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.

Part 2 of Improving epigenetic clocks’ signal-to-noise ratio

Another excellent blog post by Josh Mitteldorf, A New Approach to Methylation Clocks, that curated the same study:

“The Levine/Horvath PhenoAge epigenetic clock was calibrated using a combination of metabolic factors that correlate with health, including inflammation, DNA transcription, DNA repair, and mitochondrial activity.

Evolution is not an engineer. Living things are not constructed out of parts that are separately optimized for exactly one function.

Every molecule has multiple functions. Every function is regulated by multiple pathways.

For clock technology, using individual CpGs for a starting point may not be optimal. We suspect that CpGs, like other biological entities, work together closely in teams.

CpGs on a team might vary slightly from one individual to the next. But the team has a function and an identity and a signature that is robust. We expect the team to function more consistently than any of its individual members.

The peer-reviewed version of her paper will be published shortly. Full details of algorithms will be available on GitHub, and script in the R programming language will be released for use of other researchers. If principal component analysis clocks correlate well with previously validated clocks but offer tighter uncertainties, we’ll know we’re on the right track.”


Best wishes for Josh to recover from a bike accident.

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Your pet’s biological age

This 2021 cat study developed human-comparable epigenetic clocks:

We aimed to develop and evaluate epigenetic clocks for cats, as such biomarkers are necessary for translating promising anti-aging interventions from humans to cats and vice versa. We also provided the possibility of using epigenetic aging rate of cats to inform on feline health, for which a quantitative measure is presently unavailable. Specifically, we present here DNA methylation-based biomarkers (epigenetic clocks) of age for blood from cats.

Maximum lifespan of cats is 30 years according to the animal age data base (anAge), but most cats succumb to diseases before they are 20 years old. Age is the biggest risk factor for a vast majority of diseases in animals, and cats are no exception.

Interventions to slow aging are being sought. Ideally, testing should occur in species that are evolutionarily close to humans, similar in size, have high genetic diversity, and share the same environment as humans. It has been recognized that domestic dogs fulfill these criteria.

Investigations have yet to be extended to cats although they share similar environments and living conditions with their human owners. Identification of environmental factors and living conditions that affect aging, as well as potential mitigation measures, can be achieved by proxy with cats.

The human-cat clock for relative age exhibited high correlation regardless of whether analysis was applied to samples from both species or only to cat samples. This demonstrated that relative age circumvented skewing that is inherent when chronological age of species with very different lifespans is measured using a single formula.

Evidence is compelling that epigenetic age is an indicator of biological age. These results are consistent with the fact that epigenetic clocks developed for one mammalian species can be employed – to a limited extent – to other species, and reveal association of DNA methylation changes with age.

Human epigenetic age acceleration is associated with a wide array of primary traits, health states, and pathologies. While it is still unclear why age acceleration is connected to these characteristics, it does nevertheless suggest that extension of similar studies to cats may allow for development of epigenetic age acceleration as a surrogate or indicator of feline biological fitness.”

https://link.springer.com/article/10.1007%2Fs11357-021-00445-8 “Epigenetic clock and methylation studies in cats”


As noted earlier this summer in Smoke and die early, while your twin lives on, Dr. Steve Horvath is on a torrid publishing streak this year. He’s made it questionable for study designs based on published science to omit epigenetic clocks.

I titled this post Your pets because I’m too allergic to have cats, dogs, etc. live with me. Maybe this year’s focus on making my gut microbiota happy will change that?

My pets live free:

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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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It’s pawpaw season!

“In this episode we speak with Neal Peterson, who has devoted over 40 years to breeding pawpaws (Asimina triloba). We talk about how he first fell in love with this delicious fruit, how he tracked down remnants of the early 20th century pawpaw collections just in time, and selected 7 superior pawpaw cultivars out of 1,500 seedlings.”

Go to https://anchor.fm/plantcunning/ and episode 46.


I first ate a pawpaw while on a Capital Area Hiking Club September 2015 hike on the Susquehanna River. Our hike leader loaded up his backpack and was willing to share when we finished. Didn’t take a photo, but here’s what I picked a year later from a farm:

IMG_20160924_185415

Ugly looking, but beautiful inside.

In subsequent seasons, I found pawpaws in national and state parks. Can’t find pawpaw fruit sales online that I previously bought from, so may revisit these parks next month.

My son and I engaged in Guerrilla Planting. Maybe it’s time to check on those trees’ progress, too?

