Junqiang Tian

Treatment of vitamin D deficiency with UV light in patients with malabsorption syndromes: a case series

Background: Cystic fibrosis (CF) and short bowel syndrome (SBS) patients are unable to absorb vitamin D from the diet and thus are frequently found to be severely vitamin D deficient. We evaluated whether a commercial portable ultraviolet (UV) indoor tanning lamp that has a spectral output that mimics natural sunlight could raise circulating 25‐hydroxyvitamin D [25(OH)D] levels in subjects with CF and SBS.

Dietary glutamine and oral antibiotics each improve indexes of gut barrier function in rat short bowel syndrome

Short bowel syndrome (SBS) is associated with gut barrier dysfunction. We examined effects of dietary glutamine (GLN) or oral antibiotics (ABX) on indexes of gut barrier function in a rat model of SBS. Adult rats underwent a 60% distal small bowel + proximal colonic resection (RX) or bowel transection (TX; control). Rats were pair fed diets with or without l-GLN for 20 days after operation. Oral ABX (neomycin, metronidazole, and polymyxin B) were given in some RX rats fed control diet. Stool secretory immunoglobulin A (sIgA) was measured serially. On day 21, mesenteric lymph nodes (MLN) were cultured for gram-negative bacteria. IgA-positive plasma cells in jejunum, stool levels of flagellin- and lipopolysaccharide (LPS)-specific sIgA, and serum total, anti-flagellin- and anti-LPS IgG levels were determined. RX caused gram-negative bacterial translocation to MLN, increased serum total and anti-LPS IgG and increased stool total sIgA. After RX, dietary GLN tended to blunt bacterial translocation to MLN (-29%, P = NS) and significantly decreased anti-LPS IgG levels in serum, increased both stool and jejunal mucosal sIgA and increased stool anti-LPS-specific IgA. Oral ABX eliminated RX-induced bacterial translocation, significantly decreased total and anti-LPS IgG levels in serum, significantly decreased stool total IgA and increased stool LPS-specific IgA. Partial small bowel-colonic resection in rats is associated with gram-negative bacterial translocation from the gut and a concomitant adaptive immune response to LPS. These indexes of gut barrier dysfunction are ameliorated or blunted by administration of dietary GLN or oral ABX, respectively. Dietary GLN upregulates small bowel sIgA in this model.

Dietary Sulfur Amino Acid Supplementation Reduces Small Bowel Thiol/Disulfide Redox State and Stimulates Ileal Mucosal Growth after Massive Small Bowel Resection in Rats

Following massive small bowel resection in animal models, the remnant intestine undergoes a dynamic growth response termed intestinal adaptation. Cell growth and proliferation are intimately linked to cellular and extracellular thiol/disulfide redox states, as determined by glutathione (GSH) and GSH disulfide (GSSG) (the major cellular redox system in tissues), and cysteine (Cys) and its disulfide cystine (CySS) (the major redox system in plasma), respectively. The study was designed to determine whether dietary supplementation with sulfur amino acids (SAA) leads to a greater reduction in thiol/disulfide redox state in plasma and small bowel and colonic mucosa and alters gut mucosal growth in an established rat model of short bowel syndrome (SBS). Adult rats underwent 80% jejunal-ileal resection (RX) or small bowel transection (surgical control) and were pair-fed either isonitrogenous, isocaloric SAA-adequate (control) or SAA-supplemented diets (218% increase vs. control diet). Plasma and gut mucosal samples were obtained after 7 d and analyzed for Cys, CySS, GSH, and GSSG concentrations by HPLC. Redox status (E(h)) of the Cys/CySS and GSH/GSSG couples were calculated using the Nernst equation. SAA supplementation led to a greater reduction in E(h) GSH/GSSG in jejunal and ileal mucosa of resected rats compared with controls. Resected SAA-supplemented rats showed increased ileal adaptation (increased full-thickness wet weight, DNA, and protein content compared with RX control-fed rats; increased mucosal crypt depth and villus height compared with all other study groups). These data suggest that SAA supplementation has a trophic effect on ileal adaptation after massive small bowel resection in rats. This finding may have translational relevance as a therapeutic strategy in human SBS.

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

BACKGROUND Massive small-bowel resection (SBR) increases adaptive growth of residual intestine in animal models of short-bowel syndrome (SBS). Pyrimidine nucleotides are critical for DNA and RNA synthesis, but no previous study has evaluated whether supplementation of pyrimidines or their precursors in the diet enhances adaptive gut growth after SBR. This study determined growth responses in jejunal mucosa after 7 days of dietary supplementation with uracil, or its precursor, orotate, after massive SBR in rats. METHODS Sprague-Dawley rats ( approximately 200 g) underwent 80% jejunoileal resection (RX) or ileal transection (TX; control). Rats were pair-fed a purified (AIN-93G) powdered diet supplemented with or without 1% (wt/wt) orotate or uracil until killing at 7 days postsurgery. Defined jejunal segments were obtained for analysis of mucosal villus height (VH), crypt depth (CD), total mucosal height, bromodeoxyuridine (BrdU) incorporation, an index of cell proliferation, and full-thickness DNA and protein content as measures of intestinal adaptive growth. RESULTS Jejunal VH increased significantly with SBR, as expected, and orotate further stimulated this response. Jejunal CD and total mucosal height increased significantly with both orotate and uracil supplementation compared with resected animals receiving standard diet. Orotate administration also increased jejunal DNA content compared with the increase observed with SBR alone. Finally, orotate, but not uracil, supplementation increased BrdU incorporation compared with resected rats fed standard or uracil-supplemented diet after SBR. CONCLUSIONS Supplementation of oral diet with the pyrimidine precursor orotate and uracil stimulated adaptive jejunal growth after massive SBR in rats. Dietary orotate had more potent growth-stimulatory effects than uracil in this animal model. Dietary supplementation with orotate and uracil represents a novel nutrition approach to enhance small-bowel mucosal adaptive growth and absorptive capacity in SBS.

Intestinal redox status of major intracellular thiols in a rat model of chronic alcohol consumption.

BACKGROUND Alcohol consumption is associated with oxidative stress in multiple tissues in vivo, yet the effect of chronic alcohol intake on intestinal redox state has received little attention. In this study, we investigated the redox status of 2 major intracellular redox regulating couples: glutathione (GSH)/glutathione disulfide (GSSG) and cysteine (Cys)/cystine (CySS) in a rat model of chronic alcohol ingestion. METHODS Sprague-Dawley rats were fed the liquid Lieber-DeCarli diet consisting of 36% ethanol of total calories for 6 weeks. Control rats were pair-fed with an isocaloric, ethanol-free liquid diet. Defined mucosal samples from the jejunum, ileum, and colon were obtained and analyzed by high-performance liquid chromatography (HPLC) for GSH and Cys pool redox status. Mucosal free malondialdehyde (MDA) was measured as an indicator of lipid peroxidation. RESULTS In the ethanol-fed rats, Cys and mixed disulfide (GSH-Cys) were significantly decreased in all 3 segments of intestinal mucosa. Free MDA was increased in jejunal but not in ileal or colonic mucosa. Chronic ethanol ingestion significantly increased mucosal GSH concentration in association with a more reducing GSH/GSSG redox potential in the jejunum, but these indices were unchanged in the ileum. In the colon, chronic ethanol ingestion increased oxidant stress as suggested by decreased GSH and oxidized GSH/GSSG redox potential. CONCLUSIONS Chronic alcohol intake differentially alters the mucosal redox status in proximal to distal intestinal segments in rats. Such changes may reflect different adaptability of these intestinal segments to the oxidative stress challenge induced by chronic ethanol ingestion.