Reinforce your immune memory every day

Three papers on trained immunity, with the first a 2021 review:

“Trained immunity is realized by epigenetic reprogramming of cells, primarily monocytes/macrophages and natural killer cells, and is less specific than adaptive immunity. It may cross-protect against other infectious agents.

Various actions of trained innate immunity on precursor cells have a strong potential for therapeutic use, particularly in infected and myelosuppressed individuals. Improvements of effects of some vaccines offer other potential use of β-glucan as an inductor of trained immunity, suggesting novel uses of a traditional therapeutic.”

https://www.mdpi.com/1422-0067/22/19/10684/htm “Trained Immunity as an Adaptive Branch of Innate Immunity”


Became tired of this review’s pedantic repetitions, that cells have a finite existence, as do cell attributes such as one-time trained immunity. Readers get it.

While belaboring the obvious, this paper missed two points:

  • As An environmental signaling paradigm of aging theorized, then demonstrated in A rejuvenation therapy and sulforaphane, and continues in current studies, cells take on phenotypes the body gives them. Focusing on cell attributes missed many signals elsewhere in cells’ environmental milieu, which make a difference in cell, organ, and body functioning.
  • Trained immunity protocol also matters. I’ve trained my immune system with yeast cell wall β-glucan every day for 17 years, recently taking nothing else an hour before or an hour after. That “no effects were found after 20 days” of only one in vitro dose isn’t relevant to my immune responses. I always have cells with one day of training, cells with (pick a number) days / weeks / months / years of training, and millions of primed cells in between.

This first paper cited a 2020 in vitro study:

“(1, 3)/(1, 6)-β-glucan can induce potent trained immunity, however, immunoregulatory activity of oat (1, 3)/(1, 4)-β-glucan has been neglected. Most studies have focused on its metabolic regulatory activity in diseases such as obesity and diabetes.

This study confirmed that β-glucan from oat dietary fiber can modulate responsiveness of innate immune cells through metabolic reprogramming. Proposed mechanism of oat β-glucan for trained immunity induction in monocytes/macrophages:

oat beta glucan trained immunity

This study showed that trained immunity induced by oat (1, 3)/(1, 4)-β-glucan was dependent on glycolysis or SDH/IRG axis in TCA cycle. These findings demonstrated that oat dietary fiber could strengthen and maintain long-term responsiveness of the innate immune system.”

https://doi.org/10.1007/s10753-020-01211-2 “Oat-Derived β-Glucans Induced Trained Immunity Through Metabolic Reprogramming” (not freely available)


A 2021 rodent study cited this second paper:

“Oat beta-glucans can stimulate secretion of anti-inflammatory cytokines, and simultaneously inhibit secretion of pro-inflammatory cytokines. The immunostimulatory effect of beta-glucan intake occurs due to its ability to activate intestinal mucosa immune cells, which results from binding of these polysaccharides to specific membrane TLR and/or Dectin-1 receptors.

We analyzed effects of oat beta-glucans at two time points, 3 and 7 days after TNBS administration:

  • High molecular mass beta-glucan forms a protective coating on the internal intestinal wall, which improves tissue recovery potential and reduces the risk of secondary microbial infection.
  • Low molar mass beta-glucan forms light solutions where short chains are well distributed and dispersed, and due to low viscosity, beta-glucan is accessible for receptors to be reached. Once reaching and complementing the receptor, bonded beta-glucan short polymeric chain induces transmission on metabolic pathways.

ijms-22-04485-g005-550

Consumption of oat beta-glucans reduced levels of inflammatory markers, and recovered signaling pathways and histological changes, with stronger effects of low molar mass beta-glucan after 7 days of colitis. Dietary oat beta-glucans can reduce colitis at the molecular and organ level, and accelerate Crohn’s disease remission.”

https://www.mdpi.com/1422-0067/22/9/4485/htm “Anti-Inflammatory Activity of Oat Beta-Glucans in a Crohn’s Disease Model: Time- and Molar Mass-Dependent Effects”


I’d seen this second study’s abstract several times, but glossed over it. I curated another 2021 rodent study from the same institution as this third paper in Oat β-glucan effects on colitis.

None of these studies investigated gut microbiota. Pretty sure our hosted microorganisms had roles in their findings.

All papers called for human studies of their findings. But it would be difficult for drug companies to make money from a research area that’s cheap and readily accessible. Take responsibility for your own one precious life.

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Trained immunity mechanisms

This 2021 cell study investigated how inflammatory memory is established, maintained, and recalled:

“Cells retain a memory of inflammation that equips them to react quickly and broadly to diverse secondary stimuli. Temporal, dynamic changes to chromatin accessibility, histone modifications, and transcription factor (TF) binding occur during inflammation, post-resolution, and in memory recall following injury.

