Exploration of associations among dietary tryptophan, microbiome composition and function, and symptom severity in irritable bowel syndrome

Authors: PLANTINGA, ANNA - Williams College; KAMP, KENDRA - University Of Washington; WU, QINGLONG - Baylor College Of Medicine; CHEN, LI - University Of Washington; YOO, LINDA - University Of Washington; BURR, ROBERT - Washington State University; CAIN, KEVIN - University Of Washington; RAFTERY, DANIEL - University Of Washington; NETO, FAUSTO - University Of Washington; BADU, SHYAM - Baylor College Of Medicine; SO, SIK YU - Baylor College Of Medicine; SAVIDGE, TOR - Baylor College Of Medicine; SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC); HEITKEMPER, MARGARET - Washington University

Submitted to: Neurogastroenterology & Motility
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/24/2023
Publication Date: 5/1/2023
Citation: Plantinga, A.M., Kamp, K.J., Wu, Q., Chen, L., Yoo, L., Burr, R.L., Cain, K.C., Raftery, D., Neto, F.C., Badu, S., So, S., Savidge, T., Shulman, R.J., Heitkemper, M.M. 2023. Exploration of associations among dietary tryptophan, microbiome composition and function, and symptom severity in irritable bowel syndrome. Neurogastroenterology & Motility. 35. Article e14545. https://doi.org/10.1111/nmo.14545.
DOI: https://doi.org/10.1111/nmo.14545

Interpretive Summary: Irritable bowel syndrome causes abdominal pain and stool changes (like diarrhea) and affects 1 to 2 children and adults in 10 around the world. It can be associated with other symptoms like bloating, increased gas, fatigue, and stress symptoms like anxiety. What causes the condition remains unclear. Tryptophan is a building block of protein that is ingested in the diet and also is produced by bacteria in the intestine. Tryptophan is metabolized to other chemicals that can affect how the gut functions and affect mood and sleep. This metabolism can take place in the intestine and in the bacteria that live in the intestine. We sought to find out if the symptoms of irritable bowel syndrome were related to the amount of tryptophan in the diet, levels of tryptophan in the intestine, the genes that control tryptophan metabolism, and/or the type of bacteria in the intestines of adults. We determined that the severity of symptoms was not related to tryptophan intake or the amount of tryptophan in the stool. However, the amount of a type of bacteria in the intestine was related to the amount of tryptophan in the diet and these in turn, predicted what the individuals' stools looked like (diarrhea or constipation). Our results highlight the importance of understanding the interaction of different factors that impact symptoms so that treatment can be individualized and thus, more likely to be helpful.

Technical Abstract: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS. Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and quantitative measurement of TRP by mass spectrometry. Our cohort included 115 females, 69 with IBS and 46 HCs, with a mean age of 28.5 years (SD 7.4). TRP intake (p = 0.71) and stool TRP level (p = 0.27) did not differ between IBS and HC. Bifidobacterium abundance was lower in the IBS group than in HCs (p = 0.004). Predicted TRP metabolism gene content was higher in IBS than HCs (FDR-corrected q = 0.006), whereas predicted biosynthesis gene content was lower (q = 0.045). Within the IBS group, there was no association between symptom severity and TRP intake or stool TRP, but there was a significant interaction between Bifidobacterium abundance and TRP intake(q = 0.029)in predicting stool character. Dietary TRP intake,microbiome composition, and differences in TRP metabolism constitute a complex interplay of factors that could modulate IBS symptom severity.