Butyrate: The Microbiome's Anti-Aging "Kill Switch" for Senescent Cells

RapAdmin

Shifting to green banana flour after reading this, I plan to use it the same way as with potato flour. Mixing a full tablespoon inte my mix of low-fat yoghurt, berries, nuts and seeds.

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FWIW: Asking perplexty.ai “Which combination of green banana flour, tributyrin, acarbose and Clostridium bytericum CBM588 is most beneficial for increasing butyrate”. (In one-to-one comparisons, tributyrin is the strongest)

For maximally increasing butyrate, the most rational focus is on a fermentable substrate + a butyrate‑producer + a defined butyrate prodrug, with acarbose as an optional amplifier depending on your glycemic status and GI tolerance. ����

Roles of the four Green banana flour:
Major resistant‑starch source; directly feeds colonic microbiota and increases SCFA (especially butyrate) when tolerated.

��Clostridium butyricum CBM588: Live butyrate‑producing probiotic that can raise colonic butyrate and support microbiota diversity, especially when given fermentable carbohydrate. ��

Tributyrin: Direct, quantifiable butyrate prodrug that raises both luminal and systemic butyrate independent of your existing microbiota.

��Acarbose: Drug that shifts more starch to the colon, modulating microbiota and SCFAs, but with frequent gas/bloating at higher doses and mixed human data on microbiome impact.

��Most beneficial core combo for butyrate Green banana flour (titrated RS dose) / CBM588/Tributyrin

This triad:Supplies fermentable substrate (green banana), a specialized butyrate producer (CBM588), and a guaranteed butyrate load (tributyrin), creating both ecosystem‑level and direct butyrate gains. ���

Avoids adding a fourth variable drug (acarbose) that can strongly alter glucose handling and often limits dose by GI side effects, especially if you already use high‑RS foods. ��

When to consider acarboseAcarbose can be layered only if:You have impaired glucose tolerance / post‑prandial spikes where acarbose is clinically justified. �You tolerate gas/bloating and accept additional microbiota shifts beyond what RS + CBM588 already provide. ��In that case, acarbose is an adjunct to the above triad rather than part of the base stack.

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Thanks for posting this, it’s very good info. I’ll probably do as it suggests. :grinning:

I take Pendulum Metabolic Daily. I also take acarbose 50 mg twice daily before lunch and dinner. I recently started one scoop of Thorne Fiber supplement daily. The gas is tolerable. Pendulum Metabolic Daily contains the following bacterial strains.

The probiotic blend in Pendulum Metabolic Daily typically includes the following live bacterial species: 
1. Akkermansia muciniphila – A keystone gut bacteria associated with strengthening the gut barrier and producing metabolites that support metabolic health. 
2. Clostridium butyricum – A butyrate-producing strain that supports digestion and metabolic processes. 
3. Clostridium beijerinckii – Another butyrate producer that helps maintain a balanced gut microbiome. 
4. Anaerobutyricum hallii – A butyrate-producing bacterium involved in carbohydrate fermentation and gut health. 
5. Bifidobacterium infantis – A beneficial species that digests complex carbohydrates and supports overall digestive and immune health. 

I don’t feel any need to add Tributryin.

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This is a great issue to discuss and ask the AI about. I wanted a little more information, then I wanted to dig into the issues around dosing levels, proportions, side effect tradeoffs, and scheduling.

I started with a more indepth analysis by Gemini Deep Research, that can be found here: https://gemini.google.com/share/aaba2816a74e

THen went into the related issues around dosing levels, proportions, side effect tradeoffs, and scheduling. See here:

Based on the pharmacological mechanisms and clinical data analyzed in the previous report, here is the optimal dosing strategy, ratio, and timing for the “Butyrate Triad” and the optional amplifier.

The Optimal “Butyrate Stack” Protocol

To achieve maximal butyrate production while minimizing the risk of severe gastrointestinal distress (“the fermentation storm”), the components should not necessarily be taken in equal ratios, but rather balanced by their functional roles.

