Giving children allergies with pets

This 2021 human study investigated development and persistence of allergies:

“Allergic rhinitis (AR) is a common IgE-mediated disorder involving troublesome symptoms of nasal congestion, nasal itch, sneezing, and associated eye symptoms. Like many chronic health conditions, AR stems from complex gene–environment interactions.

130 subjects with AR were recruited. Control population included 154 healthy children who underwent a regular physical examination in the same ear, nose and throat clinic as AR patients. Individuals with history of asthma or atopic dermatitis were excluded.

AR analysis

Plenty of contradictory associations exist as whether furred pet exposure (cats and dogs) may be a risk or a protective factor for AR development. Discrepancies are likely due to the ubiquitous nature of pet allergens, while pet owners are more concerned about sanitation and many other hygiene-related reasons.

Interaction of early-life pet exposure with methylation level of ADAM33 increased the risk for AR onset 1.423 times more in children. This study provides evidence that:

  • Early-life pet exposure and low methylation level of ADAM33 increase AR risk in children; and
  • The interaction between pet exposure and methylation level of ADAM33 may play an important role in development of AR.”

https://aacijournal.biomedcentral.com/articles/10.1186/s13223-021-00526-5 “Interaction between early-life pet exposure and methylation pattern of ADAM33 on allergic rhinitis among children aged 3–6 years in China”


There’s nothing children can do about who their parents were. Exposing them to pet allergens, though, may be another example of early-life experiences causing lifelong effects.

Week 56 of Changing to a youthful phenotype with sprouts

1. Per Improving healthy compounds of broccoli sprouts and Broccoli sprouts’ immune effects, this week I added mustard sprouts and red cabbage sprouts to my twice-daily routine of eating 3-day-old microwaved broccoli sprouts.

At first, I started mustard and red cabbage seeds with the same 10.7 gram weight (one tablespoon) of seeds. They grew well such that after three days, mustard sprouts weighed an average 61.2 g, and red cabbage sprouts weighed 60.3 g average. Both of these were slightly less than broccoli sprouts’ 65.5 g average.

3-day-old mustard sprouts substantially mellowed out from mustard seeds’ effects. After microwaving mustard sprouts to ≤ 60°C (140°F) and letting them sit for five minutes, I still felt constant nose burn while eating them. 3-day-old red cabbage sprouts were milder than broccoli sprouts, so no difficulties.

The main problem with doing one tablespoon seed weights of all three Brassicaceae species consistently was that 61.2 + 60.3 + 65.5 = 187 g (6.6 ounces) twice a day was too much for me. I eat a lot of low-calorie fibrous food everyday to make my gut microbiota happy. An extra 4+ oz increase at the same time as twice-daily broccoli sprouts put my stomach over the top.

I changed to make equal contents of these three Brassicaceae species be the 10.7 g (one tablespoon) that I started sprouting twice a day.

2. I haven’t seen relevant mustard and red cabbage 3-day-old sprout studies, only 7+ day microgreen and mature plant studies. Evidence is limited in determining effects of cutting my estimated 52 mg of daily sulforaphane intake from broccoli sprouts by two-thirds starting this week.

A. I’ve eaten a clinically-relevant amount of sulforaphane every day for 4+ times longer than any clinical trial. I’ve experienced many positive effects described in studies, and look forward to further improvements.

Reducing sulforaphane intake from broccoli sprouts to 17 mg is still within boundaries of measurable effects. As an example, Upgrade your brain’s switchboard with broccoli sprouts found effects from a daily sulforaphane 17.3 mg (100 µmol) intake.

B. Mustard’s main glucosinolate, sinigrin, hydrolyzes to allyl isothiocyanate, and is in the same aliphatic group as broccoli’s glucoraphanin, which hydrolyzes to sulforaphane. An example of their similar effects was in a citation of Eat broccoli sprouts for DIM:

“Isothiocyanates are both inducers and substrates for Phase II enzymes as glutathione-S-transferases, and polymorphisms of these enzymes have a significant impact.”

Mustard’s myrosinase enzyme activities over and above broccoli myrosinase were highlighted in cited studies of Does sulforaphane reach the colon? Pretty sure that mustard sprouts’ myrosinase ≤ 60°C increases broccoli sprouts’ sulforaphane.