Epigenetic records of inflammation have been found in innate immune cells, including macrophages, monocytes, and natural killer cells, as well as CD8+ and regulatory T cells, granulocyte-monocyte progenitors, and long-term hematopoietic stem cells. Inflammatory memory was recently extended to epithelial barrier tissues, which are the first line of defense against infectious pathogens and noxious agents.

Epigenetic memory of an inflammatory experience is rooted in chromatin of a cell via retention of chromatin accessibility, histone marks, and key TFs that endow it with heightened responsiveness to diverse secondary stimuli. AP-1 (activating protein-1) is a collective term referring to transcription factors composed of JUN, FOS, or ATF (activating transcription factor) subunits that bind to a common DNA site.

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We unearth an essential, unifying role for the general stress-responsive transcription factor FOS, which partners with JUN and cooperates with stimulus-specific STAT3 to establish memory. JUN then remains with other homeostatic factors on memory domains, facilitating rapid FOS re-recruitment and gene re-activation upon diverse secondary challenges.

We offer a comprehensive, potentially universal mechanism behind inflammatory memory and less discriminate recall phenomena with implications for tissue fitness in health and disease:

  1. Stimulus-specific STAT3 and broad stress factor AP1 co-establish memory domains;
  2. Stem cell factors access open memory domains and remain bound after inflammation;
  3. FOS activates open memory domains, enabling secondary responses to diverse stimuli; and
  4. AP1 mediates epigenetic inflammatory memory across cell types, stimuli, and species.”

https://www.sciencedirect.com/science/article/abs/pii/S1934590921002861 “Establishment, maintenance, and recall of inflammatory memory” (not freely available)


Take responsibility for your own one precious life. Train your immune system every day with yeast cell wall β-glucan.

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Dementia blood factors

This 2021 human study performed blood metabolite analyses:

“Dementia is a collective term to describe various symptoms of cognitive impairment in a condition in which intelligence is irreversibly diminished due to acquired organic disorders of the brain, characterized by deterioration of memory, thinking, behavior, and the ability to perform daily activities.

In this study, we conducted nontargeted, comprehensive analysis of blood metabolites in dementia patients. Effort expended in this ‘no assumptions’ approach is often recompensed by identification of diagnostic compounds overlooked by targeted analysis.

The great variability of data in Figure 1 reflects genuine individual variation in metabolites, which were accurately detected by our metabolomic analysis. These data demonstrate that compounds having small to large individual variability are implicated in dementia.

dementia blood factors

7 group A compounds – plasma-enriched dementia factors – increased in dementia patients and might have a negative toxic impact on central nervous system (CNS) functions by themselves or their degradation products.

26 group B to E metabolites may be beneficial for the CNS, as their quantity all declined in dementia patients:

  • Red blood cell (RBC)-enriched group B metabolites all containing the trimethyl-ammonium ion may protect the CNS through their antioxidative and other activity.
  • Group C compounds, also RBC-enriched, have cellular functions implicated in energy, redox, and so forth, and may be important for maintaining CNS brain functions.
  • Group D’s 12 plasma compounds (amino acids, nucleosides, choline, and carnitine) – half of which had been reported as Alzheimer’s disease (AD)-related markers – may underpin actions of other metabolites for supply and degradation. Consistency of group D plasma metabolites as dementia markers but not group B and C RBC metabolites validated the method of searching dementia markers that we employed in the present study.
  • Group E compounds, caffeine and and its derivative dimethyl-xanthine, declined greatly in dementia subjects. Caffeine is an antagonist of adenosine, consistent with the present finding that adenosine belongs to group A compounds.

Twelve [groups B + C] of these 33 compounds are RBC-enriched, which has been scarcely reported. The majority of metabolites enriched in RBCs were not identified in previous studies.

Nine compounds possessing trimethylated ammonium ions are amphipathic compounds (with both hydrophilic and lipophilic properties) and form the basis of lipid polymorphism. All of them showed a sharp decline in abundance in dementia subjects.

amphipathic compounds

These amphipathic compounds may have similar roles, forming a higher-ordered, assembled structure. They might act as major neuroprotectants or antioxidants in the brain, and their levels are sensitive to both antioxidants and ROS.

We speculate the 7 group A compounds pathologically enhance or lead to severe dementia such as AD. This presumed dementia deterioration by group A factors is opposed if group B to E metabolites are sufficiently supplied.

However, group A markers were not found in frail subjects. If the change in group A is causal for dementia, then a cognitive cause in frailty may be distinct from that of dementia.”

https://www.pnas.org/content/118/37/e2022857118 “Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites”


Dementia subjects (ages 75-88) lived in an Okinawa hospital. Healthy elderly (ages 67-80) and young (ages 28-34) subjects lived in a neighboring village. Of the 24 subjects, 3 dementia and 1 healthy elderly were below a 18.5 to <25 BMI range, and none were above.

