Soy-Derived Di- and Tripeptides Alleviate Colon and Ileum Inflammation in Pigs with Dextran Sodium Sulfate-Induced Colitis3

Abstract

We evaluated the antiinflammatory activity of soy-derived di- and tripeptides in a dextran sodium sulfate (DSS)-induced pig model of intestinal inflammation. In the DSS-positive control (POS) and DSS-positive with soy peptide treatment (SOY) groups (n = 6/group), DSS was administered to piglets via i.g. catheter for 5 d, followed by a 5-d administration of saline or soy-derived peptides, respectively. A negative control (NEG) group received saline in lieu of the DSS and soy peptides. The severity of inflammation was assessed by clinical signs, morphological and histological measurements, gut permeability, and neutrophil infiltration. Local production of TNF and IL6 were measured by ELISA, colonic and ileal inflammatory gene expression were assessed by real-time RT-PCR, and CD4+CD25+ lymphocyte populations were analyzed by flow cytometry. Crypt elongation and muscle thickness, d-mannitol gut permeation, colonic expression of the inflammatory mediators IFNG, IL1B, TNF, RORC, and IL17A as well as the FOXP3 T-regulatory transcription factor, and myeloperoxidase activity were lower (P < 0.05) in the SOY pigs than in POS pigs. Messenger RNA levels of ileal IFNG, TNF, IL12B, and IL17A were lower (P < 0.05) and FOXP3 expression was greater (P < 0.05) in SOY piglets than in the POS group. In the mesenteric lymph nodes, CD4+CD25+ T cells were higher (P < 0.05) in both the POS and SOY groups than in NEG controls. Soy-derived peptides exert antiinflammatory activity in vivo, suggesting their usefulness for the treatment of inflammatory disorders.

The Anti-atherosclerotic Dipeptide, Trp-His, Reduces Intestinal Inflammation through the Blockade of L-Type Ca2+ Channels

“…31 Our previous studies have demonstrated that dietary di/tripeptides could attenuate the development of colitis via down-regulating the expression of pro-inflammatory mediators in animal models of colitis. 8,9,12 Here, we observed that Trp-His reduced DSS-induced colitis signs, including BW loss, colon shortening, and diarrhea, and attenuated the local expression of TNF-α, IL-6, IL-1β, IFN-γ, and MCP-1 in the colon of DSS-treated mice. These results are consistent with a previous study which demonstrated that tripeptide Val-Pro-Tyr 9 at a similar dose could lessen the severity of colitis in DSS-treated mice.…”

Disease Severity and Immune Activity Relate to Distinct Interkingdom Gut Microbiome States in Ethnically Distinct Ulcerative Colitis Patients

“…6; see Table S4b to d) (18, 20). In contrast, lower disease severity MCSs (MCS2, -3, and -4) were enriched for a range of potentially protective dipeptides (including anti-inflammatory alanyl-glutamine) (21, 22), γ-glutamyl dipeptides indicative of improved oxidative stress coping mechanisms (23), and antioxidant immunosuppressive myo -inositol (24, 25). These observed differences in gut luminal metabolic programming between MCSs associated with high and low UC severities indicate the existence of putative mechanisms to control inflammation in patients with less severe disease.…”

“…While the metabolome of high disease severity MCS1 indicated conditions of high oxidative stress, that of UC MCSs associated with lower disease severity (MCS2 to -4) exhibited an increased capacity for ROS quenching due to enhanced γ-glutamyltransferase activity indicated by enrichment of γ-glutamyl amino acids (critical for maintaining glutathione levels) and high concentrations of superoxide scavenging myo -inositol (23, 24). Metabolic signatures indicative of immunosuppressive activity, such as enrichment of anti-inflammatory dipeptides (i.e., alanyl-glutamine) and myo -inositol (both of which decrease the expression of proinflammatory cytokines and reduce leukocyte recruitment in animal models of colitis) (21, 22, 25), were also observed in MCS2 to -4 with lower disease severity. This suggests that the specific metabolic productivity associated with each MCS may govern host immune activity and resulting differences in UC severity.…”

γ-Glutamyl cysteine and γ-glutamyl valine inhibit TNF-α signaling in intestinal epithelial cells and reduce inflammation in a mouse model of colitis via allosteric activation of the calcium-sensing receptor

“…DSS causes damage to the intestinal epithelium and impairs gut barrier function by activating the NF-κB pathway, leading to mucosal inflammation and ulceration, neutrophil infiltration, colon shortening and diarrhea [47,48]. We have previously shown that dietary di-and tri-peptides could reduce the severity of inflammation and down-regulate the expression of proinflammatory mediators in animal models of colitis [26,49]. Here, treatment with γ-EC and γ-EV reduced DSS-induced clinical colitis signs, colon shortening, and histological damage.…”