Hi Friends and April Fools - this is the belated March edition!
In this issue: Focusing on the gut and diet factors that regulate our immune system and affect autoimmune disorders.
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
Introduction to the gut-driven regulation of our immune system
One of the most exciting developments in the gut world is the new understanding of the key role the gut has in regulating immune system development and function, with implications for the health of every tissue in the body.
This actually shouldn't be a surprise, because the gut is loaded with immune cells. In fact, roughly 70% of all your immune cells are living or hanging out in your gut. And it turns out that the gut is one of the main places in the body where immune cells go to mature (Kumar 2018). There are many different varieties (phenotypes) of T cells (the "generals" of the immune system that initiate and coordinate systemic immune responses) and B cells (which produce antibodies after being activated by T cells). There are also a ton of "innate" immune cells (macrophages, dendritic cells, mast cells, neutrophils, and others) that live in the gut and serve as a first line of defense.
I am embarrassed that I was one of the people who was surprised (pleasantly so, of course), as I should have known better. During the 1980s and 1990s I was doing a lot of gut anatomy work. Whenever you want to report an anatomy finding, you need photographic evidence. And it is not enough to just show an image — it has to be artistic. I was studying mostly nerves and endocrine cells. I had nice findings but getting photos was challenging because every image would be photo-bombed by immune cells, which are not the beauty queens of the cellular world. They were everywhere.
In addition to these sorts of "free-range" immune cells, the gut contains fairly large masses of "lymphoid tissue" that are pretty much the same thing as lymph nodes, but are embedded within the gut. It is in these places that T and B cells mature and become activated. Depending on their experiences in the gut, they can become pro-inflammatory or regulatory (pro-tolerance). The types of experience that can influence this are interactions with microbes and microbial products, and possibly stress hormones such as cortisol. The innate immune cells in the gut are programmed in this way as well.
Although it is clear that we have a lot more to learn about the nuances of gut immune regulation, some very important themes have already emerged. One theme is that immune function in the gut contributes to autoimmunity.
Autoimmunity occurs when someone has a genetic background that predisposes them to having an overreactive or paranoid immune system, which gets triggered by environmental factors (Veauthier 2018; Pisetsky 2023).
Environmental factors can include stress and/or exposure to toxins, or having too many, or not enough, of certain kinds of gut microbes (Miyauchi 2017; Gavy 2023; Zeng 2026).
One key factor underlying these issues is "gut permeability," aka "Leaky Gut" (Mu 2017; Kinashi 2021). For autoimmune conditions of the gut, this is the key factor. When the gut is permeable, substances such as bacterial products or other "suspicious things" can pass from the lumen into the body. This sets off an inflammatory response in the gut that, because of genetics, is very hard to turn off, and can lead to catastrophic damage to the gut.
What is happening is that these environmental factors, in the context of a "leaky gut," can bias the balance of tolerance vs. inflammation/host defense in the gut towards inflammation. When this happens, immune cells maturing in the gut can adopt a pro-inflammatory, intolerant identity. This underlies gut autoimmune conditions such as Inflammatory Bowel Disorders (Crohn's Disease, ulcerative colitis, and microscopic colitis) and food allergies. It also contributes to "extra-gut" autoimmune conditions, such as type 1 diabetes, rheumatoid arthritis, lupus, and multiple sclerosis (Miyauchi 2023; Zhu 2025). More on this in Journal Club.
Are there modifiable ways to influence this balance?
Theoretically, yes! Clinical trials are so far thin on the ground, but reports of small clinical interventions and preclinical studies support the idea that lifestyle factors, particularly diet, can help improve gut barrier permeability and re-balance gut microbe populations (Aleman 2023).
Bacterial translocation, which means bacteria getting through the gut barrier and into the body, contributes to pro-inflammatory immune programming (Twardowska 2022). This usually occurs when gut microbes are imbalanced, so supporting beneficial microbes (the old friends) by eating lots of fiber, resistant starch, fresh fruits, and vegetables can help gut barrier integrity.
Overall, diet goals should focus on consuming whole, intact, fiber-containing foods that have undergone minimal processing and don't contain additives such as emulsifiers and dyes.
Aleman et al. (2023) also point out that stress can cause or exacerbate permeability. This means that lifestyle factors that promote resilience should also improve gut barrier function in autoimmune conditions. Such factors can include regular exercise, rewarding and meaningful activities and hobbies, social interaction, and mindfulness approaches.