1. Dosing and Ratios (Target Daily Intake)

Component Role Starting Dose (Day 1–7) Target Optimal Dose Notes & Brand Equivalents
Green Banana Flour Fuel 5–10 g (1 tsp – 1 tbsp) 15–30 g (1.5 – 3 tbsp) Must be RAW (unheated). Contains ~50% Resistant Starch (RS2). Target dose provides ~8–15g of pure RS. []
C. butyricum (CBM588) Engine Standard Label Dose High Therapeutic Dose Standard: ~3 “Strong” tablets (or 9 “Standard” tablets) daily. Therapeutic: Clinical trials often use ~400mg–1g of active bacterial powder (approx. 10⁸–10⁹ CFU).
Tributyrin Bridge 300 mg 500–1,000 mg Look for “CoreBiome” or equivalent postbiotics. 300mg is the standard efficacious floor; 1,000mg is a high functional dose.
Acarbose(Optional) Amplifier 25 mg (once daily) 50–100 mg (per carb-heavy meal) Rx Only. Start very low. Dose must be matched to the carbohydrate content of the meal.

The “Golden Ratio” Logic: The ratio is functionally 30:1:1 (by weight)—roughly 30g of Substrate (GBF) to support the colonization of the Probiotic and the effects of the Prodrug. Without the massive substrate load (GBF), the probiotic (CBM588) will not have enough fuel to produce therapeutic levels of butyrate, rendering high doses of the bacteria less effective.


2. Timing and Administration Strategy

You can take these supplements together, but splitting them based on meal composition is more effective for reducing side effects and maximizing coverage.

  • Green Banana Flour: Do not heat.
    • Best Time: Morning or Mid-day smoothie.
    • Reason: Heating GBF above 55°C (130°F) gelatinizes the starch, destroying its resistant properties and turning it into simple digestible carbs. It must be consumed cold or room temperature.
  • CBM588 (Probiotic):
    • Best Time: After meals.
    • Reason: While CBM588 forms spores that are acid-resistant, taking it after a meal (when stomach pH is slightly higher) ensures maximum survival into the colon. Taking it with the GBF ensures the “Engine” arrives with the “Fuel.”
  • Tributyrin:
    • Best Time: With any meal (Breakfast/Dinner).
    • Reason: Tributyrin is a fat (triglyceride). Taking it with food stimulates lipase release, which is necessary to cleave the butyrate from the glycerol backbone.
  • Acarbose (The Critical Timing):
    • Best Time: Strictly with the first bite of a starch-containing meal.
    • Reason: Acarbose works by competitively inhibiting enzymes (alpha-glucosidase) in the small intestine. If you take it 15 minutes after eating, it is useless. If you take it with a zero-carb meal (e.g., steak and eggs), it does nothing.

3. Side Effects and Trade-offs

The primary trade-off in this protocol is Gas Production vs. Butyrate Yield. Maximizing fermentation inevitably produces gas (H₂ and CO₂).

A. The “Fermentation Storm” (Bloating/Gas)

  • Risk: High. Combining Green Banana Flour (fermentable substrate) + Acarbose (which dumps more starch into the colon) + CBM588 (which actively ferments) can create extreme distension, flatulence, and discomfort.
  • Mitigation:
    • Titrate GBF: Start with 1 teaspoon for 3 days. If tolerated, move to 1 tablespoon.
    • Do Not Stack Acarbose with GBF: This is “double-dipping.” Use GBF in your morning smoothie (low carb/high RS). Use Acarbose at dinner with pasta or rice. This spreads the fermentation load across the day rather than hitting the colon all at once.
    • Simethicone/Charcoal: Keep these on hand if bloating becomes painful during the adaptation phase (first 2 weeks).

B. Hypoglycemia (Low Blood Sugar)

  • Risk: Low to Moderate (mainly with Acarbose).
  • Context: GBF improves insulin sensitivity, and Acarbose blocks sugar absorption. If you are already on insulin or sulfonylureas, this combination can cause dangerous drops in blood sugar. If you are non-diabetic, Acarbose rarely causes hypoglycemia alone, but you may feel “flat” or low-energy if you block too many carbs without replacing calories.