Stay out of the hospital with Vitamin K

This 2021 study investigated Vitamins K1 and K2 associations with hospitalization for atherosclerotic cardiovascular disease (ASCVD):

“In this prospective cohort study, both dietary vitamin K1 intake and vitamin K2 intake were inversely related to ASCVD hospitalization risk, and very low vitamin K1 was associated with a higher risk of ASCVD hospitalizations. Given very different food sources, these data support an independent protective effect for both subtypes of vitamin K.

u-shape

Relatively higher vitamin K2 intake in our cohort permitted discovery of a nonlinear, more U‐shaped association between vitamin K2 intake and ASCVD risk, which, to the best of our knowledge, has not previously been described. This may reflect a competing increase in ASCVD risk associated with overconsumption of vitamin K2‐rich foods (ie, cheese, eggs, butter).

Our study comes with some limitations common to nutritional epidemiology, and has significant strengths:

  • A large sample size with up to 23 years of follow‐up, allowing for accumulation of a high number of events;
  • Availability of important participant characteristics, enabling appropriate methods to be employed to reduce residual confounding; and
  • Minimal loss to follow‐up (<0.3%).”

https://www.ahajournals.org/doi/10.1161/JAHA.120.020551 “Vitamin K Intake and Atherosclerotic Cardiovascular Disease in the Danish Diet Cancer and Health Study”


I came across this study through a 2021 video:

Twice-daily broccoli / red cabbage / mustard sprouts for Vitamin K1, and a supplement for Vitamin K2 is what I do. Expect more than staying out of hospitals, but don’t know whether previous damage can be repaired.

Looking forward

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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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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 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.

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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.

Resistant starch therapy

This 2021 review subject was interactions among resistant starches and gut microbiota:

“Starch that reaches the large intestine without being fully digested is termed resistant starch (RS). Starch digestibility should be considered as a kinetic property (slower to faster) affected by host-specific factors, rather than as a binary trait (resistant or nonresistant).

RS is degraded by the colon’s complex ecosystem of microbes, triggering a cascading web of metabolic interactions. RS acts as a resource that is degraded and fermented by a hierarchy of specialized gut microbes:

  1. Primary degraders grow on RS in monoculture. They penetrate outer surfaces of intact RS granules, exposing pores and deeper concentric matrices while liberating oligosaccharides and generating metabolites like lactate and acetate.
  2. Secondary degraders grow on starch in monoculture, but degrade intact RS poorly or not at all. Instead, they may adhere to abrasions and pores on RS before participating in its degradation, and opportunistically utilize solubilized oligosaccharides produced by other RS degraders.
  3. Cross-feeders do not grow on starch in monoculture. They utilize by-products generated by upstream degraders, helping to maintain stoichiometric equilibrium and thermodynamically favorable (i.e. unconstrained) fermentation.

Together, the subsystem of microbes involved in RS degradation and fermentation participates in a complex network of cross-feeding interactions. In maintaining microbiome homeostasis, the RS nutrient web expands the scope of what could be considered a ‘beneficial’ gut microbe to a cluster of metabolically interconnected microbes.

1. Primary degraders such as acetate-producing Ruminococcus bromii are thought to be necessary for RS degradation in the human gut, where they unlock RS for other community members to degrade and ferment.

Ruminococcus genus

2. Secondary degraders possess extracellular amylases to degrade regular starch, but their contribution to initiating RS degradation is negligible compared to that of primary degraders. Instead, they may require primary degraders to erode smooth RS granule surfaces before adhering to RS and/or scavenging for ‘substrate spillover’ (i.e. excess oligosaccharides generated by primary degraders).

Eubacterium genus

Roseburia genus

3. Cross-feeders utilize starch by-products or metabolites generated by upstream RS degraders, such as acetate, lactate, formate, and succinate. Describing all known gut bacteria capable of utilizing these substrates exceeds the scope of this review, but one other example is noteworthy.

Faecalibacterium prausnitzii is a prominent butyrate-producing commensal, comprising 1.5% to 9.5% of fecal bacteria in European individuals. F. prausnitzii utilizes maltose and acetate to generate butyrate.

top 1-10 species

Microbiome sequencing data are compositional, meaning that gene amplicon read counts do not necessarily reflect bacterial absolute abundances. Instead, read counts are typically normalized to sum to 100%.

