Microbiome and metabolomic profiling in humans with functional anorectal pain: Identifying key players in disease pathogenesis

Functional Anorectal Pain (FARP) is a chronic, functional, nonorganic disorder of the anorectal region, often misdiagnosed as various types of anorectal organic diseases in clinical practice. However, the pathogenesis and diagnostic markers of FARP remain poorly understood. In this study, we recruited 45 FARP patients and 35 healthy subjects to investigate the microbial and metabolomic profiles associated with FARP progression. Anorectal manometry was utilized to determine changes in anal pressure, revealing a significant decrease in FARP patients' anal resting pressure and maximum anal squeeze pressure. Through 16S rRNA gene sequencing and metabolomics analysis, we identified specific microbial genera, including Propionibacterium, Ruminococcus2, and Bilophila, and specific metabolite profiles, including Gentisic acid, 2-Naphthalenethiol, 2-Furancarboxaldehyde, Benzoic acid, Allose, and (S)-3-Amino-5-methylhexanoic acid, that were closely correlated with FARP. In-depth analysis revealed that the Phospholipase D (PLD) signaling pathway exhibited significant differences in FARP. Additionally, serum cortisol levels were found to be significantly elevated in FARP patients. These findings provide new insights into the anorectal manometry features, gut microbiota, and serum metabolome associated with FARP, potentially contributing to improved clinical diagnosis and therapeutic strategies for FARP.