August 29, 2018

Using Pigs as a Gut-Brain Model at DPP

Gut-Brain Model using Pigs

By: Dr. Caitlin Vonderohe

                Dr. David Val-Laillet presented an excellent overview of the interactions between the gut and the brain of the pig and human in his presentation “Impact of food, gut brain signals, and metabolic status on brain activity in the pig model: 10 years of nutrition research using in vivo brain imaging” at the 14th International Digestive Physiology of Pigs Symposium in Brisbane, Australia. Dr. Val-Laillet uses the mini pig to perform nutrition, physiology, and neurobiology research for human health. The mini-pig is an excellent animal model for humans because of the similarities in gastrointestinal physiology, immune system and neurocognition. Mini-pigs are also prone to obesity and related disorders commonly found in humans.

                Dr. Val-Laillet and associates have developed various methods to monitor the pig brain’s response to different taste and olfactory stimuli to better understand how nutrition and obesity-related disorders affect cognition and behavior. Notably, they have collaborated with neuroscientists to “map” the pig brain to better understand the implications of changes in blood flow and upregulations in glucose metabolism in certain parts of the brain.

                The majority of the presentation focused on the effect of obesity on brain function and nutrient sensing. Human studies have shown that obesity can result in reductions in metabolic activity and blood flow in the prefrontal cortex, therefore affecting learning and cognition, and reductions in dopamine in the “reward center” of the brain. Interestingly, successful dieting has been shown to reverse some of this effect, increasing the amount of dopamine in the reward center of the brain. Other molecules such as glucose and fructose can directly affect the “reward” center of the brain in obese and non-obese patients, however this effect is magnified in obese patients.

                Nutrition during pregnancy plays a significant role in how the brain of the offspring functions. Mini-pig sows were fed a diet high in fat and sugar and a standard diet. The piglets were then fed a standard diet. Piglets from sows fed high fat and sugar had greater cognitive ability early in life, particularly when cognitive tests involved a food reward. However, when these tests were repeated, without food motivation, there were no differences in cognition between pigs from sows fed the two diets. Pigs from sows fed the high fat, high sugar diets during gestation were not obese but had reduced formation and growth of neurons and increased inflammation in the brain. There was also evidence that the pigs from obese sows had metabolic dysfunction and reduced dopamine, much like obese animals.

                It is also possible to modify brain activity with ingestion of different foods or chemicals, such as butyrate. Butyrate supplementation modulated activity in the hippocampus of subject animals and affected nerve growth and formation. In fact, it is possible to increase neuroplasticity with butyrate administration, making it a potential clinical solution to some of the neurologic effects associated with obesity.

                Other clinical interventions for obesity in human medicine include bariatric surgery. This involves removing part of, or reducing the functional area of, the stomach. This affects the areas of the brain associated with taste, cognition, and motivation. Finally, chronic stimulation of the vagal nerve affects multiple areas of the brain to reduce food intake and may represent a treatment for obesity in the future.

                Dr. Val-Laillet presented truly innovative approaches to the problem of nutrition and diet-related disease in humans using the mini-pig model. The pig remains an excellent model for human gut and neurologic physiology and pathology. It will be interesting to see future practical clinical outcomes for both swine nutrition and human medicine from this research.