The Anti-Inflammatory Effect of Spray-Dried Plasma Is Mediated by a Reduction in Mucosal Lymphocyte Activation and Infiltration in a Mouse Model of Intestinal Inflammation.

Spray-dried preparations from porcine and bovine plasma can alleviate mucosal inflammation in experimental models and improve symptoms in patients with enteropathy. In rodents, dietary supplementation with porcine spray-dried plasma (SDP) attenuates intestinal inflammation and improves the epithelial barrier function during intestinal inflammation induced by Staphylococcus aureus enterotoxin B (SEB). The aim of this study was to discern the molecular mechanisms involved in the anti-inflammatory effects of SDP. Male C57BL/6 mice were fed with 8% SDP or control diet (based on milk proteins) for two weeks, from weaning until day 33. On day 32, the mice were given a SEB dose (i.p., 25 µg/mouse) or vehicle. SEB administration increased cell recruitment to mesenteric lymph nodes and the percentage of activated Th lymphocytes and SDP prevented these effects). SDP supplementation increased the expression of interleukin 10 (IL-10) or transforming growth factor- ß (TGF-ß) compared to the SEB group. The SEB challenge increased six-fold the expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) and intercellular adhesion molecule 1 (ICAM-1); and these effects were attenuated by SDP supplementation. SEB also augmented NF-κB phosphorylation, an effect that was prevented by dietary SDP. Our results indicate that the anti-inflammatory effects of SDP involve the regulation of transcription factors and adhesion molecules that reduce intestinal cell infiltration and the degree of the inflammatory response.

Protective effect of Blumea lacera DC aerial parts in indomethacin-induced enterocolitis in rats.

Traditionally Blumea lacera DC is used to treat inflammation and bowel ailments. Lack of specific, curative treatment for IBD enticed us to investigate the therapeutic efficacy of ethanolic extract of aerial parts of Blumea lacera DC (EEBL) against indomethacin-induced enterocolitis. Male Wistar rats were divided into six groups (n = 5) and different doses of EEBL (100 and 200 mg/kg, p.o) and sulphasalazine (100 mg/kg, p.o) were administered for seven days. Enterocolitis was induced by two subsequent doses of indomethacin (7.5 mg/kg, s.c) on 7th and 8th day. Treatments were continued up to 12th day and sacrificed. The protective effect was assessed on the basis of macroscopic scores of ileum strips, changes in biochemical parameters such as serum lactate dehydrogenase (LDH), tissue myeloperoxidase (MPO), lipid peroxidation (LPO), and total thiols (TT). Further, activity was ascertained by histopathological evaluations. HPLC fingerprinting profiling of EEBL was also carried out. Pre-treatment with EEBL or sulphasalazine significantly attenuated the indomethacin-induced proximal ileal damage, elevated levels of serum LDH, tissue MPO, LPO and lower levels of TT. Further, observed activity of EEBL was well correlated with histopathological alterations. The results revealed the protective action of the title plant against the indomethacin-induced enterocolitis in rats, which might be attributed by its antioxidant, anti-inflammatory, antimicrobial, and membrane-stabilizing properties.

Case of antibiotic-associated diarrhea caused by Staphylococcus aureus enterocolitis.

PURPOSE: A case of Staphylococcus aureus enterocolitis (SEC) misdiagnosed as toxin-negative Clostridium difficile is reported. SUMMARY: An 82-year-old white man weighing 50 kg (body mass index, 16.8 kg/m(2)) was transported from an assisted living facility to the emergency department with the chief complaints of weakness, nausea, and diarrhea for one week and one bright-red stool on the morning of admission. Before hospital admission, he was treated for a urinary tract infection with ciprofloxacin 500 mg twice daily for 10 days. Stool cultures were negative for C. difficile but positive for S. aureus. The antimicrobial stewardship pharmacist recommended treatment with vancomycin 125 mg orally every 6 hours for staphylococcal colitis. Oral vancomycin was discontinued after three doses on the morning of hospital day 8 after a gastroenterology consultation. Within 48 hours of the discontinuation of oral vancomycin, the patient had eight stools per day. Vancomycin was reinitiated and the patient's symptoms began to again improve. On hospital day 19, the patient was discharged with a prescription for 7 more days of therapy with vancomycin (to complete a 15-day course) and a diagnosis of toxin-negative C. difficile, despite having symptoms consistent with SEC and an enteric culture positive for S. aureus. CONCLUSION: An 82-year-old man was transferred from an assisted living facility to the hospital with profuse diarrhea and dehydration. Enteric cultures were positive for methicillin-resistant S. aureus with multiple negative C. difficile toxin B assays. Appropriate therapy was delayed and the patient potentially misdiagnosed with toxin-negative C. difficile when the clinical symptoms and diagnostic testing were consistent with SEC.

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants.

