Hi Friends!
Welcome to the Gut Advisor Newsletter! In this issue: Focus on interoceptive anxiety and the gut
For anyone new—this is a monthly newsletter where we address new, or older but relevant, research findings, as well as summarize recent findings or gut-related news. Here, “gut-related” is broadly interpreted, so we will be covering anything that might affect the gut, both “top down” and “bottom up.” This means brain/mind things (“top down”), such as psychology of stress, resilience, and emotion regulation, as well as body-based things (“bottom up”), including inflammation and typical comorbidities of gut disorders, such as pain conditions and autoimmunity.
Dr. Lisa Goehler
Table of Contents
Interoceptive Anxiety Overview
We usually think of anxiety as a bad thing. It’s a nasty negative emotion that can be so intrusive and hard to control. You can be anxious about being anxious! But actually, it is a normal and important emotion. Basically, it is the feeling that something is not right. Somewhere. Somehow. This can motivate us to determine and address whatever it is that isn’t right.
But what happens when the something that isn’t right is not something in the mind or in the environment, but in the gut (or other part of the body)? This is interoceptive anxiety.
I first got involved in studying this issue back in 1999, when a colleague in the Psychoneuroimmunology Research Society, Mark Lyte, asked me if I would collaborate on a study with him. He is a microbiologist interested in “host-microbe interactions”. “Host” means us and other animals. He had showed that stress in the host (mice in this case) can increase growth and virulence in potentially pathogenic bacteria, which could be one way stress contributes to disease susceptibility. While studying the mice he noticed the ones that had to swallow the bacteria (this was how it was given) seemed anxious, but the ones who had to swallow saline were not (Lyte 1998). No one believed it, because he could not find any explanation for how bacteria in the gut could affect behavior. Besides being anxious, the mice who got the bacteria looked exactly the same as the controls- no inflammation, or anything.
At the time, I was studying the role of the vagus nerve in immune-to-brain communication. Mark wondered if the vagus nerve might be somehow signaling the presence of the bacteria, and so did I. Long story short- we were able to show that the vagus nerve responded to the extra bacteria in the gut fairly quickly, within a few hours, and that this led to a brain activity pattern identical to both stress and anxiety (Gaykema 2004; Goehler 2007; Goehler 2008).
This was a surprise to many people, because at the time it was assumed that bacteria living in our guts are there only because it is a cozy place to live. Sure, they interact with each other, but why would they interact with us?
Now we know that we and our microbes interact in important ways, to the good and to the bad. We are symbiotic, really. To the good, microbes provide important nutrients and substances that help regulated our immune systems. To the bad, they can overgrow and out-compete “friendly“ microbes, which can lead to functional problems in the gut, and elsewhere. This is “something wrong” and this activates interoceptive pathways (sense of the condition of our bodies) that signal brain networks that function to address challenges. The feeling of interoceptive anxiety can be one result.
We have an epidemic of anxiety in our society, which is understandable from a “top down” point of view, in that our society is going through many changes and there is uncertainty in the future. But from a “bottom-up” view, we also have a highly industrialized food system that makes highly processed foods, which are low in fiber and nutrients, easy and cheap. This type of diet is just plain bad for the gut. Even though there has recently been a lot in the various media about the dangers of the Western Diet, most people are still eating it.
For many people, it can be hard to make the link between what is happening in the gut (or other parts of the body) and brain symptoms, such as anxiety. This may be important especially important for people who have disorders attributed to the brain such as Post-traumatic Stress Disorder (PTSD), generalized anxiety, addictions, even neurodegenerative diseases (Jones 2021), that can also often have gut symptoms as well. Even if top-down factors for anxiety (such as anxiolytic drugs and psychotherapy) are effective, there may residual symptoms that could be driven by interoceptive anxiety.
The idea that poor diets can be contributing to anxiety is supported by both epidemiological studies, which have correlated diet with mood, and intervention studies (though not enough of these) indicate that eating a Western Diet is associated with more anxiety and depression (Aucoin 2021, Melguizo-Ibáñez 2023; Alexatou 2026), and that switching people with mood disorders to a Mediterranean type diet improves symptoms (Jacka 2017; Esgunoglu 2022).
