Dietary Supplementation With Orotate and Uracil Increases Adaptive Growth of Jejunal Mucosa After Massive Small Bowel Resection in Rats

Evans, Mary; Tian, Junqiang; Gu, Li H.; Jones, Dean P.; Ziegler, Thomas R.

doi:10.1177/0148607105029005315

Cited by 11 publications

(8 citation statements)

References 45 publications

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“…13 A preclinical study demonstrated that dietary supplementation with the pyrimidine precursor orotate and uracil stimulated jejunal adaptive growth in SBS rats. 45 As a result, the enhanced pyrimidine and purine metabolism in SBS III patients may be related to a better intestinal adaption. Additionally, the reduction of pathways responsible for methane metabolism and oxidative phosphorylation in SBS patients suggests insufficient energy harvest and poor health status.…”

Section: Discussionmentioning

confidence: 99%

Fecal microbiota signatures of adult patients with different types of short bowel syndrome

Huang

Guo

et al. 2017

J of Gastro and Hepatol

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Section: Discussionmentioning

confidence: 99%

Fecal microbiota signatures of adult patients with different types of short bowel syndrome

Huang

Guo

et al. 2017

J of Gastro and Hepatol

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“…A sterile uracil stock solution (1%, Acros Organics) was used to supplement M9 minimal media (20 mg/L) or chick diets (1% wt/wt). To supplement uracil to chick diets, 100 g of chick diet (Harlan Teklad, Madison, WI) was soaked in 100 ml of 1% uracil solution and permitted to air dry [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

De novo pyrimidine synthesis is necessary for intestinal colonization of Salmonella Typhimurium in chicks

et al. 2017

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pyrE (STM3733) encodes orotate phosphoribosyltransferase (OPRTase; EC 2.4.2.10), the fifth enzyme of the de novo pyrimidine biosynthetic pathway. We identified a ΔpyrE mutant as under selection in screening of a Salmonella mutant library in 4-day old chicks. Here, we confirm that a ΔpyrE mutant colonizes 4-day old chicks poorly in competitive infection with isogenic wild type, and that the ability of this mutant to colonize chicks could be restored by providing a copy of pyrE in trans. We further show that our ΔpyrE mutant grows poorly in nutrient poor conditions in vitro, and that the ability of this mutant to grow is restored, both in vitro and in chicks, when precursors to the pyrimidine salvage pathway were provided. This finding suggests that the environment in the chick intestine during our infections lacks sufficient precursors of the pyrimidine salvage pathway to support Salmonella growth. Finally, we show that the colonization defect of a ΔpyrE mutant during infection occurs in to chicks, but not in CBA/J mice or ligated ileal loops in calves. Our data suggest that de novo pyrimidine synthesis is necessary for colonization of Salmonella Typhimurium in the chick, and that the salvage pathway is not used in this niche.

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“…In a rat model of short bowel syndrome, intravenous (IV) administration of OG‐VI, a PN formula supplemented with a nucleoside‐nucleotide mixture (inosine, 30 mmol/L; GMP, 30 mmol/L; cytidine, 30 mmol/L; uridine, 22.5 mmol/L; and thymidine, 7.4 mmol/L), increased jejunal villus height and cell proliferation 56 . Also, in a similar model of short bowel syndrome, dietary supplementation with orotate and uracil increased jejunal adaptive growth after massive small bowel resection 66 …”

Section: Representative Animal Studies With Nucleotidesmentioning

confidence: 99%

The Role of Nucleotides in the Immune and Gastrointestinal Systems

2012

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Nucleotides are low molecular weight biological molecules key to biochemical processes. Sources include de novo synthesis, recovery via salvage mechanisms, and dietary intakes. Although endogenous production serves as the main nucleotide source, evidence suggests that exogenous sources are essential to immune competence, intestinal development, and recovery. Dietary nucleotides serve a marked role in rapidly proliferating cells where they are necessary for optimal function. Accordingly, dietary nucleotides are deemed conditionally essential in the presence of various physiological stresses, including growth and development, recovery from injury, infection, and certain disease states. Clinical studies that evaluated nutrition formulations of nucleotides in combination with other specific nutrient substances demonstrated improved clinical outcomes in patients characterized as critically ill, injured, immune suppressed, or with chronic gastrointestinal conditions. However, conclusions regarding specific benefits of nucleotides are limited. Scientific substantiation of nucleotide supplementation in infant formula has been reported to improve the maturation and development of the intestinal tract as well as immune function. All medical nutrition products except for one immune-modulating formulation are devoid of nucleotides. In an effort to build on this, the current review presents the data to support potential clinical applications for nucleotides in enteral nutrition that may contribute to improved outcomes in physiologically stressed patients.

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Dietary Supplementation With Orotate and Uracil Increases Adaptive Growth of Jejunal Mucosa After Massive Small Bowel Resection in Rats

Cited by 11 publications

References 45 publications

Fecal microbiota signatures of adult patients with different types of short bowel syndrome

Fecal microbiota signatures of adult patients with different types of short bowel syndrome

De novo pyrimidine synthesis is necessary for intestinal colonization of Salmonella Typhimurium in chicks

The Role of Nucleotides in the Immune and Gastrointestinal Systems

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