Lipopolysaccharide
Episodes
Intestinal Permeability: the Bacterial link to Aging, Brain Barrier Dysfunction & Metabolic Disorder
Dr. Patrick's keynote: compromised intestinal barrier affects human health—cardiometabolic function, neurological health, behavior, and more.
In this clip, Dr. Ronald Krauss discusses the possible protective role of LDL cholesterol.
In this clip, Dr. Dominic D'Agostino and Dr. Rhonda Patrick discuss the ketogenic diet and its implications for gut health.
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Intestinal Permeability: the Bacterial link to Aging, Brain Barrier Dysfunction & Metabolic DisorderIntestinal Permeability Alzheimer's Gut Heart Disease Inflammation Depression Blood-Brain Barrier LipopolysaccharideDr. Patrick's keynote: compromised intestinal barrier affects human health—cardiometabolic function, neurological health, behavior, and more.
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In this clip, Dr. Ronald Krauss discusses the possible protective role of LDL cholesterol.
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In this clip, Dr. Dominic D'Agostino and Dr. Rhonda Patrick discuss the ketogenic diet and its implications for gut health.
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In this clip, Wim Hof describes how his breathing techniques affect the immune response and its potential use in combating disease.
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In this clip, Wim Hof discusses how his breathing techniques may allow the body to tap into its natural disease-fighting abilities.
Topic Pages
News & Publications
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Inherited Parkinson's LRRK2 mutations promote excessive inflammatory cytokines that cross blood-brain barrier, trigger neuron damage via microglia www.sciencedaily.com
From the article:
Suspecting that the LRRK2 mutations might be acting outside of the brain, the researchers used an agent – the outer shell of bacteria, called lippopolysaccharide (LPS) – that causes an immune reaction. LPS itself does not pass into the brain, nor do the immune cells it activates, which made it ideal for testing whether this second hit was acting directly in the brain.
When the researchers gave the bacterial fragments to the mice carrying the two most common LRRK2 gene mutations, the immune reaction became a “cytokine storm,” with inflammatory mediators rising to levels that 3-5 times higher than a normal reaction to LPS. These inflammatory mediators were produced by T and B immune cells expressing the LRRK2 mutation.
Despite the fact that LPS did not cross the blood-brain barrier, the researchers showed that the elevated cytokines were able to enter the brain, creating an environment that caused the microglia to activate pathologically and destroy the brain region involved in movement.
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Environmental toxins inhaled through nose may induce inflammation which culminates in the deposit of Lewy bodies in the brain, promoting Parkinson's www.sciencedaily.com
Lewy bodies found in olfactory areas suggest not only is lost smell a sign of neural damage, but rather a direct link to the mechanism creating the disorder:
The loss of a sense of smell is known to be one of the earliest signs of Parkinson’s disease (PD) and can even appear years before the characteristic tremors and loss of motor function are seen. Some scientists believe that olfactory dysfunction may not just be a sign of broader neural damage, but rather may have a more direct linkage to the generation of the disorder itself. In support of this idea, deposits of a protein called alpha-synuclein that form Lewy bodies can be found in olfactory areas, as well as in dying dopamine neurons whose loss triggers PD, and mutations in the gene encoding alpha-synuclein produce PD.
Inflammation triggered in the areas where the olfactory neurons project (recapitulated by lipopolysaccharide) culminate in alpha-synuclein that can cross the blood-brain barrier:
Results of the study, published in the journal Brain Pathology, showed that application of an irritating component of a bacterium’s cell wall induces inflammation in the areas exactly where the olfactory neurons project, called the olfactory bulb. Moreover, these areas show the hallmark signs of PD, depositions of alpha-synuclein, the core components of Lewy bodies. PD is characterized by progressive motor and non-motor symptoms linked to alpha-synuclein pathology and the loss of dopaminergic neurons in the nigrostriatal system. Toxic aggregates of alpha-synuclein can arise from either overexpression of the protein, changes in protein modifications, and from hereditary mutations.
