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.

Choosing appropriate dietary fibers

This 2021 rodent study investigated effects of dietary fibers on Type 2 diabetes:

“Nine types of dietary fibers were used to investigate and evaluate their effects on type-2 diabetic rats via physiology, genomics, and metabolomics.

In human clinical trials, supplementation with dietary fibers was found inversely associated with risks of diabetes, along with improvement on glycemic control, lipid profiles, and host homeostasis. However, mixed fibers with diverse types from dietary sources are generally used for treatment intervention in clinical trials, and effects of individual dietary fibers on T2D are seldom discussed.

We found that supplementation with β-glucan, arabinogalactan, guar gum, and apple pectin had favorable effects on alleviating T2D:

upset plot

Non-bioactive dietary fibers (NBDF) were glucomannan, arabinoxylan, carrageenan, xylan, and xanthan gum.

dietary fibers effects

Relatively high viscosity was an important driving factor of dietary fibers for hypoglycemic effects. Supplementation with β-glucan, arabinogalactan, guar gum, and apple pectin tended to restore gut microbiota composition.

Our study uncovered effects of different dietary fibers on T2D, along with their potential mechanisms. Different dietary fibers influenced host metabolism via different metabolic pathways.”

https://pubs.acs.org/doi/10.1021/acs.jafc.1c01465 “Bioactive Dietary Fibers Selectively Promote Gut Microbiota to Exert Antidiabetic Effects” (not freely available). Thanks to Dr. Yonggan Sun for providing a copy.


I eat oat β-glucan three times a day – Avena nuda whole oats for breakfast, and twice daily 3-day-old Avena sativa hulled 3-day-old oat sprouts. Not to be confused with training my immune system with daily yeast cell wall β-glucan.

I recommend “Section 6. Biological functions” of the 2021 Plants arabinogalactans: From structures to physico-chemical and biological properties (not freely available), which reviewed:

  • ACE inhibitory;
  • Anti-cancer;
  • Anti-complementary;
  • Anti-diabetic;
  • Anti-ulcer;
  • Antiaging;
  • Antinociceptive;
  • Antioxidant;
  • Antitumor;
  • Antitussive;
  • Antiviral;
  • Complementary system;
  • Complement fixation;
  • Gastrointestinal-protective;
  • Hepatoprotective;
  • Hypoglycemic;
  • Immunomodulating;
  • Immunostimulatant;
  • Immune enhancing;
  • Intestinal immune system;
  • Phagocytosis stimulating; and
  • Prebiotic activities

properties of different arabinogalactans. Thanks to Professor Michaud for providing a copy.

Arabinogalactans were favored in both papers, yet few are commercially available. In January 2021 I used an arabinogalactan supplement, but it was too expensive to continue. Maybe multiple processing steps were a cost factor?

arabinogalactan processing

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.

Seeds vs. sprouts: red cabbage and broccoli

This 2021 study compared properties of red cabbage and broccoli seeds and sprouts:

“Antioxidant and antidiabetic properties and metabolite profiling of ethanol extracts of red cabbage (RC) and broccoli (BR) seeds and sprouts were investigated:

  • BR seeds had the highest total phenolic and flavonoid contents;
  • BR sprouts had the highest saponin content;
  • RC sprouts demonstrated the highest antioxidant capacity;
  • BR and RC sprouts showed the most potent inhibition against α-glucosidase and pancreatic lipase; and
  • BR seeds demonstrated the lowest AGE inhibition.

RC and BR seeds vs sprouts

In vitro assessment of antidiabetic potential of extracts revealed that sprouts demonstrated better potential as antioxidant, α-glucosidase, and pancreatic lipase inhibitors compared to raw seeds. Amino acids and phenolic compounds were the most improved metabolites in the germination process.

Germination not only enhanced levels of metabolites, but also synthesized new compounds in seeds. Germination effectively enhanced functional properties and metabolite profiles of broccoli and red cabbage seeds, making their sprouts more applicable as functional ingredients.”

https://www.mdpi.com/2076-3921/10/6/852/htm “UHPLC-ESI-QTOF-MS/MS Metabolite Profiling of the Antioxidant and Antidiabetic Activities of Red Cabbage and Broccoli Seeds and Sprouts”


I asked coauthors for sprout ages and pertinent growing conditions for the above-pictured sprouts. I’ll guess > 3-days-old, temperature 25° C, and relative humidity 90%. What would you guess?

Update: Two coauthors replied:

“Red Cabbage and Broccoli were germinated for 6 and 7 days respectively. Temperature ranged between 20-23 °C in the dark.”