Vaccines may help protect against dementia
Vaccines Are Helping Older People More Than We Knew — The New York Times, by Paula Span (January 3, 2026) (Read article)
You may have heard that the shingles shot, in addition to preventing or reducing the severity of shingles, seems to reduce the risk of dementia in older people. But according to this article by Paula Span, the shingles vaccine is not the only vaccine that seems to provide this benefit. The respiratory syncytial virus (RSV), pneumococcal, and flu vaccines are also consistently associated with a reduced risk of dementia. This suggests that the benefits are not specific to the vaccine per se, but that in preventing disease, vaccines can reduce inflammaging.
Inflammaging is the aging-related process of priming inflammatory immune cells to be more easily activated, and with a greater degree of inflammation. Inflammaging is boosted every time our immune systems are activated, so preventing infection-related immune activation could reduce inflammaging. Inflammaging is considered to be a key mechanism underlying "aging-related" diseases, notably cardiovascular disease, cancer, and stroke, as well as dementia. Vaccinations also reduce the risk of these conditions as well. Many infections, including influenza and Covid, can affect the gut and induce persistent symptoms of post-infective irritable bowel syndrome.
For anyone who is still "on the fence" about whether to get the recommended vaccines, the potential for reducing inflammaging and its effects should be one factor to consider.
People with autoimmune conditions should avoid eating “nightshades vegetables”.
One of the questions I have often been asked involves the safety of eating "nightshade vegetables." This typically means tomatoes, peppers, eggplants, and potatoes. In particular, people who have autoimmune conditions are warned against eating them, as it is claimed that components of these foods can induce or exacerbate inflammation. The "autoimmune protocol" in particular excludes "nightshades." The reasons given are that they contain alkaloids, lectins, and capsaicin.
Another allegation: "Nightshades of all types were considered inedible prior to the 1800s, because some varieties, such as belladonna or 'deadly nightshade' (Atropa belladonna) were known to be toxic and used as a poison in ancient times"… "Nightshade vegetables contain enough toxins to cause inflammation in some people, particularly those with autoimmune disease." (source)
Is this really true?
Well, for one thing, Italians have been eating tomatoes since the 1500s. And people in the Americas were eating them, and other "nightshades" such as peppers and potatoes, for much longer than that.
Like so many misconceptions, there is a grain of truth. Yes, nightshades do contain alkaloids, lectins, and capsaicin. Most vegetables do (with the exception of capsaicin). But there is no evidence that those in the "nightshades" we eat are actually harmful. In fact, many substances, especially in tomatoes and peppers, are anti-inflammatory and/or antioxidant. Studies linking alkaloids found in "nightshades" to harm date from the early 2000s and were either performed in vitro (in a dish or test tube, basically) or used high doses of extracts (rather than whole foods) in mice. There is an absence of follow-up studies, suggesting problems with replication. What we do see now are studies of human diet and correlations with health outcomes. These studies have mostly looked at tomatoes and potatoes and report beneficial effects.
For instance, studies to date have linked tomato consumption with lower incidence of cancer, cardiovascular disease, and "all-cause mortality" (Cheng 2019; Xu 2021; Li 2021). This suggests that a diet including these fruits is likely to be beneficial for autoimmune conditions as well, or indeed any condition involving unrestrained inflammation. It may be important to remember that what we eat is the fruit of the plant. Since the whole point of fruit is to have animals eat it and spread the seeds around, it is not toxic. So even though the leafy parts of plants in the nightshade family are toxic, the fruits are not. But don't make a salad out of tomato greens.
I like this explanation from the Arthritis Foundation:
"They're a big family of around 2,500 plants, diverse enough to include potatoes, tobacco and the hallucinogen datura. Many nightshades are inedible and some, like bittersweet nightshade, a tomato relative, are notoriously toxic. All contain small amounts of a toxic compound called solanine, which helps the plants repel insects and can be poisonous to both humans and animals. Cattle, sheep and pigs are particularly sensitive to solanine and can die from eating the vines and leaves of tomatoes and potatoes. No research suggests this level of toxicity in humans, though you want to steer clear of potatoes that have turned green; they've developed exceptionally high amounts of solanine and aren't safe to eat." (source)
Based on what we know about the importance of gut health for immune tolerance and autoimmunity, and what we know about the importance of diet for gut health, it is clear that diet needs to be a target of interventions for autoimmune conditions. The key thing, though, is that recommendations need to be factual. A real concern is that cutting out "nightshades" means cutting out highly nutritious foods that contain anti-inflammatory and immune-regulatory substances.
