Soluble Protein Hydrolysate Ameliorates Gastrointestinal Inflammation and Injury in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in Mice.

Inflammatory bowel diseases (IBD) are chronic, recurring gastrointestinal diseases that severely impair health and quality of life. Although therapeutic options have significantly expanded in recent years, there is no effective therapy for a complete and permanent cure for IBD. Well tolerated dietary interventions to improve gastrointestinal health in IBD would be a welcome advance especially with anticipated favorable tolerability and affordability. Soluble protein hydrolysate (SPH) is produced by the enzymatic hydrolysis of commercial food industry salmon offcuts (consisting of the head, backbone and skin) and contains a multitude of bioactive peptides including those with anti-oxidant properties. This study aimed to investigate whether SPH ameliorates gastrointestinal injury in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Mice were randomly assigned to four groups: Control (no colitis), Colitis, Colitis/CP (with control peptide treatment), and Colitis/SPH (with SPH treatment). Colitis was induced by cutaneous sensitization with 1% TNBS on day -8 followed by 2.5% TNBS enema challenge on day 0. Control peptides and SPH were provided to the mice in the Colitis/CP or Colitis/SPH group respectively by drinking water at the final concentration of 2% w/v daily from day -10 to day 4. Then, the colon was harvested on day 4 and examined macro- and microscopically. Relevant measures included disease activity index (DAI), colon histology injury, immune cells infiltration, pro- and anti-inflammatory cytokines and anti-oxidative gene expression. It was found that SPH treatment decreased the DAI score and colon tissue injury when compared to the colitis-only and CP groups. The protective mechanisms of SPH were associated with reduced infiltration of CD4+ T, CD8+ T and B220+ B lymphocytes but not macrophages, downregulated pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6), and upregulated anti-inflammatory cytokines (transforming growth factor-ß1 and interleukin-10) in the colon tissue. Moreover, the upregulation of anti-oxidative genes, including ferritin heavy chain 1, heme oxygenase 1, NAD(P)H quinone oxidoreductase 1, and superoxide dismutase 1, in the colons of colitis/SPH group was observed compared with the control peptide treatment group. In conclusion, the protective mechanism of SPH is associated with anti-inflammatory and anti-oxidative effects as demonstrated herein in an established mice model of colitis. Clinical studies with SPH as a potential functional food for the prevention or as an adjuvant therapy in IBD may add an effective and targeted diet-based approach to IBD management in the future.

Electroacupuncture to Increase Neuronal Stem Cell Growth.

Background: Neuropathic intestinal disorders continue to pose a significant burden, and current treatment options do not target the underlying cellular deficiencies. The goal of this study is to determine whether acupuncture and electroacupuncture (EA) can affect the growth of neuronal cells. Methods: Three groups of Lewis rats received 25 minutes of acupuncture twice a week for 10 weeks. The 3 groups of rats received treatment with either sham acupuncture (SA), real acupuncture (RA), or EA. After 10 weeks of treatment, skin and intestinal tissue were collected and analyzed for histology and mRNA expression of neuronal marker genes. Results: Compared with rats that received SA, rats that received RA and EA showed a significant increase in the mRNA expression levels of multiple neuronal genes in the skin. No significant histologic changes were seen. Conclusions: Acupuncture and EA result in significant changes in the expression of genes implicated as markers for neural stem cells, neural cell development, and neurons. This may, therefore, provide a novel avenue for developing treatments in patients suffering from intestinal aganglionic and neuropathic diseases.

Intravenous Fish Oil and Serum Fatty Acid Profiles in Pediatric Patients With Intestinal Failure-Associated Liver Disease.

