Happiness

Week 127 of Changing to a youthful phenotype with sprouts

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Stress ,

1. My third gut microbiome test results came in this week. I submitted a sample earlier this month to follow methods in the second paper of Improving dietary fiber research in a continuing effort to treat my gut microbiota well.

But that study’s vendor was unable to ship an EU-approved product from The Netherlands to the US because it wasn’t FDA-approved. Our US pets can eat dried chicory root products every day, but we can’t? I haven’t received any positive responses from US vendors of dried chicory root products, so I’ll keep taking up to 10 grams of EU-manufactured inulin daily.

I also followed Dr. Horvath’s suggestion in Epigenetic clocks so far in 2022 to “measure epigenetic age because there’s always an opportunity to make a discovery” and submitted a blood test. Will link to those results when they arrive – How to measure biological age?

2. These gut microbiome test results highlight a 16S ribosomal RNA technology flaw that Resistant starch therapy pointed out:

“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.”

Here are my top two relative abundance results, genus Faecalibacterium and genus Bacteroides:

relative abundance2

  • 25.330% (46,844 total count) of my gut microbiota being a butyrate producer is relatively higher than 22.567% (42,156 total count) 14 months ago. Here’s a review of butyrate’s effects.
  • 25% cross-feeder genus Faecalibacterium didn’t relatively crowd out a primary degrader, genus Ruminococcus, which comparatively stayed at 6%. It may have relatively reduced secondary degrader genus Eubacterium abundance from 6% to 5%.

I don’t assign importance per the above graphic that other people achieve 12% relative abundance of a butyrate producer but I have 25%. Our 10,000+ microbiota species perform many overlapping functions.

Conversely, why should I care that other people host an average 25% genus Bacteroides and I relatively have 17% as I did 14 months ago? It’s similar to irrelevant comparisons of clinical biomarkers in Week 120 of Changing to a youthful phenotype with sprouts.

3. So what are appropriate gut microbiome measurements? They aren’t fine-grained relative measurements of my current gut microbiome, either vs. my previous measurements or vs. other people.

I could make a p < .05 finding out of 25.330% vs. 22.567%. But would those numbers be an adequate proxy for understanding truth?

I think science and industry will affordably catch up to these discrepancies as it has with epigenetic clocks. Haven’t come across well-designed gut microbiota studies that use technologically preferable shotgun metagenomic sequencing with absolute measures of both form and function. I’ve read plenty that are stuck in a relative abundance paradigm.

In the meantime, I’m alright, but have to toughen up quickly so that I can transition later this month from summer weather on my sunrise walk every day to a freezing destination.

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Minds of their own

gettingwell4 5+ stars Premium, Brain development, Brain hemispheres, Epigenetics, Memory, Neurochemicals, Serotonin, Stress , , , , , ,

It’s the weekend, so it’s time for: Running errands? Watching sports? Other conditioned behavior?

Or maybe broadening our cognitive ability with Dr. Michael Levin’s follow-ups to his 2021 Basal cognition paper and 2020 Electroceuticals presentation with a 2022 paper and presentation starting around the 13:30 mark:

Michael Levin - Cell Intelligence in Physiological and Morphological Spaces

“A homeostatic feedback is usually thought of as a single variable such as temperature or pH. The set point has been found to be a large-scale geometry, a descriptor of a complex data structure.”

His 2022 paper Technological Approach to Mind Everywhere: An Experimentally-Grounded Framework for Understanding Diverse Bodies and Minds:

“It is proposed that the traditional problem-solving behavior we see in standard animals in 3D space is just a variant of evolutionarily more ancient capacity to solve problems in metabolic, physiological, transcriptional, and morphogenetic spaces (as one possible sequential timeline along which evolution pivoted some of the same strategies to solve problems in new spaces).

Developmental bioelectricity works alongside other modalities such as gene-regulatory networks, biomechanics, and biochemical systems. Developmental bioelectricity provides a bridge between the early problem-solving of body anatomy and the more recent complexity of behavioral sophistication via brains.

This unification of two disciplines suggests a number of hypotheses about the evolutionary path that pivoted morphogenetic control mechanisms into cognitive capacities of behavior, and sheds light on how Selves arise and expand.

While being very careful with powerful advances, it must also be kept in mind that existing balance was not achieved by optimizing happiness or any other quality commensurate with modern values. It is the result of dynamical systems properties shaped by meanderings of the evolutionary process and the harsh process of selection for survival capacity.”

