Toll-like-receptors-resistant-starch

From Gut to Immune System to Brain…pay the toll with potatoes!

Within our body are small structures called “Toll-like Receptors (TLRs).” These receptors are an important part of our immune system. TLRs are used by components of our immune system to detect the presence of microbes, ie. fungal and bacterial pathogens, that do not belong inside of us, and need to be eliminated. This is a key feature of our “innate immune system.”  The innate immune system is our first-line defense against microbial infections. Prolonged over-stimulation of our innate immune system leads to chronic inflammation and a steady decline in health, often resulting in autoimmune diseases such as diabetes, arthritis, Crohn’s disease, etc… The list is long. The TLRs found in our gut have been shown to interact with resistant starch, as found in potatoes. The interaction reduces inflammation and strengthens the immune system as well as guiding the development of serotonin, an important brain chemical.

RS2 as an Immunity Booster

Resistant Starch (RS) is a key-player in the maintenance and upkeep of TLRs. In just the last couple years, researchers from around the world have been examining just how  closely related TLRs and our intake of RS actually are.

The 2015 paper, “Resistant starches differentially stimulate Toll-like receptors and attenuate proinflammatory cytokines in dendritic cells by modulation of intestinal epithelial cells,” examined exactly how RS interacts with the immune system. This paper opened an entire new line of thinking in how researchers view RS, as stated in the paper:

Immune effects of dietary fibers are often attributed to microbiota-dependent effects. However, some dietary fibers have been reported to bind to specific receptors on immune cells, suggesting microbiota-independent, immune-modulatory effects.

For decades, researchers thought that “fiber” acted by feeding beneficial bacteria (probiotics) who did all the work. Now, for the first time, we see that certain fiber…resistant starch…due to its size and shape, directly binds with TLRs and has an immediate effect on our innate immune system!

The fiber used in this study was high amylose corn starch, a type 2 resistant starch (RS2), sold as a cooking ingredient called Hi-Maize. This same type of RS2 is also found in raw potato starch and banana flour. Also used in the study was Novelose 330, a cooked and cooled (RS3) product not available for consumer purchase, but easily made at home by cooking and cooling your beans, rice, potatoes, and corn meal.

This study clearly shows that RS works much of its magic by simply being there. A spoonful or two of the raw powders, or a serving or two of leftovers every day.

Up to now it was assumed that resistant starch mainly contributes to anti-inflammatory effects by enhancing production of short chain fatty acids by the microbiota. Here, we show that resistant starch by direct interaction with [the innate immune system] can induce a regulatory immune phenotype independent of effects on microbiota. This effect is to our opinion profound…(emphasis mine).

And a second study…

Of further note, another 2015 paper, “Responses in Colonic Microbial Community and Gene Expression of Pigs to a Long-term High Resistant Starch Diet,” Studied the effects of the innate immune system in pigs fed raw potato starch long-term.

Intake of raw potato starch (RPS) has been associated with various intestinal health benefits, but knowledge of its mechanism in a long-term is limited.

Much to the researchers surprise, they discovered that the real “magic” in raw potato starch (RPS) is not the effects on bacteria, butyrate, and all of the other attributes of fiber, but the effect of RPS on the innate immune system!

We found that compared with the control diet, the RPS diet changed the colonic expression profile of the host gene involved in immune response pathway…

We can assume, then, that much of the beneficial change we see to the gut flora is due, in part, to the effects of resistant starch on our immune system.

Toll-like Receptors and Brain Function

Toll-like Receptors have been in the news recently.

Two papers from 2016 suggest that TLRs are responsible not only for keeping our innate immune system running smoothly, but also in directing the flow of chemicals produced by gut bugs and destined for the brain.

The first: “Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation (2016).”

It is clear that microbiota could play a key role in intestinal homeostasis, not only through activation of TLRs but also as a producer of metabolites as butyrate or serotonin.

If you are brave, read the paper. It describes how TLR-2 can control the byproducts produced by gut bacteria and ensure they are turned into serotonin. Serotonin is an important brain chemical, involved in processes like breathing, body temperature, and appetite. In the gut, serotonin reduces inflammation and controls gut motility. It’s quite a lot to grasp, but rest assured that the resistant starch found in potato diets contributes immensely to the success of these diets.

And the second paper…”The Effect of Microbiota and the Immune System on the Development and Organization of the Enteric Nervous System (2016).

