Nutritional strategies to enhance adaptation in intestinal failure

Lamprecht, Georg; Bodammer, Peggy

doi:10.1097/mot.0000000000000289

Cited by 10 publications

(4 citation statements)

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“…SBS is characterized by diarrhea, malnutrition, and dehydration. Intestinal adaptation is the physiological response to major resections and involves structural and functional changes of the remnant bowel (25,42). It either compensates SBS from its beginning or in many cases allows intestinal failure to revert to oral autonomy over prolonged periods of time.…”

Section: Introductionmentioning

confidence: 99%

Nod2 deficiency functionally impairs adaptation to short bowel syndrome via alterations of the epithelial barrier function

Berlin

Reiner

Witte

et al. 2019

American Journal of Physiology-Gastrointestinal and Liver Physi

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Nucleotide-binding oligomerization domain-containing protein 2 ( NOD2) gene mutations are a risk factor for Crohn’s disease and also associated with worse outcome in short bowel syndrome (SBS) patients independent of the underlying disease. The aim of this study was to analyze the effect of Nod2 deficiency on barrier function and stool microbiome after extensive ileocecal resection in mice. Male C57BL6/J wild-type (WT) and Nod2-knockout (KO) mice underwent 40% ileocecal resection. Sham control mice received simple transection of the ileum. Clinical outcome was monitored daily. Barrier function was measured with Ussing chambers using FITC-4-kDa-Dextran flux, transmucosal electrical resistance, and dilution potentials. Immunofluorescence of claudin-2 was studied. Composition of the stool microbiome was assessed by 16S rRNA gene sequencing. Resected Nod2-KO mice had impaired clinical outcome compared with resected WT mice. This was accompanied by increased stool water contents and increased plasma aldosterone. Histomorphological adaptation was independent of Nod2. Barrier function studies revealed impaired sodium to chloride permeability and altered claudin-2 localization in the absence of Nod2. Resection induced decreases of bacterial diversity and a shift of bacteriodetes-to-firmicutes ratios. Ileum and cecum resection-induced increase in proteobacteria was absent in Nod2-deficient mice. Verrucomicrobia were temporarily increased in Nod2-KO mice. Nod2 deficiency functionally impairs adaptation to short bowel syndrome via a lesser increase of epithelial sodium pore permeability, altered epithelial barrier function, and the microbiome. NEW & NOTEWORTHY NOD2 gene mutations are associated with the development of severe short bowel syndrome and intestinal failure. The influence of Nod2 mutations on intestinal adaptation in experimental short bowel syndrome has not been studied yet. Here, we provide data that Nod2 deficiency worsens clinical outcome and functional adaptation under SBS conditions in mice, indicating that NOD2 is required for successful adaptation after ileocecal resection.

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Section: Introductionmentioning

confidence: 99%

Nod2 deficiency functionally impairs adaptation to short bowel syndrome via alterations of the epithelial barrier function

Berlin

Reiner

Witte

et al. 2019

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…While adaptation may eventually result in oral autonomy in some patients, temporary or permanent parenteral nutrition and surgical interventions such as reconstructive surgery, lengthening procedures, or—in selected cases—intestinal transplantation are the treatment options for intestinal failure [ 5 , 6 ]. Additionally, nutritional approaches as well as hormone and growth factor stimulation are strategies to enhance intestinal adaptation in SBS patients [ 7 ]. Teduglutide, a GLP-2 analogue, has recently been introduced into clinical practice and has been shown to reduce fluid requirements of parenteral support [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome