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Estimating bioavailability of oat compounds

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Stress , , ,

Two papers on oat compounds’ bioavailability, starting with a 2022 review:

“There are many nutrients and bioactive chemical compounds exerting beneficial properties in oats. Results indicated that oats and their extracts possessed essential roles in preventing chronic diseases.

However, most studies focused on Avns’ [avenanthramides] functions were performed using cell models. In animal models, one disadvantage of Avns was low bioavailability.

Avns were also metabolized in the gastrointestinal tract in a gut microbiota (especially Faecalibacterium prausnitzii) dependent or independent manner. Administration of Avns usually ranged from 100−300 mg/ kg, which was much higher than that for cell treatment.

After eating cookies with 9.2 mg or 0.4 mg (control) Avns for 8 weeks, plasma level of TNF-α after exercise was significantly reduced in young women (16 women aged 18−30 years). Similar results were obtained in a study enrolling postmenopausal women (16 women aged 50−80 years), and Avns supplementation (9.2 mg in cookies) dramatically reduced plasma levels of IL-1β and C-reactive protein after exercise.

More attention should be given to studying preventative effect of Avns on chronic diseases and underlying molecular mechanisms, and further revealing potential roles of small molecules with powerful regulatory activity, such as miRNAs.”

https://pubs.acs.org/doi/full/10.1021/acs.jafc.1c05704 “The Progress of Nomenclature, Structure, Metabolism, and Bioactivities of Oat Novel Phytochemical: Avenanthramides” (not freely available)

This first paper’s Reference 25 was a 2018 paper on oat compounds’ bioaccessibility that used an in vitro digestion system without microbiota:

“Malting was performed for 5 days, from M0 (non-malted oat grains) to M5 (oat grains malted for 5 days), using the following: steeping at 20 °C for 24 h, germination in the dark at 15 °C, and kilning in an air oven at 100 °C for 12 h.

The cookie formulation with lowest phenol concentration showed highest bioaccessibility. This result was surprising, as we expected an increase in SP [soluble phenols] bioaccessibility, in parallel with increasing SP concentration of cookies.

bioavailability avena nuda avn sp

A portion of 5B cookies provides 4.8 mg of AVNs, which is more than double a maximal daily AVN intake in oat consumers.”

https://ifst.onlinelibrary.wiley.com/doi/10.1111/ijfs.14020 “In vitro bioaccessibility of avenanthramides in cookies made with malted oat flours” (not freely available)

Every day I eat Avena nuda oats that start out as 82 grams of seeds, and two servings of 3-day-old Avena sativa oat sprouts that each start out as 20 grams of seeds. Using this second paper’s 50 gram Avena nuda methods to develop estimates:

avena nuda avn sp

  • (82 g / 50 g) x 42 µg = 69 µg total AVNs; and
  • (82 g / 50 g) x 660 µg = 1,082 µg soluble phenols.

My Avena nuda whole oat grain total AVNs and soluble phenol weights aren’t much. They aren’t bioavailability estimates. Their species and growing conditions are different from this second paper, etc.

That’s all okay with me. I eat Avena nuda oats primarily to make my trillion+ gut microbiota partners happy with indigestible-to-me whole grain contents, expecting that they will reciprocate.

Plugging in the study’s 3-day figures to estimate Avena sativa oat sprouts:

  • (40 g / 50 g) x 324 µg = 259 µg total AVNs; and
  • (40 g / 50 g) x 1350 µg = 1,080 µg soluble phenols.

Using the first graphic’s 3-day relative bioaccessibility percentages:

  • 259 µg x .28 = 72 µg total bioavailable AVNs; and
  • 1,080 µg x .41 = 442 µg bioavailable soluble phenols.

Both papers cited studies that found with eccentric exercise, “9.2 mg per day AVNs are sufficient to provide effects on exercise induced inflammation.” I exercise at least 30 minutes every day, but don’t perform eccentric exercises more frequently than every five days per Eat broccoli sprouts for your workouts.

Advantages of 3-day-old oat sprouts over oat grains provided methods comparable to my Avena sativa 3-day-old oat sprouts intake, although it didn’t assess bioavailability. Sprouts’ beneficial effects compared with seeds “were mainly related to their high content of avenanthramides A (2p), B (2f), and C (2c), quercetin 3-O-rutinoside [rutin], kaempferol, sinapoylquinic acid, and apigenin and luteolin derivatives.”

