Gut-muscle axis may provide novel strategy for promoting better health
The healthy dietary choice seems easy.
Consuming fish oil or sea food along with their omega-3 fatty acids — good. Consuming too much red meat along with its omega-6 fatty acids — bad. In fact, the impact of arachidonic acid, an omega-6 polyunsaturated fat found only in animal products, upon human health remains a complicated, poorly understood matter.
A Purdue University collaboration led by James Markworth, assistant professor of animal sciences, will carefully test the health effects of omega-6 in laboratory experiments. Funded by the USDA National Institute of Food and Agriculture, the experiments also will clarify which omega-3 fatty acids found in fish oil and sea food are responsible for yielding their health benefits.
Both omega-3 and omega-6 are long-chain, polyunsaturated fatty acids, and some of these fatty acids are also essential fatty acids. “These polyunsaturated fatty acids are essential because you need to acquire them through the diet,” Markworth said. “They can’t be made in the body. And in particular it’s the long-chain versions, which are found in products of animal or marine origin, that are thought to potentially influence human health.”
The long chain omega-6 fat arachidonic acid is found only in meat, poultry and eggs. “You can’t get it from vegetable sources, and you can’t get it from fish. We think that these nutrients found in meat and poultry products might have similar benefits as, say, fish oil or fish products. And that’s something you don’t hear very often,” Markworth said.
Previous research has well-established that fish oil fatty acids have metabolic benefits. But which fatty acids convey those benefits and how remains unclear. The major ones are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
“When you take fish oil supplements or you eat fish, it’s a complex mixture of these different nutrients and we don’t really know which ones are doing what. We don’t know precisely which essential fatty acids benefit metabolic health, obesity, insulin resistance and how they may do so by impacting upon skeletal muscle as the largest organ in the body,” Markworth said.
Collaborating with Markworth on the project Tzu-Wen Cross in the College of Health and Human Sciences, along with Tim Johnson and Kolapo Ajuwon, both in the College of Agriculture’s Department of Animal Sciences. Cross, an assistant professor of nutrition science, and Johnson, an associate professor of animal sciences, specialize in gut microbiome. Ajuwon specializes in animal nutrition.
“What we’re suggesting is when you eat these lipids in the diet or dietary supplements, the systemic response your body has might depend on the resident microbes first encountered in the gastrointestinal tract,” said Markworth, a muscle biologist. “And we’re proposing that the systemic response is largely mediated by the effect on the skeletal muscle.” As the largest site of glucose disposal and insulin sensitivity, the skeletal muscle determines metabolic health, obesity and diabetes, he noted.
Markworth cited a study showing that if mice are given antibiotics together with fish oil, the fish oil works differently than it does without antibiotics. “What is it about consuming antibiotics that stops fish oil supplements from having their metabolic benefit on peripheral metabolic health in mice or potentially in humans? That study suggests that the gut bacteria are required, and we don't know why,” he said.
To find out why, the team will work with mice in Purdue’s gnotobiotic animal facility, which Cross directs. These germ-free mice lack any bacteria, either on their skin or inside their bodies.
The researchers will carefully control the gut microbiomes of the mice and the diet they eat for more insight into what Cross sees as a chicken or egg kind of puzzle. Does diet affect the microbiome, which then brings about good or bad health effects? Or does the diet affect other bodily processes that then change the microbiome? “We’re trying to tease that part out a bit,” she said.
About a decade ago, scientists were just beginning to recognize the importance of the microbiome. “Now we realize how much it impacts our health in various aspects,” Cross said. “A lot of the things that we do in using diet to promote health is actually through affecting our gut microbiome. But we still don’t understand enough to know how to modify the microbiome in a specific way to achieve our outcome."
In one set of experiments, the scientists will monitor gut-microbe interactions in mice fed with a diet of polyunsaturated fatty acids. Then they will measure the metabolic byproducts of these fatty acids in the feces, blood and muscle.
In another set of experiments, the team will feed a diet high in fat and refined sugars to the mice, creating metabolic problems such as obesity, insulin resistance and Type 2 diabetes. Some of the mice will be fed a high-fat diet with the saturated fats replaced by purified forms of omega-3 and omega-6 fatty acids.
“Can such essential fatty acids protect the mice against metabolic dysfunction in mice fed a Western-style high saturated fat sugar rich diet?” Markworth asked. “And if so, do the microbes in some way play a role in this?”
The researchers also will attempt to transfer the beneficial effects of the essential fats from fish oil from the mice that get them in their diets to those that don’t via fecal microbiota transplants. Sometimes used to treat Clostridium difficile infections of the colon in humans, fecal microbiota transplants are a way to transfer gut bacteria from one individual to another.
“This is a good model for us to identify interactions between the microbiome and host to understand how the microbiome affects metabolism and physiology,” Cross said. “Through that, we can potentially identify mediators we can use as targeted therapeutics.”
Click here for a 2023 news article about some of Dr. Markworth’s on the role of lipid metabolites in muscle biology.
