Junk food is detrimental to both your waist and wellness. (Rimma Bondarenko/Shutterstock)
In A Nutshell
- Junk food shifted 100 gut molecules in male rats and went along with low-mood behavior.
- Running pulled many gut changes back and cut “floating” time in the swim test.
- Three gut compounds, anserine, indole-3-carboxylate, and deoxyinosine, rebounded with exercise.
- Insulin and leptin climbed on junk food; exercise helped. New brain cells grew mainly with a healthier diet.
Ever wonder why you feel sluggish and down after weeks of eating pizza, burgers, and ice cream? Or why hitting the gym seems to turn things around? Irish scientists have identified gut changes that may help explain why weeks of rich foods can leave rats sluggish and low.
Researchers at University College Cork have uncovered that junk food changes the chemistry in the digestive system in ways that may link to low mood in rats. But here’s the good news: exercise dialed back many of those gut shifts, even when the animals still had access to the same foods.
The study, published in Brain Medicine, spotlighted three gut-made compounds that fell with junk food and rose with exercise. These compounds have been linked in past studies to mood and thinking. When rats ate a diet packed with cheese, chocolate, peanut butter, and jam, levels of these compounds dropped, and the animals showed more low-mood-like behavior. Give those same rats access to running wheels, and both their gut chemistry and behavior moved back toward control levels.
Your Gut Makes Chemicals That Shape Your Mood
The research team fed adult rats either normal food or a rotating “cafeteria diet” of high-fat, high-sugar treats for about two months. Then they analyzed what was happening in the cecum, a pouch in the large intestine where gut bacteria break down food and create hundreds of different compounds.
The junk food changed 100 out of 175 compounds the scientists measured. Exercise by itself barely changed anything in rats eating healthy food (just 5 compounds), but when combined with junk food, exercise reversed dozens of those harmful changes.
Some gut compounds tended to rise or fall along with behavior, no matter what the rats ate or whether they exercised. Rats with higher levels of one compound called cytosine spent more time floating passively in water instead of actively swimming. Four other compounds tended to go with memory problems. Animals with more of these substances in their guts struggled to tell similar locations apart.
Here’s where it gets interesting for anyone who’s ever stress-eaten their way through a bag of chips: junk food pushed more tryptophan into side routes in the gut. Your brain needs tryptophan to make serotonin, the “feel-good” neurotransmitter. If more tryptophan gets used up in the gut, that could leave less available for the brain. The study did not measure brain serotonin, so treat this as a clue rather than proof.
Exercise Pulled Rats Out of Their Slump
The researchers used a swimming test that measures depression-like behavior in rodents. When placed in water, healthy rats swim actively. Depressed rats mostly float.
Rats on the junk food diet who stayed sedentary gave up quickly, floating more than swimming. Rats on the same junk food diet who could exercise swam more and floated less so they looked closer to controls.
This improvement happened alongside a restoration of those three key gut compounds. Separately, some human studies that include anserine report lower depression scores or better thinking. Those trials differ from this rat study.
Exercise also made rats less anxious about eating in a scary environment, but only if they were already eating healthy food.
Junk Food Sends Hormones Haywire; Exercise Helps
On junk food without exercise, insulin was about two to three times higher than controls and leptin rose as well. Exercise helped move both hormones toward healthier ranges despite the rats continuing to eat junk food. This matters because when these hormones stay elevated too long, your body stops responding to them properly. That resistance is linked to both depression and memory problems.
Another gut hormone called GLP-1 (you might recognize it from new weight-loss drugs) increased with exercise in healthy-eating rats but not in those on junk food. This suggests diet quality affects whether exercise can boost certain beneficial hormones.
Your Diet Determines Whether Exercise Grows New Brain Cells
Scientists counted newborn neurons in the hippocampus, a brain region crucial for memory and mood regulation. Exercise grew more new brain cells in the hippocampus, the brain’s memory hub, mainly in rats eating normal food. Junk food blunted about half of that boost.
This finding is significant: even when you exercise regularly, what you eat determines how much your brain can repair and grow. Exercise and a healthy diet work together, not independently.
The rats showed modest improvements in spatial learning with exercise, though diet differences were less pronounced in memory tests than in mood tests. Pattern recognition and object memory barely budged.