BACKGROUND: In-home iron fortification for infants in developing countries is recommended for control of anaemia, but low absorption typically results in >80% of the iron passing into the colon. Iron is essential for growth and virulence of many pathogenic enterobacteria. We determined the effect of high and low dose in-home iron fortification on the infant gut microbiome and intestinal inflammation. METHODS: We performed two double-blind randomised controlled trials in 6-month-old Kenyan infants (n=115) consuming home-fortified maize porridge daily for 4 months. In the first, infants received a micronutrient powder (MNP) containing 2.5 mg iron as NaFeEDTA or the MNP without iron. In the second, they received a different MNP containing 12.5 mg iron as ferrous fumarate or the MNP without the iron. The primary outcome was gut microbiome composition analysed by 16S pyrosequencing and targeted real-time PCR (qPCR). Secondary outcomes included faecal calprotectin (marker of intestinal inflammation) and incidence of diarrhoea. We analysed the trials separately and combined. RESULTS: At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae but there were high prevalences of pathogens, including Salmonella Clostridium difficile, Clostridium perfringens, and pathogenic Escherichia coli. Using pyrosequencing, +FeMNPs increased enterobacteria, particularly Escherichia/Shigella (p=0.048), the enterobacteria/bifidobacteria ratio (p=0.020), and Clostridium (p=0.030). Most of these effects were confirmed using qPCR; for example, +FeMNPs increased pathogenic E. coli strains (p=0.029). +FeMNPs also increased faecal calprotectin (p=0.002). During the trial, 27.3% of infants in +12.5 mgFeMNP required treatment for diarrhoea versus 8.3% in -12.5 mgFeMNP (p=0.092). There were no study-related serious adverse events in either group. CONCLUSIONS: In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and causing intestinal inflammation. TRIAL REGISTRATION NUMBER: NCT01111864.

Neutropenic enterocolitis in a patient with colorectal carcinoma: unusual course after treatment with 5-fluorouracil and leucovorin--a case report.

BACKGROUND: Neutropenic enterocolitis is observed in approximately 25% of patients with acute leukemia, but has been reported rarely in patients with solid tumors. If treatment is not initiated promptly, the mortality is high. The incidence of this disease is rising in patients with hematologic malignancies. Increasing numbers of patients with solid tumors are subject to high dose chemotherapy regimens or new drugs known to cause severe neutropenia. Therefore, the frequency of this disease can be expected to increase. METHODS: The authors report a patient with colorectal carcinoma who developed neutropenic enterocolitis after treatment with 5-fluorouracil and leucovorin. RESULTS: The patient developed the typical clinical picture of abdominal pain, diarrhea, and neutropenia. The course was complicated by a recurrence of symptoms after initially successful antibiotic therapy without the patient receiving further chemotherapy. CONCLUSIONS: This case indicates that neutropenic enterocolitis may occur in patients with colorectal carcinoma receiving 5-fluorouracil and leucovorin.

Pectin-supplemented enteral diet reduces the severity of methotrexate induced enterocolitis in rats.

BACKGROUND: Administration of methotrexate (MTX) to rats fed an elemental diet results in a high mortality from severe enterocolitis. Previous studies have shown that pectin is an important precursor of substrates for intestinal structure and function and may facilitate intestinal recovery after enterocolitis. The aim of this study is to evaluate the effect of pectin on MTX-induced enterocolitis in rats. METHODS: Rats received intragastric infusion of either 1% pectin-supplemented or pectin-free elemental diet from the beginning of the study via a gastrostomy. On the 4th day animals received either MTX, 20 mg/kg intraperitoneally, or saline injection and were killed on the 7th day for sampling. RESULTS: Pectin supplementation significantly decreased body weight loss, organ water content, and intestinal myeloperoxidase levels and increased mucosal protein, DNA, and RNA content in enterocolitis rats. The intestinal permeability was increased by administration of MTX, and pectin supplementation significantly reversed the increased permeability in the distal small bowel and colon. Pectin supplementation also lowered the magnitude of bacterial translocation, decreased plasma endotoxin levels, and restored bowel microecology. CONCLUSIONS: Pectin significantly decreased MTX-induced intestinal injury and improved bowel integrity.

A significant methotrexate-glutamine pharmacokinetic interaction.

Previous studies indicate that glutamine-supplemented diets decrease the enterocolitis associated with methotrexate administration. The influence of glutamine on the pharmacokinetics of methotrexate and the formation of its major hepatic metabolite, 7-hydroxy-methotrexate was examined in 36 adult, female Lewis rats. Animals were randomly assigned to receive either a 3% glycine-supplemented solid diet (GLY; 25.0% protein; 17.6 kJ/g, or 4.2 kcal/g) or a 3% glutamine-supplemented solid diet (GLN; 25.0% protein; 17.6 kJ/g, or 4.2 kcal/g) ad libitum for 35 days. Animals were separated into two groups (serum methotrexate pharmacokinetics, n = 20; or methotrexate renal elimination, n = 16) and given a 10 mg/kg dose of methotrexate. There was a 25% decrease in mean methotrexate total serum clearance in the GLN group compared with the control group (0.63 +/- 0.09 L.h-1.kg-1 and 0.47 +/- 0.13 L.h-1.kg-1, respectively, p = 0.01). Renal methotrexate elimination was decreased by 65%. There was no significant difference in methotrexate volume of distribution or half-life between the two groups. Glutamine decreases methotrexate systemic clearance, thus exposing the host as well as the tumor to greater methotrexate concentrations.