Gut microbes metabolize dietary fiber and resistant starch to produce a wide variety of metabolites, including short-chain  fatty  acids  (SCFAs),  which  are  used  as nutrients by colonic epithelial cells and influence host physiology. Recent studies have uncovered a role of SCFAs in the production of serotonin (5-hydroxytryptamine [5-HT]) by enterochromaffin cells (ECs) of the intestinal epithelium. ECs are the largest source of serotonin in the body, which, among other functions, regulate GI motility and platelet function.

OK, OK…this second paper is even harder to read than the first, so again, if you are brave and have a deep understanding of the immune system, click and read. Otherwise, I’ll end with a nice drawing from the paper to illustrate how incredibly complex this all really is. But feel free to read and make your own conclusions! Potatoes contain ample amounts of both fiber and resistant starch, making potatoes the perfect food for immune-boosting, weight loss diets.

toll like receptors

Conclusion

Toll-like Receptors are an important part of our overall health, TLR genes are influenced directly by the consumption of resistant starch, both uncooked and cooked. My book, The Potato Hack describes an all-potato diet that leads to weight loss. Possibly the best feature of a potato diet is not the weight loss, but the effects on our immune system which will lead to long term health benefits. Can The Potato Hack be used to prevent, or even cure, autoimmune diseases? Already the FDA has approved statements that Hi-Maize can help to prevent diabetes, a well-known autoimmune condition.

I’m far from an expert in immunology, people spend entire careers studying this field. I hope my attempts to explain the topic were adequate.

In parting, I’d like to point out that, despite my earlier attempts to compare Toll-like Receptors with toll-booths on highways, the name actually came from  German speaking researchers, who, upon discovering TLRs, proclaimed, “Das ist ja toll!”

Translation:

That’s cool!

And it is cool, isn’t it, how everything is connected?

Eat your spuds.

Tim

25 Comments on “From Gut to Immune System to Brain…pay the toll with potatoes!”

  1. Ingrid January 2, 2017 at 12:15 pm #

    I’m following this blog with great interest here from the northen, snowy part of Sweden. Thank’s for all the work your putting down!

    Like

    • Tim Steele January 2, 2017 at 6:28 pm #

      Won’t be long until that midnight sun is shining! Hang in there.

      Like

  2. Jo tB January 2, 2017 at 7:06 pm #

    I’ve just started reading The Good Gut by Erica Sonnenburg en Justin Sonnenburg and their opening sentences speak volumes:

    “Our gut bacteria belong on the endangered species list.”

    “Thanks to our typical diet, the average American gut bacteria is starving.”

    “It is possible that gut bacterial species that make important contributions to our health will become extinct.”

    So we definitely have to immediately start looking after our “friends” and keep them VERY happy and well fed. Your article is very well timed, as a New Year resolution, to do some serious work on making magic happen. Every study that comes out seems to be even more exciting than the last one. Keep them coming!

    Like

    • Tim Steele January 2, 2017 at 8:14 pm #

      Keep reading all you can, the story is far from done. The Sonnenberg’s book, The Good Gut (http://amzn.to/2j2zKXN), is great. I read it last summer when it came out. But I was a bit disappointed that they lump all fibers together as “Microbial Accessible Carbs,” a phrase that they coined in a 2014 paper. Basically, the book outlines their research from their 2014 paper, Starving our Microbial Self: The Deleterious Consequences of a Diet Deficient in Microbiota-Accessible Carbohydrates (full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896489/). I remember when this paper came out, I was surprised they did not discuss the individual importance of RS, in fact, the term “resistant starch” appears only once in the paper. They focus almost completely on the bacterial changes that accompany a high fiber diet and completely ignore the interaction between fiber and the immune system, except as mediated by microbes.

      From the paper: “Interactions between resident microbes and host leading to immune dysregulation may explain several diseases that share inflammation as a common basis.” What they are overlooking is that some fibers (RS, cough, cough) can and do interact directly outside of microbial influence. Early on, I was amazed to find that RS can be persorbed into the bloodstream, and also acted as a target and trap for pathogens due to molecular mimicry, very similar to the fibers found in human breast milk.

      Also missing from the Sonnenberg’s research is the powerful impact that fiber, particularly RS, has on Treg development…one of the most important factors in immune system regulation. They missed the dozens of papers written on the observations of Treg improvements on high RS diets.

      But, that’s OK…they are getting the word out on the importance of gut health.

      If you are interested, they’ve written a couple more papers this year. Both also miss RS and immune system interactions, but they are both very good:

      Diet-induced extinction in the gut microbiota compounds over generations (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850918/)

      Individualized Responses of Gut Microbiota to Dietary Intervention Modeled in Humanized Mice (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069738/)

      I think that they are focusing too much on the species present and not enough on the interactions between food and immunity. But perhaps that will change in 2017 in light of new research such as the studies on TLR and RS.