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“Data from our study show that the bacterial trigger does not move across the blood-brain barrier,” said Quan. “Rather, a sequential inflammatory activation of the olfactory mucosa triggers a subsequent expression of inflammatory molecules within the brain, propagating the inflammation.”
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Chronic systemic inflammation induced by lipopolysaccharide can cause microglia to attack the blood-brain barrier www.sciencedaily.com
Obesity promotes circulation of lipopolysaccharide. In animals, chronic systemic inflammation, experimentally induced by injection with LPS, also known as “LPS challenge,” can cause microglia into the brain to switch from protecting the blood-brain barrier to damaging it.
From the article:
Nearly 50 percent of all dementias, including Alzheimer’s, begins with the breakdown of the smallest blood vessels in the brain and their protective “gatekeeper cells,” according to a Keck School of Medicine of USC study.
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A key point of interest was the systemic inflammation induced by injecting the mice with an inflammation-inducing substance. Such injections resulted in the movement of microglia to the blood vessels and increased the permeability of the blood-brain barrier within a few days. Then, the microglia initially acted to protect the blood-brain barrier and limit increases in permeability, but as inflammation progressed, the microglia reversed their behavior by attacking the components of the blood-brain barrier, thus increasing the barrier’s permeability. The subsequent leakage of molecules into the brain had the potential to cause widespread inflammation in the brain and consequent damage to neurons (cells of the nerves).
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50% of all dementias and Alzheimers may start with leaky blood-brain barrier www.sciencedaily.com
From the article:
“Many scientists have focused their Alzheimer’s disease research on the buildup of toxic amyloid and tau proteins in the brain, but this study and others from my lab show that the problem starts earlier – with leaky blood vessels in the brain,” said Berislav Zlokovic, senior author of the study
Reducing fibrinogen that enters the brain through leaky gatekeeping may be important for preventing decline:
Fibrinogen develops blood clots so wounds can heal. When gatekeeper cells are compromised, an unhealthy amount of fibrinogen slinks into the brain and causes white matter and brain structures, including axons (nerve fibers) and oligodendrocytes (cells that produces myelin), to die.
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Inflammatory injury from obesity is mediated by activation of TLR4 (but may be ameliorated by omega-3) www.sciencedaily.com
Knocking out TLR4 in mice ameliorates obesity-associated inflammation, which may come as no surprise since increased circulation of LPS (a potent activator of TLR4) has been implicated in obesity due to associations with increased presence of LPS binding protein.
While genetically knocking out TLR4 is probably not a practical solution to the inflammatory cascade associated with human obesity, which may also be a smoking gun in obesity-associated brain shrinkage and diminished cognition, dietary intake of omega-3 fatty acids EPA and DHA may at least be partly ameliorative (see review). Additionally, a study in breast cancer patients showed that 5 grams per day of EPA and DHA ultimately lead to hypermethylation (usually interpreted as suppressive) of TLR4.
From the article:
When a person consumes more calories than needed, the excess calories are stored in the form of triglycerides inside fat tissue, also known as white adipose tissue (WAT). Researchers know that in obese people, WAT becomes overworked, fat cells begin to die, and immune cells become activated. But the exact mechanism by which this inflammation occurs isn’t fully understood.
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After five months on a high-fat diet, the mice lacking Tlr4 had gained just as much weight, and just as much fat, as other mice on a high-fat diet. But the genetically engineered mice – with [fibro-inflammatory progenitors] that could no longer generate the same signals – no longer had high levels of inflammation. Instead, the levels of inflammatory molecules in their WAT were closer to the levels seen in mice on low-fat diets.
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Polyphenols prevent leaky gut syndrome. www.eurekalert.org
Intestinal hyper-permeability, often referred to as “leaky gut,” is a condition in which the gaps between the cells that line the gut expand. These gaps allow pathogens such as bacteria or endotoxins (i.e., lipopolysaccharide, a major component of the cell membrane of gram-negative bacteria) to leak through the intestinal wall and pass directly into the bloodstream. Leaky gut is common among older adults, putting them at risk for many acute and chronic diseases. Findings from a recent study suggest that a polyphenol-rich diet reduces the risk of leaky gut in older adults.