For this reason, relative abundances of smaller keystone communities (e.g. primary degraders) may increase, but appear to decrease simply because cross-feeders increase in relative abundance to a greater extent. These limitations illustrate the necessity of sufficiently powering RS interventions where microbiome composition is the primary endpoint, collecting critical baseline data and employing appropriate statistical techniques.”

https://www.tandfonline.com/doi/full/10.1080/19490976.2021.1926842 “Resistant starch, microbiome, and precision modulation”

Don’t count on broccoli compounds bailing out a high-fat diet’s effects on gut microbiota

Two rodent studies of mature broccoli and broccoli sprouts’ effects on a high-fat diet, with the first from 2021 investigating broccoli florets and stalks:

“Addition of broccoli florets to a HFD ameliorated insulin sensitivity. Florets further promoted gut microbiota diversity and low-grade inflammatory-associated strains.

Stalk supplementation also altered gut microbiota, leading to increased Bacteroidetes/Firmicutes ratio and levels of communities that preserve mucus layer and gut integrity while simultaneously decreasing levels of potentially harmful species.

Addition of broccoli to a HFD did not ameliorate body and tissues weight gain or food intake. Both broccoli stalks and florets did not affect fat accumulation, carbohydrate, or lipid metabolism-related parameters.”

https://www.frontiersin.org/articles/10.3389/fnut.2021.680241/full “Broccoli Florets Supplementation Improves Insulin Sensitivity and Alters Gut Microbiome Population – A Steatosis Mice Model Induced by High-Fat Diet”


A 2020 study cited by this first study investigated compounds extracted from 1-day-old broccoli sprouts:

Bioaccessibility of aliphatic glucosinolates was shown to 76.2 ± 0.6%:

aliphatic glucosinolate bioavailability

Glucoraphanin was the predominant glucosinolate with the highest bioaccessibility in broccoli, and could effectively prevent HFD-induced body weight gain in mice, especially increases in liver weight and the accumulation of lipids in adipocytes. Furthermore, supplementation with glucoraphanin reduced the level of oxidative stress, regulated genes of FAS, PPARα, CPT1 and ACOX associated with lipid metabolism, and might be associated with changes in composition of gut microbiota.”

https://www.frontiersin.org/articles/10.3389/fnut.2021.680241/full “Effect of glucoraphanin from broccoli seeds on lipid levels and gut microbiota in high-fat diet-fed mice”

This study’s title was “Effect of glucoraphanin from broccoli seeds..” although its Materials and methods section disclosed:

“1 day after germination from broccoli seeds, sprouts were boiled in water for 30 min. The resulting aqueous extract was processed by liquid solid separation and condensation and was subsequently spray-dried to yield an extract powder containing 249 mg glucoraphanin.”


Eat broccoli sprouts every day and its predecessor study demonstrated that broccoli intake every day had beneficial effects during shorter periods than either of these studies.

Both studies had many “may”, “could”, and “might” statements. Not sure that broccoli compounds / gut microbiota relationships are adequately investigated by choosing a few out of tens of thousands of gut microbiota species as both studies attempted to do.

There are too many additive / antagonistic / synergistic combinations to analyze even before reaching twenty gut microbiota species. But researchers aren’t often sponsored for studies unless they conform to existing research.


I haven’t made headway in understanding my top 10 of 42,156 gut microbiota species’ exact causes, effects, and interactions. The top three by themselves are considered beneficial:

top 1-10 species

Uncertainty is fine for now, though, with a 40-hour work week interfering. Finding out what my gut microbiota generally want and giving that to them has been a productive approach this year.

If you aren’t where you want to be, change yourself

This 2021 human study evaluated associations among epigenetic clocks and socioeconomic status:

“We conducted a comprehensive, comparative analysis of associations between various dimensions of socioeconomic status (SES) (education, income, wealth, occupation, neighbourhood environment, and childhood SES) and eight epigenetic clocks in two well-powered US ageing studies:

  • The Multi-Ethnic Study of Atherosclerosis (MESA); and
  • The Health and Retirement Study (HRS).

We found robust associations between SES measures in adulthood and the GrimAge and DunedinPoAm [Dunedin New Zealand (P)lace (o)f (A)ging (m)ethylation clock)] clocks. In the HRS, significant associations with the Levine and Yang clocks were also evident.

These associations were only partially mediated by smoking, alcohol consumption, and obesity, which suggests that differences in health behaviours alone cannot explain the SES gradient in epigenetic ageing in older adults. Further analyses revealed concurrent associations between polygenic risk for accelerated intrinsic epigenetic ageing, SES, and the Levine clock, indicating that genetic risk and social disadvantage may contribute additively to faster biological aging.”

https://www.medrxiv.org/content/medrxiv/early/2021/03/02/2021.03.01.21252660.full.pdf “The Socioeconomic Gradient in Epigenetic Ageing Clocks: Evidence from the Multi-Ethnic Study of Atherosclerosis and the Health and Retirement Study”


This study had a lot of squishy data. Didn’t see peer review comments, but I’d require evidence for several of these categorizations and subsequent findings.