      While the microbes make interesting study material, the focus of the public needs to be on the food they eat. It makes me happy that I wrote a gut health book disguised as a fad diet, lol. People see weight loss results and then realize they were tricked into getting a healthy gut.

      Gelukkig nieuwjaar!

      Like

  3. Sal January 3, 2017 at 4:54 am #

    I remember reading something in the book ‘…..we inherit our microbes from our mothers generation after generation…’ I often wonder about the mobility/migration effects on our gut when we stop eating our ancestral diet. Also, I am stuck here quarantined in my bedroom with a cold. Anyway to weaponize PS to combat the common cold? Finally, have there ever been mental health studies on cultures with high RS, like the Irish? Maybe it was the humble potato that help them survive 700 hundred years of English oppression and atrocities.

    Like

    • Tim Steele January 3, 2017 at 8:04 am #

      The weaponization comes before you catch the cold! But, I was just reading that catching the occasional cold proves that your immune system is not overly activated..a good thing.

      Like

      • Wilbur January 3, 2017 at 8:18 am #

        Huh? Getting knocked out once in a while proves a boxer is not overtrained? It seems to suggest more strongly that he is undertrained (or overmatched).

        This doesn’t seem right at all. An overly active immune system might not have the resources to fight off a cold.

        Like

        • Tim Steele January 3, 2017 at 8:41 am #

          I have to credit Dr. Ayers with that tidbit. People who are chronically inflamed also rarely get sick, until they get really, really sick. Inflammation is the bodies response to fight minor illness and injury. It’s normal. I think a sign you are healthy is that when you get a cold or food poisoning, you fight it off easily.

          Like

          • Wilbur January 3, 2017 at 9:25 am #

            Dr. Ayer and I have what seem to be disagreements at the outset that turn into agreement once I understand what he means!

            As I currently understand the discussion, this study agrees with my thoughts

            https://www.ncbi.nlm.nih.gov/m/pubmed/22474371/?i=27&from=chronic%20inflammation%20common%20cold

            Indeed, it identifies the symptoms of a cold as side effects of the inflammation, and those less able to control inflammation are more likely to catch colds (Study 2).

            Now here’s how Dr. Ayers and I might agree: We are constantly catching colds since we are awash in viruses. The immune system must catch colds (be infected with some viruses) so that the body learns and adapts. Without this, yes the body would risk catastrophic disease. But, since the SYMPTOMS of a cold are signs of inflammation, a person with a well-functioning immune system might never feel anything from a viral infection (cold). So, yes, I might be getting colds all the time, but I don’t know since they do not make me feel sick. Someone who often feels the symptoms might have chronic inflammation issues. I like this hypothesis actually.

            Good smell and fast wound healing are also signs of low chronic inflammation. I’m A+ on those!

            Like

            • Tim Steele January 3, 2017 at 9:44 am #

              I think Art’s comment may have been to show some irony that a person with chronic inflammation is constantly fighting infections, so will not catch colds and such easily.

              This paper about Vit D deficiency kind of says the same thing, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4160567/.

              From person experience, I used to get sick quite easily. Flu almost every year and really bad nasal infections every winter. I haven’t had a hint of flu in many years now, and no nasal infections, either.

              Sometimes I’ll feel like I’m coming down with something, you know, that stuffy head, congestion, runny nose thing…but next day I’ll be fine while coworkers are missing a couple days of work.

              Like

              • Wilbur January 3, 2017 at 10:02 am #

                Agree on the last statement! Sometimes I feel like I might be catching a cold but get distracted, and by the time I think about it the feeling is gone. Sometimes I wonder if I just imagine the original feelings. My poor wife, who doesn’t do all that I do, is currently suffering. I don’t even try to distance myself from her anymore when she is sick.

                I also agree with the second to last statement. I used to get sick a lot too.

                Not sure about the first. Like I said, I’ve always agreed with Art once I understand what he’s saying. No matter. I’ll just enjoy not feeling sick!

                Like

              • Jo tB January 4, 2017 at 11:13 pm #

                Do I have chronic low grade inflammation as I have never gotten the flu only a cold when the flu abounds? Since I started taking vitamin D in large doses 10 years ago, I rarely get a cold anymore, which starts with a “tickle” in my throat and very rarely continue onto the nose blowing version. If I start to feel a cold coming on I realise I have been slacking off on my D intake.

                Anyway, nice to know that I am “healthy” !!

                Now all I have to do is get my gut buddies “healthy” as well….