Every month, we pick a published (and peer reviewed) article to highlight and discuss.
This month’s selected article
Title
The impact of the gut microbiome on extra-intestinal autoimmune diseases.
Authors
Miyauchi E, Shimokawa C, Steimle A, Desai MS, Ohno H.
Publication
Nat Rev Immunol. 2023
I think this paper is worth a read! Check it out →
One of the exciting implications of gut health for autoimmune conditions is the role of gut microbes in regulating immune tolerance. The article by Miyauchi et al. describes how different gut microbe populations may be contributing to immune dysfunction that sustains autoimmunity, focusing on multiple sclerosis (MS), rheumatoid arthritis, type 1 diabetes, and lupus. Some highlights include:
Gut microbe populations associated with extra-intestinal autoimmunity share in common that they promote the development of certain T cells (e.g., TH17) that are characteristically overactive in autoimmune conditions.
The key T cell type that promotes tolerance and suppresses autoimmunity — the Treg cell — is reduced in people who have autoimmune conditions. Gut microbes that promote the development of Tregs are decreased in number in autoimmune conditions, and this may contribute to the observed lower activity of Treg cells.
Components of some gut microbes can cross-react with human tissue components. This molecular mimicry may be another way that certain microbes initiate or drive autoimmune conditions. Evidence for autoantibodies that cross-react with parts of gut microbes has been found in patients with MS, rheumatoid arthritis, and lupus.
These observations suggest that modulating gut microbes may be an effective treatment for autoimmune conditions, but so far there is not much information on how effective this may be for patients. Findings from animal models are encouraging, however, as are studies in mice and humans showing that supplementing the diet with short-chain fatty acids such as propionate and butyrate (normally produced by the missing microbes) can improve symptoms in MS.
A key challenge identified in studies of modulating microbes to benefit autoimmunity is that there are marked individual differences between patients. Some people respond and some don't. Thus, to be effective, treatments will need to be tailored to each individual patient.
Overall, even though there is a ways to go before we have "tried and true" microbe-based interventions for autoimmunity, I feel the field is heading in the right direction.
Reading this paper reminded me of a short conversation I had a couple of years ago with a woman who had Sjögren's syndrome. Sjögren's is an autoimmune condition affecting exocrine glands, often the tear and salivary glands, leading to dry and painful eyes and mouth. When she visited her new ophthalmologist (she made a point that he was "younger") and told him she had Sjögren's, he said, "We need to fix your microbes!" When they did that, she had no more problems with her eyes, except when it was really windy. I didn't get a chance to ask what they did to fix her microbes, but her experience is certainly "proof of concept" that fixing microbes can indeed improve autoimmune conditions.
Every month we will highlight an easy to make, gut-healthy dish that we are eating now!
Mushroom “Irish stew”
March is the month of one of my favorite holidays, St. Patrick's Day. When I was growing up, we always celebrated the day by listening to Irish folk and trad records and eating soda bread and stew. When we got a little older we added green food coloring to our beverages, and we still do that for fun. Over the years, corned beef and cabbage replaced the stew, probably because that's how everyone else celebrates the day. But actually, I prefer the stew.
This is my update of what I remember we ate — though Mom made it with lamb or pork.
The main changes I make are to substitute mushrooms for meat and to roast some of the vegetables rather than boil them. And I cook the potatoes in Guinness; Mom would likely have used the lamb drippings. Unless you add butter, the stew is vegan. I find that the olive oil from roasting the vegetables adds enough fat to bring out the flavors.
Ingredients
Portobello mushrooms (4-6 large caps)
Potatoes (about 2 lbs)
Turnip (1 large, peeled)
Carrot (1-2 cups chopped)
Cabbage (about ½ large head; we like Napa cabbage)
Sweet white onion (1 large)
Olive oil
Balsamic vinegar, a splash
Guinness Stout (2 cans; 28 ounces)
Water (about 4 cups; 32 ounces)
Poultry seasoning (1- 2 tablespoons) divided
Garlic powder (1 tablespoon)
Flour (1/2 to 1 cup, sifted)
Instructions
Cut mushrooms into large chunks, toss in olive oil, garlic powder, and poultry seasoning. Roast at 350 degrees for 20 minutes.
Slice carrots, cabbage, and onion into small chunks. Toss in olive oil, garlic powder, poultry seasoning (1 TB), a splash or two of balsamic vinegar, and roast at 350 degrees until carrots are softening and onion and cabbage beginning to caramelize (around 20 minutes). The carrots can be roasted separately from the cabbage and onion if convenient.
