Fecal Microbiota Transplantation Improves Clinical Symptoms and Promotes Intestinal Microecological Remodeling in Patients with Constipation Complicated by Anxiety: A Multi-omics Study

Background: Constipation is frequently accompanied by anxiety and depressive symptoms, suggesting coordinated disturbances in the gut microbiota, intestinal metabolism, and gut-brain axis. Fecal microbiota transplantation (FMT), as a microbiome-targeted intervention, has shown potential in functional gastrointestinal disorders. However, its clinical response and multi-omics mechanisms in constipation complicated by anxiety remain unclear. Methods: Eighteen patients with constipation complicated by anxiety received two cycles of oral FMT capsules, and 10 healthy individuals were enrolled as controls. Phenotypes were assessed before and after treatment using Wexner, PAC-QOL, ODS, SDS, and HAMA scores. Fecal samples from patients before and after FMT and from healthy controls were subjected to shotgun metagenomic sequencing and untargeted metabolomics. Microbial composition, MetaCyc pathways, fecal metabolites, efficacy-stratified features, and microbiota-metabolite-clinical phenotype correlation networks were analyzed. Results: After FMT, Wexner, PAC-QOL, ODS, SDS, and HAMA scores were reduced. Metagenomic analysis showed that baseline gut microbial structure in patients was distinct from healthy controls and shifted toward a healthy-like profile after FMT. Differential species analysis suggested partial microbial recovery, with reversible species mainly involving Clostridium, Blautia, and Lachnospira. Functional pathway analysis showed recovery of selected amino acid metabolism and anaerobic fermentation pathways, whereas pathways related to bacterial surface structures and polysaccharide biosynthesis remained persistently abnormal. Untargeted metabolomics revealed broad fecal metabolic remodeling, characterized by a shift from a relatively suppressed state toward a more active profile. Efficacy-stratified analyses indicated that the Effective and No_Effective groups differed in baseline microbial composition, functional niches, and metabolic background. Integrated correlation network analysis identified associations among differential species, metabolites, and clinical phenotypes. In particular, Butyricicoccus sp. AM29-23AC was negatively correlated with constipation, quality-of-life, anxiety, and depression-related scores and was embedded in a short-chain fatty acid-related microbiota-metabolite network. Conclusions: Oral FMT capsules were associated with improvement in constipation, quality-of-life, anxiety, and depression-related scores in patients with constipation complicated by anxiety, accompanied by coordinated remodeling of gut microbial composition, microbial functional potential, and fecal metabolic profiles. Baseline microbial and metabolic states may influence clinical response to FMT. Butyricicoccus sp. AM29-23AC and short-chain fatty acid-related microbiota-metabolite networks may represent candidate links between FMT-associated ecological remodeling and clinical improvement.