Get neuroprotectants working for you. Previous relevant curations included:

Epigenetic clocks so far in 2021

2021’s busiest researcher took time out this month to update progress on epigenetic clocks:

Hallmarks of aging aren’t all associated with epigenetic aging.

epigenetic aging vs. hallmarks of aging

Interventions that increase cellular lifespan aren’t all associated with epigenetic aging.

epigenetic aging vs. cellular lifespan

Many of his authored or coauthored 2021 papers developed human / mammalian species relative-age epigenetic clocks.

epigenetic clock mammalian maximum lifespan

Relative-age epigenetic clocks better predict human results from animal testing.

pan-mammalian epigenetic clock


Previously curated papers that were mentioned or relevant included:

Natural products vs. neurodegenerative diseases

I was recently asked about taking rapamycin for its effects on mTOR. I replied that diet could do the same thing. Here’s a 2021 review outlining such effects:

“As common, progressive, and chronic causes of disability and death, neurodegenerative diseases (NDDs) significantly threaten human health, while no effective treatment is available. Recent studies have revealed the role of phosphoinositide 3-kinase (PI3K)/Akt (Protein kinase B)/mammalian target of rapamycin (mTOR) in some diseases and natural products with therapeutic potentials.

Growing evidence highlights the dysregulated PI3K/Akt/mTOR pathway and interconnected mediators in pathogenesis of NDDs. Side effects and drug-resistance of conventional neuroprotective agents urge the need for providing alternative therapies.

1-s2.0-S0944711321002075-ga1_lrg

Polyphenols, alkaloids, carotenoids, and terpenoids have shown to be capable of a great modulation of PI3K/Akt/mTOR in NDDs. Natural products potentially target various important oxidative/inflammatory/apoptotic/autophagic molecules/mediators, such as Bax, Bcl-2, p53, caspase-3, caspase-9, NF-κB, TNF-α, GSH, SOD, MAPK, GSK-3β, Nrf2/HO-1, JAK/STAT, CREB/BDNF, ERK1/2, and LC3 towards neuroprotection.

This is the first systematic and comprehensive review with a simultaneous focus on the critical role of PI3K/Akt/mTOR in NDDs and associated targeting by natural products.”

https://www.sciencedirect.com/science/article/abs/pii/S0944711321002075 “Natural products attenuate PI3K/Akt/mTOR signaling pathway: A promising strategy in regulating neurodegeneration” (not freely available) Thanks to Dr. Sajad Fakhri for providing a copy.


Natural products mentioned in this review that I eat in everyday foods are listed below. The most effective ones are broccoli and red cabbage sprouts, and oats and oat sprouts:

  • Artichokes – luteolin;
  • Blackberries – anthocyanins;
  • Blueberries – anthocyanins, gallic acid, pterostilbene;
  • Broccoli and red cabbage sprouts – anthocyanins, kaempferol, luteolin, quercetin, sulforaphane;
  • Carrots – carotenoids;
  • Celery – apigenin, luteolin;
  • Green tea – epigallocatechin gallate;
  • Oats and oat sprouts – avenanthramides;
  • Strawberries – anthocyanins, fisetin;
  • Tomatoes – fisetin.

Four humpback whales

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All about vasopressin

This 2021 review subject was vasopressin:

“Vasopressin is a ubiquitous molecule playing an important role in a wide range of physiological processes, thereby implicated in pathomechanisms of many disorders. The most striking is its central effect in stress-axis regulation, as well as regulating many aspects of our behavior.

Arginine-vasopressin (AVP) is a nonapeptide that is synthesized mainly in the supraoptic, paraventricular (PVN), and suprachiasmatic nucleus of the hypothalamus. AVP cell groups of hypothalamus and midbrain were found to be glutamatergic, whereas those in regions derived from cerebral nuclei were mainly GABAergic.

In the PVN, AVP can be found together with corticotropin-releasing hormone (CRH), the main hypothalamic regulator of the HPA axis. The AVPergic system participates in regulation of several physiological processes, from stress hormone release through memory formation, thermo- and pain regulation, to social behavior.

vasopressin stress axis

AVP determines behavioral responses to environmental stimuli, and participates in development of social interactions, aggression, reproduction, parental behavior, and belonging. Alterations in AVPergic tone may be implicated in pathology of stress-related disorders (anxiety and depression), Alzheimer’s, posttraumatic stress disorder, as well as schizophrenia.

An increasing body of evidence confirms epigenetic contribution to changes in AVP or AVP receptor mRNA level, not only during the early perinatal period, but also in adulthood:

  • DNA methylation is more targeted on a single gene; and it is better characterized in relation to AVP;
  • Some hint for bidirectional interaction with histone acetylation was also described; and
  • miRNAs are implicated in the hormonal, peripheral role of AVP, and less is known about their interaction regarding behavioral alteration.”

https://www.mdpi.com/1422-0067/22/17/9415/htm “Epigenetic Modulation of Vasopressin Expression in Health and Disease”


Find your way, regardless of what the herd does.