C. Red cabbage’s main glucosinolate is also glucoraphanin. Here’s a graphic from a 2010 study RED CABBAGE, A VEGETABLE RICH IN HEALTH-RELATED GLUCOSINOLATES which compared its glucoraphanin content with white cabbage:

red cabbage glucoraphanin vs white cabbage

The seeds I received were an “Agnostic” variety. In clarification correspondence with my supplier, I received a response “It means in this use ‘Generic’ or Variety not stated. Meaning it is just whatever variety of Red cabbage we bought and we don’t know the exact specifics.” 🙄

Red cabbage anthocyanins have a larger extent than broccoli anthocyanins, which was highlighted in Colorize your diet, Red cabbage pigments and the brain, and Measuring bioavailability. Figure 5 of Lab analyses of broccoli sprout compounds had analysis of three red cabbage cultivars’ 9-day-old sprouts. Glucosinolates are on top, hydrolysis products on the bottom. Glucoraphanin is red 4MSOB in A, and sulforaphane is red 4MSOB-ITC in C:

red cabbage 9-day-old sprouts

D. In summary, I don’t think I’ve significantly reduced broccoli sprouts’ effects by substituting two-thirds weight with two other Brassicaceae species. I haven’t noticed that growth characteristics / compounds interfered with each other.

Still looking for mustard and red cabbage 3-day-old sprout studies. My current Brassicaceae species composite is tasty, and doesn’t cause mustard nose burn.

3. This Brassicaceae species composite isn’t photogenic:

PXL_20210502_214348538

Red cabbage sprouts by themselves are pretty.

PXL_20210504_212505224

4. I still eat 3-day-old oat sprouts twice a day per Sprouting hulled oats. I don’t eat them with Brassicaceae species, but wait at least an hour later with Avena nuda oats in the morning, and AGE-less chicken vegetable soup in the evening.

Colorize your diet

This 2020 review subject was anthocyanins in Brassicaceae species:

“Anthocyanins provide red to blue colors in Brassicaceae plants, have nutritional value, and pharmaceutical potential. This review summarizes chemical composition, stability, bioavailability, and health benefits.

Edible sprouts are good sources of anthocyanins. Even within the same species, content of anthocyanins may vary with cultivar, growing season, growth condition, and plant organ.

Acylated anthocyanins were more stable than non-acylated anthocyanins. Bioavailability is the proportion of nutrient reaching systemic circulation.

Brassicaceae anthocyanins

Large amounts of unabsorbed anthocyanins reached the large intestine, where they were extensively metabolized by microbiota, forming simple anthocyanins, which were much more bioavailable. Degradation products can also be absorbed.

When these events are taken into account, Brassicaceae anthocyanins might be more bioavailable than previously perceived.

Stability of Brassicaceae anthocyanins may be beneficial in preventing certain chemical degradation in the gastrointestinal tract. Anthocyanins reaching blood circulation may be different from original food compounds.

Brassicaceae anthocyanins possess potential:

  • Antioxidant;
  • Anti-cancer;
  • Anti-inflammatory activities;
  • Protection against hepatic andrenal damage; and
  • Cardiovascular disease.

Most evidence is based on in vitro studies. More studies are necessary to further understand health benefits, as well as levels of consumption to maximize benefits, and mechanisms involved.”

https://www.tandfonline.com/doi/abs/10.1080/10408398.2020.1852170 “Anthocyanins in Brassicaceae: composition, stability, bioavailability, and potential health benefits” (not freely available)


I found this review as a fourth-order citation of related papers.

One aspect of research on short-chain fatty acids

To further understand An overlooked gut microbiota product, a 2018 rodent study found:

“Microbial metabolites short-chain fatty acids (SCFAs) have been implicated in gastrointestinal functional, neuroimmune regulation, and host metabolism, but their role in stress-induced behavioural and physiological alterations is poorly understood

SCFAs are primarily derived from fermentation of dietary fibres, and play a pivotal role in host gut, metabolic and immune function. All these factors have previously been demonstrated to be adversely affected by stress.

Administration of SCFAs to mice undergoing psychosocial stress alleviated enduring alterations in anhedonia and heightened stress-responsiveness, as well as stress-induced increases in intestinal permeability.

experimental design

SCFA treatment alleviated psychosocial stress-induced alterations in reward-seeking behaviour, and increased responsiveness to an acute stressor and in vivo intestinal permeability. In addition, SCFAs exhibited behavioural test-specific antidepressant and anxiolytic effects, which were not present when mice had also undergone psychosocial stress.”

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/JP276431 “Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations”


One way researchers advance science is to relate aspects of their findings to previous studies. That approach works, but may miss items that weren’t covered in previous research.

This study fed specific quantities of three SCFAs – acetate, butyrate, and propionate – apparently due to previous research findings. If other SCFAs produced by gut microbiota were ignored – like crotonate (aka unsaturated butyrate) – how would that approach advance science?

I found this study from its citation in Harnessing endogenous defenses with broccoli sprouts.