For example, I quit smoking on February 5, 1985, the day I left my third submarine. This study would have categorized me 36 years later as a former smoker.

This categorization defied human cell turnover, with exceptions of our:

  • Cerebrum and cerebellum neurons;
  • Eye inner lens cells; and
  • Heart muscle cells.

Neither these cells nor other cells are associated with current status and quitting smoking four decades earlier. Consider that “associated” relationships don’t necessarily have any causal origins.

Another example from this study. My parents’ educational achievements of Masters degrees were during the 1950s. Pretty sure they weren’t causal to my degrees during the 1980s when I focused on advancing in the U.S. Navy.

Your responses to life events and subsequent behaviors are up to you, when and where you need them to be.

Do you feel a need to be consciously aware of who you really are? If not, unconsciously move along with the herd.


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Advantages of 3-day-old oat sprouts over oat grains

This 2021 in vitro study investigated different composition and resultant effects of oat grain and sprouts:

“The aim of this study was to:

  • Evaluate the effect of polyphenols and avenanthramides extracted from oat grains and sprouts on glucose and lipid metabolisms in 3T3 L1 adipocytes; and
  • Identify compounds associated with their beneficial effects through a chemometric approach.

Oat (Avena sativa var. Turquesa) seeds soaked in distilled water at 1:6 w/v ratio for 12 hr. Seeds were then placed in trays covered with a wet filter paper, then into a germination chamber for 3 days at 25°C and 60% relative humidity.

Both polyphenol and avenanthramide extracts from oat sprouts showed a greater beneficial effect than those from oat grains:

Effect of oat grain and sprouts on glucose (a) and lipid (b) metabolism

Effect of oat grain and sprouts on glucose (a) and lipid (b) metabolism. PE-OG Polyphenol extract from oat grain; PE-OS polyphenol extract from oat sprout; AE-OG avenanthramide extract from oat grain; AE-OS avenanthramide extract from oat sprout. Glucose metabolism (a) Glut4, glucose transporter-4; Irs1, insulin receptor substrate-1; Pi3k, phosphoinositide 3-kinase. Lipid metabolism (b) Fasn, fatty acid synthase; Acaca, acetyl-CoA carboxylase; Cpt1, carnitine palmitoyltransferase 1a; Acadm, acyl-CoA dehydrogenase.

Flavonoids:

  • Twelve major and minor flavonols were found in greater amount in sprouts, whereas two were lost; and
  • Two flavones were found in greater amounts in sprouts, whereas seven were reduced or lost. This is the first study that reports the profile of flavone derivatives in oat grains and sprouts.

Phenolic acids:

  • Six hydroxybenzoic acids were found in greater amounts in sprouts, whereas two were reduced or lost.
  • Fifteen hydroxycinnamic acids were found in greater amounts in sprouts, whereas four were reduced or unchanged or lost. Hydroxycinnamic acids esterified with quinic acid such as sinapoylquinic, coumaroylquinic, and feruloylquinic acids, as well as other derivatives, were identified in this study for the first time in oat grain and oat sprouts.

Avenanthramides: all avenanthramides were significantly increased during sprouting (1.7 to 9.0-fold).

Health beneficial effects of oat grains and sprouts were mainly related to their high content of:

  • Avenanthramides A (2p), B (2f), and C (2c);
  • Flavonols quercetin 3-O-rutinoside and kaempferol;
  • Hydroxycinnamic acid sinapoylquinic acid; and
  • Flavones apigenin and luteolin derivatives.

Polyphenol and avenanthramide extracts from oat grains and oat sprouts increased expression of genes involved in glucose uptake and fatty acids β-oxidation, and decreased expression of genes involved in fatty acids de novo synthesis (Fasn and Acaca) in 3T3 L1 adipocytes. Oat sprout extracts exerted an overall greater beneficial effect as compared to oat grain extracts.

This is the first study that demonstrates that oat avenanthramides and polyphenols modulate expression of key genes involved in glucose and lipid metabolisms in adipocytes. Further studies are necessary to validate these results using an in vivo approach.”

https://onlinelibrary.wiley.com/doi/10.1111/jfbc.13738 “Polyphenols and avenanthramides extracted from oat (Avena sativa L.) grains and sprouts modulate genes involved in glucose and lipid metabolisms in 3T3 L1 adipocytes” (not freely available) Thanks to Dr. Iza F. Pérez-Ramírez for providing a copy.


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