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Choosing your gut immune response

This 2021 paper reviewed evidence for immune system effects associated with specific gut areas:

“The intestinal immune system must not only contend with continuous exposure to food, commensal microbiota, and pathogens, but respond appropriately according to intestinal tissue differences. The entire intestine, inclusive of its lymph nodes, is considered a immunosuppressive organ overall compared to most other tissues, indicating that a state of tolerance to food and commensals – yet vigilance toward pathogens – was an evolutionarily stable strategy.

By operating in compartments, the immune system may generate multiple immune outcomes, even with simultaneous opposite goals e.g., tolerance or inflammation. Generation of unique immunologic niches within the intestine is influenced by a combination of tissue intrinsic properties, extrinsic environmental factors, and regionalized immune populations.

intestinal immune compartmentalization

Complexity of intrinsic and extrinsic driving forces shaping an intestinal niche makes it very challenging to determine causality in disease development and predicting effective therapeutic approaches. We really only stand at the beginning of understanding this interplay.”

https://www.nature.com/articles/s41385-021-00420-8 “Intestinal immune compartmentalization: implications of tissue specific determinants in health and disease”


I patterned this post after Choosing your future with β-glucan:

“So where do you choose to be? In an 80% survival group who were administered β-glucan before they encountered a serious infection? Or in a < 20% survival group who didn’t take β-glucan?”

and Long-lasting benefits of a common vaccine:

“As inferred by “induction of trained immunity by both Bacillus Calmette-Guerin tuberculosis vaccine and β-glucan” many of these findings also apply to yeast cell wall β-glucan treatments.”

This paper’s food allergy references were interesting. It’s an area that personally requires further work, although avoidance has historically been effective.

This paper briefly mentioned broccoli’s effects in the proximal small intestine. It wasn’t informative per gut compartment with this year’s focus on making my gut microbiota happy, such as what our colonic microbiota can do to reciprocate their host giving them what they want.

This review’s human studies referenced what could be done post-disease like surgery etc. in different gut compartments. Very little concerned an individual taking responsibility for their own one precious life to prevent such diseases in the first place. Its Conclusions section claim was a fallacy:

“..very challenging to determine causality in disease development and predicting effective therapeutic approaches.”

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Take taurine for your mitochondria

This 2021 review summarized taurine’s beneficial effects on mitochondrial function:

“Taurine supplementation protects against pathologies associated with mitochondrial defects, such as aging, mitochondrial diseases, metabolic syndrome, cancer, cardiovascular diseases and neurological disorders. Potential mechanisms by which taurine exerts its antioxidant activity in maintaining mitochondria health include:

  1. Conjugates with uridine on mitochondrial tRNA to form a 5-taurinomethyluridine for proper synthesis of mitochondrial proteins (mechanism 1), which regulates the stability and functionality of respiratory chain complexes;
  2. Reduces superoxide generation by enhancing the activity of intracellular antioxidants (mechanism 2);
  3. Prevents calcium overload and prevents reduction in energy production and collapse of mitochondrial membrane potential (mechanism 3);
  4. Directly scavenges HOCl to form N-chlorotaurine in inhibiting a pro-inflammatory response (mechanism 4); and
  5. Inhibits mitochondria-mediated apoptosis by preventing caspase activation or by restoring the Bax/Bcl-2 ratio and preventing Bax translocation to the mitochondria to promote apoptosis.

taurine mechanisms

An analysis on pharmacokinetics of oral supplementation (4 g) in 8 healthy adults showed a baseline taurine content in a range of 30 μmol to 60 μmol. Plasma content increased to approximately 500 μmol 1.5 h after taurine intake. Plasma content subsequently decreased to baseline level 6.5 h after intake.

We discuss antioxidant action of taurine, particularly in relation to maintenance of mitochondria function. We describe human studies on taurine supplementation in several mitochondria-associated pathologies.”

https://www.mdpi.com/1420-3049/26/16/4913/html “The Role of Taurine in Mitochondria Health: More Than Just an Antioxidant”


I take a gram of taurine at breakfast and at dinner along with other supplements and 3-day-old Avena sativa oat sprouts. Don’t think my other foods’ combined taurine contents are more than one gram, because none are found in various top ten taurine-containing food lists.

As a reminder, your mitochondria come from your mother, except in rare cases.