Couldn’t say whether I benefit more from bioavailability of 3-day-old oat sprouts’ directly soluble phenols, or from bioavailability of their phenolic breakdown byproducts provided by gut microbiota. For example, regarding oat sprouts rutin content, a 2019 review pointed out:

“Humans lack the enzyme needed to hydrolyze this bond. Consequently, microorganisms in the colon mediate hydrolysis of this rutinoside, resulting in minimal intestinal absorption, and production of phenolic acid metabolites in the colon.”

Osprey below a bird-like cloud

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Eat oat avenanthramides for your gut microbiota

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Stress , , ,

This 2021 paper covered a 2016 human clinical trial, and several in vitro and rodent follow-up studies:

“Oat has been widely accepted as a key food for human health. It is becoming increasingly evident that individual differences in metabolism determine how different individuals benefit from diet. Both host genetics and gut microbiota play important roles on metabolism and function of dietary compounds.

Results:

  • Avenanthramides (AVAs), the signature bioactive polyphenols of whole-grain (WG) oat, were not metabolized into their dihydro forms, dihydro-AVAs (DH-AVAs), by both human and mouse S9 fractions.
  • DH-AVAs were detected in colon and distal regions, but not in proximal and middle regions of the perfused mouse intestine, and were in specific pathogen–free (SPF) mice but not in germ-free (GF) mice.
  • A kinetic study of humans fed oat bran showed that DH-AVAs reached their maximal concentrations at much later time points than their corresponding AVAs (10.0–15.0 hours vs. 4.0–4.5 hours, respectively).
  • We observed interindividual variations in metabolism of AVAs to DH-AVAs in humans.
  • Faecalibacterium prausnitzii was identified as the individual bacterium to metabolize AVAs to DH-AVAs by 16S rRNA sequencing analysis.
  • Moreover, as opposed to GF mice, F. prausnitzii–monocolonized mice were able to metabolize AVAs to DH-AVAs.

AVA metabolizers

These findings demonstrate that intestinal F. prausnitzii is indispensable for proper metabolism of AVAs in both humans and mice. We propose that abundance of F. prausnitzii can be used to subcategorize individuals into AVA metabolizers and nonmetabolizers after WG oat intake.

Our findings pave the way to use AVAs and DH-AVAs as exposure biomarkers to reflect WG oat intake, which could more accurately record WG oat intake. Whether production of DH-AVAs is part of the beneficial effect of oats on human health will require further investigation.”

https://academic.oup.com/jn/article/151/6/1426/6165027 “Avenanthramide Metabotype from Whole-Grain Oat Intake is Influenced by Faecalibacterium prausnitzii in Healthy Adults”

Commentary at Faecalibacterium prausnitzii Abundance in Mouse and Human Gut Can Predict Metabolism of Oat Avenanthramides.

This study advanced an understanding of inter-individual variability, rather than usual practices that try to sweep individual differences under a statistical rug. Study designs such as four mentioned in Part 2 of Switch on your Nrf2 signaling pathway could have benefited from a similar approach to their research areas.

Not sure why it took over five years to get this paper published after its clinical trial’s January 21, 2016 completion. Meanwhile, science marched on to study effects of specific F. prausnitzii strains, providing results such as three human studies curated in Gut microbiota strains:

  • The third 2018 study found:

    “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.”

  • The second 2021 study investigated 135 known strains of F. prausnitzii; and
  • The first 2021 study found beneficial F. prausnitzii strains not yet covered in genomic databases.

Resistant starch therapy recommended de-emphasizing relative gut microbiota abundance measurements, because:

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

Four humpback whales successively diving for lunch

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Choosing your gut immune response

gettingwell4 0-1 star Wasted resources, Epigenetics, Immune system, Memory, Stress , , , ,

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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Changing your immune system / gut microbiota interactions with diet

gettingwell4 0-1 star Wasted resources, Epigenetics, Immune system, Memory, Stress ,

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.

Your pet’s biological age

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Telomeres , , , ,

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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Eat oats for β-glucan and resistant starch

gettingwell4 2-3 stars Required further work, Epigenetics, Immune system ,

This 2021 review highlighted effects of processing oat products:

“Starch contents in oats ranges from 51% to 65%. Resistant starch (RS) accounts for 29.31% of starch content in raw granular form of oat starch.