An overlooked gut microbiota product

This 2021 review subject was histone crotonylation:

“Histone crotonylation is a newly identified epigenetic modification that has a pronounced ability to regulate gene expression. It belongs to an expanding group of short chain lysine acylations that also includes the extensively studied mark histone acetylation.

Histone Kcr was first identified in 2011 where it was found to be mainly associated with active chromatin. Kcr occurs on the ε-amino group of the lysine side chain, where it neutralizes the positive charge of this residue. The loss in positive charge on histone Lys residues weakens DNA interaction, thus making chromatin less compact and accessible to DNA-binding factors.

Crotonate, like other short chain fatty acids (SCFAs), is mainly produced by gut microbiota during fermentation of partially and nondigestible carbohydrates. Circulating SCFAs (acetate, crotonate, butyrate, and propionate) can be taken up by tissues and converted into their cognate short-chain acyl-CoAs, the direct donors of histone Lys acylations.

fcell-09-624914-g001

Crotonyl-CoA is generated as a by-product of fatty acid and amino acid metabolism. Synthesis of crotonyl-CoA can occur in mitochondria or the cytoplasm. Evidence suggests that histone acylations are directly sensitive to changes in concentrations of their corresponding acyl-CoA metabolites, and therefore can act as indicators of cellular metabolic state.

Only a small number of Kcr sites in human histones have been identified so far. This is in part due to a lack of commercially available Kcr site-specific antibodies, which has meant much of the research in this field has focused on studying total histone crotonylation. This is likely to limit our understanding of the importance of histone Kcr, as functional impact of modification at specific sites cannot be readily assessed.”

https://www.frontiersin.org/articles/10.3389/fcell.2021.624914/full “The Regulation and Function of Histone Crotonylation”


At first I thought I had missed recent studies of gut microbiota producing crotonate. Searching again for “crotonate” “microbiota” 2020 2021, I didn’t find any that weren’t cited by this paper.

A lack of research could be due to factors mentioned above. It may also be that researchers just don’t look for evidence of the circulating SCFA crotonate.

Broccoli sprouts’ immune effects

Two 2021 papers, with the first’s subject being sulforaphane’s immune effects:

“Effects of sulforaphane (SFN) on immune response generate scientific interest because of its bioavailability, which is much higher than other phytochemicals, and its capacity to induce Nrf2 target genes. Clinical trials suggest that sulforaphane produces favorable results in cases where pharmaceutical products fail.

SFN exhibits the highest bioavailability among well-known antioxidant phytochemicals, such as quercetin (20-fold higher) and curcumin (80-fold higher). SFN confers a high potential to be used either as a nutraceutical to improve health status, or as pharmaceutical to treat disease states.

molecules-26-00752-g001

Sulforaphane exerts a pleiotropic effect on immunological response, and the final effect depends on cell type.

  • In lymphocyte T-cells, SFN induces ROS production, GSH depletion, and repression of inflammatory cytokines, resulting in suppression of immune and inflammatory responses.
  • In monocytes and macrophages, SFN stimulates immune response by inducing Nrf2, thus triggering antioxidant and anti-inflammatory responses.”

https://www.mdpi.com/1420-3049/26/3/752/htm “Potential of Sulforaphane as a Natural Immune System Enhancer: A Review”


A second study was Fertilization and Pre-Sowing Seed Soaking Affect Yield and Mineral Nutrients of Ten Microgreen Species:

“Ten tested microgreen species [amaranth, arugula, basil, broccoli, red cabbage, Daikon radish, kale, kohlrabi, mustard, and green pea] in this study varied in fresh and dry shoot weights, shoot height, and mineral nutrient concentrations.”

This study grew sprouts for 6 – 18 days before harvesting. Its study design didn’t require sampling along the way to discover informative compositional changes, as did 2020’s 3-day-old broccoli sprouts have the optimal yields and Broccoli sprout compounds include sinapic acid derivatives.

Their supplier was the same as I used for broccoli and red cabbage seeds. No endorsement is intended.

I’d rather use an unknown broccoli variety than this study’s broccoli cultivar, Waltham 29. It was found to be relatively glucoraphanin-deficient when measured in a 2004 study referenced in Tailoring measurements for broccoli sprouts, 32nd of 34 tested.

Received these today:

PXL_20210424_191628875

I’ve asked for clarification of the red cabbage seed variety I received. Not sure what “Agnostic” means in a “Red Cabbage Microgreen – Agnostic” context. 🙂

Mustard and red cabbage sprouting will follow Improving healthy compounds of broccoli sprouts efforts, minus that study’s laboratory setup and duration. I expect synergistic effects from handling both species’ sprouts with my protocol for microwaved 3-day-old broccoli sprouts.

