also showed distinct microbial patterns, with slow-transit constipation enriched in taxa linked to reduced motility and defecatory disorder characterized by motility-promoting microbes. These findings underscore the pathophysiological heterogeneity of FC and support the development of age- and subtype-specific microbiota-targeted therapies for precision diagnosis and treatment.