C. Contraindication: SIBO (Small Intestinal Bacterial Overgrowth)

  • Trade-off: If you have SIBO, this entire protocol (except Tributyrin) is contraindicated. Adding fermentable starch (GBF) or blocking absorption (Acarbose) will feed the bacteria in the small intestine, worsening SIBO symptoms significantly. In this case, use Tributyrin only (softgels), as it absorbs before reaching the bacterial overgrowth.

Summary of Daily Routine (Example)

  • Breakfast (The “Fuel” Meal):
    • Smoothie with 5–15g Green Banana Flour (Raw).
    • 3 Tablets CBM588 (Probiotic).
    • 1 Capsule Tributyrin (300–500mg).
  • Lunch:
    • Normal eating (no supplements required).
  • Dinner (The “Amplifier” Meal):
    • If eating rice, potatoes, or bread: 25–50mg Acarbose with the first bite.
    • Note: Do not take GBF at this meal if taking Acarbose to minimize bloating.
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Where would I find this in the US (besides maybe a Japanese store? Google said it is popular in Japan, but not apparently in the US. Anyone found it?

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Thanks, I appreciate the link. :smile:

Top 20 Lowest Cost Raw Green Banana & Plantain Flour Options (USA)

This list prioritizes raw, unripe green banana and plantain flours available for purchase and shipment within the USA. Cost analysis includes package sizes up to 5kg (approx. 11 lbs).

Criteria:

  • Type: Raw Green Banana or Plantain Flour (excluding cooked/processed “fufu” unless specified raw).
  • Weight: Up to 5kg (11 lbs).
  • Ranking: Lowest cost per 100g.

Note on “Plantain” vs. “Green Banana”: Plantains are a member of the banana family. In flour form, both “Green Banana” and “Green Plantain” flours are nutritionally similar, high in resistant starch (RS2), and used interchangeably for health benefits. “Plantain” flours are often significantly cheaper due to their staple status in African and Caribbean cuisines.

Rank Product Name Vendor / Brand Weight Price (US$) Cost per 100g
1 Plantain Flour (Unripe Green) Iya Foods (Wazobia Market) 5 lb (2.27 kg) $19.99 $0.88
2 Khitan Food 100% Natural Plantain Flour Khitan / Walmart 4.85 lb (2.2 kg) $29.99 $1.36
3 Plantain Flour (Amala) Unripe Generic / Walmart 5 lb (2.27 kg) $33.50 $1.48
4 Organic Dried Green Banana Powder (8 lb) Food to Live 8 lb (3.63 kg) $58.32 $1.61
5 Dogah Foods Plantain Flour Dogah Foods 2 lb (907 g) $15.00 $1.65
6 Let’s Do Organic Green Banana Flour Edward & Sons / Walmart 14 oz (396 g) $6.74 $1.70
7 Green Banana Powder (11 lb Bulk) Rainforest Supply 11 lb (4.99 kg) $88.49 $1.77
8 Organic Green Banana Flour (4 lb) Food to Live 4 lb (1.81 kg) $36.05 $1.99
9 Yupik Organic Green Banana Flour Yupik 2.2 lb (1 kg) $24.99 $2.50
10 LiveKuna Organic Banana Flour LiveKuna 2 lb (907 g) $22.99 $2.53
11 Spicy Yum! Green Plantain Flour Spicy Yum! 1.5 lb (680 g) $16.99 $2.50
12 Unripe Plantain Flour (Bulk) Generic / Walmart 2.21 lb (1 kg) $26.95 $2.69
13 Green Banana Powder (Organic) Z Natural Foods 1 lb (454 g) $16.82 $3.70
14 Nutricost Organic Green Banana Flour Nutricost 2 lb (907 g) $29.99 $3.31
15 Blue Lily Organics Green Banana Flour Blue Lily Organics 1 lb (454 g) $17.95 $3.95
16 Natural Evolution Green Banana Flour Natural Evolution 1 lb (454 g) $19.95 $4.39
17 Judee’s Green Banana Flour Judee’s 12 oz (340 g) $14.99 $4.41
18 Hearthy Foods Green Banana Flour Hearthy Foods 16 oz (454 g) $21.99 $4.84
19 Terrafertil Green Banana Flour Terrafertil 1 lb (454 g) $22.50 $4.96
20 Peregrine / Pereg Banana Flour Pereg Natural Foods 16 oz (454 g) $23.90 $5.26