Benefits of eating fermentable fiber

This 2021 review subject was effects of short-chain fatty acids produced by gut microbiota:

“SCFAs are the main players in the interplay between diet, microbiota, and health. SCFAs contribute to intestinal homeostasis and regulation of energy metabolism.

SCFAs regulate the blood–brain barrier and neuroimmunoendocrine functions. During gestation, SCFAs can cause epigenetic imprinting and protect against allergic airway disease.

gr3_lrg

Fiber reaching the colon is anaerobically fermented by gut bacteria, which produce SCFAs. Nondigestible polysaccharides are found in plant cell walls, and are further classified into soluble and nonsoluble dietary fibers.

A role for SCFAs in histone modification of tissues in the body was definitively shown by dietary supplementation of germ-free mice with microbially produced acetate, propionate, and butyrate. These SCFAs increased acetylation of histone H4 and H3 in a tissue-specific fashion.

Most research to date has focused on butyrate but unlike acetate and propionate, it is typically present in undetectable or very low concentrations in the body. SCFAs appear to influence health through three principal mechanisms:

  1. Altering levels of HAT [histone acetyltransferase] and HDAC [histone deacetylase] activity;
  2. Signaling by specific fatty acid-sensing GPCRs [G-protein-coupled receptors]; and
  3. Anti-inflammatory mechanisms in the periphery and tissues due to the first two mechanisms.”

https://www.cell.com/trends/microbiology/fulltext/S0966-842X(21)00035-4 “Microbial Regulation of Host Physiology by Short-chain Fatty Acids”


PXL_20210412_104327851

Effects of another broccoli sprout compound

This 2020 rodent study investigated effects of broccoli sprout hydrolysis compound indole-3-carbinol:

“I3C metabolites act as ligands of the aryl hydrocarbon receptor (AhR), an important sensor for environmental polyaromatic chemicals. We investigated how dietary AhR ligand supplementation influences AhR target gene expression and intestinal microbiota composition.

Environmental signals, such as dietary, microbial, or xenobiotic factors, are sensed in intestinal tissue AhR, an important regulator of metabolism. It influences immune cell homeostasis and immune activation in the intestine.

AhR activation plays an important role in intestinal immunity, contributing to intestinal homeostasis, inflammation, and host defense:

  • AhR activation through high affinity AhR ligands has been shown to stimulate production of antimicrobial peptides.
  • AhR has been shown to be an important regulator of T cell immunity.

This indicates a major role of AhR in resolving intestinal inflammation.

High fat diet and control diet lead to reduced expression of Ahrr in intestinal immune cells.

High fat diet and control diet lead to reduced expression of Ahrr in intestinal immune cells.

Mucosal surface area of the gut represents an enormous area in direct contact with the environment. In addition to occasional pathogen encounters, the intestinal immune system is constantly exposed to antigens from diet or microbiota.

Gut-associated immune cells maintain a balance between protection against harmful infections and tolerating harmless food-derived antigens and commensals.

Our findings are in agreement with reports that dietary I3C supplementation restored AhR activation in intestinal mucosa under conditions of malnutrition and deprivation of natural AhR ligands. In humans, such malnutrition may result from a severely reduced consumption of vegetables and fruit in favor of a carbohydrate rich, high fat diet.”

https://www.mdpi.com/1422-0067/21/9/3189/htm “Dietary AhR Ligands Regulate AhRR Expression in Intestinal Immune Cells and Intestinal Microbiota Composition”


Our gut microbiota outnumber our human cells. Treat them well with broccoli sprout compounds, resistant starch, and fermentable fibers, and expect reciprocity.

Every hand’s a winner, and every hand’s a loser

Another great blog post Know When To Fold ‘Em by Dr. Paul Clayton:

“Newly formed proteins entering the endoplasmic reticulum must be correctly folded to achieve their final form and function. This is a complex procedure with a failure rate of over 80%.

When metabolism is sufficiently skewed, accuracy of protein folding in the endoplasmic reticulum falls below an already low baseline of 20%. Accumulation of misfolded or unfolded proteins in the endoplasmic reticulum then triggers stress.

Integrated Stress Response (ISR) is something that cells do when they are affected by major stressors:

  • ISR turns down global protein synthesis, which is designed to kill virally infected or cancerous cells. If it kills the cancer cell or virally infected cell, that is the end of it.
  • If the stressor is in the heat / hypoxia / nutrient group, however, ISR effectively puts a cell into dark mode until hard times are over. Once the stressor has passed, a cell can then start to recover and return to homeostatic health.
  • But if the stressor is sustained, a low-grade ISR continues to smolder away, causing long-term impairment locally and ultimately systemically. Accumulation of misfolded or unfolded proteins activates ISR, leading to a down-regulation of protein synthesis, and increasing protein folding and degradation of unfolded proteins.

