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Background Mucosal healing assessed by histology is now a key therapeutic target in ulcerative colitis (UC), but non-invasive biomarkers of segmental histological activity remain poorly defined. This study aimed to evaluate the predictive value of faecal SCFA profile for histological activity across colonic segments in UC patients.Methods A multicentre cross-sectional study was conducted at three research clinical centers (St. Petersburg, Moscow, Kazan). The UC cohort included 40 patients (20 male / 20 female, mean age 39.8±14.2 years; mean Mayo score 4.9±1.8) with left-sided (47.5%) and total (52.5%) colitis. All patients performed a complete faecal SCFA profile (gas chromatography) and step-biopsy histology (5 segments: caecum, ascending, transverse, descending, and sigmoid colon). Histological parameters were scored per segment: neutrophil infiltration of the lamina propria (NLP, 0–3), crypt abscesses, cryptitis, erosions, and chronic inflammatory infiltrate. Composite scores for left-sided (descending + sigmoid, S5–S6) and right-sided (caecum + ascending, S2–S3) segments were computed. Statistical analysis included Spearman correlation, Mann–Whitney U test, and ROC analysis with Youden index optimisation; multiple comparisons were adjusted by Benjamini–Hochberg FDR correction.Results Faecal butyrate (C4) positively correlated with NLP in the descending colon (r=0.367, p=0.020) and with left-sided composite NLP score (r=0.328, p=0.039). Total SCFA concentration showed similar associations with left-sided NLP (r=0.350, p=0.027) and NLP across all segments (r=0.418, p=0.007). Propionate (C3) and acetate (C2) demonstrated weaker but directionally similar associations with overall NLP (r=0.348, p=0.028 and r=0.344, p=0.030, respectively). After Benjamini–Hochberg correction, no association reached FDR < 0.05, consistent with the hypothesis-generating nature of this pilot dataset. ROC analysis identified C4 ≥ 1.104 mg/g as the optimal threshold for predicting active left-sided histological inflammation (NLP ≥ 1 in S5 or S6): AUROC=0.752, specificity=100%, sensitivity=48%, PPV=100%, NPV=63%.Conclusions Faecal butyrate (C4) and total SCFA concentration demonstrate consistent positive associations with neutrophil infiltration of the lamina propria across left-sided colonic segments, suggesting that faecal SCFA profile may serve as a non-invasive biomarker of histological activity in UC. A threshold of C4 ≥ 1.104 mg/g identifies active left-sided inflammation with absolute specificity and positive predictive value (AUROC=0.752). These pilot data need further validation in larger cohorts with rectal biopsy inclusion and standardised SCFA quantification.