Cost Calculation Notes:

  • Shipping: Prices listed are for the product only. Shipping costs vary by location and vendor (e.g., Walmart+ or Amazon Prime may offer free shipping, while direct suppliers like Rainforest Supply charge based on weight/distance).
  • Bulk Advantage: The lowest costs are consistently found in 5lb+ bulk bags or ethnic market brands (Iya, Khitan) rather than specialty health-food brands sold in small pouches.
  • Raw/Resistant Starch: All selected options are “raw” or “unripe,” preserving the Type 2 Resistant Starch content critical for longevity and metabolic health applications.

Key Market Observations

  • Lowest Absolute Cost: Iya Foods and Khitan Food offer the best value, utilizing the “plantain” supply chain which is more established and commoditized than the “green banana superfood” market.
  • Best Bulk “Superfood” Brand: Food to Live provides the most accessible mid-range bulk option (8lb) with high reliability for raw/organic certification if you prefer to avoid generic brands.
  • Best Small Package Value: Let’s Do Organic (Edward & Sons) is surprisingly competitive per 100g compared to other small-pack premium brands.

Would you like me to identify specific high-resistant starch recipes or dosage protocols for longevity based on these raw flour options?

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Thank you @RapAdmin - going to give this a try. $50. Why not. Here is what I am doing:

image

Could you add to your prompt and post “What is the easiest and most accurate way to measure the results of doing this protocol?” - Or, something like that. Thank you!

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That is clostridium butyricum but I’m pretty sure not the strains found in the dirt in Japan which is the proven one.

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There are also the Galacto-Oligosaccharides which are effective at low dose and produce comparatively less gas (their take).

Open Acess paper: Galacto-Oligosaccharides Exert Bifidogenic Effects at Capsule-Compatible Ultra-Low Doses


Figure 3 GOS boosted SCFA production in a dose-related manner, which was accompanied by only mild increases in gas production. The impact on (A) total SCFA (mM), (B) gas production (mbar), and (C) the ratio of gas being produced per mole of SCFA.


Figure 4 GOS boosted production of the three main SCFAs and lactate in a dose-related manner. The impact on (A) acetate (mM), (B) lactate (mM), (C) propionate (mM), and (D) butyrate (mM).


Figure 5 GOS exerted significant bifidogenic effects from the lowest dose onwards, relating to enhanced acetate and butyrate production. Average level (cells/mL) of (A) microbial phyla and (B) Bifidobacteriaceae (main family within Actinomycetota; deconvoluted in its main OTUs) (n = 8), along with correlations of absolute Bifidobacteriaceae levels with (C) acetate and (D) butyrate.


Figure 6 GOS significantly stimulated Lachnospiraceae members from the lowest test dose onwards, relating to enhanced acetate and butyrate production. Average level (cells/mL) of (A) Lachnospiraceae (main family within Bacillota_A; deconvoluted in its main OTUs) (n = 8), along with correlations of absolute Lachnospiraceae levels with (B) acetate and (C) butyrate.

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Good find. Yes - it sounds good.

More information:

Galacto-Oligosaccharides (GOS) are non-digestible carbohydrates composed of chains of galactose units. They are widely recognized as one of the most effective “bifidogenic” prebiotics available. Unlike inulin or FOS (Fructo-Oligosaccharides), which are fermented broadly, GOS has a high specificity for stimulating Bifidobacterium species in the human gut.