This is analogous to inflammation. Acute inflammatory responses to a pathogen or to tissue damage are entirely adaptive, and essential. Chronic inflammation, on the other hand, causes local and eventually systemic damage if left unchecked for long enough.”


A 2020 rodent study was cited for “reversing age-related cognitive decline”:

“This suggests that the aged brain has not permanently lost cognitive capacities. Rather, cognitive resources are still there, but have been somehow blocked, trapped by a vicious cycle of cellular stress.

Our work with ISR inhibition demonstrates a way to break that cycle, and restore cognitive abilities that had become walled off over time.

stress response inhibitor effects

If these findings in mice translate into human physiology, they offer hope and a tangible strategy to sustain cognitive ability as we age.”

https://elifesciences.org/articles/62048 “Small molecule cognitive enhancer reverses age-related memory decline in mice”


I’m curious as to why sulforaphane hasn’t been mentioned even once in Dr. Paul Clayton’s blog, which started three years ago. Do hundreds of sulforaphane studies performed in this century not contribute to his perspective? Polyphenols are mentioned a dozen times, yet they are 1% bioavailable compared with 80% “small molecule” sulforaphane.

Advice from the song depends on your definition of money:

“Know when to walk away
Know when to run
Never count your money
When you’re sitting at the table”

Several diseases, one treatment?

This 2021 review summarized three dietary supplements’ effects on psychiatric symptoms:

“Upregulation of Nrf2 has been suggested as a common therapeutic target for major neuropsychiatric disorders. In this paper, evidence is presented showing how NAC [N-acetyl-cysteine], coenzyme Q10 (CoQ), and melatonin can ameliorate many important effects of oxidative stress by upregulating Nrf2.

Given its key role in governing cellular antioxidant response, upregulation of Nrf2 has been suggested as a common therapeutic target in neuropsychiatric illnesses such as major depressive disorder, bipolar disorder, and schizophrenia. These are associated with chronic oxidative and nitrosative stress, characterised by elevated levels of reactive oxygen species, nitric oxide, and peroxynitrite.

CoQ:

  • Acts as a superoxide scavenger in neuroglial mitochondria;
  • Instigates mitohormesis;
  • Ameliorates lipid peroxidation in the inner mitochondrial membrane;
  • Activates uncoupling proteins;
  • Promotes mitochondrial biogenesis; and
  • Has positive effects on the plasma membrane redox system.

Melatonin:

  • Scavenges mitochondrial free radicals;
  • Inhibits mitochondrial nitric oxidesynthase;
  • Restores mitochondrial calcium homeostasis;
  • Deacetylates and activates mitochondrial SIRT3;
  • Ameliorates increased permeability of the blood-brain barrier and intestine; and
  • Counters neuroinflammation and glutamate excitotoxicity.”

https://www.researchgate.net/publication/348309816_Increasing_Nrf2_Activity_as_a_Treatment_Approach_in_Neuropsychiatry “Increasing Nrf2 Activity as a Treatment Approach in Neuropsychiatry” (registration required)


These reviewers explored three selected supplements, citing 380 references. They overlooked something, though. There was only one mention of sulforaphane in their paper, yet four references’ titles included sulforaphane?

I take two of the three exogenous supplements discussed. The one I stopped taking over a year ago – NAC – was thoroughly discussed, but not in contexts directly related to the Nrf2 transcription factor. Why?

Switch on your Nrf2 signaling pathway pointed out:

“We use NAC in the lab all the time because it stops an Nrf2 activation. So that weak pro-oxidant signal that activates Nrf2, you switch it off by giving a dose of NAC. It’s a potent antioxidant in that right, but it’s blocking signalling. And that’s what I don’t like about its broad use.”

The current review noted that Nrf2 is activated by oxidative stress. NAC is a precursor to glutathione – our main endogenous antioxidant – and neither one activates Nrf2 pathways.

What does? Sulforaphane.

PXL_20210412_104353167

A bat epigenetic clock

This 2021 study subject was bats:

“Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity.

Hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that:

  • Age-related methylation change is influenced by developmental processes, while
  • Longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that
  • Bat longevity results from augmented immune response and cancer suppression.

Molossus molossus [a short-lived species] age genes are not enriched for immunity genes or genes that frequently mutated in cancer. However, M. molossus longevity genes exhibit significant overlap with genes involved in immunity and genes frequently mutated in human tumors.

Similar overlap patterns among immunity, longevity, and tumor-mutated genes also exist for long-lived bats.