Changing your immune system / gut microbiota interactions with diet

This 2021 human clinical trial investigated associations between gut microbiota and host adaptive immune system components:

“Diet modulates gut microbiome, and gut microbes impact the immune system. We used two gut microbiota-targeted dietary interventions – plant-based fiber or fermented foods – to determine how each influences microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study design combined with -omics measurements of microbiome and host and extensive immune profiling, we found distinct effects of each diet:

  • Those in the high-fiber diet arm increased their fiber consumption from an average of 21.5±8.0 g per day at baseline to 45.1±10.7 g per day at the end of the maintenance phase.
  • Participants in the high-fermented food diet arm consumed an average of 0.4±0.6 servings per day of fermented food at baseline, which increased to an average of 6.3±2.9 servings per day at the end of the maintenance phase.
  • Participants in the high-fiber diet arm did not increase their consumption of fermented foods (Figure 1.C dashed line), nor did participants consuming the high-fermented food diet increase their fiber intake.

fiber vs fermented

Fiber-induced microbiota diversity increases may be a slower process requiring longer than the six weeks of sustained high consumption achieved in this study. High-fiber consumption increased stool microbial protein density, carbohydrate-degrading capacity, and altered SCFA production, indicating that microbiome remodeling was occurring within the study time frame, just not through an increase in total species.

Comparison of immune features from baseline to the end of the maintenance phase in high-fiber diet participants revealed three clusters of participants representing distinct immune response profiles. No differences in total fiber intake were observed between inflammation clusters. A previous study demonstrated that a dietary intervention, which included increasing soluble fiber, was less effective in improving inflammation markers in individuals with lower microbiome richness.

In both diets, an individual’s microbiota composition became more similar to that of other participants within the same arm over the intervention, despite retaining the strong signal of individuality.

Coupling dietary interventions to longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Our results indicate that fermented foods may be valuable in countering decreased microbiome diversity and increased inflammation.”

https://www.cell.com/cell/fulltext/S0092-8674(21)00754-6 “Gut-microbiota-targeted diets modulate human immune status” (not freely available). See https://www.biorxiv.org/content/10.1101/2020.09.30.321448v2.full for the freely available preprint version.


Didn’t care for this study’s design that ignored our innate immune system components yet claimed “extensive immune profiling.” Not.

There was sufficient relevant evidence on innate immunity cells – neutrophils, monocytes, macrophages, natural killer cells, and dendrites – when the trial started five years ago. But maybe this didn’t satisfy study sponsors?

This study found significant individual differences in the high-fiber group. These individual differences failed to stratify into subgroup p-value significance.

I won’t start eating fermented dairy or fermented vegetable brines to “counter decreased microbiome diversity and increased inflammation.” I’m rolling the die with high-fiber intake (2+ times more grams than this clinical trial, over a 3+ times longer period so far).

Changing to a high-fiber diet this year to increase varieties and numbers of gut microbiota is working out alright. No worries about “increased inflammation” because twice-daily 3-day-old microwaved broccoli sprouts since Day 70 results from Changing to a youthful phenotype with broccoli sprouts have taken care of inflammation for 15 months now.

What effects have this year’s diet changes had on my adaptive and innate immune systems? 2021’s spring allergy season wasn’t pleasant. But late summer’s ragweed onslaught hasn’t kept me indoors – unlike other years – despite day after day of readings like today’s:

ragweed

Regarding an individual’s starting point and experiences, those weren’t the same as family, friends, significant other, identified group members, or strangers. Each of us has to find our own way to getting well.

Agenda-free evidence may provide good guidelines. So does how you feel.

Preventing human infections with dietary fibers

This 2020 review covered interactions of gut microbiota, intestinal mucus, and dietary fibers. I’ve outlined its headings and subheadings, and ended with its overview:

“I. Dietary fibers and human mucus-associated polysaccharides: can we make an analogy?

I.1 Brief overview of dietary fibers and mucus polysaccharides structures and properties

I.I.1 Dietary fibers

  • Dietary fiber intake and health effects

I.I.2 Intestinal mucus polysaccharides

  • Structure
  • Main functions

I.2 Similarities and differences between dietary fibers and mucus carbohydrates

  • Origin and metabolism
  • Structure

II. Interactions of dietary fibers and mucus-associated polysaccharides with human gut microbiota

II-1 Substrate accessibility and microbial niches

  • Dietary fibers
  • Mucus polysaccharides

II-2 Recognition and binding strategies

  • Dietary fibers
  • Mucus polysaccharides

II-3 Carbohydrate metabolism by human gut microbiota

II-3.1 Specialized carbohydrate-active enzymes

II-3.2 Vertical ecological relationships in carbohydrate degradation

  • Dietary fibers
  • Mucus polysaccharides

II-3.3 Horizontal ecological relationships in carbohydrate degradation

II.4 Effect of carbohydrates on gut microbiota composition and sources of variability

II.4.1 Well-known effect of dietary fibers on the gut microbiota

II.4.2 First evidences of a link between mucus polysaccharides and gut microbiota composition

III. Gut microbiota, dietary fibers and intestinal mucus: from health to diseases?

[no III.1]

III.2 Current evidences for the relationship between dietary fibers, mucus and intestinal-inflammatory related disorder

III.2.1 Obesity and metabolic-related disorders

  • Dietary fibers
  • Mucus polysaccharides

III.2.2 Inflammatory bowel diseases

  • Dietary fibers
  • Mucus polysaccharides

III.2.3 Colorectal cancer

  • Dietary fibers
  • Mucus polysaccharides

IV. How enteric pathogens can interact with mucus and dietary fibers in a complex microbial background?

IV.1 Mucus-associated polysaccharides: from interactions with enteric pathogens to a cue for their virulence?

