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Protecting the gut from the damaging consequences of obesity

Diets containing high levels of fat that lead to obesity, also damage the lining of the intestine. Here we are investigating strategies to limit this damage and its downstream consequences.

Obesity is considered to be a global epidemic, with prevalence increasing at an alarming rate in many parts of the world. According to the World Health Organisation (WHO) over 2.1 billion adults were estimated to be obese or overweight in 2016, with worldwide prevalence of obesity doubling since 1980. In Australia, two-thirds of the adult population is obese or overweight.

Damage at the level of the gut in obesity or in response to obesogenic diets has been associated with increased intestinal permeability, often referred to as “leaky gut”. Strong evidence points to gut leakiness, and consequent entry of endotoxins, as a contributing factor in the initiation of systemic low-grade chronic inflammation and organ damage.

In this project you will determine whether protection of enteric neurons and the intestinal barrier can improve gut symptoms and impede chronic low-grade inflammation associated with obesity using a clinically approved therapeutic compound.

Reference:

McQuade RM, Stojanovska V, Donald E, Abalo R, Bornstein J, Nurgali K.Gastrointestinal dysfunction and enteric neurotoxicity following treatment with anticancer chemotherapeutic agent 5‐fluorouracil, Neurogastroenterology & Motility. 2016;28(12):1861-75.

McQuade RM, SCarbone SE, Stojanovska V, Rahman A, Gwynne RM, Robinson AM, Goodman CA, Bornstein JC, Nurgali K.Role of oxidative stress in oxaliplatin‐induced enteric neuropathy and colonic dysmotility in mice, British Journal of Pharmacology. 2016;173(24):3502-21.

McQuade RM, Stojanovska V, Stavely R, Timpani C, Petersen AC, Abalo R, Bornstein JC, Rybalka E, Nurgali K.Oxaliplatin‐induced enteric neuronal loss and intestinal dysfunction is prevented by co‐treatment with BGP‐15, British Journal of Pharmacology. 2018;175(4):656-77.

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