Misoprostol accelerates colonic mucosal repair in acetic acid-induced colitis.

The objectives of this study were 1) to determine whether misoprostol (MISO) (prostaglandin E1 analog) pretreatment protects the colonic mucosa from the injurious effects of acetic acid by attenuating the initial injury or by enhancing the rate of repair and 2) to assess the relationship between the protective effect of MISO pretreatment and mucosal ornithine decarboxylase activity in the inflamed colon. We found that the intrarectal administration of acetic acid caused rapid and extensive injury to the colonic mucosa, such that mucosal permeability increased 88-, 75-, 26-, 7.5- and 9.3-fold at 1, 2, 6, 24 and 48 hr after the enema, respectively. Intrarectal pretreatment with 50 micrograms of MISO for 30 min did not attenuate the increase in mucosal permeability at 1 hr after enema; however, it did significantly reduce mucosal permeability by 50 to 60% at 2, 6 and 48 hr after enema. We also demonstrated that acetic acid produced an 8.4-fold increase in colonic myeloperoxidase activity and a 1.8-fold increase in colonic weight at 48 hr after enema. MISO significantly reduced the increases in both myeloperoxidase activity and colon weight. Ornithine decarboxylase activity in the descending colon of vehicle-pretreated animals increased significantly only at 24 hr after the acetic acid enema. In addition, MISO pretreatment followed by acetic acid enema resulted in significantly higher ornithine decarboxylase activities in the descending colon at 2 and 6 hr, compared with the vehicle plus acetic acid and MISO plus saline groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary manipulation of methotrexate-induced enterocolitis.

Administration of chemotherapy is limited by host toxicity, which is often manifested by severe enterocolitis. This study evaluated the effects of a liquid, elemental, chemically defined diet (ED) supplemented with 2% glutamine (Glu-ED) compared with a polypeptide diet (PPD) on the morbidity and mortality after methotrexate (MTX) administration. Fischer 344 rats (n = 80) were fed either a regular rat chow diet (RD), a 2% glycine supplemented elemental diet (Gly-ED), a 2% glutamine-supplemented elemental diet (GLU-ED), and a glycine-supplemented polypeptide diet(Gly-PPD) for 7 days prior to administration of MTX (20 mg/kg, ip). After 72 hours, eight rats per group were killed; portal vein and vena cava blood, mesenteric lymph nodes (MLN), liver, small intestine, and cecum were sampled for bacterial culture. Remaining animals were followed to calculate survival. One hundred percent of the Gly-PPD and 25% of the Glu-ED animals survived compared with 0% of the Gly-ED animals. Our data showed that ED resulted in an increased quantity of intestinal Gram-negative bacteria and diminished intestinal mucosal height and mucosal DNA/protein content. The polypeptide diet prevented intestinal mucosal atrophy, avoided MTX-induced enterocolitis and significantly improved animal survival compared with an elemental diet with or without glutamine supplementation.

A review of the effects of glutamine-enriched diets on experimentally induced enterocolitis.

Studies in animal models of enterocolitis have failed to confirm the purported metabolic and functional benefits of bowel rest induced by use of an elemental diet. Recent reports have demonstrated that glutamine-supplemented diets ameliorate or reverse many of the adverse effects of experimentally induced enterocolitis. Human studies are needed to confirm these findings.

Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis.

Administration of an elemental diet to rats given methotrexate (MTX), 20 mg/kg intraperitoneally (ip), results in 100% mortality from severe enterocolitis. Previous studies indicate that glutamine (GLN), which is not present in elemental diets, is the preferred oxidative substrate for the gut and may facilitate intestinal recovery after injury. This study investigated the effects of a glutamine-supplemented elemental diet (GLN-ED) on nutritional status, intestinal morphometry, bacterial translocation and survival in this lethal model of intestinal injury. Three experiments were performed. In the first experiment, rats received an intragastric elemental diet supplemented with either 2% GLN or an equivalent amount of glycine (Control). After 4 days animals received either MTX, 20 mg/kg ip, or saline ip and were killed 3 days later. The GLN-ED resulted in significantly decreased weight loss, improved nitrogen retention, and increased mucosal weight, protein, and DNA content of the jejunum and colon. In the second experiment rats were assigned to diet as in the first experiment, but all animals received MTX. Control diet animals died within 120 hrs of MTX administration. The GLN-ED group had significantly longer survival time and decreased mortality. In the third experiment animals were assigned to diet and MTX as in the first experiment. Ninety-six hrs later aortic blood cultures revealed enteric bacteremia in animals administered MTX. GLN-ED resulted in a significant reduction in the incidence of bacteremia. These experiments showed that a GLN-ED significantly improved nutritional status, decreased intestinal injury, decreased bacterial translocation, and resulted in improved survival in a lethal model of enterocolitis.