Two species’ genetic adaptations for tumor suppression have been described to help explain their extreme longevity. Bats also have genetic mechanisms that enable strong antiviral immune responses without inducing damaging inflammatory reactions that may enable them to tolerate high levels of viral exposure.

Our results are consistent with an epigenetic clock theory of aging that connects beneficial developmental and cell maintenance processes to detrimental processes causing tissue dysfunction.”

https://www.nature.com/articles/s41467-021-21900-2 “DNA methylation predicts age and provides insight into exceptional longevity of bats”


The founder of the epigenetic clock has been busy, coauthoring more published studies than there have been weeks in this year! I’ve read five other 2021 studies he’s coauthored on dogs, horses, mammals (2), and humans in DNA methylation biomarker for cumulative lead exposure is associated with Parkinson’s disease. This one stood out for its “longevity results from augmented immune response and cancer suppression” findings.

If we’re interested in longevity, this clarity can direct efforts to both improve our immune systems and avoid problems like cancer. Symptoms may be subclinical, but that doesn’t provide adequate rationale to not address causes.

Peer review comments and responses were informative:

Reviewer #1 – “Developing an aging clock that works for a diverse set of bat species is a spectacular achievement.”

Reviewer #2 – “This is a tour de force study.”

Replies to Reviewer #3:

“Difference in recorded lifespans between three long-lived species and two short-lived species that we used to identify longevity DMPs [differentially methylated positions] is 20 years or more, even though they have similar body sizes (20-40 g). The three long-lived species [maximum ages 29.9, 30.5, and 37.1 years] also represent three different phylogenetic lineages.

CpG sites that undergo hypomethylation with age do so largely at random. In contrast, sites that undergo hypermethylation with age are highly nonrandom, and as has been noted before, are near genes associated with development. So yes, we believe there are predictable methylation changes with age.”

Train your gut microbiota with taurine

This 2021 rodent study found:

“We show that gut microbiota from previously infected hosts display enhanced resistance to infection. This long-term functional remodeling is associated with altered bile acid metabolism leading to expansion of taxa that utilize taurine.

Supplying exogenous taurine alone is sufficient to induce this alteration in microbiota function and enhance resistance. Taurine potentiates microbiota production of sulfide, an inhibitor of cellular respiration, which is key to host invasion by numerous pathogens.

fx1_lrg

This work reveals a process by which the host, triggered by infection, can deploy taurine as a nutrient to nourish and train microbiota, promoting its resistance to subsequent infection.”

https://www.cell.com/cell/fulltext/S0092-8674(20)31681-0 “Infection trains the host for microbiota-enhanced resistance to pathogens” (not freely available)


News coverage added:

“The studied infections induced host taurine production and expansion of taurine utilizers. Taurine was the trigger for activity of a class of bacteria that fight these infections.

The group’s data suggest that low levels of taurine allow pathogens to colonize the gut, but high levels produce enough hydrogen sulfide to prevent colonization. Taurine given to mice in drinking water prepared microbiota to prevent infection. However, when mice drank water containing bismuth subsalicylate, a common over-the-counter drug used to treat diarrhea and upset stomach, infection protection waned because bismuth inhibits hydrogen sulfide production.”

Can’t calculate a human equivalent dose without access to this study. I take 1 gram of taurine twice a day.

Per Treating psychopathological symptoms will somehow resolve causes? I resumed taurine supplementation last year after taking a year’s break. From that paper’s taurine section:

“Most studies that reported enhanced GSH [glutathione] in the brain following taurine treatment were performed under a chronic regimen and used in age-related disease models.

Such positive effects of taurine on GSH levels may be explained by the fact that cysteine is the essential precursor to both metabolites, whereby taurine supplementation may drive metabolism of cysteine towards GSH synthesis.”

If that paper’s hypothesis is correct, and the current study’s evidence is replicable, taurine supplementation is a win-win for both our brain and gut microbiota.


Sunrise minus 5 minutes

Let β-glucan train your brain

This 2021 rodent study investigated yeast cell wall β-glucan’s effects on the brain’s immune system:

“Innate immune memory can manifest in two different ways, [1] immune training and [2] immune tolerance, which means [1] an enhanced or [2] suppressed immune response towards a secondary challenge. Lipopolysaccharide (LPS) and β-glucan (BG) are two commonly used ligands to induce immune training and tolerance.

Microglia, the innate immune cells of the central nervous system, can adopt diverse phenotypes and functions in health and disease. In our previous study, we have shown that LPS preconditioning induces immune tolerance in microglia.

