Black raspberries (BRB) are rich in anthocyanins with purported anti-inflammatory properties. However, it is not known whether dietary supplementation would ameliorate Western-diet enhanced gut inflammation and colon tumorigenesis. We employed a mouse model of colitis-associated colorectal cancer (CAC) to determine the effects of dietary supplementation with 5 to 10% (w/w) whole, freeze-dried BRB in male C57BL/6J mice fed either a standard healthy diet (AIN93G) or the total Western diet (TWD). In a pilot study, BRB suppressed colitis and colon tumorigenesis while also shifting the composition of the fecal microbiome in favor of taxa with purported health benefits, including Bifidobacterium pseudolongum. In a follow-up experiment using a 2 ´ 2 factorial design with AIN and TWD basal diets with and without 10% (w/w) BRB, supplementation with BRB reduced tumor multiplicity and increased colon length, irrespective of the basal diet, but it did not apparently affect colitis symptoms, colon inflammation or mucosal injury based on histopathological findings. However, BRB intake increased alpha diversity, altered beta diversity and changed the relative abundance of Erysipelotrichaceae, Bifidobacteriaceae, Streptococcaceae, Rikenellaceae, Ruminococcaceae and Akkermansiaceae, among others, of the fecal microbiome. Notably, changes in microbiome profiles were inconsistent with respect to the basal diet consumed. Overall, these studies provide equivocal evidence for in vivo anti-inflammatory effects of BRB on colitis and colon tumorigenesis; yet, BRB supplementation led to dynamic changes in the fecal microbiome composition over the course of disease development.
Epidemiological information relating to cardiac metastases is predominantly based on autopsy studies. The reported incidence ranges from 2.3-18.3%. It is usually found in the presence of widely disseminated disease. Here, a case of an isolated, asymptomatic cardiac metastasis from colonic adenocarcinoma is reported. The metastasis was detected later, following bowel resection and was not amenable to surgical resection. The patient is receiving ongoing care from the oncology team.
Objectives
Approximately 1.4 million people suffer from inflammatory bowel disease, which is a major risk factor for developing colitis associated colorectal cancer (CAC). Dietary interventions with the goal to reduce colon inflammation and encourage gut microbiome homeostasis may be a strategy to reduce the risk of CAC. The antioxidants and anti-inflammatory compounds present in black raspberries (BRB) have demonstrated protective effects in the colon epithelium and may alter the composition of the gut microbiome. Previously, we showed that dietary supplementation with black raspberries significantly suppressed colitis and colon tumorigenesis promoted by the consumption of a Western type diet in mice. The goal of this study was to compare the efficacy of dietary intervention with whole, freeze-dried black raspberries on colitis and colon tumorigenesis in mice consuming either a standard diet or a Western type diet that emulates typical U.S. nutrient intakes.
Methods
C57BL/6 J male and female mice were fed a standard diet (AIN93G) or the total Western diet (TWD) supplemented with 0 to 10% (w/w) black raspberry powder for a total of 16 weeks. All mice were dosed with axozymethane and provided 1% dextran sodium sulfate in drinking water for 10 days to promote colonic inflammation and tumorigenesis.
Results
As previously observed, mice fed TWD experienced more pronounced symptoms of colitis with a 40% increase in the disease activity index (DAI) score. Preliminary analyses suggest that dietary supplementation with 10% BRB suppressed the DAI score in mice fed TWD such that the colitis symptoms in these mice were not apparently different compared to the AIN93G-fed controls. However, addition of 10% BRB did not appear to provide a benefit to mice fed the AIN basal diet. Composition of the fecal microbiome over the course of disease development will be determined by standard 16S rRNA sequencing, and assessment of tumor outcome is ongoing.
Conclusions
Consumption of a Western type diet increased symptoms of colitis, whereas dietary supplementation with 10% BRB appeared to ameliorate TWD-enhanced colitis in mice.
Funding Sources
USDA NIFA Grant# 2018-67017-27516 and UAES Project UTA-1178.
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