Polyphenols are bioactive compounds present in fruits and vegetables. Evidence suggests that polyphenols influence the composition and function of the gut microbiota, have beneficial effects on gut metabolism and immunity, and exert anti-inflammatory properties.
The randomized, controlled, crossover trial involved 51 adults (60 years and older) who were living in a residential care facility and had elevated zonulin, a biomarker of impaired gut barrier function. Half of the participants followed their typical diet, but they substituted some items with polyphenol-rich foods while maintaining the same caloric and nutrient intake for eight weeks. The other half consumed their normal diet with no substitutions. After eight weeks, the two groups switched to the opposite diet. Participants underwent physical exams before, during, and after the study and provided blood and fecal samples for analysis.
The polyphenol-rich foods included berries, blood oranges (and their juice), pomegranate juice, green tea, apples, and dark chocolate. On average, participants who ate the polyphenol-rich diet consumed 1391 milligrams of polyphenols per day, while those who ate a typical diet consumed only 812 milligrams of polyphenols per day. The study investigators noted that participants on the polyphenol-rich diet had higher levels of beneficial gut bacteria than those on the typical diet. They also noted that metabolites from cocoa and green tea polyphenols were associated with having higher levels of butyrate (a short-chain fatty acid that benefits gut health) and lower levels of zonulin. These changes improved overall gut health in the study participants, but the participants' age, baseline zonulin levels, and numbers of beneficial gut bacteria, especially those of the Porphyromonadaceae family, influenced the extent of benefit.
These findings suggest that polyphenol-rich foods improve gut health and reduce the risk of leaky gut in older adults. They also underscore the importance of developing dietary habits that promote consumption of polyphenol-rich foods throughout the lifespan. For an easy way to get more polyphenols in your diet, try this polyphenol-rich smoothie.
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Eating spices reduces chronic inflammation. academic.oup.com
Obesity causes chronic inflammation, which promotes atherosclerosis and cardiovascular disease. Previous research suggests that spices such as cinnamon, cumin, and ginger exert short-term anti-inflammatory effects; however, studies with longer durations are needed to confirm these findings. Authors of a recent study found that four weeks of spice consumption reduced inflammation and altered monocyte function in adults at risk of cardiometabolic disease.
Monocytes are white blood cells that respond to infection by promoting inflammation. Obesity and dyslipidemia cause inappropriate activation of monocytes, promoting chronic inflammation in the arteries. Pro-inflammatory monocytes carrying excess lipids, called foam cells, accumulate in arterial walls, narrowing the arteries and restricting blood flow. Consuming spices that contain anti-inflammatory bioactive compounds may help reduce cardiovascular disease risk.
The authors recruited 71 participants and assigned them to consume a standard American diet with added spices in three doses: low (a dash), medium (a quarter teaspoon), or high (a half teaspoon). Participants consumed each dose of spices for four weeks and completed the doses in random order. The spice mixture contained the most common spices used in the United States, the most abundant of which were cinnamon, coriander, ginger, cumin, and parsley. Participants provided blood samples at multiple points throughout the study. Finally, the investigators isolated monocytes from the participants’ blood and exposed the cells to bacterial endotoxin in order to promote inflammation.
Compared to baseline, participants had lower fasting serum levels of the pro-inflammatory cytokine interleukin-6 following four weeks of the medium dose spice blend. The monocytes from these participants also secreted less interleukin-6 when challenged with bacterial endotoxin. Participants consuming the medium and high spice blends had fewer foam cells and more conventional monocytes than participants consuming the low spice blend.