                Like

                • Tim Steele January 5, 2017 at 8:25 am #

                  Actually, if you’ve never gotten the flu, you are probably what’s known as a “FUT-2 Non-secretor.” It means that the tips of the villi in your gut do not secrete fucose, and bacteria behave differently for you than others. Approximately 25% of people have this and don’t know it. Personally, I think non-secretors need to follow a completely different diet, very high in carbs and RS.

                  People with blood type B are most likely to be non-secretors, and also prone to Crohn’s disease, diabetes, and pancreatitis. But, nearly immune to norovirus, H. pylori, and even HIV.

                  Some light reading: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916706/

                  Lots written, get tested, I think it’s easy to test for any doctor should be able to order the labwork needed, or get a 23andMe test kit, it will show up there, too.

                  Like

      • Tanya January 4, 2017 at 4:52 pm #

        I’ve read the same thing, though I don’t really understand the basis of it. I can see it in my life in a close family member, who’s clearly got some chronic health stresses going on, but who gets sick much less frequently than anyone else in the household and for much shorter time periods. I’m a bit worried that he’ll develop autoimmune stuff as part of an overactive immune system.

        Like

        • Tim Steele January 4, 2017 at 7:54 pm #

          You hear all the time about people who were “never sick a day in their life” suddenly coming down with cancer. I don’t know that any of us are immune from cancer and AI disease (cancer is an AI disease, too!), but I do know that the best chance we have at preventing this is to eat right, stay fit, and remove stress from our lives…get plenty of sleep and plenty of sunshine.

          Like

  4. Wilbur January 3, 2017 at 7:26 am #

    That is indeed cool!

    Am I reading the study about long-term RPS and the pigs correctly? That “long-term” is 50 days? If so, maybe the “negative” effects of increased lipopolysaccharides (I had to look that up) were really the effects of a gut still transitioning to a more beneficial microbial community? It would go away after a true long term? It’s funny what researchers call long term. Or sad. I read recently that new, serious complications in immunotherapy drugs are being discovered several years after, but these were unnoticed by researchers because they don’t get funding that spans that long.

    I had known about the connection of beta-glucans to the toll-like receptors (maybe I read the earlier papers). That’s why I enjoy powdered dried mushrooms most days. It’s nice to know that the RPS helps too. We don’t get colds very often anymore.

    Like

    • Tim Steele January 3, 2017 at 8:01 am #

      The pig study was designed quite poorly to study actual physiological response, they simply replaced several pounds of digestible corn starch with indigestible potato starch. It was no surprise there were bacterial and other changes, the surprise seemed to be the large impact on the pig’s immune system. Thanks for reading!

      Like

  5. Teddy January 4, 2017 at 4:16 pm #

    Talking about long term and short term response to an intervention, I am wondering why do tissues heal and recover from major surgery like a C-section in about a week to 10 days and a treatment with antibiotics takes the same time to wipe out gut bugs good, bad or both and then it takes so long for gut wall tissues to recover? Is it that maybe on individual basis one needs to find the right tool to fix the problem and then things will fall into place within a week to 10 days? Maybe that is why some “cures” work for some and not for others. Simply because it was the right tool in one case and it was not for the other.
    What do you guys know/think about this?

    Like

    • Tim Steele January 4, 2017 at 7:48 pm #

      I have pondered over that question for years. To make matters even worse (or better?) the cells that line the gut replace themselves every 3-5 days! Throughout the intestines, there is a continual turnover of cells. Fiberless diets slow the cell turnover (called apoptosis) and polyps and cancer develop easily.

      Also, within the cells that line the gut, are specialized cells that form an integral part of our immune system, such as Peyer’s patches where T-cells and B-cells are exposed to potential pathogens (antigens) among other immune system-related functions. Special immune cells are found in the entire gut from the tonsils to the rectum and even in the mesentery (see Friday’s blog post!). This is known as Gut Associated Lymphoid Tissue (GALT) and makes up something like 60% of your total immune system.

      Here’s where it gets really interesting…even though these GALT cells replace themselves on a weekly basis, the tiny little T-cells that drive your immune system live for years! T-cells, or T-lymphocytes, are a type of white blood cell. They are born in stem cells in bone marrow, then travel around the body and eventually specializing in a task. Some spend months or years in the thymus or tonsils just sampling the foods we eat for pathogens before they travel around the body looking for things to kill. When things go awry, they try to kill us. In a healthy person, there are specialized T-cells whose job is to find and destroy T-cells who are wrongly attacking the host.