Compared to LPS, relatively little is known about effects of BG on microglia. In this study, we report for the first time that systemic administration of BG activates microglia in vivo, and that BG preconditioning induces immune training in microglia.

dectin-1

Our results show that BG activated microglia without inducing significant cytokine expression.

BG- and LPS-preconditioning both induced immune training in microglia two days after the first challenge. However, with an interval of 7 days between the first and second challenge, LPS-preconditioning induced immune tolerance in microglia where BG-induced immune training was no longer detected.”

https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-021-02103-4 “Systemic administration of β-glucan induces immune training in microglia”


One solution to “BG-induced immune training was no longer detected” after 7 days is to take β-glucan every day. I haven’t seen studies that found β-glucan induced immune tolerance, i.e. “suppressed immune response towards a secondary challenge.”

I take allergy medicine twice a day. Switched over to a different β-glucan vendor and dose per Year One of Changing to a youthful phenotype with broccoli sprouts.

I take 1 gram of Glucan 300 capsules without eating anything an hour before or an hour afterwards. I’ve only been doing it for a week, though, and haven’t been able to separate out β-glucan effects on seasonal allergies. I’ll try stopping allergy medicine when pollen stops coating my car.

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Swarming a spring sea trout run. Ospreys outcompeted gulls for breakfast.

Reversing osteoporosis with Nrf2

This 2021 rodent study made old females out of young females by removing their ovaries, which induced osteoporosis. They then demethylated the Nrf2 gene promoter with exercise, increasing its expression, which reversed osteoporosis:

“Nrf2 repression due to aberrant Dnmt elevation and subsequent Nrf2 promoter hypermethylation is an important epigenetic feature of osteoporosis (OP) pathogenesis.

Nrf2 promoter demethylation

Ovariectomized mice display increased femoral Dnmt1/3a/3b (Dnmts), Nrf2 promoter hypermethylation, and Nrf2 suppression, which promote oxidative stress (OS), osteoclastogenesis (OCG) and OP (dashed line).

Running exercise (RE, solid line) normalizes Dnmt aberrations, resulting in Nrf2 promoter demethylation, Nrf2 recovery and reduced femoral osteoporotic pathologies.

Nrf2 repression due to aberrant Dnmt elevations and associated promoter hypermethylation contributes significantly to epigenetic development of OP. RE effectively corrects epigenetic abnormalities and pathogenesis of OP.”

https://www.nature.com/articles/s41413-020-00128-8 “Nrf2 epigenetic derepression induced by running exercise protects against osteoporosis”


Running an hour every day has effects on Nrf2 gene promoter expression similar to eating broccoli sprouts. A 2021 study Sulforaphane prevents angiotensin II‐induced cardiomyopathy by activation of Nrf2 through epigenetic modification found:

“SFN reduced Ang II‐induced CpG hypermethylation and promoted Ac‐H3 accumulation in the Nrf2 promoter region, accompanied by inhibition of global DNMT and HDAC activity, and a decreased protein expression of key DNMT and HDAC enzymes.”

A 2019 study Sulforaphane‑induced epigenetic regulation of Nrf2 expression by DNA methyltransferase in human Caco‑2 cells found:

“DNMT1 protein expression was inhibited by sulforaphane. Nrf2 promoter methylation decreased significantly in the sulforaphane group.

Sulforaphane may promote demethylation of the Nrf2 promoter region to increase activation of Nrf2.”


Per Week 6, my running days are over, though not walking, climbing, etc. Nrf2 activation with broccoli sprouts began after two weeks of self-quarantine more than a year ago.

Improving one’s own health provides sufficient rationale to act.

Oat β-glucan effects on colitis

This 2021 rodent study investigated oat β-glucan effects on colitis:

“In this study, we determined effects of consumption of low- and high-molar-mass oat beta-glucans on expression of selected markers of apoptosis and autophagy in colonocytes in TNBS colitis-induced rats. We analyzed expression of colon wall receptors, including TLRs and Dectin-1, which are involved in recognition of molecular patterns of pathogens in colon epithelial cells.

Rats were divided into two main groups: healthy control (H) and a TNBS (2,4,6-trinitrobenzosulfonic acid)-induced colitis (C) group, both including subgroups fed feed without beta-glucans (βG−) or feed supplemented with low- (βGl) or high-molar-mass oat beta-glucans (βGh) for 3, 7, or 21 days. Expression of autophagy (LC3B) and apoptosis (Caspase-3) markers, as well as Toll-like (TLRs) and Dectin-1 receptors in colon epithelial cells, was determined.

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1. [Autophagy] Autophagy contributes to adaptation of cells and maintenance of intracellular homeostasis enabling cells to survive under stressful conditions. The autophagy marker in colon wall and intestinal epithelial cells (IECs) investigated was expression of LC3B protein, which participates in formation and maturation of autophagosomes.