BACKGROUND: Intravenous fish oil (FO) treats pediatric intestinal failure-associated liver disease (IFALD). There are concerns that a lipid emulsion composed of ω-3 fatty acids will cause an essential fatty acid deficiency (EFAD). This study's objective was to quantify the risk for abnormal fatty acid concentrations in children treated with FO. METHODS: Inclusion criteria for this prospective study were children with intestinal failure. Intravenous soybean oil (SO) was replaced with FO for no longer than 6 months. Serum fatty acids were analyzed using linear and logistic models, and compared with age-based norms to determine the percentage of subjects with low and high concentrations. RESULTS: Subjects (n = 17) started receiving FO at a median of 3.6 months (interquartile range 2.4-9.6 months). Over time, α-linolenic, linoleic, arachidonic, and Mead acid decreased, whereas docosahexaenoic and eicosapentaenoic acid increased (P < 0.001 for all). Triene-tetraene ratios remained unchanged (P = 1). Although subjects were 1.8 times more likely to develop a low linoleic acid while receiving FO vs SO (95% CI: 1.4-2.3, P < 0.01), there was not a significant risk for low arachidonic acid. Subjects were 1.6 times more likely to develop high docosahexaenoic acid while receiving FO vs SO; however, this was not significant (95% CI: 0.9-2.6, P = 0.08). CONCLUSION: In this cohort of parenteral nutrition-dependent children, switching from SO to FO led to a decrease in essential fatty acid concentrations, but an EFAD was not evident. Low and high levels of fatty acids developed. Further investigation is needed to clarify if this is clinically significant.

Long-Term Outcomes in Children With Intestinal Failure-Associated Liver Disease Treated With 6 Months of Intravenous Fish Oil Followed by Resumption of Intravenous Soybean Oil.

BACKGROUND: Intravenous soybean oil (SO) is a commonly used lipid emulsion for children with intestinal failure (IF); however, it is associated with IF-associated liver disease (IFALD). Studies have demonstrated that intravenous fish oil (FO) is an effective treatment for IFALD. However, there is a lack of long-term data on children who stop FO and resume SO. This study's objective was to investigate our institution's outcomes for children with IFALD treated with 6 months of FO and who then restarted SO. METHODS: Inclusion criteria for FO included children with IFALD. Parenteral nutrition (PN)-dependent children resumed SO after FO and were prospectively followed for 4.5 years or until death, transplant, or PN discontinuation. The primary outcome was the cumulative incidence rate (CIR) for cholestasis after FO. RESULTS: Forty-eight subjects received FO, and conjugated bilirubin decreased over time (-0.22 mg/dL/week; 95% confidence interval [CI]: -0.25, -0.19; P < .001). The CIR for cholestasis resolution after 6 months of FO was 71% (95% CI: 54%, 82%). Twenty-seven subjects resumed SO and were followed for a median of 16 months (range 3-51 months). While the CIR for enteral autonomy after 3 years of follow-up was 40% (95% CI: 17%, 26%), the CIR for cholestasis and transplant was 26% (95% CI: 8%, 47%) and 6% (95% CI: 0.3%, 25%), respectively. CONCLUSION: In this study, FO effectively treated cholestasis, and SO resumption was associated with cholestasis redevelopment in nearly one-fourth of subjects. Long-term FO may be warranted to prevent end-stage liver disease.

Pediatric intestinal failure-associated liver disease is reversed with 6 months of intravenous fish oil.

BACKGROUND: Studies have suggested that when intravenous (IV) soybean oil (SO) is replaced with fish oil (FO), direct hyperbilirubinemia is more likely to resolve. The necessary duration of FO has not been established. This study seeks to determine if 24 weeks of FO is an effective and safe therapy for intestinal failure-associated liver disease (IFALD). MATERIALS AND METHODS: This is a clinical trial using patients with IFALD between the ages of 2 weeks and 18 years. SO was replaced with FO (1 g/kg/d) in 10 patients who were receiving most of their calories from parenteral nutrition (PN). Patients were compared with 20 historic controls receiving SO. SO for both groups was prescribed by the primary medical team at variable doses. The primary outcome was time to reversal of cholestasis. Secondary outcomes were death, transplant, and full enteral feeds. Safety measurements included growth, essential fatty acid deficiency, and laboratory markers to assess bleeding risk. RESULTS: The Kaplan-Meier method estimated that 75% in the FO group would experience resolution of cholestasis by 17 weeks vs 6% in the SO group (P < .0001). When compared with the SO group, the FO group had decreased serum direct bilirubin concentrations at weeks 8 (P = .03) and 12, 16, 20, and 24 weeks (P < .0001). Although length z score at the end of the study increased in the FO group compared with baseline (P = .03), there were no significant differences in other outcomes. CONCLUSIONS: A limited duration of FO appears to be safe and effective in reversing IFALD.

Short-term intravenous fish oil and pediatric intestinal failure associated liver disease: 3-year follow-up on liver function and nutrition.

Intravenous fish oil (FO) has changed the management of intestinal failure associated liver disease (IFALD). This report describes two IFALD patients who received FO for 5 and 10 months, respectively and reports on their 3-year follow-up.