The effects of multi-strain probiotics on liver disease

Briskey, David (2015). The effects of multi-strain probiotics on liver disease PhD Thesis, School of Medicine, The University of Queensland. doi:10.14264/uql.2015.290

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Author Briskey, David
Thesis Title The effects of multi-strain probiotics on liver disease
School, Centre or Institute School of Medicine
Institution The University of Queensland
DOI 10.14264/uql.2015.290
Publication date 2015-01-30
Thesis type PhD Thesis
Open Access Status Other
Supervisor Luis Vitetta
Jonathan Peake
Total pages 207
Language eng
Subjects 119999 Medical and Health Sciences not elsewhere classified
0601 Biochemistry and Cell Biology
110104 Medical Biochemistry: Lipids
Formatted abstract
The microbiome in the human gastrointestinal tract (GIT) is the largest body community of bacteria. In conjunction within an appropriate internal milieu, the microbiome induces the development of regulated pro– and anti–inflammatory signals that promote immunological tolerance. In addition, microbial interactions provide cues for upholding metabolic regulations and controlling and regulating GIT inflammation. Failure to regulate inflammatory responses can increase the risk of developing inflammatory conditions such as Inflammatory Bowel Diseases (IBD) or Irritable Bowel Syndrome (IBS). Disruption to the microbiome homeostasis can also affect other end–organs (e.g., liver, kidneys). For example, the liver receives 70% of its blood supply from the GIT, making regulation of the gut-liver-axis vital. Inflammation of the GIT may lead to inflammatory conditions of the liver and the development of diseases such as non-alcoholic fatty liver disease (NAFLD). The first study in this thesis examined the effects of a multi–strain probiotics supplement that was administered to mice prone to tumour development (atm-/-) and housed in a ‘dirty’ environment. This study proved unsuccessful due to uncontrollable changes in animal housing conditions. The changes limited the exposure of mice to pathogens that have previously been reported to accelerate tumour development. The second study investigated the effects of a multi–strain probiotics supplement that was administered to mice fed a high fat diet (HFD). The results suggested that the multi–strain probiotic investigated may assist with reducing HFD induced steatosis and lipid disposal by reducing the accumulation of fat deposits in the liver and preventing reductions in tight junction proteins ZO-1 and ZO-2. The third study investigated the effectiveness of a multi–strain probiotics supplement in mice on a HFD that were prone to iron overload (hemochromatosis). This study showed that a multi-strain probiotic supplement had reduced efficacy in the presence of high iron concentrations. Probiotics fed to hfe-/- mice partly rescued genes involved in lipid metabolism (Cpt1, Lfabp, AdipoR2), hepatic iron concentration, proteins involved in iron uptake (Tfr2), serum ALT, AST and triglycerides. However, probiotics did not alter serum cholesterol, hepatic lipid peroxidation, triglycerides, genes involved in lipid metabolism (PPAR-α, PPAR-γ, LDLr, CD36) and proteins involved in iron uptake (Tfr1). The fourth study investigated the effectiveness of curcumin, vitamin E or a combination of the two in both wild type and mice prone to iron overload (hemochromatosis). The combination of curcumin (CU) and vitamin E (VE) proved to be the most effective for reducing the effects of a HFD. Curcumin plus vitamin E (CUVE) reduced total body and liver weight and reduced the severity of steatosis and liver injury. Treatment groups CU or VE alone showed reduced fat deposits; however, the combination treatment, CUVE, resulted in a greater reduction of both macro- and micro-vesicular fat deposits and the degree of change was similar to the chow group. However, nothing compared with simply returning the animals to a healthy, balanced diet. Removal of the HFD resulted in a reduction of body and liver weight and a return to normal liver pathology in 80-90% of mice. These findings propose that neither probiotics, curcumin, vitamin E or a combination treatment is a panacea for over consumption of calories through a high saturated fat diet in the hope of down–regulating GIT inflammation and or liver fatty acid metabolism. However, they may provide a therapeutic measure whereby there is a significant reduction in risk for NAFLD progression.
Keyword Probiotics
Fatty liver disease
Inflammation
Lipid Peroxidation
Cell signaling
High fat diet (HFD)
High iron

Document type: Thesis
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Created: Mon, 19 Jan 2015, 21:58:17 EST by David Briskey on behalf of Scholarly Communication and Digitisation Service