RS in raw oat starch is RS2 starch, where its slow digestion is mainly due to the compact nature of starch granules making starch less accessible to enzymes. Since amylose–lipid complex is resistant to enzymatic breakdown, high lipid content in oats (3–7%) may be another reason why oat has a relatively high level of RS starch. This type of RS is called RS5.

Although RS2 occurs naturally, most starch needs to be cooked for consumption. RS3 that is formed due to recrystallization of gelatinized starch is more commonly consumed by processing via gelatinization and retrogradation.

β-glucans are found in cell walls of endosperm and aleurone layers of oats, accounting for 1.73-5.70% of oat grains dry basis. Oat β-glucans are not digested in the upper gastric tract, but instead can be consumed by gut microbiota in the colon. This kind of prebiotic can be fermented by colonic microbiota, resulting in production of short chain fatty acids (SCFA) metabolites.

From field to table, oats are processed into various foods for consumption, and these foods exhibit high variability of GI values:

  • β-glucan dose and molecular weight are crucial determinants affecting viscosity and gastric emptying rate; and
  • Higher content of protein in oats is an important factor that deserves attention.”

https://www.mdpi.com/2304-8158/10/6/1304/htm “Oat-Based Foods: Chemical Constituents, Glycemic Index, and the Effect of Processing”

Didn’t care for this focus on one dimension of health, glycemic index. Why not focus on healthy individuals’ behaviors? See An oats β-glucan clinical trial for more human in vivo evidence regarding β-glucan molecular weight.

I eat oats three times a day, and it’s worked out alright.

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Gut microbiota strains

gettingwell4 5+ stars Premium, Epigenetics, Stress , , ,

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

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Memory, Stress , ,

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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Part 3 of Make your gut microbiota happy

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Memory, Stress ,

Continuing from Part 2, my 7/15/2021 sample found that no bad bacteria needed work. Top three reasons why this may be are:

1. I’ve eaten microwaved broccoli sprouts every day for 68 weeks now. Relevant research:

helicobacter 0

2. This is the 17th year of training my immune system every day with yeast cell wall β-glucan.

acinetobacter

3. Basic hygiene practices such as brushing my teeth twice a day.

aggregatibacter 0

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Part 2 of Make your gut microbiota happy

gettingwell4 4-5 stars Advanced knowledge, Epigenetics ,

Continuing from Part 1, 7/15/2021 test results received 7/27 showed I was putatively below average in four gut bacteria. The most relatively deficient (percentage-wise) were populations in genus Bifidobacterium:

bifido level

Looking through Thryve’s recommended foods, eating all but one (green lentils) of twenty legumes increased genus Bifidobacterium. Here’s a sample:

legumes

I already had dried garbanzo and Adzuki beans in my pantry. One serving (35 grams, 1/4 cup) of each are soaking overnight.

Adzuki beans would be expected to improve genus Bifidobacterium populations through resistant starch 2. Garbanzo beans would be expected to improve genus Bifidobacterium populations primarily through resistant starch 3, while also improving relatively-deficient Akkermansia and Lactobacillus bacteria.

Resistant starch was curated in studies such as:

Resistant starch types and their effects were summarized in https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/resistant-starch.

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Week 56 of Changing to a youthful phenotype with sprouts

gettingwell4 2-3 stars Required further work, Epigenetics, Immune system, Memory, Stress

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

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

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

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

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

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

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

Reducing sulforaphane intake from broccoli sprouts to 17 mg is still within boundaries of measurable effects. As an example, Upgrade your brain’s switchboard with broccoli sprouts found effects from a daily sulforaphane 17.3 mg (100 µmol) intake. Plus red cabbage’s main glucosinolate, like broccoli sprouts, is glucoraphanin, which may hydrolyze to sulforaphane.

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

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

Mustard’s myrosinase enzyme activities over and above broccoli myrosinase were highlighted in cited studies of Does sulforaphane reach the colon? Don’t know whether mustard sprouts’ myrosinase ≤ 60°C boosts broccoli and red cabbage sprouts’ hydrolyzation of glucoraphanin into sulforaphane.

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

red cabbage glucoraphanin vs white cabbage

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

Red cabbage anthocyanins are greater than broccoli anthocyanins, which was highlighted in Colorize your diet, Red cabbage pigments and the brain, and Measuring bioavailability.

