Fiber plays a pivotal role in fueling good bacteria in the gut, which produce compounds that keep the immune system in check and prevent autoimmune responses. Research suggests that maintaining a protective mucin layer in the gut helps restrict the release of endotoxin from intestinal bacteria, a major source of inflammation. In this clip, Dr. Peter Attia and Dr. Rhonda Patrick discuss how a healthy digestive tract interacts with the immune system to curb inflammation.
Rhonda: So your approach seems to really look at insulin response. It's looking at obviously the IGF-1, mTOR, dietary nutritional factors that are influencing those pathways and then, of course, the rest being fat. For me, I like to think about food as what you're putting in your body not only to activate these pathways or try to keep the pathways from being too active. But also, I like to think about it at the level of the gut because the gut, one, regulates the immune system, big time. I mean that's you've got more immune cells in your gut than you do in any other organ of your body and your gut bacteria, the interaction between your gut bacteria and your gut are also, you know regulating the types of immune cells that you're making, regulatory T cells being put in that.
And also because it's the major source of inflammation, and inflammation,even very recently has been identified to be a driver of the aging process. So eating things that are good for your gut like fiber and avoiding things that are going to cause a lot of gut damage. So I think about those things as well. And then micronutrients which is also a very important. Micronutrients are cofactors for a variety of enzymes and proteins in the body. It makes sure they're functioning proteins that are involved in these processes we're talking about, keeping cancer cells in check. You know, like p53 zinc-dependent proteins, magnesium which is important for repairing damage, things like that. Are those things that you consider at all when you're thinking about the influence of diet on the aging process?
Peter: I don't think about it as much as a lot of people do. And I would hate to use the term I'm a gut skeptic because I think that conjures up a whole bunch of negative images but...so I'm going to be a late adopter on this one, all right? So there are a whole bunch of facts that everybody can rattle off about the gut. A lot of them by the way are kind of BS. So the cells in the gut outnumber the cells in our body 10 to 1, that actually turns out to be false.
Rhonda: So you mean bacterial cells?
Peter: Yeah, sorry, the bacterial cells within our gut. So putting all that stuff aside, there are a whole bunch of really interesting facts. But it reminds me of what a good friend of mine once told me when I was trying to rationalize something I needed to do or thought I needed to do to him. He said, "Why are you doing this?" And I said, "Blah, blah, blah." And he said, "That's a fact, but is it a reason?" And so that's kind of how I feel a little bit about the gut. Like, there's a whole bunch of really interesting stuff but I don't know that it actually matters that much, right?
I'll give you a really idiotic example. The number of ants on this earth outnumber us 10 to 1. I'm making that up. Ergo, we should be doing more to protect the ants by avoiding climate change.
Rhonda: Yeah, but that's irrelevant.
Peter: And I'm saying, "No, that might be true. There might be more ants than us, but we're the species of interest." So that's my first, sort of, kind of, lack of interest. The second is I don't really know what to do with it, right? So I've been through it all, I've gone through all the sequencing, I've done it with patients, and I have found that it's like there's a very crude set of tools that I can use in really obvious cases.
So, all right, a patient that came to me two years ago who had a history of sinusitis, horrible history of sinusitis. So she probably had to do an Augmentin course six times a year because of recurrent sinusitis. She had three surgical procedures, just couldn't get better. So I started working with her. It became pretty clear to me that there was something in her diet that was creating an inflammatory environment that wasn't a structural problem. So we made a lot of dietary changes, things got better, but in parallel to that I sort of suspected that 10 years of 6 cycles of Augmentin probably altered her gut.
And so, yeah, she's an example of someone where I would do a sequence and can be like, "Lo and behold, you're all yeast." Right? Not surprisingly, and disproportionate bacterial overgrowth. Okay, so she's an example of someone in whom the signal was so big that I felt like there was an intervention I could make which was both fixing her diet but also utilizing agents that could alter that. But for the most part, I don't have a clue what to do. And all the people I see who claimed to know what they do, like, they can't convince me that they're knowing what they're doing.
Now, that doesn't mean that you can't...I mean I'm talking outside of a couple of really amazing examples. So we're familiar with how C. diff colitis works and the reversal of C. diff with stool transplants. So those are remarkable examples, but some of the other stuff I'm still not clear of. So I guess what I'm saying is I'm happy to be convinced but I'm not convinced yet that this is a reason and not just a fact.
