Administration of tryptophan and some of its metabolites reduces the severity of colitis in mice, whereas removing tryptophan from the diet increases susceptibility to colitis.
Transfer of the intestinal microbiome transfers the colitogenic phenotype from tryptophan starved animals to normally nourished mice.
Dr Stefan Schreiber and colleagues from Germany systematically evaluated serum levels of tryptophan and its metabolites in patients with inflammatory bowel diseases (IBD), and studied their association with clinical and serologic features.
The team studied 535 consecutive patients with IBD, enrolled in Germany from 2013 through 2014 and followed until 2016.
|Serum concentration of interleukin 22 associated with disease activity |
Serum samples were collected from patients and 291 matched individuals without IBD (controls); levels of tryptophan were measured using high-performance liquid chromatography.
Metabolites of tryptophan were measured in serum from 148 patients, and 100 controls by mass spectrometry. We measured levels of interleukin 22 in serum from 28 patients by enzyme-linked immunosorbent assay.
Paired stool and serum samples were collected from a subset of patients with active UC or CD to investigate associations between serum levels of tryptophan and composition of the fecal microbiota, analyzed by 16S ribosomal DNA amplicon sequencing.
The research team used real-time polymerase chain reaction to measure levels of messenger RNAs in colonic biopsies from 60 patients with UC, 50 with CD, and 30 controls.
The team collected information on patients’ disease activity scores, medications, laboratory assessments, and clinical examinations during recruitment and follow-up visits.
Serum levels of tryptophan were significantly lower in patients with IBD than in controls with a stronger reduction in patients with CD than UC.
The researchers found a negative correlation between serum levels of tryptophan and disease activity or levels of C-reactive protein.
Levels of messenger RNAs encoding tryptophan 2,3-dioxygenase-2 and solute carrier family 6 member 19 (also called B0AT1) were significantly decreased in colonic biopsies from patients with IBD compared with controls, whereas level of messenger RNA encoding indoleamine 2,3-dioxygenase-1 was significantly increased.
The researchers found that the composition of the fecal microbiota associated with serum levels of tryptophan.
Analysis of tryptophan metabolites revealed activation of the kynurenine pathway, based on high levels of quinolinic acid, in patients with IBD compared with controls.
Serum concentration of interleukin 22 associated with disease activity in patients with IBD.
The research team observed an inverse association between levels of interleukin 22, and serum levels of tryptophan.
Dr Schreiber's team concludes, "In an analysis of serum samples from more than 500 patients with IBD, we observed a negative correlation between serum levels of tryptophan and disease activity."
"Increased levels of tryptophan metabolites—especially of quinolinic acid—indicated a high activity of tryptophan degradation in patients with active IBD."
"Tryptophan deficiency could contribute to development of IBD or aggravate disease activity."
"Interventional clinical studies are needed to determine whether modification of intestinal tryptophan pathways affects the severity of IBD."