1. Mechanism of Action

  • Resistance to Digestion: GOS resists hydrolysis by human salivary and pancreatic enzymes (amylases) due to their β-glycosidic linkages. They reach the colon largely intact.
  • Selective Fermentation: In the cecum and proximal colon, GOS are selectively fermented by Bifidobacterium and Lactobacillus species. These bacteria possess specific β-galactosidase enzymes required to break down GOS.
  • SCFA Production: The fermentation of GOS results in the production of Short-Chain Fatty Acids (SCFAs) and gases (H2​, CO2​).
    • Acetate: The primary SCFA produced by Bifidobacteria via the “bifid shunt.” It is the most abundant SCFA in the blood and supports muscle and heart tissue energy.
    • Butyrate: Produced through cross-feeding. Bifidobacteria degrade GOS into acetate and lactate, which are then utilized by butyrate-producing species (e.g., Faecalibacterium prausnitzii, Eubacterium rectale, Roseburia) to generate butyrate. Butyrate is the preferred energy source for colonocytes (gut lining cells) and is crucial for maintaining the gut barrier and regulating inflammation.
    • Propionate: Produced in smaller quantities, involved in hepatic gluconeogenesis and satiety signaling.

2. Clinical Evidence

  • Bifidogenic Effect: Numerous Randomized Controlled Trials (RCTs) confirm that GOS doses of 2.5g to 5g/daysignificantly increase fecal Bifidobacterium counts in healthy adults, infants, and the elderly.

  • Symptom Management:

    • IBS: GOS is generally better tolerated than Inulin/FOS, producing less gas/bloating at equivalent effective doses.
    • Constipation: Evidence supports GOS increasing stool frequency and softening stool consistency, particularly in the elderly.
    • Anxiety/Mood: Emerging evidence (e.g., Schmidt et al., 2015) suggests GOS may attenuate the waking cortisol response and improve anxiety, likely via the gut-brain axis modulated by SCFAs.

3. Limitations & Debates

  • Dosage Threshold: While 2.5g is effective, higher doses (>10-15g) can cause osmotic diarrhea and flatulence.
  • Individual Variability: The “cross-feeding” effect relies on the presence of resident butyrate producers. If a user lacks F. prausnitzii, GOS alone may not maximize butyrate production compared to direct butyrate supplements, though it will still drive Acetate.

Top Cost-Effective Brands of Galacto-Oligosaccharides (GOS)

Market Note: Unlike Inulin or Psyllium, pure GOS is difficult to find as a standalone bulk powder in the consumer market. It is most frequently sold as a branded prebiotic blend or a high-end specific supplement (e.g., Bimuno).

The table below identifies the top consumer-accessible sources, ranked by Value (Cost per 100g). Prices are estimated based on current retail data and may fluctuate.

Rank Brand Product Name Form GOS Content Cost / 100g (Approx)
1 Natural Chemist Galacto-oligosaccharide (GOS) Powder Powder ~80% Pure GOS $22.00
2 Bimuno Daily Prebiotic Supplement (Powder) Powder High (B-GOS) $35.00*
3 Invivo Bio.Me Prebio GOS Powder Pure GOS $37.00
4 Klaire Labs Galactomune Prebiotic Powder GOS + Beta-Glucan $38.00
5 Microbiome Labs MegaPre Powder GOS + FOS + XOS $41.00
6 Moss Nutrition Select GOS (GI Select) Powder Pure GOS $45.00
7 Swanson Prebiotic GOS (Discontinued/Rare) Caps Varies N/A (Market Gap)
8 Vitalus Vitagos (Ingredient Source) Bulk Pure GOS Wholesale
9 Liposomals Prebiotic GOS Liquid GOS Syrup $48.00
10 ProThera Galactomune Powder Same as Klaire Labs $50.00

*Note on Bimuno: Calculated based on the 90-sachet bulk pack price (~£90 / ~$115 USD for 328g). Small trial packs are significantly more expensive per 100g (~$113/100g).

Practical Insight: If you cannot find a pure GOS product locally, look for “Prebiotic Blends” that list Galacto-oligosaccharides as the first ingredient. Avoid products that label themselves “Prebiotic” but only contain Inulin (Chicory Root) or FOS, as these are cheaper and less specific for Bifidobacteria.