The authors concluded that spices reduced fasting inflammation and altered monocyte behavior. They did not know why the medium dose was more effective in reducing inflammation than the high dose, but they hypothesized that the high dose of spices may have contained such a high level of polyphenols that it promoted oxidative stress. More research is needed to test this hypothesis. This study was funded by the McCormick Science Institute.
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Time-restricted feeding reduces weight gain and cholesterol in male mice. www.sciencedaily.com
A Western diet pattern, characterized by a low intake of fruits and vegetables and a high intake of sugar and processed foods, promotes the development of obesity and metabolic disease. Time restricted eating has been shown to decrease weight and improve metabolic health in humans. However, factors such as age and sex modulate both susceptibilty to obesity and likelihood of responding to weight-loss treatments. Authors of a new report found that male mice experienced greater metabolic benefit from time-restricted feeding than females.
Time-restricted eating, the practice of limiting food intake to an 8- or 12-hour window, is an emerging therapy for the treatment and prevention of metabolic diseases. Much of the research about time-restricted eating in humans is based on research of time-restricted feeding in mice, which has elucidated many of the cellular mechanisms related to [time-restricted eating’s benefits.](https://journals.physiology.org/doi/full/10.1152/ajpregu.00775.2005) These two terms distinguish which population, humans or non-human animals, is practicing time-restricted food intake.
The prevalence of obesity is on the rise in the industrialized world, a problem compounded by an increasing average age in the same populations. The accumulation of extra fat throughout life puts a person at greater risk of metabolic disease as they age. Females are more likely to gain and retain fat mass than males; however, pre-menopausal females tend to have lower rates of type 2 diabetes and cardiovascular disease due to the protective effects of estrogen. Previous research in humans has demonstrated weight loss and improved metabolic health with time-restricted eating; however, additional research is needed to understand the sex- and age-dependent effects of time-restricted eating.
The researchers used male and female mice of two ages: three months old (equivalent to 20-year-old humans) and 12 months old (equivalent to 42 year-old-humans). They fed mice a chow diet representative of a Western diet pattern with 17 percent of calories from sugar (human equivalent of about 25 ounces of soda per day) and 45 percent of calories from fat including lard and soybean oil. Current dietary guidelines recommend limiting solid fats such as lard). Half of the mice had 24-hour access to food while the other half only had restricted access, limited to just nine hours per day. Mice continued their diet for a total of 12 to 13 weeks. After 10 weeks, the researchers measured changes in the animals' body weight, glucose sensitivity, serum cholesterol, fatty liver, muscle performance, and immune response when challenged with bacterial endotoxin.
Although mice in the time-restricted feeding group consumed the same amount of food as mice with constant access to food, time-restricted feeding resulted in 15 percent less weight gain in young male mice and 23 percent less weight gain in older male mice. Time-restricted feeding did not significantly prevent weight gain in female mice. Male mice also experienced a greater reduction in serum cholesterol with time-restricted feeding compared to females. Both older male and female mice had lower rates of insulin resistance and fatty liver while on time-restricted feeding. This protection was likely due to changes in gene expression that increased glucose uptake by and decreased glucose output from the liver. In young male mice, time-restricted feeding preserved muscle mass, function, and performance, but not in young females. Finally, when challenged with bacterial endotoxin, older mice practicing time-restricted feeding were significantly more likely to survive septic shock than mice with 24-hour access to food, demonstrating better health and resilience.
Time-restricted feeding improved survival of septic shock and provided protection against insulin resistance and fatty liver in both sexes; however, male mice experienced greater reductions in body weight and serum cholesterol and maintained greater muscle mass and performance compared to female mice. The authors noted that their research is of particular interest considering the increased risk of severe COVID-19 illness in those with poor metabolic health.
- [Link to full publication.](https://pubmed.ncbi.nlm.nih.gov/34407415/)
- Learn more about the effects of time-restricted feeding and its effects on obesity, muscle mass, and heart health from expert Dr. Satchin Panda in this episode of the Found My Fitness podcast.
- Visit our topic article on time-restricted feeding to learn even more.