Fortunately there is more better information becoming available regarding what, actually is a “good diet”. In particular, diets with plenty of fiber attract and nourish the microbes that keep our guts healthy, and improve interactions between the gut and brain.
So it seems that the alarming level of anxiety in our society may well follow from top down psychological experiences interacting with bottom-up interoceptive factors. When people are struggling with symptoms of anxiety, they should also think about their diets, and get more fiber!
Resistant Starch: A Reprieve for Potato Lovers
Good news for people who love potatoes, but try avoid them because they have a high glycemic index. Foods with high glycemic indices should be avoided by people with diabetes or other blood sugar problem because the sugars in the foods are quickly and easily broken down and absorbed. This can cause hyperglycemia. But potatoes, in addition to being starchy, are highly nutritious. And they are delicious and easy to cook with. What to do?
The good news is that, according to a recent Washington Post article, there is a trick that can be used to cause starchy, high glycemic foods such as potatoes, pasta, and white rice, into food high in “resistant starch”.
What is resistant starch? It is “a cousin of dietary fiber”, in that it is made of carbohydrates that are not digested in the small intestine, but feed microbes in the large intestine. Foods that naturally contain resistant starch are “beans, peas, lentils, nuts, seeds, green bananas (!), potatoes and some whole grains”.
So how do we change simple starches to resistant starch? Refrigerate them. This is one more way which left-overs rock! Apparently, the process of heating and then cooling starches causes them to bind together to become more stable and “resistant” to digestion by our enzymes. One suggestion is to cook potatoes, then refrigerate them, and then cut them up to put in salads, omelets, or serve with another “favorite protein”. I suggest use in tacos too!
This trick of cooking, then refrigerating works for rice and pasta as well.
The Gut-Brain Axis: Not as New as You Think
While searching the literature regarding the history of the thinking about relationships of the gut to mood states such as anxiety, I came across this delightful article.
It is a report and commentary about attitudes about the relationship between gut health and psychology, emotion, and behavior in the 18th and 19th Century Great Britain. It strongly refutes the idea that linking gastrointestinal health to emotions is new for the “Western” world.
For instance, (in the 18th and 19th centuries) “Organs had traditionally been attributed emotional qualities: the heart and love, for instance. However, the gut seemed particularly menacing as doctors associated the region with negative or ‘morbid’ emotions which needed to be carefully suppressed.”
In addition to linking of diet with mental health for individuals, Dr. Miller highlights the ways in which views regarding how personal gut health and eating habits became associated with societal health in the 19th century as well.
“However, in contrast to the eighteenth century, gastric distress now seemed to be affecting all sections of society, partly due to changing food consumption patterns in the new urban areas. The gut was a useful metaphorical resource for expressing concern about the physical and emotional well-being of the nation”.
Great Britain was undergoing rapid industrialization at the time, which disrupted society. Physicians were reporting that stomach problems were becoming alarmingly common. It strikes me that our society seems to undergoing analogous changes, while gut problems seem nearly ubiquitous.
There is also an interesting section on the dangers of “excessive tea drinking”, especially for women… Hmmm. Overall I found this to be an entertaining historical account of ideas about gut and behavior.
Gut symptoms are caused by neurotic personalities.
This is more like the misconception of the previous century (20th). As elaborated by Dr. Miller, people in the 19th century readily attributed mental problems to gut function, if sometimes in hilarious ways. But by the 20th century, a more top-down view of the relationship between gut and brain dominated. Personality (especially “neurotic” personality) and stress were blamed for gastric and duodenal ulcers (Alp 1970, Jass 1994, Piper 1993). Eventually it was revealed in the 1990s that gastric ulcers are triggered by overgrowth of Helicobacter pylori (Malfertheiner, 2023). But even after that, the emotions of people with other gut disorders, especially the functional bowel disorders such as IBS, were still being blamed for the gut symptoms.