IV.1.1 Pathogens binding to mucus

  • Binding structures
  • Sources of variations

IV.1.2 Mucus degradation by pathogens

  • Bacterial mucinases
  • Glycosyl hydrolases

IV.1.3 Mucus-based feeding of pathogens

  • Primary degraders or cross-feeding strategies
  • Importance of microbial background

IV.1.4 Pathogens and inflammation in a mucus-altered context

IV.1.5 Modulation of virulence genes by mucus degradation products

IV.2 How can dietary fiber modulate enteric pathogen virulence?

IV.2.1 Direct antagonistic effect of dietary fibers on pathogens

  • Bacteriostatic effect
  • Inhibition of cell adhesion
  • Inhibition of toxin binding and activity

IV.2.2 Indirect effect of dietary fibers through gut microbiota modulation

  • Modulation of microbiota composition
  • Modulation of gut microbiota activity

IV.2.3 Inhibition of pathogen interactions with mucus: a new mode of dietary fibers action?

  • Binding to mucus: dietary fibers acting as a decoy
  • Inhibition of mucus degradation by dietary fibers

V. Human in vitro gut models to decipher the role of dietary fibers and mucus in enteric infections: interest and limitations?

V.1 Main scientific challenges to be addressed

V.2 In vitro human gut models as a relevant alternative to in vivo studies

V.3 In vitro gut models to decipher key roles of digestive secretions, mucus and gut microbiota

V.4 Toward an integration of host responses

V.5 From health to disease conditions

dietary fibers prevent infections

Overview of the potential role of dietary fibers in preventing enteric infections. Reliable and converging data from scientific literature are represented with numbers in circles, while data more hypothetical needing further investigations are represented with numbers in squares.

  1. Some dietary fibers exhibit direct bacteriostatic effects against pathogens.
  2. Dietary fiber degradation leads to short-chain fatty acids (SCFAs) production that can modulate pathogens’ virulence.
  3. By presenting structure similarities with receptors, some dietary fibers can prevent pathogen adhesin binding to their receptors.
  4. By the same competition mechanism, dietary fibers can also prevent toxins binding to their receptors.
  5. Dietary fibers are able to promote gut microbiota diversity.
  6. Dietary fibers may promote growth of specific strains with probiotic properties and therefore exhibit anti-infectious properties.
  7. Suitable dietary fiber intake prevents microbiota’s switch to mucus consumption, limiting subsequent commensal microbiota encroachment and associated intestinal inflammation.
  8. Dietary fibers may prevent pathogen cross-feeding on mucus by limiting mucus degradation and/or by preserving diversity of competing bacterial species.
  9. By preventing mucus over-degradation by switcher microbes, dietary fibers can hamper pathogen progression close to the epithelial brush border, and further restrict subsequent inflammation.”

https://doi.org/10.1093/femsre/fuaa052 “Tripartite relationship between gut microbiota, intestinal mucus and dietary fibers: towards preventive strategies against enteric infections” (not freely available)


There were many links among gut microbiota studies previously curated. For example, Go with the Alzheimer’s Disease evidence found:

“Akkermansia cannot always be considered a potentially beneficial bacterium. It might be harmful for the gut–brain axis in the context of AD development in the elderly.”

The current review provided possible explanations:

“Akkermansia muciniphila could be considered as a species that fulfills a keystone function in mucin degradation. It is a good example of a mucus specialist.”

Points #7-9 of the above overview inferred that insufficient dietary fiber may disproportionately increase abundance of this species. But Gut microbiota strains also found that effects may be found only below species at species’ strain levels.

These reviewers provided copies in places other than what’s linked above. Feel free to contact them for a copy.


Moon bandit

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No magic bullet, only magical thinking

Consider this a repost of Dr. Paul Clayton’s blog post The Drugs Don’t Work:

“The drug industry has enough funds to:

  • Rent politicians;
  • Subvert regulatory agencies;
  • Publish fake data in the most august peer-reviewed literature; and
  • Warp the output of medical schools everywhere.

Their products are a common cause of death. Every year, America’s aggressively modern approach to disease kills over 100,000 in-hospital patients, and twice that number of out-patients.

In 1900, a third of all deaths occurred in children under the age of 5. By 2000 this had fallen to 1.4%. The resulting 30-year increase in average life expectancy fed into the seductive and prevailing myth that we are all living longer; which is manifestly untrue. Improvements in sanitation were far more significant in pushing infections back than any medical developments.