Cut potatoes into chunks and place in a large pot. Cover with Guinness and water. Bring to a boil, then simmer until the potatoes are soft.
Cut up turnip into chunks and add to potatoes about when potatoes are starting to get soft.
When the potatoes and turnips are cooked add the mushrooms and their broth. Add roasted carrots, onions, and cabbage, and 1 tablespoon poultry seasoning. To thicken the liquid, sift flour in gradually.
Serve in a bowl of over Champ (mashed potatoes with cheese, milk, butter, garlic, and chives), and a wedge of soda bread. The soda bread here is from my adaption of the family recipe to use sourdough instead of buttermilk.
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.
References
Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021 Nov;21(11):739-751. doi: 10.1038/s41577-021-00538-7. Epub 2021 Apr 12. PMID: 33846604.
Aleman RS, Moncada M, Aryana KJ. Leaky Gut and the Ingredients That Help Treat It: A Review. Molecules. 2023 Jan 7;28(2):619. doi: 10.3390/molecules28020619. PMID: 36677677; PMCID: PMC9862683.
Christovich A, Luo XM. Gut Microbiota, Leaky Gut, and Autoimmune Diseases. Front Immunol. 2022 Jun 27;13:946248. doi: 10.3389/fimmu.2022.946248. PMID: 35833129; PMCID: PMC9271567.
Gavzy SJ, Kensiski A, Lee ZL, Mongodin EF, Ma B, Bromberg JS. Bifidobacterium mechanisms of immune modulation and tolerance. Gut Microbes. 2023 Dec;15(2):2291164. doi: 10.1080/19490976.2023.2291164. Epub 2023 Dec 6. PMID: 38055306; PMCID: PMC10730214.
Kinashi Y, Hase K. Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity. Front Immunol. 2021 Apr 22;12:673708. doi: 10.3389/fimmu.2021.673708. PMID: 33968085; PMCID: PMC8100306.
Kumar BV, Connors TJ, Farber DL. Human T Cell Development, Localization, and Function throughout Life. Immunity. 2018 Feb 20;48(2):202-213. doi: 10.1016/j.immuni.2018.01.007. PMID: 29466753; PMCID: PMC5826622.
Miyauchi E, Shimokawa C, Steimle A, Desai MS, Ohno H. The influence of the gut microbiome on extra-intestinal autoimmunity. Nat Rev Immunol. 2023 Jan;23(1):9-23. doi: 10.1038/s41577-022-00727-y. Epub 2022 Jun 16. PMID: 35710874.
Mu Q, Kirby J, Reilly CM, Luo XM. Leaky Gut As a Danger Signal for Autoimmune Diseases. Front Immunol. 2017 May 23;8:598. doi: 10.3389/fimmu.2017.00598. PMID: 28588585; PMCID: PMC5440529.
Pisetsky DS. Pathogenesis of autoimmune disease. Nat Rev Nephrol. 2023 Aug;19(8):509-524. doi: 10.1038/s41581-023-00720-1. Epub 2023 May 10. PMID: 37165096; PMCID: PMC10171171.
Twardowska A, Makaro A, Binienda A, Fichna J, Salaga M. Preventing Bacterial Translocation in Patients with Leaky Gut Syndrome: Nutrition and Pharmacological Treatment Options. Int J Mol Sci. 2022 Mar 16;23(6):3204. doi: 10.3390/ijms23063204. PMID: 35328624; PMCID: PMC8949204.
Veauthier B, Hornecker JR. Crohn's Disease: Diagnosis and Management. Am Fam Physician. 2018 Dec 1;98(11):661-669. PMID: 30485038.
Zeng L, Yang Q, Luo Y, Luo Y, Sun L. The Gut Microbiota: Emerging Evidence in Autoimmune and Inflammatory Diseases. Research (Wash D C). 2026 Feb 4;9:1097. doi: 10.34133/research.1097. PMID: 41647244; PMCID: PMC12868559.
Zhu JH, Wu LP, Deng L, Zang SG, Li XB, Chen X, Yu JX. Gut microbiota and metabolism in systemic lupus erythematosus: from dysbiosis to targeted interventions. Eur J Med Res. 2025 Oct 14;30(1):971. doi: 10.1186/s40001-025-03264-1. PMID: 41088420; PMCID: PMC12522637.