I had a similar experience. I had IBS-D since teenager years. I initially mostly managed it with low FODMAP diet. But in the past 1-2 years I managed a full remission with green-med diet that includes about 60-80 grams of fiber a day - all dietary sourced. I was able to reintroduce most of the FODMAPS although I still stay away from added inulin and garlic powder.

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They are talking about butyrate and more of the miracles it participates in. I think my CB must be coming all the way from Japan it’s taking forever.

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Gemini AI Video Summary:

Executive Summary

This transcript features a technical dialogue between a host and Dr. Zain Kassam, a gastroenterologist and biotechnology expert, regarding the intersection of the gut microbiome, metabolic health, and body composition. The conversation moves beyond the antiquated “Firmicutes/Bacteroidetes ratio” to focus on mechanistic pathways, specifically identifying butyrate as a master signaling molecule.

The primary thesis is that the gut microbiome functions as a metabolic organ that modulates host energy harvest, insulin sensitivity, and appetite through secondary metabolites. Dr. Kassam highlights seminal research where fecal microbiota transplants (FMT) from lean donors into obese mice—and later humans with metabolic syndrome—transferred phenotypic traits like leanness and improved insulin sensitivity. He posits that the efficacy of these shifts is increasingly linked to the stimulation of intestinal GLP-1 (glucagon-like peptide-1) via the gut’s L-cells, which signal the vagus nerve to increase satiety.

Furthermore, the discussion explores the “gut-muscle axis,” referencing data that suggests certain microbial profiles are associated with higher physical function in the elderly. Mechanisms proposed include optimized protein breakdown (anabolism) and the suppression of systemic inflammation (catabolism). A notable highlight is the identification of Veillonella in elite athletes, a bacteria that metabolizes lactic acid into propionate, potentially enhancing endurance performance.

Dr. Kassam concludes by emphasizing the clinical importance of cross-feeding. He argues that the microbiome is an interdependent ecosystem where “bystander” bacteria must first process fiber into intermediate metabolites before butyrate-producing organisms can function. For those seeking actionable longevity benefits, the focus should be on dietary diversity and specific prebiotics (inulin, pectin) to fuel this butyrate factory, thereby reducing low-grade chronic inflammation and optimizing metabolic substrate switching.


Bullet Summary

  • Fecal Transplants & Phenotype: Early studies demonstrated that transferring stool from obese vs. lean human twins into germ-free mice successfully transferred the corresponding weight phenotype.
  • Insulin Sensitivity: FMT from healthy donors into humans with metabolic syndrome significantly improved insulin sensitivity, though direct weight loss results remain maturing.
  • Obsolete Metrics: The Firmicutes to Bacteroidetes ratio is no longer considered a reliable hallmark for obesity due to high variability and confounding factors.
  • Butyrate as Master Regulator: Butyrate, a short-chain fatty acid (SCFA), is identified as the primary driver of metabolic and gut barrier health.
  • L-Cell Activation: Butyrate interfaces with intestinal L-cells to trigger the release of GLP-1, affecting satiety and appetite via the vagus nerve.
  • Chronic Inflammation: Obesity is framed as a state of low-grade chronic inflammation; gut microbes can modulate this by influencing the inflammatory cascade (e.g., HDAC inhibition).
  • Gut-Muscle Axis: Microbial profiles from high-functioning elderly individuals, when transplanted into mice, resulted in increased grip strength.
  • Anabolic Optimization: Specific microbes may improve the breakdown and absorption of proteins, facilitating better muscle protein synthesis.
  • Veillonella & Performance: This specific genus is elevated in marathon runners and metabolizes exercise-induced lactic acid to improve performance.
  • Waste Elimination: Emerging science suggests certain microbes can sequester heavy metals and break down microplastics.
  • Estrobolome Function: Specific gut bacteria possess enzymes to deconjugate estrogen, potentially recycling it back into the bloodstream—a factor in hormonal health.
  • Cross-Feeding Necessity: Butyrate production often requires a multi-step process where one species prepares the metabolite for another; isolation of “good” bugs is often insufficient.
  • Specific Prebiotics: Inulin (Jerusalem artichokes) and Pectin (apples) are prioritized for their ability to specifically increase butyrate production.
  • Polyphenols: Dark chocolate is noted as a dietary source that can stimulate butyrate-producing bacteria.