      I am simplifying this all tremendously, but my point is that it all starts in the gut. In many RS studies, they examine the GALT produced under conditions of RS feeding, and find that there are more and bigger Peyer’s patches, deeper mucin producing crypts and more complete apoptosis of old and damaged cells.

      Once gut dysbiosis sets in, and the immune system goes rogue, it’s anyone’s guess what exactly is happening and how or if it can be turned around. My focus is, and always will be, on the prevention of gut dysbiosis through targeted application of fiber and RS. For those hoping to cure themselves of autoimmune disease, it may take a long time to get an immune system that behaves. It is imperative to continue eating a very gut-friendly diet so that your new immune cells come from a friendly, healthy place.

      Pharmaceutical attempts to cure AI disease relies on suppressing the immune system (chemotherapy) or relieving symptoms (antiinflammatory drugs). They hope is that the body will start to heal itself if the chronic inflammation is slowed. Alternative medicines for AI are acupuncture, homeopathic meds, and hypnosis. All of these approaches also need a focus on the gut and eating the foods required to create a healthy GALT.

      Whew.

      Like

      • Jo tB January 4, 2017 at 11:34 pm #

        T-cells attacking the host and trying to kill it, made me think of diabetes T1 where the insuline producing Beta cells in the pancreas are killed. That is a process that cannot be reversed, unless you catch it during the “honeymoon” period (first year after diagnosis). I read somewhere the other day that alternate cells in the pancreas can be stimulated to take on the insuline producing role (if I read that correctly). Mimicking capability I think the term was.

        Like

  6. Dominic January 5, 2017 at 8:23 am #

    I have a few queries about prebiotics that a bit of googling around did not answer.
    Does anyone know the following?

    1) Jerusalem Artichokes are high in inulin. Does the inulin survive cooking or do they need to be eaten raw?
    2) Cooked and cooled beans appear to have more RS3 than cooked and cooled potatoes. So why is the focus more on potatoes than on beans for RS3 in most blogs? (I understand potatoes starch is a good source of RS2).
    3) A boiled and cooled potato has about 3g of RS3 / 100g. I’ve read that the figure is higher for oven baked and cooled potatoes but have not seen any figures. Is this correct?
    4) Apples are a source of pectin. Does eating one apple per day provide enough pectin to actually make a difference to my gut? If not I’d rather eat another fruit I enjoy the taste of more.

    Thanks to anyone who can answer any of the above and thanks to Tim for a very interesting blog. I look forward to following it for a long time!

    Like

    • Tim Steele January 5, 2017 at 9:09 am #

      1. Inulin can be heated. The inulin extraction process involves boiling and drying at high temperatures, there is no degradation of inulin in normal cooking.

      2. Yes, beans are a better source of fiber and RS than potatoes or rice. I mention beans quite frequently, and I think they should be in everyone’s rotation of staple foods. I tend to focus on potatoes around here because of the potato hack. A “bean hack” does not work as well as the all-potato diet because beans (and rice) are much more calorie-dense than potatoes and do not have the same satiety profile. Also, many people are sensitive to certain compounds in beans that cause gas or allergies, and all beans are not created equal. I love beans and try to eat them several times a week.

      3. Yes, correct, but hard to accurately measure. In general, potatoes cooked using dry methods will be higher in RS3 than with wet preparations. RS3 formation, called retrogradation, is a function of staling. As the moisture is driven out of the cooked starch, it forms crystalline structures that are resistant to digestion. Moist foods stale slower than dry foods, bread that has gone stale is also higher in RS3 than fresh bread. The difference between roasted and boiled potatoes is similar to the difference between toast and bread pudding, if that makes sense to you.

      4. Just eat the fruit you enjoy most. It’s all good. I think that berries blow apples away in terms of gut health.

      Like

    • Wilbur January 5, 2017 at 11:24 am #

      Baobab is an excellent source of pectin, about 35-50%. I too prefer berries (esp. blackberries) to apples for their nutritional density. I don’t eat my grocery store’s apples at all – tasteless bags of water.

      Like

      • Jo tB January 6, 2017 at 12:00 am #

        I just came across this novel use of Boabab powder:

        “I take two teaspoons of Baobab in a bottle of water to replenish my body’s electrolytes, because it contains potassium, magnesium, and calcium. Add 1/4 teaspoon of Himalayan pink salt and you have yourself a really natural, sugar-free sports drink.”

        I have already added boabab to my fibre mix, which I add to a green smoothie or some joghurt.

        Like

      • Teddy January 6, 2017 at 6:26 am #

        Good to know. I really like it in my cooled down morning green tea. It tastes like lemon juice. I guess it is from the high vit C content.

        Like

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