Is the Vagus Nerve Partly to Blame for Your Sweet Tooth? 

A gut-to-brain axis mediated by the vagus nerve may drive sugar cravings.

Posted Apr 17, 2020

 Stokkete/Shutterstock
Source: Stokkete/Shutterstock

For the first time, researchers have identified that the brain receives specific sugar-related information from the gut via vagus nerve pathways.

The discovery of a gut-brain circuit in mice dedicated solely to sending "sugar signals" offers fresh clues as to why so many humans have an insatiable sweet tooth. These findings (Tan, Sisti, Jin, et al., 2020) were published on April 15 in the journal Nature.

This mouse study builds on decades of research on the brain's taste system, conducted by Charles Zuker in his lab at Columbia University. The co-first authors of this paper, Hwei-Ee Tan and Alexander Sisti, are graduate researchers in the Zuker Lab.

According to Zuker and his team, the discovery of a specialized gut-brain axis that drives sugar preference could have a positive impact on public health.

As the authors explain in a news release: "Excess sugar intake has been linked to obesity-related conditions such as diabetes, which affects more than 500 million people worldwide. By laying the foundation for new ways to modify this gut-brain circuit, this research offers promising new paths to reducing sugar overconsumption."

How Much Sugar Do You Consume Per Day?

The United States Department of Agriculture (USDA) estimates that the average American consumes about 17 teaspoons of sugar per day. This adds up to a whopping 57 pounds of added sugar per year.

The American Heart Association (AHA) recommends that, on average, women should consume no more than six teaspoons (25 grams) of added sugar per day; men should aim for less than nine teaspoons per day. For children, their recommendations vary depending on a child's age and his or her caloric needs. That said, the AHA recommends a ballpark range of 3-6 teaspoons of sugar per day for kids.

The sugar consumption guidelines from the American Heart Association align with the World Health Organization's (WHO) recommended guideline that only 5 percent of caloric intake should come from added sugar, high fructose corn syrup, or natural sugars found in honey, maple syrup, fruit juice, etc. Five percent of a 2,000-calorie daily diet is about 25 grams of sugar per day.

Why Don't Artificial Sweeteners Satisfy Sugar Cravings?

One reason that artificial sweeteners never quite satisfy someone's sugar cravings or sweet tooth may be linked to this newly discovered gut-brain circuit that only responds to real sugar.

When we eat or drink, specific taste receptors on the tongue send hardwired signals to the brain that differentiate between sweet, salty, bitter, sour, and umami. Artificial sweeteners can trick the brain into thinking that sugar is touching sweet taste receptors on the tongue. However, even though artificial sweeteners such as Equal, Splenda, and Sweet 'n' Low may taste like sugar on the tongue, they don't activate the gut-brain axis like real sugar.

"When we drink diet soda or use sweetener in coffee, it may taste similar, but our brains can tell the difference," Hwei-Ee Tan said in a news release. "The discovery of this specialized gut-brain circuit that responds to sugar—and sugar alone—could pave the way for sweeteners that don't just trick our tongue but also our brain." 

Interestingly, when Zuker and his team deleted the sweet taste receptors in mice during this experiment, the mice still displayed a preference for real sugar over an artificial sweetener. This 38-second YouTube video illustrates how this study was conducted and highlights its findings.

The caption of this YouTube clip sums up the main takeaway of this research: "The sensation of sweetness starts on the tongue, but sugar molecules also trip sensors in the gut that directly signal the brain. This could explain why artificial sweeteners fail to satisfy the insatiable craving for sugar."

How Does the Vagus Nerve Send Sugar-Specific Information From Gut-to-Brain?

At the beginning of this research, Zuker and his team realized that even when they bypassed the sweet taste receptors on the tongue and delivered sugar directly to the gut, part of the brainstem called the caudal nucleus of the solitary tract (cNST) lit up with activity. "Something was transmitting a signal, indicating the presence of sugar, from the gut to the brain," Sisti said in a news release. 

The researchers decided to focus on the vagus nerve because it's a well-known pathway for sending bidirectional messages along the gut-brain axis. Monitoring the real-time activity of specific cells in the vagus nerve made it possible to observe how cell activity changed when there was sugar in the gut.

"By recording brain-cell activity in the vagus nerve, we pinpointed a cluster of cells in the vagus nerve that respond to sugar," Sisti said. "We saw, for the first time, sugar-sensing via this direct pathway from the gut to the brain."

During some elaborate follow-up experiments, Zuker's team zeroed in on a specific "sugar-transporting protein" called SGLT-1 that appears to communicate the presence of sugar in the gut up to the cNST brain region via the vagus nerve. The researchers also discovered that silencing this gut-brain circuit abolishes sugar cravings in mice. 

"Taken together, these findings demonstrate the existence of two complementary, yet independent, systems for sensing energy-rich sugar, one getting input from the tongue, the other from the gut," the authors conclude. 

"These findings could spur the development of more effective strategies to meaningfully curtail our unquenchable drive for sugar, from modulating various components of this circuit to potentially sugar substitutes that more closely mimic the way sugar acts on the brain," Tan added.

Although this research was conducted in mice, Zuker speculates that the same glucose-sensing vagus nerve pathway exists in humans. "Uncovering this circuit helps explain how sugar directly impacts our brain to drive consumption," he says. "It also exposes new potential targets and opportunities for strategies to help curtail our insatiable appetite for sugar."

The recent discovery (2020) from Zuker's lab at Columbia of a gut-brain axis that mediates sugar preferences complements another vagus nerve study (Fernandes et al., 2020) published on April 6 in the journal Neuron. This study by researchers from the Champalimaud Centre for the Unknown in Lisbon identified how the vagus nerve is part of a "digestive-brain axis" that appears to play a vital role in unconscious learning related to food-seeking behaviors. (See "Vagus Nerve Pathways May Drive Food-Seeking Behavior")

Want to Learn More Science-Based Facts About Sugar and Its Impact on Health?

SugarScience is an evidence-based consortium founded by a team of health scientists from the University of California, San Francisco (UCSF). The extensive resources on their interactive website are based on the systematic review and meta-analysis of over 8,000 scientific papers. 

References

Hwei-Ee Tan, Alexander C. Sisti, Hao Jin, Martin Vignovich, Miguel Villavicencio, Katherine S. Tsang, Yossef Goffer, Charles S. Zuker. "The Gut–Brain Axis Mediates Sugar Preference." Nature (First published: April 15, 2020) DOI: 10.1038/s41586-020-2199-7

Ana B. Fernandes, Joaquim Alves da Silva, Joana Almeida, Guohong Cui, Charles R. Gerfen Rui M. Costa, Albino J. Oliveira-Maia. "Postingestive Modulation of Food Seeking Depends on Vagus-Mediated Dopamine Neuron Activity." Neuron (First published: April 06, 2020) DOI: 10.1016/j.neuron.2020.03.009