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Daily apple consumption decreases multiple markers of obesity-associated inflammation. academic.oup.com
Obesity is characterized by chronic low-grade inflammation, which contributes to the development of cardiovascular disease. While processed foods and beverages high in saturated fats and simple sugars are associated with a higher risk of cardiovascular disease, diets rich in plant-based foods, including fruits, are associated with a lower risk. Findings of a recent report detail the effects of daily apple consumption on inflammation, endotoxemia, and metabolism.
Causes of obesity-associated inflammation include leaky gut, a condition where the intestinal barrier is compromised, leading to increased levels of bacterial endotoxin (toxins that are released when bacteria die) in the bloodstream (called endotoxemia). This increase in endotoxin levels activates white blood cells to secrete pro-inflammatory cytokines such as interleukin (IL)-6 and IL-17. Plant foods such as apples are beneficial for people with obesity because they are rich in bioactive compounds that decrease inflammation and dietary fibers that strengthen the gut barrier.
The researchers recruited 46 participants with overweight and obesity and directed them to avoid foods and beverages rich in polyphenols and/or dietary fibers (e.g., coffee, vegetables, grains, beans, and red/purple/blue fruits) for two weeks. Next, they assigned half of the participants to consume three Gala apples per day for six weeks or to avoid apples. Both groups continued to eat a diet with limited polyphenols and dietary fibers. Participants provided blood samples for the collection of white blood cells and measurement of pro-inflammatory cytokines. After isolating the white blood cells, the researchers stimulated them with endotoxin and measured their response.
Apple consumption decreased plasma C-reactive protein (a pro-inflammatory cytokine) by 17 percent, IL-6 by 12 percent, and endotoxin-binding protein by 20 percent compared with no apple consumption. White blood cells from participants who consumed apples secreted 28 percent less IL-6 and 11 percent less IL-17. While apple consumption increased total antioxidant capacity in blood by 10 percent, it had no effect on cardiovascular disease markers.
These findings suggest that six weeks of daily Gala apple consumption helped mitigate inflammation in those consuming a diet low in polyphenols and fiber, a common feature of the Western diet pattern. Apple consumption may decrease cardiovascular disease risk in those with obesity, even without weight loss.
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Compounds in e-cigarettes trigger inflammation, promoting a leaky gut. ucsdnews.ucsd.edu
In recent years, vaping, or smoking electronic cigarettes (e-cigarettes), has emerged as a popular substitute for smoking tobacco-containing cigarettes. E-cigarettes produce a vapor that may contain nicotine as well as a variety of toxic substances, including some carcinogens. Findings from a new study suggest that some compounds in e-cigarettes trigger inflammation, promoting a leaky gut.
Leaky gut, otherwise known as intestinal permeability, is a condition in which gaps form between the tight junctions between 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. Leaky gut has been linked with a number of chronic diseases, including Alzheimer’s disease and cardiovascular disease.
The authors of the study exposed mice to e-cigarette vapors for one hour per day and then they examined the animals' colons at one week and three months after the chronic exposure. Then they measured gene expression in the colons. They also built gut enteroids – three-dimensional tissue models that incorporate many of the features of human gut tissue, including an epithelial layer surrounding a functional lumen and all of the cell types normally found in the gut. They exposed the enteroids to e-cigarette vapor (with or without nicotine).
They found that exposure to e-cigarette vapor promoted leaky gut, increasing the susceptibility of the gut lining to bacterial infections, and triggering gut inflammation. Use of the two models established that the primary components in the vapor responsible for the harmful effects were propylene glycol and vegetable glycerol, compounds present in more than 99 percent of all e-cigarettes. They also found that e-cigarette vapor altered expression of genes involved in the cellular response to stress, infection, and inflammation.
These findings demonstrate that commonly used substances present in e-cigarettes promote leaky gut and drive inflammation and provide insights into the long-term health effects of e-cigarettes. They also underscore public health efforts to reduce e-cigarette use.
