Anthocyanins in chronic inflammatory bowel disease in rats

PhD Thesis


Ghattamaneni, Naga Koteswara Rao. 2018. Anthocyanins in chronic inflammatory bowel disease in rats. PhD Thesis Doctor of Philosophy. University of Southern Queensland. https://doi.org/10.26192/5c09fb18f0cd2
Title

Anthocyanins in chronic inflammatory bowel disease in rats

TypePhD Thesis
Authors
AuthorGhattamaneni, Naga Koteswara Rao
SupervisorBrown, Lindsay
Panchal, Sunil K.
Institution of OriginUniversity of Southern Queensland
Qualification NameDoctor of Philosophy
Number of Pages147
Year2018
Digital Object Identifier (DOI)https://doi.org/10.26192/5c09fb18f0cd2
Abstract

Inflammatory Bowel Disease (IBD), including Crohn’s disease and ulcerative colitis, is an uncontrolled inflammation of the gastrointestinal tract with unclear aetiology affecting over 85,000 Australians and 5 million globally. IBD produces symptoms such as weight loss, bloody diarrhoea and severe abdominal pain. Multiple factors are involved in IBD pathogenesis including genetic predisposition, gut microbial imbalance, mucosal barrier malfunction, immune system dysfunction and environmental factors.

Current drug therapy for IBD includes sulphasalazine, aminosalicylates, corticosteroids, tumour necrosis factor blockers, immunomodulators (azathioprinemercaptopurine/
methotrexate), anti-integrins alpha4beta2 (vedolizumab), antiinterleukin-12 (ustekinumab), and small molecules including janus kinase inhibitor (tofacitinib). As nutrition can influence some of the causative factors, dietary modulation in IBD patients may be a preventive and therapeutic approach. In particular, anthocyanins such as cyanidin 3-glucoside (C3G) present in common foods such as Queen Garnet plum and purple carrots and pelargonidin 3-glucoside (P3G) in strawberry have anti-inflammatory activities that may be effective in IBD. The aim of my thesis is to understand whether these anthocyanin-containing functional foods improve the structure and function of the gastrointestinal tract, and improve gut bacteria in a rat model of chronic IBD.

The first objective of my thesis was to mimic chronic human IBD in rats. I developed a model of reversible chronic IBD in young male Wistar rats using 0.5% dextran sodium sulphate (DSS) in drinking water for 12 weeks. DSS induced IBD with increased diarrhoea, haematochezia (passage of fresh blood through the anus, usually with stools), infiltration of inflammatory cells in ileum and colon, depletion of mucosal epithelial layer including villi, crypts, goblet cells, and gut microbiota imbalance with increased Proteobacteria phylum and decreased commensal bacteria. IBD symptoms were reversed with replacement of 0.5% DSS with water or the standard IBD drug treatment, sulphasalazine (300 mg/kg body weight/day) for the final 6 weeks.

The second objective was to investigate the effects of functional foods to attenuate IBD in the rat model. For the last 6 weeks of the protocol, either Queen Garnet plum juice, purple carrot juice or pure C3G at 8mg/kg/day, or strawberry powder at 8mg P3G/kg/day was added in the food to the rats fed with either 0% or 0.5% DSS water. Queen Garnet plum, purple carrot and C3G improved IBD symptoms with reduced diarrhoea and haematochezia. The ileum and colon showed reduced infiltration of inflammatory cells and increased villi length and crypt depth. C3G improved the gut bacteria homeostasis. Similarly, P3G-containing strawberry mitigated the signs of IBD with reduced stool bleeding and diarrhoea, improved ileum and colon structure, suppressed infiltration of inflammatory cells and restored goblet cells. C3G and P3G were as effective as the standard drug sulphasalazine in this model suggesting their promising role in human IBD therapy.

My PhD thesis concludes that functional foods containing anthocyanins may be an alternate or complementary treatment for IBD patients owing to their anti-inflammatory activity, and the ability to balance gut bacteria. Further mechanistic studies and clinical trials are warranted for their inclusion in complementary therapy of human IBD.

Keywordsinflammatory bowel disease, dextran sodium sulphate, anthocyanins, Queen Garnet plums, purple carrots, strawberries
ANZSRC Field of Research 2020321004. Nutritional science
321401. Basic pharmacology
Byline AffiliationsInstitute for Agriculture and the Environment
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