Exploring the Gut-Brain Axis

digestive system and intestinal flora abstract
Second Brain © Thinkstock.com/coolgraphic

If you’ve ever felt the sensation of “butterflies” in your stomach or had a “gut feeling” about a situation, you’ve experienced the connection of the brain and the gut. This two-way communication between the nervous system and digestive tract goes beyond emotional response; it has been implicated in numerous health conditions. Interventions involving the gut-brain axis are seen as potential new strategies for addressing a multitude of issues.

The gut-brain axis is a topic of interest in fields from neurology and gastroenterology to psychology and integrative and functional medicine. While most available evidence on the gut-brain axis comes from animal studies, emerging human research is providing valuable insights into the complex integration of psychology and physiology of the human body.

The gut is a busy place. Not only does it house the influential microbiome, it also includes immune cells, neuropeptides, microbial metabolites and enteroendocrine cells, which secrete hormones. The vagus nerve is a key connection point linking the brain and gut, while nerves along the gut allow for direct communication with contents of the stomach and intestine.

The digestive tract is one of the major entry points for external substances, from food and supplements to drugs and bacteria. These substances all have the potential to impact the gut-brain axis.

Intestinal permeability refers to the physical gaps between intestinal cells, which is thought to be partly regulated by the microbiome. The term “leaky gut” was coined to describe when those gaps are enlarged and external substances and waste products are allowed to pass into the bloodstream. This has been associated with changes in mood, immune function and inflammation. Intestinal permeability may be associated with numerous conditions including inflammatory bowel disease and autoimmune disorders such as Type 1 diabetes and celiac disease.

“RDNs can play an integral role in preventing and repairing intestinal permeability,” says Mary Purdy, MS, RDN, the 2017- 2018 chair of the Academy’s Dietitians in Integrative and Functional Medicine dietetic practice group. According to Purdy, consuming adequate amounts of vitamins A and D, with plentiful dietary fiber, prebiotics and probiotics to keep the gut microbiota healthy, can maintain and improve the integrity of the gut.

It also is becoming clear that the microbiome can influence its host’s appetite and eating behavior. Animal and human research has found a link between specific species of microbes and increased host intake of nutrients that the microbes prefer. “Cravings and feelings of hunger we experience may not be just our own,” says April N. Winslow, MS, RDN, CEDRD, who is working toward her doctorate in food science and human nutrition with an emphasis in nutritional neuropsychology.

The metabolites microbes produce and the neurochemicals they influence impact secretion of satiety-promoting hormones; researchers suspect the microbiome also can influence taste, smell, thoughts, impulsivity and compulsivity about food. Short-chain fatty acids, a major metabolite of gut microbes, and their possible link to obesity and metabolic syndrome are an active area of research. In fact, administering the short-chain fatty acid proprionate to the colon of adults who are overweight led to greater satiety hormone release and reduced calorie intake and weight gain.

Disrupting the gut-brain axis already is used as a treatment for obesity through Roux-en-Y gastric bypass surgery, a restrictive and malabsorptive intervention that in 2015 accounted for an estimated 23 percent of bariatric surgeries. This surgery is unique compared to purely gastric restrictive bariatric surgeries, such as laparoscopic adjustable gastric banding, because part of the stomach is stapled off and attached to the middle part of the small intestine, bypassing the lower portion of the stomach and parts of the small intestine. This may affect not only the absorption of certain micronutrients, but also hunger and satiety hormones.

People who undergo gastric bypass surgery tend not to experience the same increase in the hunger hormone ghrelin as people who achieve non-surgical weight loss through diet and exercise alone. Bariatric experts suspect this is a major contributor to the success of the surgery. In addition, sometimes the vagus nerve is severed during gastric bypass surgery, which could affect hunger hormones and innervation of the gut, therefore impacting appetite.

Nina Crowley, PhD, RDN, LD, metabolic and bariatric surgery program coordinator at the Medical University of South Carolina, says it is imperative to counsel bariatric candidates on the mechanisms at work in various bariatric surgeries, how they differ and how this impacts metabolism. “I like to discuss how the change in gut hormones may be what is required for them to see a metabolic change, and keep a focus on biology, rather than blaming the person for their eating habits or behavior,” Crowley says.

When the body is underfed, such as with bariatric surgery recovery and anorexia nervosa, gut microbiota composition and diversity changes. This has been correlated with depression and anxiety in people with anorexia nervosa and may be related to the fact that 95 percent of the neurotransmitter serotonin, which plays a role in depression, is produced in the gut.

Research is examining what happens when fecal samples from people with anorexia nervosa are transplanted into mice born in a germ-free environment, compared to what happens when fecal samples from healthy people are transplanted into germ-free mice. This science serves as a foundation for potential new treatments for anorexia nervosa as well as furthering the understanding of the underlying mechanisms of this complex disease.

There is not enough evidence to explain the role of the gut-brain axis in binge-eating disorder, although some researchers suspect the gut microbiome’s impact on impulsivity and compulsivity may play a role.

While research on the gut microbiome is booming, human research is needed on other parts of the gut-brain axis, especially as it pertains to risk and development of psychological and chronic disease. As more human evidence becomes available, novel intervention strategies involving food and nutrition likely will come to light.

“Registered dietitian nutritionists are the ideal medical professionals to lead research in this area because they have the training and skills to obtain nutritional data from human participants and conduct motivational interviewing,” Winslow says.

Taylor Wolfram, MS, RDN, LDN
Taylor Wolfram, MS, RDN, LDN, is a dietetics content manager at the Academy of Nutrition and Dietetics and associate editor of Food & Nutrition.