Gut metagenomes, IBD vs healthy, Israel, case-control

The gut microbiome mediates the reductive catabolism of bilirubin into urobilinoids, yet the bacteria and enzymes responsible for the later steps of this pathway remain largely unknown. Here, we combine untargeted UPLC/HRMS metabolomics with shotgun metagenomic sequencing of fecal samples from 119 participants, including patients with Crohn's disease, ulcerative colitis, and healthy controls, to map disruptions in the bilirubin catabolic pathway in inflammatory bowel disease (IBD). We show that stercobilinogen and stercobilin, the terminal metabolites of this pathway, are depleted (p < 0.01) in IBD patients irrespective of disease subtype, while upstream intermediates, D-urobilinogen, remain unchanged. This metabolic bottleneck coincides with a marked reduction in members of the Lachnospiraceae family, specifically Blautia sp. SG-772 and three uncharacterized species, which show strong positive correlations with stercobilinogen and stercobilin levels. These findings implicate Lachnospiraceae as key mediators of the yet unknown enzymatic conversion of I-urobilinogen to stercobilinogen, extending the family's known metabolic repertoire beyond short-chain fatty acid production. Given that bilirubin and its reduced metabolite stercobilinogen possess antioxidant properties, their depletion may contribute to the oxidative burden in the IBD gut. Conversely, the concurrent elevation of D-urobilin, which lacks these protective 2 properties and has been linked to metabolic dysfunction in other contexts, may further exacerbate inflammation. Our results identify fecal bilirubin metabolites as candidate biomarkers of microbial dysbiosis in IBD and nominate specific Lachnospiraceae taxa for functional characterization of the missing stercobilinogen reductase.

Classified as human gut / stool shotgun DNA metagenome of age unknown by sonnet_x2 with confidence 0.75. Assay shotgun_dna.

• host run.host_tax_id · “9606”
• host run.scientific_name · “human gut metagenome”
• body site study.description · “fecal samples from 119 participants”

124 runs over 124 samples · mean 0.45 Gbp per run (median 0.47 Gbp, total 56.12 Gbp; 124 runs with a base count) · layout SINGLE 124 · platform ILLUMINA 124 · models Illumina NovaSeq 6000 (124) · 0% of runs with a Sandpiper profile · first public 2026-08-13

Sabti O first · Lialin-Tzadikov K · Ivanova V · Dori-Bachash M · Uzi-Gavrilov S · Tik Z · Mashiach R · Zorea A · Mizrahi I · Segal A · Moyal-Attias K · Elinav E · Meijler MM last

PRJEB122858.csv.gz (4.6 KB) · parquet (76.5 KB) — all 124 samples, every field with route and confidence · PRJEB122858_determinations.csv.gz (9.4 KB) — 1,408 evidence rows