This was dramatically illustrated to me around 1984, when I was a graduate student at UCLA. I attended a Grand Rounds lecture given by the Eating Disorders Center and (I think) the Department of Gastroenterology. For this presentation, they interviewed a very, very thin (nearly skeletal) woman. She presented as highly strung, anxious, and a little defensive. She lived with her ailing grandfather, whom she supported financially and as a care-giver. Money was tight. She was referred to the Eating Disorders (ED) Clinic because she had lost so much weight, and said that she could only eat “Mrs. See’s chocolate” (the good stuff in those days), due to excessive gut pain if she ate anything else. As you might expect, this explanation was not believed. She bounced around psychiatrists before one referred her to UCLA’s ED clinic. When interviewed, she stated very clearly that she wanted to eat but couldn’t. Since she reported severe gut pain, the practitioners at the ED clinic thought she should be “scoped” to see if there was anything wrong with her gut to explain her pain. When that was done, it was found that she had severe inflammation extending from her top of her esophagus to her rectum. She had severe Crohn’s disease. What shocked me though, was how long she had gone before her story was taken seriously. She presented as neurotic, so that must be her problem, right?
We have come a long ways in understanding gut-brain interactions since then, but advice about dealing with mood symptoms for people with gut problems is still top-down: the emphasis is managing stress, but much less on dietary improvements that could alleviate interoceptive anxiety.
Every month, we pick a published (and peer reviewed) article to highlight and discuss.
This month’s selected article
Title
Gamma-aminobutyric acid as a potential postbiotic mediator in the gut-brain axis.
Authors
Braga JD, Thongngam M, Kumrungsee T.
Publication
NPJ Sci Food. 2024
I think this paper is worth a read! Check it out →
One of the key questions for us when we were thinking about how microbes can influence the mind, was: what is the link between microbes and activation of the vagus nerve? There was evidence that signals from gram negative bacteria (endotoxin) can activate the vagus, which could well be driving the feeling that something isn’t right. Overgrowth of gram-negative bacteria are a key feature in dysbiosis that can drive inflammation in the gut.
Over the years there have also many papers reporting that certain bacterial strains can improve mood, and sometimes cognition. Therefore, there must also be other signals from microbes, beyond those that signal problems. Metabolomics, the identification of what cells produce, has shown that microbes can make neurotransmitters, including dopamine serotine, and GABA, that could influence the gut and gut-brain signaling. These substances are now being called post-biotics.
This paper reviews evidence for microbial produced GABA, a neurotransmitter that that has long been linked to regulation of anxiety (benzodiazepines act on GABA-related systems) in gut-brain interactions influencing mental health and brain function. Some highlights include:
Key GABA producing microbes are in the Lactobacillus family, although others such as Bifidobacteria and Saccharomyces also make it.
Lactobacillus species are consistently found in probiotic formulations and fermented food that are reported to improve gut and brain health.
Good dietary sources of GABA- producing lactobacillus species are kimchi and fermented dairy. It can also be found in fermented meats, including “Chinese fermented sausage” which had a whopping amount of GABA in it.
Dysbiosis of gut microbes is associated with most brain disorders, including neurological disorders, mood and stress disorders, autism spectrum disorders, and epilepsy. One theme of the dysbiosis is fewer lactobacillus and other GABA-making species.
Both clinical and pre-clinical studies have linked increased populations of gut microbes that consume GABA (so less GABA for us) with anxiety and stress, and that probiotic supplantation with GABA-making microbes alleviate stress and anxiety-related symptoms
A pilot study with people who have drug-resistant epilepsy found that a probiotic formula increased systemic GABA and reduced frequency of seizures during a 12 week treatment. This was only a small pilot study, but given how serious and frustrating a problem that treatment resistant epilepsy is, this finding indicates a promising approach that should be further studied.
Bottom line?
Overall, there is a consistent story supporting GABA-producing microbes in modulating brain function, especially mood and stress. So, more reasons to eat kimchi and fermented dairy. No fermented Chinese sausage for me. I have the alpha gal meat allergy. Plenty of other foods to choose from though!
