Beneficial Effects of Resveratrol Against Colitis and Colorectal Cancer Mediated by the Host Microbiome, Epigenome, and Immune Response

Resveratrol, a natural polyphenol compound found in red wine, the skins of grapes, and other plant products, has been used as a traditional medicine for thousands of years throughout human history, but current research has revealed this natural component is capable of modulating a variety of immunological, microbial, and epigenetic mechanisms to improve overall health and well-being of hosts that consume it. Colitis, an inflammatory bowel disease characterized by chronic inflammation in the colon and rectum, which has been associated with colon cancer. This cancer incidence is rising in younger adults in the US. Thus, newer approaches to prevent colitis and colon cancer are critical. In this dissertation, data and evidence is presented which demonstrate that resveratrol, natural polyphenol can attenuate murine models of colitis and prevent colitis- associated colon cancer. In addition, in-depth mechanistic studies will provide evidence that resveratrol suppresses inflammation in the colon by regulating the host-gut microbiome, as well as inducing epigenetic changes via modulation of small noncoding RNA molecules that target key gene transcripts involved in key immunologic processes

Role of anti-inflammatory interleukin 10 in asymptomatic heartworm infection (Dirofilariasis) in dogs

Background: Dirofilaria immitis causes heartworm disease (HWD), a vector-borne zoonotic disease that primarily affects dogs and cats. Occasionally, human beings were reported to be infected as well. The current study aims to discover the asymptomatic dirofilariasis infection in dogs. In addition, to determine the prevalence of heartworm disease and the role of anti-inflammatory interleukin 10 (IL10) in developing the disease. Household dogs were selected from 10 veterinary clinics throughout Basrah, south of Iraq.Methods: The study included 117 dogs older than 12 months, none of them had received heartworm vaccinations, and all of them lived in their owners’ houses for at least 9 months. Animal ethics instructions were followed after the owner’s consent was obtained.  Physical and biochemical examinations were conducted including the examination of circulating antigens of microfilaria. The levels of anti-inflammatory IL10 and pro-inflammatory IL17, IL4, and IFN-γ were measured using ELISA tests. Descriptive statistics were used to evaluate the prevalence and the clinical and immunological results of the study.Results: Canine heartworm disease prevalence was 29.05% (34 out of 117). The physical examination showed normal vital signs for both infected and non-infected dogs. A significant elevation in the total WBC count was noticed in the infected group.  On the other hand, a significant decrease in RBCs count and hemoglobin was found in the infected group. There were neither changes in the platelet count nor the liver enzymes concentration between infected and non-infected groups.  A significant increase in anti-inflammatory interleukin 10 level and a significant decrease in pro-inflammatory IL17, IL4, and IFN-γ were noticed in the infected dogs. Conclusion: It is concluded that dirofilariasis infection is considered to be a serious life-threatening disease for dogs in Iraq. Therefore, a periodic test for heartworm infection every six months is recommended to eradicate heartworm infestations. The infected animals must be treated according to the American Heartworm Association recommendations

Alterations in the Gut Microbiome and Suppression of Histone Deacetylases by Resveratrol Are Associated with Attenuation of Colonic Inflammation and Protection Against Colorectal Cancer

Inflammatory bowel disease (IBD) is known to significantly increase the risk for development of colorectal cancer (CRC), suggesting inflammation and cancer development are closely intertwined. Thus, agents that suppress inflammation may prevent the onset of cancer. In the current study, we used resveratrol, an anti-inflammatory stilbenoid, to study the role of microbiota in preventing inflammation-driven CRC. Resveratrol treatment in the azoxymethane (AOM) and dextran sodium sulphate (DSS) CRC murine model caused an increase in anti-inflammatory CD4 + FOXP3 + (Tregs) and CD4 + IL10 + cells, a decrease in proinflammatory Th1 and Th17 cells, and attenuated CRC development. Gut microbial profile studies demonstrated that resveratrol altered the gut microbiome and short chain fatty acid (SCFA), with modest increases in n-butyric acid and a potential butyrate precursor isobutyric acid. Fecal transfer from resveratrol-treated CRC mice and butyrate supplementation resulted in attenuation of disease and suppression of the inflammatory T cell response. Data also revealed both resveratrol and sodium butyrate (BUT) were capable of inhibiting histone deacetylases (HDACs), correlating with Treg induction. Analysis of The Cancer Genome Atlas (TCGA) datasets revealed increased expression of Treg-specific transcription factor FoxP3 or anti-inflammatory IL-10 resulted in an increase in 5-year survival of patients with CRC. These data suggest that alterations in the gut microbiome lead to an anti-inflammatory T cell response, leading to attenuation of inflammation-driven CRC