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Tryptophan deficiency linked to IBD development
Patients with inflammatory bowel disease showed significantly lower serum levels of tryptophan than healthy controls in a recent study. Further, researchers found that among IBD patients, lower tryptophan levels were significantly correlated with increased disease activity.
They concluded that “tryptophan deficiency could contribute to development of IBD.”
Prompted by data from mouse models, investigators from Germany analyzed serum samples from 211 patients with ulcerative colitis and 234 patients with Crohn’s disease to evaluate whether clinical and serologic factors were correlated with levels of tryptophan and its metabolites. They also analyzed serum samples from 291 matched controls, and evaluated stool samples and colonic biopsies from subsets of the study participants.
They found that patients with IBD, especially those with Crohn’s disease, showed significantly lower serum levels of tryptophan compared with controls.
“This confirms earlier observations of reduced [tryptophan] serum levels in smaller cohorts,” the investigators wrote.
Additionally, tryptophan levels were negatively correlated with disease activity or C-reactive protein levels.
They also found that serum tryptophan levels were correlated with fecal microbiota composition, and that patients with active IBD showed higher levels of tryptophan metabolites, especially quinolinic acid, compared with controls, which indicated higher tryptophan degradation in these patients.
“Reduction of [tryptophan] serum levels could be caused by different factors,” including a reduced nutritional state in Crohn’s vs. UC patients, a specific absorption defect, increased catabolism of tryptophan in inflamed mucosa, and the gut microbiota itself, the investigators wrote. “Larger cohort studies in healthy subjects and patients with other inflammatory disorders are therefore warranted to understand the exact influence of host [tryptophan] metabolism on gut microbial communities.”
Finally, the researchers noted that the findings suggest tryptophan and its metabolites show promise as potential biomarkers and therapeutic targets in IBD. – by Adam Leitenberger
Disclosures: One of the researchers reports he is employed by CONARIS Research Institute AG.
Perspective
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Nikolaus and colleagues present an evaluation of the potential relationship between tryptophan and IBD, comparing patients with both ulcerative colitis and Crohn’s disease with normal controls. The authors were able to take an interesting association between tryptophan levels and severity of colitis in mouse models and examine this on a larger scale in 535 patients with IBD.
By demonstrating lower levels of tryptophan in patients with IBD compared with controls, and by demonstrating a negative correlation between serum tryptophan levels and disease activity, the authors have prompted multiple questions for future studies including many that were examined in exploratory analyses in this study (eg, the relationship between tryptophan and the microbiome and the potential for tryptophan levels to serve as a predictor of complex disease or response to biologic therapies).
Many of the exploratory analyses were performed in smaller sub-groups of the entire study population, such as the microbial analyses and the analysis of dietary intake of tryptophan. One of the key results from the validated food frequency questionnaire data, however, is the lack of an association between disease activity and tryptophan consumption through an altered diet, which would seem to suggest that other mechanisms are driving these differences in tryptophan levels.
I agree with the authors’ assessments that follow-up studies in larger populations will be informative in further examinations of the relationship between tryptophan and many of the outcomes evaluated, in addition to delineating the differences between the effects of low tryptophan and those of ongoing inflammation. These further prospective studies will be quite helpful in identifying the potential for tryptophan in the clinical management of IBD, as a biomarker or predictor of disease course, or as a therapeutic target that can be manipulated to improve clinical outcomes.