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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 reaction

Two papers on broccoli compounds and gut microbiota relationships, with the first a 2021 article:

“We provide a supportive environment and a supply of nutrition and, in return, the microbiome delivers benefits to our health. What exactly are those benefits, and how can we maximise them?

Fibre component of food was thought to be completely indigestible roughage, but we now know that there is a digestible (a.k.a. soluble) component that can be fermented by bacteria resident in the large intestine, providing them with nutrition. There is also non-digestible fibre (a.k.a. insoluble fibre), which is not fermented by gut bacteria and includes plant cell walls formed from cellulose and lignin.

However, when cell walls remain intact, they encapsulate starch contained within cells and physically protect it from full digestion in the small intestine, ensuring that more passes into the large intestine where it can then be fermented by bacteria.

A bioactive is any chemical found in plant-based food that affects biological processes in the body, promoting better health or reducing risk of disease. Unlike macronutrients, such as carbohydrates and proteins, bioactive compounds are usually found in small amounts.

One class of bioactives where this has been known for some time is glucosinolates. For some compounds, including glucosinolates, we have identified particular bacteria that perform this task. For others, we still do not know which microbes are responsible.

S-methylcysteine sulphoxide (SMCSO) is found in brassicas but also in garlic and its relatives. Its metabolic breakdown products have been associated with protective effects against prostate and colon cancer, diabetes, and cardiovascular disease.

SMCSO-derived compounds are highly bioactive, so understanding how they affect the body’s central metabolic pathways could explain some of their health benefits. Only recently have we found clues to bacteria responsible.”

https://ifst.onlinelibrary.wiley.com/doi/10.1002/fsat.3501_6.x “Gut reaction”


The 2020 study cited for SMCSO was an in vitro 2020 study by their coworkers:

“We examined effects of a broccoli leachate (BL) on composition and function of human faecal microbiomes of five different participants under in vitro conditions. Bacterial isolates from these communities were then tested for their ability to metabolise glucosinolates and SMCSO.

We believe that this is the first study that shows reduction of dietary compound SMCSO by bacteria isolated from human faeces. Microbial communities cultured in vitro in BL media were observed to have enhanced growth of lactic acid bacteria, such as lactobacilli, with a corresponding increase in levels of lactate and short-chain fatty acids (SCFAs).

lactate

These results would have been strengthened by analysing soluble fibre content of BL media. As such, it is difficult to relate these results to in vivo SCFA production following consumption of broccoli.”

https://link.springer.com/article/10.1007/s00394-020-02405-y “Effects of in vitro metabolism of a broccoli leachate, glucosinolates and S-methylcysteine sulphoxide on the human faecal microbiome”


Which one of this pair is a male? I’ll guess on the right, as it subsequently turned to face me – a threat – when I walked passed them at a distance.

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An IBD trigger?

Three papers on interactions of the virus and inflammatory bowel disease, beginning with a 2021 review:

“Analysis signaling pathways of innate and adaptive immunity components during SARS-CoV-2 infection in IBD (inflammatory bowel disease) patients through a putative alternative route – the gastrointestinal tract, with virus attachment to ACE2 (angiotensin-converting enzyme 2) expressed on IECs (intestinal enterocytes) – allows identifying some molecular pathways and establishing possible mechanisms of immune response formation.

In general, any virus infecting intestinal tissues and/or entering the host’s body through receptors located on intestinal IECs, may be a trigger for the onset of IBD in individuals.”

https://link.springer.com/article/10.1007%2Fs11033-021-06565-w “Pathogenesis of the inflammatory bowel disease in context of SARS-COV-2 infection”


A second 2021 review continued:

“Patients with COVID-19 may develop various gastrointestinal symptoms, which may be pre-existing or not accompanied by respiratory symptoms. Positive detection of SARS-CoV-2 in stool specimens was a breakthrough because it demonstrated that the virus could replicate and exist in the digestive tract. Duration of viral nucleic acid in feces is longer than that in respiratory specimens, and the peak of viral load is later.

COVID-19 induces an acute inflammatory response which accelerates consumption of nutrients. Gastrointestinal symptoms caused by SARS-CoV-2 further impacted nutrition absorption and exacerbated malnutrition. Patients’ anxiety and poor appetite were also potential contributors to malnutrition.”

https://www.wjgnet.com/1007-9327/full/v27/i24/3502.htm “COVID-19 and its effects on the digestive system”


I found the above two papers by their citing a 2020 review:

“Based on data on over 1400 patients with IBD from an international registry, compared with TNF monotherapy, thiopurine monotherapy and combination thiopurines with TNF antagonists are associated with significantly increased risk of severe COVID-19. Mesalamine/sulfasalazine may be associated with an increased risk, particularly when compared with TNF antagonists. There are no significant differences between biological classes (TNF, interleukin-12/23 and integrin antagonists) on the risk of severe COVID-19.”

https://gut.bmj.com/content/70/4/725 “Effect of IBD medications on COVID-19 outcomes: results from an international registry”


I rated these three papers as requiring more work because they didn’t address an individual’s preparation for originating causes. Managing symptoms isn’t an appropriate response for what all of us face.