Rhonda: So I think that focusing on the gut microbiome and the number of bacterial cells that supposedly outnumber our human cells and all that, I don't think that's the important point. You know, so I've become very interested in the gut mostly because of a colleague of mine, Mark Shigenaga, who has been working doing gut research at Children's Hospital in Oakland, and is brilliant. He's been showing me data and I've just been convinced more and more that gut health, making sure that you're keeping the mucin which your gut goblet cells are producing that disgustingly slimy mucus-like material that's keeping and separating the immune cells in your gut from all the microorganism in your gut. And that's very important because when that starts to break down, the immune cells recognize bacteria and they start [crosstalk]...
Peter: Is there...and I'm not asking this rhetorically, I just don't know. Is there an effective way to diagnose that in patients?
Rhonda: So the problem is that endotoxin released into the blood system would be the way to measure it and to diagnose...
Peter: I see, so you could measure it through the lack of barrier basically.
Rhonda: You can measure the endotoxin levels in someone's blood which is a marker, a proxy, if that helps.
Peter: Yeah, like the throughput, yeah.
Rhonda: But the problem is that there's also a lot of false positives. So that's the only concern until that test, the diagnostic test can be defined...
Peter: Because it seems to be a stool test would be a more effective way to measure that.
Rhonda: Yeah, there might be. There might be a way to do that, to measure it in a stool. That would be an interesting thing to explore because the...so what I'm getting at here is I'm a scientist, obviously, you're a scientist and like to understand the mechanism and see solid data before you think something is true. And I've become more convinced that the endotoxin released from the gut which is a constant...I mean, really the major source of inflammation in the body is coming from the...
Peter: And to be clear Rhonda, I'm not disputing that. So to be clear, I bought that thesis actually when I was a surgical resident because we would see endotoxemia, right? A surgical procedure gone bad endotoxemia, ICU, death. I know what that looks like in its most extreme state. What I think I'm more of a skeptic of, and again, a skeptic waiting to be convinced, is that I can make that diagnosis in a non-catastrophic case which is basically the chronic case and make an intervention either through some alteration in the microbiome itself or meaning directly or indirectly through diet or other variables. And I think that it would be very interesting, sort of, path to go down but, again, there's so many things I don't know at the moment, I'm just trying to focus on the ones that I do know.
Rhonda: Yeah. There is some interesting work coming out of, like, Justin and Erica Sonnenburg Lab over at Stanford. I recently had a discussion with them on looking at the role of fiber and certain types of fiber in fueling different species of bacteria in the gut and how those are generating short-chain fatty acids and other signaling molecules which are regulating hematopoiesis, they're regulating the number of Tregs that we're making. So it is very interesting that feeding our gut certain types of fiber which are present in vegetables and a variety of fruits even, do have a positive effect on the immune system via the signaling molecules that are being made in the gut.
So that's very interesting, and it is one thing that I consider when I'm thinking about the effects of diet on longevity.
Also known as Amoxicillin/clavulanic. An antibiotic useful for the treatment of a number of bacterial infections. It is a combination antibiotic consisting of amoxicillin trihydrate, a beta-lactam antibiotic, and potassium clavulanate, a beta-lactamase inhibitor.
A substance whose presence is essential for the activity of an enzyme. Many minerals and vitamins are cofactors for enzymes.
Presence in the blood of endotoxin, which, if derived from gram-negative rod-shaped bacteria may cause shock.
A type of toxin released when bacteria die. Endotoxins can leak through the intestinal wall and pass directly into the bloodstream. The most common endotoxin is lipopolysaccharide (LPS), a major component of the cell membrane of gram-negative bacteria. If LPS leaks into the bloodstream, it can trigger an acute inflammatory reaction. LPS has been linked with a number of chronic diseases, including Alzheimer’s disease, inflammatory bowel disease (Crohn’s disease or ulcerative colitis), cardiovascular disease, diabetes, obesity, autoimmune disorders (celiac disease, multiple sclerosis, and type 1 diabetes), and psychiatric disorders (anxiety and depression).
Any of a group of complex proteins or conjugated proteins that are produced by living cells and act as catalyst in specific biochemical reactions.
