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. 2018 Apr 25;9(3):345-355.
doi: 10.3920/BM2017.0059. Epub 2018 Apr 10.

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

M M Heitkemper  1 , K C Cain  2 , R J Shulman  3 , R L Burr  1 , C Ko  4 , E B Hollister  5 , N Callen  6 , J Zia  4 , C J Han  1 , M E Jarrett  1
Affiliations

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

M M Heitkemper et al. Benef Microbes. .

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.

Keywords: Christensenellaceae; anti-microbial peptide; diarrhoea; hormone contraception.

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Figures

Figure 1:
Figure 1:
Stool (A) and urine (B) trefoil factor 3 (TFF3) by age and hormone contraceptive use.
Figure 2:
Figure 2:
Relationship of stool trefoil factor 3 (TFF3) with diarrhea and constipation. Percent of days with moderate/severe diarrhea (A) and constipation (B) were derived from a 28-day symptom diary.
Figure 3:
Figure 3:
Relationship of stool trefoil factor 3 (TFF3) with permeability. Permeability is a ratio of urine lactulose to mannitol collected overnight following ingestion of a testing solution.
Figure 4:
Figure 4:
Relationship of stool trefoil factor 3 (TFF3) with Christensenellaceae. Relative abundance of stool Christensenellaceae (logit transform) as determined by 16S rRNA.
See this image and copyright information in PMC

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