Run For Your Gut
This study was done in male rats over about two months, so we can’t draw direct conclusions about people, women specifically, or long-term effects. Human eating patterns develop over years, not weeks. But the findings do suggest some interesting possibilities.
Exercise may help on several fronts at once: hormones, gut chemistry, and brain plasticity. Diet quality seems to matter for that last one.
The gut findings are key to understanding the larger relationship at play between diet and mood. Your digestive system isn’t just processing food; it’s creating compounds that reach your brain and affect how you feel. When you eat poorly, you’re not just gaining weight or risking diabetes. You’re changing your gut’s chemical factory in ways that can drag down your mood.
The practical takeaway? While exercise can’t completely undo an unhealthy diet’s effects on everything researchers measured, it substantially reduces junk food’s impact on mood and metabolism. But if your goal includes maximizing brain health and new cell growth, diet quality matters as much as hitting the gym.
Future research needs to determine whether these same changes happen in human digestive systems and whether supplements containing these gut compounds could help people struggling with diet-related mood problems.
Disclaimer: This article discusses animal research and is provided for informational purposes only. It is not intended as medical advice. If you’re concerned about diet, exercise, or mental health, talk with your doctor or a qualified healthcare professional.
The Irish Research Council, Research Ireland, and Health Research Board Ireland funded the research.
Paper Summary
Methodology
Researchers divided 48 adult male rats into four groups: some got regular food, others got junk food (regular food plus rotating treats like peanut butter, cheese, chocolate, and jam); some had running wheels, others didn’t. After 7.5 weeks, scientists tested the rats’ behavior in various ways to measure depression, anxiety, motivation, and memory. They also collected blood to check hormone levels and cecum contents to analyze gut chemistry. Half the rats were examined for new brain cell growth in the hippocampus. The team identified 175 different compounds in the gut for comparison.
Results
Junk food made sedentary rats gain more weight, but exercise helped control that gain. In the depression test, junk food made sedentary rats give up and float, but exercise prevented this. Exercise showed mild anti-anxiety effects regardless of diet. Exercise increased new brain cell production in rats eating healthy food (from approximately 190 to 350 cells per square millimeter in the dorsal region), but junk food reduced this benefit to only about 240 cells per square millimeter. Blood tests showed junk food approximately doubled insulin levels and nearly doubled leptin levels in sedentary animals, and exercise brought levels back down. Exercise increased GLP-1 in healthy-eating rats but not junk-food eaters. Gut analysis revealed junk food altered 100 of 175 compounds in sedentary rats and 62 in exercising rats. Exercise restored three specific compounds that junk food depleted: anserine, indole-3-carboxylate, and deoxyinosine. Some gut compounds tended to go with depression-like behavior and memory performance regardless of diet or exercise.
Limitations
The study used only male rats, so results might differ in females. The 7.5-week timeframe is short compared to how human eating habits develop over years. The rats were young adults, so effects might differ in adolescents or older individuals. The junk food was offered alongside unlimited regular food, which may not perfectly mirror how people eat. Memory effects were modest, possibly because the study period was brief or adult brains are more resilient than adolescent ones. The study found associations between gut compounds and behavior but can’t prove causation. Scientists only measured gut contents, not whether the same compounds appear in blood or brain tissue. The swimming test, while standard, has limitations as a model for human depression. Small sample sizes in some tests may have missed subtler effects.
Funding and Disclosures
Minke H.C. Nota received support from an Irish Research Council Ph.D. Scholarship. Research Ireland and the Health Research Board Ireland funded the work. Study funders played no role in collecting, analyzing, or interpreting data. Two authors have received funding from Marigot Limited. One author received speaking fees from Yakult. One author received funding for separate research from Alkermes and a speaking fee from Janssen. Other authors reported no conflicts of interest.
Publication Details
Nota, M.H.C., Nicolas, S., Dohm-Hansen, S., Harris, E.P., Foley, T., O’Leary, O.F., & Nolan, Y.M. (2025). Exercise mitigates the effects of a cafeteria diet on antidepressant-like behavior associated with plasma and microbial metabolites in adult male rats. Brain Medicine, 1-15. doi:10.61373/bm025a.0116