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Obesity can break down our protective blood brain barrier resulting in problems with learning and memory: overactivity of adenosine in obesity www.sciencedaily.comBrain Alzheimer's Obesity Diabetes Coffee Insulin Blood Sugar Blood-Brain Barrier Lipopolysaccharide
Diet-induced insulin resistance caused blood vessels to become leaky which impaired blood and oxygen flow to a brain region involved in learning and memory (animal evidence).
Obesity and insulin resistance are associated with a leaky blood-brain barrier. This new animal study found that a high-sugar combined with a high-fat diet caused shrinkage of the tight junctions between endothelial cells that make up the blood-brain barrier and actual holes in those cells.
Obesity is known to increase toll-like receptor activation through a variety of mechanisms. One of the mechanisms is through through associated increases of circulating of lipopolysaccharide. Another mechanism is the leaking of fatty acids from fatty acids, triggering toll-like receptors through the recognition of damage-associated molecular patterns (DAMPs). (See “obesity” section of toll-like receptor article.)
Furthermore, LPS challenge in animal studies induces microglia in the brain to attack and damage the blood-brain barrier.
Blocking adenosine may play a role in preventing impairment of the blood-brain barrier by diet-induced obesityHowever, adenosine, which helps us sleep and helps regulate our blood pressure and is blocked by caffeine may play a role in preventing some of the damaging effects obesity has on the blood-brain barrier, which promotes dementia.
From the article:
They knew that chronic activation of the receptor Adora2a [an adenosine receptor] on the endothelial cells that line this important barrier in our brain can let factors from the blood enter the brain and affect the function of our neurons.
Now Medical College of Georgia scientists have shown that when they block Adora2a in a model of diet-induced obesity, this important barrier function is maintained.
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In the brain, adenosine is a neurotransmitter that helps us sleep and helps regulate our blood pressure; in the body it’s also a component of the cell fuel adenosine triphosphate, or ATP. Adenosine also activates receptors Adora1a and Adora2a on endothelial cells, which normally supports healthy relationships between brain activity and blood flow.
Problems arise with chronic activation, particularly in the brain, which is what happens with obesity, says Stranahan.
People who have obesity and diabetes have higher rates of cognitive impairment as they age and most of the related structural changes are in the hippocampus, a center of learning and memory and Stranahan’s focus of study. Fat is a source of inflammation and there is evidence that reducing chronic inflammation in the brain helps prevent obesity-related memory loss.
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Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults microbiomejournal.biomedcentral.com
Full Title: Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics
Background: One way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring sugar recovery in urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure was also assessed.
Results: IVS-1 reached significantly higher cell numbers in fecal samples than BB-12 (P < 0.01) and, remarkably, its administration induced an increase in total bifidobacteria that was comparable to that of GOS. Although GOS showed a clear bifidogenic effect on the resident gut microbiota, both probiotic strains showed only a non-significant trend of higher fecal cell numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were reduced in groups IVS-1 (P = 0.050), IVS-1 + GOS (P = 0.022), and GOS (P = 0.010), while sucralose excretion was reduced with BB-12 (P = 0.002) and GOS (P = 0.020), indicating improvements in colonic permeability but no synergistic effects. No changes in markers of endotoxemia were observed.
Conclusion: This study demonstrated that “autochthony” of the probiotic strain has a larger effect on ecological performance than the provision of a prebiotic substrate, likely due to competitive interactions with members of the resident microbiota. Although the synbiotic combinations tested in this study did not demonstrate functional synergism, our findings clearly showed that the pro- and prebiotic components by themselves improved markers of colonic permeability, providing a rational for their use in pathologies with an underlying leakiness of the gut.
Keywords: Synbiotic, Probiotic, Prebiotic, Obesity, Gut barrier function, Autochthonous, Allochthonous, Galactooligosaccharide, Bifidobacteria, Bifidobacterium
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The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons.