Figure 5 of Lab analyses of broccoli sprout compounds had analysis of three red cabbage cultivars’ 9-day-old sprouts. Glucosinolates are on top, hydrolysis products on the bottom. Glucoraphanin is red 4MSOB in A, and sulforaphane is red 4MSOB-ITC in C:

red cabbage 9-day-old sprouts

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

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

3. This Brassicaceae species composite isn’t photogenic:

PXL_20210502_214348538

Red cabbage sprouts by themselves are pretty.

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

Week 37 of Changing to a youthful phenotype with broccoli sprouts

gettingwell4 4-5 stars Advanced knowledge, Beliefs, Cerebrum, Cortisol, Dopamine, Glutamate, Limbic system, Lower brain, Memory, Neurochemicals, Primal Therapy, Stress , , , , , , ,

1. Been wrong about a few things this past week:

A. I thought in Week 28 that extrapolating A rejuvenation therapy and sulforaphane results to humans would produce personal results by this week. An 8-day rat treatment period ≈ 258 human days, and 258 / 7 ≈ 37 weeks.

There are just too many unknowns to say why that didn’t happen. So I’ll patiently continue eating a clinically relevant 65.5 gram dose of microwaved broccoli sprouts twice every day.

PXL_20201015_105645362

The study’s lead researcher answered:

“Depends, it might take 37 weeks or more for some aspects of ‘youthening’ to become obvious. It might even take years for others.

Who really cares if you are growing younger every day?

For change at the epigenomic/cellular level to travel up the biological hierarchy from cells to organ systems seems to take time. But the process can be repeated indefinitely (so far as we know) so by the second rejuvenation you’re already starting at ‘young’. (That would be every eight to ten years I believe.)”

His framework is in An environmental signaling paradigm of aging.

B. I thought that adding 2% mustard seed powder to microwaved broccoli sprouts per Does sulforaphane reach the colon? would work. Maybe it would, maybe it wouldn’t, but my stomach and gut said that wasn’t for me.

C. I thought I could easily add Sprouting whole oats to my routine. I ran another trial Sprouting hulled oats using oat seeds from a different company and Degree of oat sprouting as a model.

2. Oat sprouts analysis paired studies were very informative, don’t you think? One study produced evidence over 18 germination-parameter combinations (hulled / dehulled seeds of two varieties, for 1-to-9 days, at 12-to-20°C).

Those researchers evaluated what mix of germination parameters would simultaneously maximize four parameters (β-glucan, free phenolic compounds, protease activity, and antioxidant capacity) while minimizing two (enzymes α-amylase and lipase). Then they followed with a study that characterized oat seeds sprouted under these optimal conditions.

I doubted PubMed’s “oat sprout” 20 search results for research 1977 to the present. Don’t know why they didn’t pick up both of these 2020 studies, but I’m sure that .gov obvious hindrances to obtaining relevant information like this won’t be fixed. What other search terms won’t return adequate PubMed results?

3. The blog post readers viewed this week that I made even better was Do delusions have therapeutic value? from May 2019. Sometimes I’ve done good posts describing why papers are poorly researched.

4. I’ve often changed my Week 4 recipe for an AGE-less Chicken Vegetable Soup dinner (half) then the next day for lunch. The biggest change brought about by 33 weeks of behavioral contagion is that I now care more about whether vegetables are available than whether or not they’re organic. Coincidentally, I’ve developed a Costco addiction that may require intervention.

  • 1/2 lemon
  • 4 Roma tomatoes
  • 4 large carrots
  • 6 stalks organic celery
  • 6 mushrooms
  • 6 cloves garlic
  • 6 oz. organic chicken breast fillet
  • 1 yellow squash, alternated with 1 zucchini
  • 1 cup sauvignon blanc
  • 32 oz. “unsalted” chicken broth, which still contains 24% of the sodium RDA

Pour wine into a 6-quart Instant Pot; cut and strain squeezed lemon; cut chicken into 1/4″ cubes and add; start mixture on Sauté. Wash and cut celery and stir in. Wash and cut carrots and stir in.

When pot boils around 8 minutes, add chicken broth and stir. Wash mushrooms, slicing into spoon sizes.

Wash and slice yellow squash / zucchini. Crush and peel garlic, tear but don’t slice. Turn off pot when it boils again around 15 minutes.

Wait 2-3 minutes for boiling to subside, then add yellow squash / zucchini, mushrooms, garlic, whole tomatoes. Let set for 20 minutes; stir bottom-to-top 5 and 15 minutes after turning off, and again before serving.

AGE-less Chicken Vegetable Soup is tasty enough to not need seasoning.