There is currently no pharmaceutical cure for Alzheimer’s or Parkinsonism, nor can there be when these syndromes are in most cases driven by multiple metabolic distortions caused by today’s diet. The brain is so very complex, and it can go wrong in so many ways. The idea that we can find a magic bullet for either of these syndromes is ill-informed and philosophically mired in the past.

It is also dangerous. There is a significant sub-group of dementia sufferers whose conditions are driven and exacerbated by pharmaceuticals. Chronic use of a number of commonly prescribed drugs – and ironically, anti-Parkinson drugs – increases the risk of dementia by roughly 50%.

Big Pharma’s ability to subvert regulatory authorities is even more dangerous. The recent FDA approval of Biogen’s drug aducanumab is a scandal; not one member of the FDA Advisory Committee voted to approve this ineffective product, and three of them resigned in the aftermath of the FDA’s edict. This ‘anti-Alzheimer’s’ drug, which will earn Biogen $56,000 / patient / year, was licensed for financial reasons; it reduced amyloid plaque but was clinically ineffective.

So did the eagerly awaited gantenerumab and solanezumab. But they, too, failed to produce any significant clinical benefit.”


A knee-replacement patient enduring her daily workout

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Eating sprouts prevents AGEs

This 2021 in vitro study found:

“Prolonged and chronic hyperglycemia is a leading factor in inducing formation of advanced glycation end-products (AGEs) generated by reaction of free amino groups of proteins and carbonyl groups in reducing sugars, especially glucose and fructose. Metabolism of glucose via the glycolysis pathway also produces the most reactive compounds such as methylglyoxal (MG), a potent precursor of AGEs.

Previous studies reported that red cabbage extract could decrease glycated hemoglobin concentration in streptozotocin-induced diabetic rats and oxidative stress makers including protein carbonyl content and malondialdehyde in red blood cells. Emerging evidence supports that inhibition of protein glycation and oxidative damage may be attributed to free radical scavenging activity of plant extracts.

three brassicae

Extracts of Brassica vegetables cauliflower, cabbage and Chinese cabbage:

  • Inhibited formation of AGEs;
  • Prevented loss of protein thiol group; and
  • May act as a MG-trapping and antioxidant agent.

Phenolic acids, particularly sinapic acid and p-hydroxybenzoic acid, were commonly found in Brassica vegetables. These findings suggest that Brassica vegetables may be promising antiglycation and antioxidant agents for preventing formation of AGEs.”

https://link.springer.com/article/10.1007/s11130-021-00903-w “Phytochemical Composition, Antiglycation, Antioxidant Activity and Methylglyoxal‑Trapping Action of Brassica Vegetables” (not freely available)


Regarding this study’s sinapic acid findings, Broccoli sprout compounds include sinapic acid derivatives found with 6-day-old broccoli sprouts:

“Sprouting in darkness results in overall decrease in total content of sinapic acid derivatives with growth time, but promotes replacement of relatively low active constituents, such as sinapine, by stronger antioxidants. These structural changes are beneficial for total antioxidant capacity of broccoli sprouts, and are correlated with their increasing ability to scavenge free radicals, reduce transition metal ions, and inhibit lipid peroxidation.”

Regarding this study’s p-hydroxybenzoic acid findings, Advantages of 3-day-old oat sprouts over oat grains found with 3-day-old oat sprouts:

“Six hydroxybenzoic acids were found in greater amounts in sprouts, whereas two were reduced or lost.”


Getting onboard before sunrise

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Gut microbiota functional relationships

This 2021 study investigated environmentally-organized gut microbiome functional relationships:

“There has been a substantial gap between understanding microbiome assemblage and how its functionality is organized. In this study, we demonstrated the usefulness of metaproteomics in gaining a system-level understanding of microbiome functionality.

Our current finding highlights the value of further investigation into functional hubs and hub functions in microbiome proteomic content networks. This will provide a unique and systematic insight for prediction of community functional responses, or manipulation of microbiome functioning.

Across all metaproteomics datasets, Eubacterium, Faecalibacterium, Ruminococcus, Bacteroides, Clostridium and Coprococcus were found to be the most frequent functional hubs.

functionally related genera

Taxon-function bipartite network based on functional distances between microbial genera. Size of a node corresponds to its degree.

Highly connected functions were enriched in metabolism of carbohydrates and amino acids, suggesting that microbial acquisition of nutrients from the environment and trophic interactions between microbes could be major factors that shape their active functional organization. Our result showing robustness of between-taxa functional distances across individual microbiomes implied a more fundamental mechanism that underlies selective organization of microbiome functionalities by environment.

We observed a universal pattern of between-taxa functional distances (dij) across all analyzed datasets. Notably, this pattern was fully shifted by a global increase in dij values, and subsequently a significant decrease of normalized taxonomic diversity in a subset of inflammatory bowel disease samples mostly obtained from inflamed areas.