A molecule composed of carboxylic acid with a long hydrocarbon chain that is either saturated or unsaturated. Fatty acids are important components of cell membranes and are key sources of fuel because they yield large quantities of ATP when metabolized. Most cells can use either glucose or fatty acids for this purpose.
A glandular, modified simple columnar epithelial cell whose function is to secrete gel-forming mucins, the major components of mucus. They are found scattered among the epithelial lining of organs, such as the intestinal and respiratory tracts. They are found in the trachea, bronchi and larger bronchioles in the respiratory tract, small intestines, the large intestine, and conjunctiva in the upper eyelid. Goblet cells are a source of mucus in tears.
The production of red bloods cells, white blood cells, and platelets from hematopoietic stem cells, which occurs in the bone marrow. Also called hematogenesis, or hematopoiesis.
A critical element of the body’s immune response. Inflammation occurs when the body is exposed to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective response that involves immune cells, cell-signaling proteins, and pro-inflammatory factors. Acute inflammation occurs after minor injuries or infections and is characterized by local redness, swelling, or fever. Chronic inflammation occurs on the cellular level in response to toxins or other stressors and is often “invisible.” It plays a key role in the development of many chronic diseases, including cancer, cardiovascular disease, and diabetes.
A peptide hormone secreted by the beta cells of the pancreatic islets cells. Insulin maintains normal blood glucose levels by facilitating the uptake of glucose into cells; regulating carbohydrate, lipid, and protein metabolism; and promoting cell division and growth. Insulin resistance, a characteristic of type 2 diabetes, is a condition in which normal insulin levels do not produce a biological response, which can lead to high blood glucose levels.
One of the most potent natural activators of the AKT signaling pathway. IGF-1 stimulates cell growth and proliferation, inhibits programmed cell death, mediates the effects of growth hormone, and may contribute to aging and enhancing the growth of cancer after it has been initiated. Similar in molecular structure to insulin, IGF-1 plays a role in growth during childhood and continues later in life to have anabolic, as well as neurotrophic effects. Protein intake increases IGF-1 levels in humans, independent of total caloric consumption.
An enzyme that participates in genetic pathways that sense amino acid concentrations and regulate cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription. mTOR integrates other pathways including insulin, growth factors (such as IGF-1), and amino acids. It plays key roles in mammalian metabolism and physiology, with important roles in the function of tissues including liver, muscle, white and brown adipose tissue, and the brain. It is dysregulated in many human diseases, such as diabetes, obesity, depression, and certain cancers. mTOR has two subunits, mTORC1 and mTORC2. Also referred to as “mammalian” target of rapamycin.
Rapamycin, the drug for which this pathway is named (and the anti-aging properties of which are the subject of many studies), was discovered in the 1970s and is used as an immunosuppressant in organ donor recipients.
The collection of genomes of the microorganisms in a given niche. The human microbiome plays key roles in development, immunity, and nutrition. Microbiome dysfunction is associated with the pathology of several conditions, including obesity, depression, and autoimmune disorders such as type 1 diabetes, rheumatoid arthritis, muscular dystrophy, multiple sclerosis, and fibromyalgia.
Vitamins and minerals that are required by organisms throughout life in small quantities to orchestrate a range of physiological functions. The term micronutrients encompasses vitamins, minerals, essential amino acids, essential fatty acids.
A mucopolysaccharide or glycoprotein that is the chief constituent of mucus secreted by the epithelial cells lining the gut in order to produce a barrier preventing infection by microorganisms inhabiting the gut.
Also known as TP53, this gene homolog is crucial in multicellular organisms, where it prevents cancer formation, thereby functioning as a tumor suppressor. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence, TP53 is classified as a tumor suppressor gene.
Also known as T regulatory cells or Tregs. A component of the immune system that suppress immune responses of other cells. This is an important "self-check" build into the immune system to prevent excessive reactions. Regulatory T cells come in many forms with the most well-understood being those that express CD4, CD25, and Foxp3 (CD4+CD25+ regulatory T cells).
A molecule that allows cells to perceive and correctly respond to their microenvironment, which enables normal cellular function, tissue repair, immunity, cognition, and more. Hormones and neurotransmitters are examples of signaling molecules. There are many types of signaling molecules, however, including cAMP, nitric oxide, estrogen, norepinephrine, and even reactive oxygen species (ROS).
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