A decrease in this protein was found in colon wall after TNBS administration, which indicates intense repair processes of intestinal epithelium accompanying / preceding the period of Crohn’s disease (CD) remission. The above data indicate a significant effect of oat beta-glucans in restoring autophagy in inflamed IECs, and a stronger effect of oat beta-glucans with a high molar mass, which also increased activity of autophagy in colon tissue of control animals without colitis.

2. [Apoptosis] In early development of acute colitis, expression of Caspase-3, the executive enzyme of apoptosis, was very low. The highest expression of Caspase-3 protein was observed in control (HβGh+), feed supplemented with high-molar-mass oat beta-glucans.

  • After 7 days of TNBS administration, Caspase-3 expression in colitis-induced animals was approximately eight times higher than in control group, which indicates an increase in apoptosis in response to intestinal inflammation.
  • Consumption of feed supplemented with high-molar-mass oat beta-glucans by colitis animals resulted in approximately two times lower Caspase-3 expression after 7 days. Physical properties of high-molar-mass beta-glucans favor formation of a protective layer on inner wall of intestine, effectively supporting development of beneficial microbiota producing short-chain fatty acids.
  • Consumption of feed with low-molar-mass oat beta-glucans resulted in expression of this enzyme in colitis animals at a similar level as in control group.

This confirms significant effect of oat beta-glucans in reducing expression of Caspase-3 during ongoing inflammation, with low-molar-mass beta-glucans having a stronger effect.

3. [Dectin-1] Expression of Dectin-1 across all experimental time points was found to be reduced due to induced inflammation. We analyzed Dectin-1 expression in intestinal epithelial cells, not in colon wall or immune cells. Decrease in Dectin-1 expression in colonocytes noticed in our study may be related to disrupted intestinal barrier integrity by the ethanolic TNBS solution, that as a consequence, causes infiltration of pathogens / antigens into deeper layers of colon wall and allows their direct contact with cells of the immune system.

Results showed an increase in expression of Dectin-1 in inflamed IECs under influence of oat beta-glucans. A similar effect on expression of LC3B protein was noted, with oat beta-glucans of a high molar mass having a stronger effect.

4. [TNF-α] Concentration of TNF-α and other proinflammatory cytokines in colon wall of animals with TNBS-induced inflammation was significantly increased at all time points. Consumption of oat beta-glucans reduced concentration of these inflammatory factors.

The extrinsic pathway of apoptosis is induced by binding of this factor to the TNFR1a receptor. Increased autophagy in inflamed intestinal epithelium protected cells against TNF-α-induced apoptosis, which in turn helped to maintain integrity of the intestinal barrier and reduce inflammation.

5. [TLRs] After 3 days of TNBS administration, expression of TLR 4 and TLR 6 receptors in colonocytes was significantly lower in the colitis group receiving feed without beta-glucans as compared to control group. In the same group of rats (CβG−), TLR 5 expression was lower.

Decrease in expression of these receptors is mostly influenced by acute intestinal inflammation. Oat beta-glucans caused a significant increase in expression, especially TLR 5 and TLR 6, in inflamed IECs.

In summary, oat beta-glucans were found to alleviate the course of induced inflammation.”

https://www.mdpi.com/2072-6643/13/2/321/htm “Effects of Dietary Oat Beta-Glucans on Colon Apoptosis and Autophagy through TLRs and Dectin-1 Signaling Pathways – Crohn’s Disease Model Study”


Eat oats to prevent inflammatory diseases:

“Oat beta-glucans with a high molar mass increased activity of autophagy in colon tissue of control animals without colitis.”

If we don’t do that, eat oats to treat inflammation:

“Confirms significant effect of oat beta-glucans in reducing expression of Caspase-3 during ongoing inflammation, with low-molar-mass beta-glucans having a stronger effect.”

I eat primarily low- and medium-molecular-weight oat β-glucan twice a day with 3-day-old hulled Avena sativa oat sprouts. For breakfast I eat primarily high-molecular-weight oat β-glucan in hulless Avena nuda oats soaked 12+ hours and microwaved 20 minutes at 80% power in a 1000W microwave.

An oats β-glucan clinical trial tested low-, medium-, and high-molecular-weight oat β-glucan in 14 people. It found:

Bioprocessing of oat bran with enzyme treatment, causing depolymerization of β-glucan, affects nutritional properties of bran and functional properties of β-glucan in human gastrointestinal tract.”

Neither study investigated gut microbiota. Pretty sure our hosted microorganisms had roles in both studies’ findings.