Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis

Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT). Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI) ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT) mice and mice lacking the mdr1a gene (KO) were fed diets supplemented with either SBI (2% w/w) or milk proteins (Control diet), from day 21 (weaning) until day 56. Leucocytes in mesenteric lymph nodes (MLN) and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05). The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05) and SBI supplementation reduced this variable (p < 0.05). The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05). In the colon of KO mice, there was an increased production of mucosal proinflammatory cytokines such as IL-2 (2-fold), IL-6 (26-fold) and IL-17 (19-fold), and of chemokines MIP-1β (4.5-fold) and MCP-1 (7.2-fold). These effects were significantly prevented by SBI (p < 0.05). SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis

Randomized Study of the Effect of Vitamin D and Omega-3 Fatty Acids Cosupplementation as Adjuvant Chemotherapy on Inflammation and Nutritional Status in Colorectal Cancer Patients

This study aimed to evaluate the effects of vitamin D3 and omega-3 fatty acids cosupplementation on inflammation and nutritional status in colorectal cancer patients. In this clinical trial, 81 colorectal cancer patients were randomly assigned into four groups: (1) control group: receiving a vitamin D3 placebo weekly + omega-3 fatty acid placebo capsules daily; (2) omega-3 fatty acid group: receiving 2 omega-3 fatty acid capsules (each capsule containing 330 mg of omega-3 fatty acids) daily + a vitamin D3 placebo weekly; (3) vitamin D group: receiving a 50,000 IU vitamin D3 soft gel weekly + 2 omega-3 fatty acid placebo capsules daily; (4) cosupplementation group: receiving a 50,000 IU vitamin D3 soft gel weekly + 2 omega-3 fatty acids capsules daily for 8 weeks. Before and after the intervention, height, weight, fat-free mass (FFM), serum levels of 25(OH)D, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6), C-reactive protein (CRP), and albumin, were measured. After 8 weeks of intervention, patients who received combined vitamin D3 and omega-3 fatty acids supplements compared with omega-3, vitamin D3, and placebo groups had significantly decreased CRP and TNF-α. In addition, serum level of IL-6 was decreased significantly in omega-3, vitamin D3, and cosupplementation groups compared with baseline. Regarding nutritional status, weight, BMI, and FFM were increased significantly in vitamin D3, omega-3, and cosupplementation groups at the end of the intervention. Vitamin D3 plus omega-3 fatty acids cosupplementation in colorectal cancer patients has beneficial impacts on inflammation and nutritional status. © 2019, © 2019 Taylor & Francis Group, LLC

Chemoprevention of colorectal cancer

Colorectal cancer is a major cause of mortality and treatment costs are considerable. Advocating lifestyle modification, faecal occult blood testing and surveillance colonoscopy in appropriate populations are already in practice. A developing concept is chemoprevention. Several models of carcinogenesis in colorectal cancer have been developed and there is an increasing database on the major molecular mechanisms involved in carcinogenesis mainly from preclinical experiments and phase I trials. There have been several large epidemiological and observational studies to evaluate possible protective effects of >200 agents. More recently, case-control and cohort studies and well-conceived, phase II/III clinical trials have been done or are under way to evaluate putative chemopreventive agents including established drugs like aspirin and non-steroidal anti-inflammatory drugs (NSAIDs), 5-aminosalicylates and statins; more controversial drugs like cyclo-oxygenase-2 (COX-2) inhibitors, ursodeoxycholic acid; various vitamins and micronutrients including calcium, selenium, folic acid, and dietary fibre, fat and protein content. Despite promising outcome in preclinical studies, there is currently very limited data from well-controlled and appropriately powered clinical studies. The most promising agents currently are aspirin, traditional NSAIDs and COX-2 inhibitors. The recent reports of cardiovascular risks of the COX-2 inhibitors and some traditional NSAIDs have resulted in stagnation of the field. Pending the expected release of results from several phase III trials in the near future, chemoprevention for colorectal cancer can only be practically considered in the very-high-risk population like those with familial adenomatous polyposis and ulcerative colitis, in conjunction with surveillance colonoscopy. This article reviews the major models of colorectal carcinogenesis, the concept of chemoprevention with special reference to colorectal cancer and the current state of clinical literature and the future direction of colorectal cancer chemoprevention for both researcher and clinician alike. Copyright © 2007 S. Karger AG