Tips for managing anxiety
Here we will pass on “tips” or observations from practitioners or patients about approaches they found helpful for dealing with symptoms of gut problems or ways to keep the gut healthy that have not yet been tested with clinical trials. So, the evidence is anecdotal, but may be worth trying.
A warm shower/bath can help, both with anxiety and gut stress.
I also do warm drinks when I’m anxious, especially lavender. Also ginger tea or hot honey lemon juice.
Do you have a tip for us? Let us know!
Every month we will highlight an easy to make, gut-healthy dish that we are eating now!
Mushroom, spinach, and barley casserole with puff pastry
This is a favorite of ours for Fall and Winter months. It is a bit more elegant to serve than the average casserole, and the left-overs heat well in the microwave.
It is hearty and filling, and thanks to the barley it should be a good source of resistant starch when reheated.
A riff on a recipe from Sunset Magazine.
Makes about 10-12 servings
Ingredients
1.5 pounds mixed mushrooms, sliced or cut in chunks
1 cups red wine (optional)
0.5 cups olive oil (or so)
1 dried herbs (thyme, marjoram, cayenne), to your preference
0.5 teaspoons ground nutmeg
1 head garlic, coarsely chopped, divided
1 cups barley
2.5 cups mushroom broth (see note below)
10 ounces jar roasted red peppers, chopped
1 cups pine nuts
1 cups olive tapenade (or so)
10 ounces package frozen spinach, thawed and drained
16 ounces full fat ricotta cheese
10 ounces shredded parmesan cheese (8–12 oz)
1 sheet puff pastry, partly thawed according to directions
Instructions
Make the mushroom broth: Soak 6–8 oz of dried mushrooms in 2.5 cups mushroom broth (see note below) of boiling or near-boiling water for at least a half hour — longer is better for a more richly flavored broth. Porcini mushrooms are very good for this, but other full-bodied mushrooms such as portobello, or a mix, is nice too. Shiitake mushrooms tend to be a little too light in flavor.
Roast the mushrooms: Toss 1.5 pounds mixed mushrooms, sliced or cut in chunks with the 1 dried herbs (thyme, marjoram, cayenne), to your preference, 0.5 teaspoons ground nutmeg, 0.5 cups olive oil (or so), and 1 cups red wine (optional) (if desired), and roast at 350°F for 20 minutes
Combine mushrooms with broth and tapenade: Remove from oven. Pour off the roasting liquid and reserve it, adding it to the dried mushroom broth. Add the rehydrated mushrooms used to make the broth to the roasted mushrooms, then stir in half of the 1 head garlic, coarsely chopped, divided and all of the 1 cups olive tapenade (or so).
Cook the barley: Cook 1 cups barley in the combined 2.5 cups mushroom broth (see note below) until the broth is absorbed and barley is tender. Add the chopped 10 ounces jar roasted red peppers, chopped, 1 cups pine nuts, and the remaining 1 head garlic, coarsely chopped, divided, and stir to combine.
Layer the casserole: In a large casserole dish (e.g. 4.5 quart), layer the mushroom mixture evenly across the bottom. Add half of the 10 ounces package frozen spinach, thawed and drained, then sprinkle half of the 10 ounces shredded parmesan cheese (8–12 oz) over it. Layer the barley and pepper mixture on top. Add the rest of the 10 ounces package frozen spinach, thawed and drained. Layer 16 ounces full fat ricotta cheese evenly over that, then sprinkle with the remaining 10 ounces shredded parmesan cheese (8–12 oz).
Top with puff pastry and bake: Lay 1 sheet puff pastry, partly thawed according to directions on top of the casserole. We usually find that less thawed pastry puffs better. Bake at 350°F until the pastry puffs up and is golden brown, about 40 minutes.
Enjoy!
About the Author
Lisa E. Goehler, Ph.D. is a neuroscientist and expert in the science and treatment of psychological stress, chronic inflammation, and gut-related disorders. She pioneered the study of how GI-tract related bacteria can interact with the brain to lower mood and increase anxiety. Throughout her career, she authored over fifty publications and contributed to peer review for scientific journals and funding agencies, including the National Institute for Health.
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