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Title: Stool and urine trefoil factor 3 levels: Associations with symptoms, intestinal permeability, and microbial diversity in irritable bowel syndrome

item HEITKEMPER, M - University Of Washington
item CAIN, K - University Of Washington
item SHULMAN, R - Children'S Nutrition Research Center (CNRC)
item BURR, R - University Of Washington
item KO, C - University Of Washington Medical School
item HOLLISTER, E - Baylor College Of Medicine
item CALLEN, N - University Of Washington
item ZIA, J - University Of Washington Medical School
item HAN, C - University Of Washington
item JARRETT, M - University Of Washington

Submitted to: Beneficial Microbes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2018
Publication Date: 4/25/2018
Citation: Heitkemper, M.M., Cain, K.C., Shulman, R.J., Burr, R.L., Ko, C., Hollister, E.B., Callen, N., Zia, J., Han, C.J., Jarrett, M.E. 2018. Stool and urine trefoil factor 3 levels: Associations with symptoms, intestinal permeability, and microbial diversity in irritable bowel syndrome. Beneficial Microbes. 9(3):345-355.

Interpretive Summary: Irritable bowel syndrome (IBS) is a common health care problem in the United States, as well as around the world. It is characterized by abdominal pain and alterations in bowel function - diarrhea, constipation or both. Trefoil factor 3 (TFF3) is a protein produced by the intestine that protects the lining of the intestine. We sought to determine if TFF3 as measured in stool was related to IBS symptoms, the ability of the intestinal lining to act as a barrier, and the types of bacteria present in the intestine. The results suggest that TFF3 levels are related to stooling symptoms and intestinal barrier function. It appeared that TFF3 increased in response to the gut bacterial population being less diverse in the types of the bacteria present. These results underscore the importance of the gut bacteria in promoting disease and human health, as well as dietary approaches to alleviate such concerns.

Technical Abstract: Previously we showed that urine trefoil factor 3 (TFF3) levels were higher in females with irritable bowel syndrome (IBS) compared to non-IBS females. To assess if TFF3 is associated with symptoms and/or reflect alterations in gastrointestinal permeability and gut microbiota in an IBS population, we correlated stool and urine TFF3 levels with IBS symptoms, intestinal permeability, stool microbial diversity and relative abundance of predominant bacterial families and genera. We also tested the relationship of stool TFF3 to urine TFF3, and compared results based on hormone contraception use. Samples were obtained from 93 females meeting Rome III IBS criteria and completing 4-week symptom diaries. TFF3 levels were measured by ELISA. Permeability was assessed with the urine lactulose/mannitol (L/M) ratio. Stool microbiota was assessed using 16S rRNA. Stool TFF3, but not urine TFF3, was associated positively with diarrhoea and loose stool consistency. Higher stool TFF3 was also associated with lower L/M ratio and microbial diversity. Of the 20 most abundant bacterial families Mogibacteriaceae and Christensenellaceae were inversely related to stool TFF3, with only Christensenellaceae remaining significant after multiple comparison adjustment. There were no significant relationships between stool or urine TFF3 levels and other symptoms, nor between stool and urine levels. In premenopausal females, urine TFF3 levels were higher in those reporting hormone contraception. Collectively these results suggest that higher stool TFF3 levels are associated with IBS symptoms (loose/diarrhoeal stools), lower gut permeability, and altered stool bacteria composition (decreased diversity and decreased Christensenellaceae), which further suggests that TFF3 may be an important marker of host-bacteria interaction.