Gut Microbiota, Tryptophan Metabolism, Quality of Life, Psychoemotional and Cognitive Impairments in Functional Constipation

Aim: to investigate the relationship between tryptophan metabolism features, gut microbiota composition, systemic inflammation markers, cortisol levels, quality of life, and psychoemotional and cognitive status in female patients with functional constipation (FC). Materials and methods. The study included 64 female patients with FC and 26 age- and BMI-matched women without FC ( p > 0.05). All participants underwent assessment of gut microbiota composition in stool samples (via 16S rRNA sequencing), health-related quality of life (SF-36), psychoemotional status (4DSQ, Spielberger — Hanin test, Hamilton scale), and cognitive function (BACS cognitive tests). Tryptophan metabolism was evaluated by measuring levels of interleukin-1β, cortisol, brain-derived neurotrophic factor (BDNF), tryptophan, kynurenine, kynurenic acid, and serum and platelet serotonin. Results. Compared to women without FC, female patients with FC had higher levels of cortisol (325 [266; 403] vs. 275 [255; 304] nmol/L; p = 0.025), interleukin-1β (10.0 [9.2; 11.2] vs. 7.2 [6.5; 7.8] pg/mL; p < 0.001), and blood kynurenine (0.65 [0.54; 0.82] vs. 0.44 [0.35; 0.48] μg/mL; p < 0.001), as well as lower plasma serotonin levels (108 [85; 134] vs. 163 [117; 190] ng/mL; p < 0.001). No differences were found between groups in plasma tryptophan, BDNF, kynurenic acid, or platelet serotonin. Patients with FC exhibited more pronounced depression (Hamilton scale: 8 [6; 9] vs. 3 [2; 3] points; p < 0.001) and somatization (9 [7; 12] vs. 5 [3; 9] points; p < 0.001); lower cognitive function scores (50 [45; 54] vs. 54 [53; 56] points; p < 0.001), particularly in auditory-verbal memory ( p < 0.001) and information processing speed ( p < 0.001); and reduced quality of life (SF-36) in physical functioning (90 [83; 95] vs. 95 [95; 95] points; p < 0.001) and bodily pain (60 [50; 70] vs. 75 [56; 85] points; p < 0.001). Cortisol levels positively correlated with bodily pain ( r = 0.379; p = 0.003), while interleukin-1β levels inversely correlated with bodily pain ( r = –0.391; p = 0.002), physical functioning (r = –0.448; p < 0.001), and verbal memory (r = –0.252; p = 0.046), and positively correlated with depression ( r = 0.311; p = 0.013) and somatization ( r = 0.266; p = 0.035). Cortisol levels correlated positively with Oscillospira ( r = 0.45; p = 0.01), while kynurenine levels correlated with Alistipes ( r = 0.36; p = 0.04) abundance. Plasma serotonin positively correlated with Haemophilus ( r = 0.37; p = 0.03) and inversely with Bacteroides plebeius ( r = –0.40; p = 0.02) abundance. Physical functioning (SF-36) positively correlated with Lachnospiraceae NK4B4 group ( r = 0.35; p = 0.04), while depression severity (4DSQ) inversely correlated with Alistipes abundance ( r = –0.37; p = 0.03). Information processing speed is inversely correlated with abundance of Bacilli ( r = –0.48; p = 0.004), Lactobacillales ( r = –0.48; p = 0.004), Pasteurellales ( r = –0.36; p = 0.03), Pasteurellaceae ( r = –0.36; p = 0.03), Streptococcaceae ( r = –0.47; p = 0.006), Haemophilus ( r = –0.41; p = 0.02), and Streptococcus ( r = –0.38; p = 0.02). Conclusion. The findings indicate that women with functional constipation exhibit altered tryptophan metabolism and gut microbiota dysbiosis, associated with depression, somatization, cognitive impairment, and reduced health-related quality of life.