This finding may support, from a functional angle, the hypothesis that there are alternative stable states (bi-stability or multi-stability) in the gut ecosystem. One frequently discussed mechanism behind these alternative states has been continuous exposure of the microbiome to a altered environmental parameter:

  • An inflamed area in the gut will have a reduced mucus layer and elevated host defense responses.
  • Host mucus layer is a nutritional source of cross-feeding in the gut microbiome.
  • Loss of this layer may firstly affect network hub functions of carbohydrate and amino acid metabolism, and subsequently affect functional interactions in the whole community.

In addition, host defense responses attenuate microbial oxidative stress responses, which have been associated to microbiome dysfunction. Decrease of within-sample functional redundancy has been associated with impaired microbiome stability and resilience.

Resilient microbiota resist external pressures and return to their original state. A non-resilient microbiome is likely to shift its composition permanently and stay at an altered new state instead of restoring to its original state of equilibrium.”

https://www.biorxiv.org/content/10.1101/2021.07.15.452564v1.full “Revealing Protein-Level Functional Redundancy in the Human Gut Microbiome using Ultra-deep Metaproteomics”


My top genus Faecalibacterium – a cross-feeding, acetate-consuming, butyrate-producing commensal – would be more than twice the size of this study’s Faecalibacterium network projection in the above graphic. In this year’s efforts to make my gut microbiota happy, I’ve apparently done much to express its relevant gene network.

my genera

I came across this study by it citing Gut microbiota guilds.

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Microwave your Brassica vegetables

This 2021 review evaluated effects on glucoraphanin and sulforaphane content of cooking broccoli and other Brassica vegetables:

“The amount of glucosinolates (GLS) in brassica vegetables can be affected significantly during processing and cooking, depending on their specific conditions and types:

  • Microwaving can retain or even increase content of glucoraphanin (GLR), and can increase production of sulforaphane (SLR) within a short time;
  • Fermentations generally decrease content of GLR;
  • Short-time steaming may promote formation of SLR; and
  • Short-time microwaving may promote formation of SLR from GLR better than fermentation and steaming.

Other processing and cooking effects include:

  • Packaging and freezing can reduce loss of GLR content. Freezing treatment promotes hydrolysis of GLS to form SLR, and freezing stress may lead to GLS degradation;
  • Boiling and blanching result in the largest loss of GLR from broccoli, as loss of GLR content is mainly due to its leakage into the water; and
  • Stir-frying may be a suitable and healthful cooking option to prevent loss of GLR, but contents of GLR and SLR were still influenced due to different factors.

It is better for consumers to microwave or steam brassica vegetables before consumption to obtain greater health benefits.”

https://www.sciencedirect.com/science/article/abs/pii/S030881462101013X “The effect of processing and cooking on glucoraphanin and sulforaphane in brassica vegetables” (not freely available). Thanks to Dr. Jing Sun for providing a copy.


This review found mainly negative effects of cooking Brassica vegetables with boiling, stir frying, blanching, or high pressure on glucoraphanin and sulforaphane content. Previously curated studies cited were:


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Blue heron on its way to the breakfast buffet

Prevent your brain from shrinking

My 800th curation is a 2021 human diet and lifestyle study:

“Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane, and (b) compares this association to that of 3 industrialized populations in the United States and Europe.

Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population, and present few cardiovascular disease (CVD) risk factors. They have a high burden of infections and inflammation, reflected by biomarkers of chronic immune activation, including higher leukocytes counts, faster erythrocyte sedimentation rates, and higher levels of C-reactive protein, interleukin-6, and immunoglobulin-E than in Americans of all ages.

The Tsimane have endemic polyparasitism involving helminths and frequent gastrointestinal illness. Most morbidity and mortality in this population is due to infections.

brain volume

The Tsimane exhibit smaller age-related BV declines relative to industrialized populations, suggesting that their low CVD burden outweighs their high, infection-driven inflammatory risk. If:

  1. Cross-sectional data (which we believe are population-representative of Tsimane adults aged 40 and older) represent well the average life course of individuals; and
  2. The Tsimane are representative of the baseline case prior to urbanization;

these results suggest a ~70% increase in the rates of age-dependent BV decrease accompanying industrialized lifestyles.

Despite its limitations, this study suggests:

  • Brain atrophy may be slowed substantially by lifestyles associated with very low CVD risk; and
  • There is ample scope for interventions to improve brain health, even in the presence of chronically high systemic inflammation.

Lastly, the slow rate of age-dependent BV decrease in the Tsimane raises new questions about dementia, given the role of both infections and vascular factors in dementia risk.”

https://gurven.anth.ucsb.edu/sites/default/files/sitefiles/papers/irimiaetal2021.pdf “The indigenous South American Tsimane exhibit relatively modest decrease in brain volume with age despite high systemic inflammation”


I came across this study by its citation in Dr. Paul Clayton’s 2021 blog post We’ve got to get ourselves back to the garden.