Instead, take personal responsibility for your own one precious life.

Looking forward, looking back

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Gut microbiota strains

Three human studies investigated strains within microbiota species. The first from 2021 had obese child subjects:

“Dietary intervention is effective in human health promotion through modulation of gut microbiota. Diet can cause single-nucleotide polymorphisms (SNPs) to occur in gut microbiota, and some of these variations may lead to functional changes in human health.

Compared with normal diet, the WTP diet provided large quantities of whole-grain mix that was rich in starch, soluble and insoluble dietary fiber, protein, and amino acids, but contained a small amount of fat. When this excess and/or indigestible nutrition reached the colon, it brought environmental pressures to microbiota that stayed there.

This pressure could facilitate utilization of indigestible nutrition by causing microbial SNPs. Metabolic efficiencies of indigestible nutrition substrates would be enhanced to adapt to the shifted environment better.

Although abundance of Bifidobacterium increased significantly by the intervention and became dominant strains responsible for nutrition metabolism, they had less BiasSNPs between the pre- and post-intervention group in comparison with Faecalibacterium. Finding F. prausnitzii as important functional strains influenced by intervention highlights the superiority of applying SNP analysis in studies of gut microbiota.

Though F. prausnitzii were well known for their biodiversity, we could not find functional reports about these SNPs. Future efforts are needed to verify/discern specific effects of these SNPs on encoded protein activity, their role on metabolism under high-fiber dietary intervention, and their potential beneficial or detrimental influences on host health.”

https://www.frontiersin.org/articles/10.3389/fmicb.2021.683714/full “Gut Microbial SNPs Induced by High-Fiber Diet Dominate Nutrition Metabolism and Environmental Adaption of Faecalibacterium prausnitzii in Obese Children”


A second 2021 human study investigated strain diversity in liver cirrhosis and Crohn’s disease:

“We constructed a computational framework to study strain heterogeneity in the gut microbiome of patients with liver cirrhosis (LC). Only Faecalibacterium prausnitzii showed different single-nucleotide polymorphism patterns between LC and healthy control (HC) groups.

Strain diversity analysis discovered that although most F. prausnitzii genomes are more deficient in LC group than in HC group at the strain level, a subgroup of 19 F. prausnitzii strains showed no sensitivity to LC, which is inconsistent with the species-level result.

More experiments need to be conducted so as to confirm the hypothesis of physiological differences among subgroups of F. prausnitzii strains. Our results suggest that strain heterogeneity should receive more attention.

With rapid development of sequencing technologies and experimental approaches, an increasing number of metagenomic studies will involve strain-level analysis. Such analysis of human metagenomes can help researchers develop more reliable disease diagnoses and treatment methods from a microbiological perspective.”

https://journals.asm.org/doi/10.1128/mSystems.00775-21 “Comprehensive Strain-Level Analysis of the Gut Microbe Faecalibacterium prausnitzii in Patients with Liver Cirrhosis”


A 2018 study investigated dietary fibers’ effects on Type 2 diabetics:

“In this study, we identified a group of acetate- and butyrate-producing bacterial strains that were selectively promoted by increased availability of diverse fermentable carbohydrates in the form of dietary fibers. These positive responders are likely key players for maintaining the mutualistic relationship between gut microbiota and the human host. Promoting this active group of SCFA producers not only enhanced a beneficial function but also maintained a gut environment that keeps detrimental bacteria at bay.

Only a small number of bacteria with genetic capacity for producing SCFAs were able to take advantage of this new resource and become dominant positive responders. The response, however, was strain specific: only one of the six strains of Faecalibacterium prausnitzii was promoted.

positive responders

The 15 positive responders are from three different phyla, but they act as a guild to augment deficient SCFA production from the gut ecosystem by responding to increased fermentable carbohydrate availability in similar ways. When they are considered as a functional group, the abundance and evenness of this guild of SCFA producers correlate with host clinical outcomes.”

https://science.sciencemag.org/content/359/6380/1151.full “Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes”


These studies favored a prebiotic approach to make gut microbiota happy and reciprocal in human health. The second study investigated 135 known strains of F. prausnitzii, and the first study found beneficial F. prausnitzii strains not yet covered in genomic databases.

I found the first two studies by them citing the third. The third study was cited in Gut microbiota guilds.

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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.

PXL_20210809_101612117

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:


PXL_20210809_101626026

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.