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Consumption of broccoli sprouts during late gestation & lactation confers protection against developmental delay induced by maternal inflammation. www.sciencedirect.com
This is an interesting rodent study. The problem is, however, broccoli sprouts are not usually advisable for women that are pregnant because they can be a source of foodborne illness. If proven safe, however, it seems (at the surface) plausible that there could be ways to reduce the risk of in the future. Perhaps through supplementation?
FTA:
Methods: Pregnant Long-Evans rats were administered i.p. Injections of saline (100 μl) or lipopolysaccharide (LPS, 200 μg/kg), every 12 h on embryonic day (E) 19 and 20. In the treatment groups, dams were supplemented with 200 mg/day of dried BrSp from E14 until postnatal day 21. Pups underwent a series of neurodevelopmental reflex tests from postnatal day 3–21 followed by neuropathological analyses.
Note: LPS elicits a strong immune response.
Results: Pups born from the LPS group were significantly growth restricted (p < 0.001) and delayed in hindlimb placing (p < 0.05), cliff avoidance (p < 0.05), and gait (p < 0.001) compared to controls. […] Dietary supplementation with [broccoli sprouts] to offspring exposed to LPS had increased birth weights (p < 0.001), were no longer delayed in acquiring hindlimb placing, cliff avoidance, gait, and posture, and groomed less compared to LPS alone pups (p < 0.01). Histological analyses revealed that LPS pups had reduced myelin basic protein compared to controls.
The discussion had some interesting things to say about why mitigating the fetal inflammatory response is a big deal:
An important recognized antepartum risk factor is the systemic fetal inflammatory response (FIR) [3], which is associated with a four-fold increase in the risk of developing [cerebral palsy]. Both clinical and experimental studies have provided strong evidence supporting the association between FIR and brain injury leading to [cerebral palsy].
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Sulforaphane (found in broccoli sprouts) causes 20% fat loss by changing gut bacteria & increasing mitochondria in fat in mice. www.sciencedaily.comGut Obesity Microbiome Metabolism Inflammation Sulforaphane Fatty Liver NRF2 Endotoxemia Lipopolysaccharide Visceral Fat
Sulforaphane from broccoli sprouts causes 20% visceral fat loss by changing gut bacteria and increasing mitochondria in fat in mice. The mice fed sulforaphane also lowered fatty liver and reduced blood glucose levels. Sulforaphane reduced inflammation by decreasing a species of bacteria in the gut that is responsible for producing endotoxin, which is a major source of inflammation. Also, sulforaphane increased the levels of UCP1, which is responsible for increasing mitochondrial biogenesis (the generation of new mitochondria) in fat (called browning of fat). The browning of fat increases fat metabolism and can lead to fat loss. There have been human studies showing that sulforaphane decreases inflammatory biomarkers and improves blood glucose levels. It will be interesting to see future studies looking at these two new functions of sulforaphane in humans. For more information check out my video on sulforaphane or my podcast with Dr. Jed Fahey, who discovered broccoli sprouts are the best source of sulforaphane. Sulforaphane video: https://youtu.be/zz4YVJ4aRfg Sulforaphane podcast: https://youtu.be/Q0lBVCpq8jc
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Just watched the interview, and it’s easy to see why people do it. He seems very authentic, and his enthusiasm is infectious!
What I was wondering though.. why is an immune response to endotoxin injection a bad thing? Or put another way, why is it better for adrenaline to kick in instead of the immune system… seems counterintutive, no? Or at least, I always thought stress horomones (Cortisol, Adrenaline) are PRO-inflammatory, much like the cytokines that norephinephrine wants to supress.
Minus the epinephrine inducing breathing technique of letting in, more than you let out, is the Wim Hof Method the same as doing Whole Body Cryotherapy (as touted by Tony Robbins)?
I think I’d like to buy his ($200?) course, but doesn’t seem like any theory is covered in it… i.e. why cold exposure increases norephinephrine, and why that may be useful for treating psychological disorders. Can purely physiological / generic disorders (ex. TMAU) be improved?