2017 - CIRTA


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5- Outcomes after Intestinal Transplantation

16.10 - Impact of Intestinal Motility, Mucosal Inflammation and Fecal Microflora on Transplant Intestine Function

Presenter: Shekhar, Kubal, Indianapolis, United States
Authors: Shekhar Kubal, Richard Mangus, Lin Huaiying, Gao Xiang , Qunfeng Dong, Evelyn Toh, Natalia Rush, Romil Saxena, Mark Tann, Benjamin Maccaby, Burcin Ekser, Jonathan Fridell, David Nelson

Impact of Intestinal Motility, Mucosal Inflammation and Fecal Microflora on Transplant Intestine Function

Shekhar Kubal1, Richard Mangus1, Lin Huaiying2, Gao Xiang 2, Qunfeng Dong2, Evelyn Toh3, Natalia Rush5, Romil Saxena5, Mark Tann4, Benjamin Maccaby1, Burcin Ekser1, Jonathan Fridell1, David Nelson3.

1Department of Surgery, Division of Transplantation, Indiana University School of Medicine, Indianapolis, IN, United States; 2Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Chicago, IL, United States; 3Department of Microbiology & Immunology, Indiana University School of Medicine, Indianapolis, IN, United States; 4Department of Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States; 5Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, United States

Background: Alterations in intestinal motility, fecal microflora and mucosal inflammatory microenvironment may impact allograft intestinal function. 

Methods: In a cross sectional study, stool samples, intestine biopsies were collected and gastrointestinal scintigraphy using a 6-hour modified gastric emptying test were performed prospectively in adult intestine/ multivisceral transplant recipients with (n=10) and without (n=10) excessive diarrhea. Mucosal biopsies were stained for CD163+, CD4+ and CD8+ cells to assess mucosal cellular infiltration. Fecal microorganisms were characterized using shotgun paired-end metagenomic sequencing on the Illumina HiSeq platform. Fecal samples from 6 healthy controls were also compared. 

Results: Colonic transit time ranged from as short as 1 hour to >6 hours. Overall intestinal motility was within normal limits [1] in 14 (70%) patients, rapid in 5 (25%) patients [Figure 1] and slow in 1(5%) patient, with no correlation between intestinal motility and excessive diarrhea. There were no differences in the mucosal cellular infiltration between the two groups. Overall there were more macrophage infiltration than CD8+ and CD4+ T cells in the mucosal biopsies [Figure 2]. Taxonomic classification of the fecal microflora sequences revealed that, 7 bacterial taxa at the genus level were significantly different in the diarrhea group, including Veillonella (p-value < 0.001), Bifidobacterium (p-value < 0.02), Alistipes (p-value < 0.02), Enterococcus (p-value < 0.02), Odoribacter (p-value < 0.02), Streptococcus (p-value < 0.05), and Lactobacillus (p-value < 0.05) [Figure 3a].  The diversity measured by the Bray-Curtis dissimilarity for the microbial communities in the fecal samples from patients with diarrhea was significantly lower than that in the healthy control samples at the genus level (p-value < 0.05), although the difference between diarrhea and non-diarrhea samples was not statistically significant [Figure 3b]. 

Conclusions: Excessive diarrhea in intestine transplant recipients without rejection may be a result of less diverse fecal microflora, whereas intestinal motility and mucosal inflammation may not play a significant role. Manipulation of fecal microflora may be useful in controlling chronic diarrhea after intestine transplantation. A study with larger sample size may better define fecal microbial alterations in the setting of intestine transplantation. 

  Figure3

 

[1] 1. Maurer AH. Gastrointestinal Motility, Part 2: Small-Bowel and Colon Transit. J Nucl Med Technol. 2016;44(1):12-8.


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