et al. 2018

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Background Short bowel syndrome results from extensive small bowel resection and induces adaptation of the remaining intestine. Ileocecal resection (ICR) is the most frequent situation in humans. Villus hypertrophy is one hallmark of mucosal adaptation, but the functional mechanisms of mucosal adaptation are incompletely understood. Aims The aim of the study was to characterize a clinically relevant model of short bowel syndrome but not intestinal failure in mice and to identify outcome predictors and mechanisms of adaptation. Methods Male C57BL6/J mice underwent 40% ICR and were followed for 7 or 14 days. Small bowel transection served as control. All mice underwent autopsy. Survival, body weight, wellness score, stool water content, plasma aldosterone concentrations, and paracellular permeability were recorded. Results Unlike controls, resected mice developed significant diarrhea with increased stool water. This was accompanied by sustained weight loss throughout follow-up. Villus length increased but did not correlate positively with adaptation. Plasma aldosterone concentrations correlated inversely with body weight at day 14. After ICR, intestinal epithelial (i.e., tight junctional) sodium permeability was increased. Conclusions 40% ICR results in moderate to severe short bowel syndrome. Successful adaptation to the short bowel situation involves villus elongation but does not correlate with the degree of villus elongation alone. In addition, increased intestinal epithelial sodium permeability facilitates sodium-coupled solute transport. Hyperaldosteronism correlates with the severity of weight loss, indicates volume depletion, and counterregulates water loss. Electronic supplementary material The online version of this article (10.1007/s10620-018-5420-x) contains supplementary material, which is available to authorized users.

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“…[11][12][13][14] Nutritional options for stimulation of physiological GLP-2 analog teduglutide significantly reduces need for parenteral nutrition and stool frequency in a real-life setting 2 journals.sagepub.com/home/tag adaptation in intestinal failure are available but limited. 15 Intestinal transplantation has gained importance since the 1990s and important advances have been made since. 16 But it is costly, related to a high post-transplantation morbidity and mortality rate and the available long-term data…”

Section: Introductionmentioning

confidence: 99%

GLP-2 analog teduglutide significantly reduces need for parenteral nutrition and stool frequency in a real-life setting

Schoeler

Klag

Wendler

et al. 2018

Therap Adv Gastroenterol

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Background:To evaluate the benefits of teduglutide in a real-life setting, we analyzed the data of 14 patients with short bowel syndrome treated with teduglutide. Additionally, we studied glucagon-like peptide 2 (GLP-2) receptor expression in samples of small intestinal and colonic tissue to provide explanations for clinical observations.Methods:Stool frequency and consistency, sensation of thirst, parental calorie or fluid uptake and the number of days on parenteral support per week were collected for up to 2 years. Quantitative real-time polymerase chain reaction of the GLP-2 receptor in healthy controls was performed to better understand clinical response in different patient subgroups.Results:There was a significant reduction in parenteral support after 24 and 48 weeks (by 11.0 and 36.6%, respectively; p < 0.05). Further major improvements were made in several patients after over 1 year (reduction by 79.3%, p < 0.05). The proportion of patients who reduced parenteral support by at least 20% was 33.3%, 54.5% and 71.3% after 24 weeks, 48 weeks and beyond 1 year, respectively. Patients on daily parenteral support showed late but strong amelioration. The reduction of thirst was the earliest marker for response. While stool consistency increased (p < 0.01), stool frequency decreased (p < 0.05) significantly after 12 weeks. This reduction was even more pronounced in patients with colon in continuity. Supporting these clinical observations, we found a stronger physiological expression of the GLP-2 receptor in the colon than in the small intestine.Conclusions:Patients benefit from teduglutide in a real-life setting, but in contrast to randomized, controlled studies reduction of parenteral support took longer. We identified early clinical markers of response, such as stool consistency and frequency as well as sensation of thirst. Clinical and molecular observations support the role of the colon as an important target organ of teduglutide.

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Nutritional strategies to enhance adaptation in intestinal failure

Cited by 10 publications

References 72 publications

Nod2 deficiency functionally impairs adaptation to short bowel syndrome via alterations of the epithelial barrier function

Nod2 deficiency functionally impairs adaptation to short bowel syndrome via alterations of the epithelial barrier function

Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome

GLP-2 analog teduglutide significantly reduces need for parenteral nutrition and stool frequency in a real-life setting

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