How time-restricted eating affects leaky gut and systemic inflammation | Satchin Panda
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A leaky gut, otherwise known as intestinal permeability, is a condition in which gaps form between the tight junctions of the endothelial cells that line the gut. These gaps allow pathogens like bacteria or endotoxins – toxins that are released when bacteria die – to leak through the intestinal wall and pass directly into the bloodstream, potentially triggering an acute inflammatory reaction. Leaky gut has been linked with a number of chronic diseases, including Alzheimer’s disease and cardiovascular disease. But overnight fasting during time-restricted eating provides the gut time to heal, preventing leaky gut. In this clip, Dr. Satchin Panda describes the role fasting plays in maintaining a healthy gut and reducing systemic inflammation.
- Rhonda: Do you think that part of the reduced systemic inflammation has to do with the fact that, you know, if you're eating within the time-restricted window... And this is something, you know, your metabolism is optimal during this certain time window. So the first time you take in food sort of starts these peripheral clocks on the liver, for example, which regulate glucose metabolism.
- Satchin: Yeah.
- Rhonda: And if you, you know, don't eat within a window where you're most insulin-sensitive and you start eating later, then you're going to have more inflammation because your blood glucose levels are going to rise and it's going to cause all sorts of problems. Same thing goes with, you know, fatty acid metabolism, right?
- Satchin: Yeah.
- Rhonda: And the intake of fat itself actually can inhibit the beta oxidation process.
- Satchin: Yeah, yeah.
- Rhonda: Right? So, you know, if you're eating within this certain window, you're affecting your metabolism. And that, in turn, would then affect inflammation.
- Satchin: Yeah.
- Rhonda: Possibly.
- Satchin: Yeah. So there's also this idea that there is some amount of gut leakiness. And so some of the bacterial proteins or bacterial membrane component, for example LPS and a few other things, can leak through our gut lining into circulation. And that can illicit immune response. But we know that with time-restricted eating, since our gut repairs itself at night for us, then during fasting time the gut has enough time to repair so that the gut leakiness goes down. So in that way our immune system is actually less exposed to these antigens that might leak through the gut.
- Rhonda: Right.
- Satchin: That's another way that inflammation can go down.
- Rhonda: I remember a colleague of mine who his name is Mark Shigenaga. He was a former colleague of mine when I was doing a postdoc with Bruce Ames, he's a brilliant guy, gut expert. And he was telling me all about... I remember him telling me about how the gut can handle a high fat meal the best in early in the morning.
- Satchin: Yeah.
- Rhonda: Because of all these repair mechanisms and things that are happening. Like, the first thing in the morning, like, it's better to eat...he was saying your high fat meal was more...your gut could handle it better than it could, like, later on in the evening. So it's kind of interesting. But the LPS leakage and all this, very relevant for inflammation.
- Satchin: Yeah.
- Rhonda: And the gut is one of the major sources of inflammation.
- Satchin: Yeah.
The process by which fatty acid molecules are broken down. Beta-oxidation occurs in the mitochondria and produces acetyl-CoA, FADH2, NADH, and H+. Under conditions where glucose is limited, beta-oxidation is an important preceding step for producing the acetyl-CoA needed for ketogenesis.
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).
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 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.
Otherwise known as intestinal permeability – a condition in which gaps form between the tight junctions of the endothelial cells that line the gut. These gaps allow pathogens like bacteria or endotoxins – toxins that are released when bacteria die – to 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 and cardiovascular disease.
Large molecules consisting of a lipid and a polysaccharide with an O-antigen outer core. Lipopolysaccharides are found in the outer membrane of Gram-negative bacteria and elicit strong immune responses in animals through pattern recognition conferred by a toll-like receptor known as TLR4. Even a low dose LPS challenge of 0.6 ng/kg body weight given intravenously can induce a profound, if transient, 25-fold and 100-fold increase in plasma IL-6 and TNF-alpha, respectively.[1] Also known as bacterial endotoxin.
- ^ Boutagy, Nabil E.; McMillan, Ryan P.; Frisard, Madlyn I.; Hulver, Matthew W. (2016). Metabolic Endotoxemia With Obesity: Is It Real And Is It Relevant? Biochimie 124, .
The thousands of biochemical processes that run all of the various cellular processes that produce energy. Since energy generation is so fundamental to all other processes, in some cases the word metabolism may refer more broadly to the sum of all chemical reactions in the cell.
A chemical reaction in which an atom, molecule, or ion loses one or more electrons. Oxidation of biological molecules is associated with oxidative stress, a key driver of many chronic diseases.
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