Claims & Evidence Table

Claim made in video Evidence provided Assessment
FMT can transfer obesity/leanness. University of Washington study (Turnbaugh et al.) involving human twin stool in mice. Strong (Well-replicated in preclinical models).
Butyrate stimulates intestinal GLP-1. Mention of L-cell interfacing and vagus nerve signaling. Strong (Established biological pathway).
Microbes can improve grip strength. Preclinical mouse models using stool from high-functioning vs. weak elderly humans. Speculative (Strong in mice; emerging in humans).
Veillonella improves athletic endurance. Harvard Medical School study on Boston Marathon runners (Nature Medicine). Strong (Published in high-impact peer-reviewed literature).
Gut bacteria can break down microplastics. Reference to work by a Turkish gastroenterologist. Speculative (Very early stage/emerging).
Firmicutes/Bacteroidetes ratio is a hallmark for obesity. Historically cited, but countered by a recent “Nutrients” journal meta-analysis. Weak/Refuted (Current consensus favors metabolic function over simple ratios).

Actionable Insights

  1. Prioritize Inulin-Rich Foods: Incorporate Jerusalem artichokes, leeks, and onions to provide the specific substrate for butyrate-producing bacteria.
  2. Consume Pectin: Eat whole apples (with skin) to utilize pectin for SCFA production.
  3. Optimize the Estrobolome: For hormonal balance, maintain a high-fiber diet to ensure proper estrogen conjugation and excretion, preventing unwanted recycling.
  4. Target “Cross-Feeding”: Do not rely on a single probiotic strain; eat a wide variety of plant fibers to support the “bystander” bacteria that facilitate butyrate production.
  5. Utilize Dark Chocolate: Use high-cacao (85%+) dark chocolate as a functional food to support butyrate levels.
  6. Focus on Satiety Signaling: View fiber intake not just as “bulk,” but as a chemical trigger for GLP-1 to naturally manage appetite.
  7. Monitor Metabolic Markers: If struggling with weight, check insulin sensitivity (HOMA-IR), as gut health interventions often improve metabolic markers before scale weight changes.

Technical Deep-Dive

The Butyrate-GLP-1 Axis

The most significant technical argument presented is the role of Short-Chain Fatty Acids (SCFAs)—specifically butyrate—as ligands for G-protein-coupled receptors (GPCRs) like GPR41 and GPR43. These receptors are expressed on enteroendocrine L-cells in the distal ileum and colon. When butyrate binds to these receptors, it stimulates the secretion of Glucagon-like peptide-1 (GLP-1) and Peptide YY (PYY). Unlike systemic GLP-1 agonists (e.g., Semaglutide), which have a long half-life, intestinal GLP-1 acts locally on the vagal afferent nerves to signal the nucleus tractus solitarius (NTS) in the brain to induce satiety.

The Veillonella Pathway

The breakdown of lactic acid by Veillonella atypica represents a unique metabolic bypass. During intense exercise, lactate accumulates in the blood and can cross the intestinal barrier into the lumen. Veillonella utilizes the methylmalonyl-CoA pathway to convert lactate into propionate. Propionate is then absorbed by the host and can serve as a precursor for gluconeogenesis or provide an additional energy source, effectively turning a metabolic byproduct into a performance-enhancing fuel.


Fact-Check Important Claims

  • Claim: FMT improves insulin sensitivity in metabolic syndrome.

  • Fact-Check: Verified. The 2012 study by Vrieze et al. (Max Nieuwdorp’s group) showed that infusion of microbiota from lean donors increased insulin sensitivity in men with metabolic syndrome at 6 weeks. Link to Study (PubMed)

  • Claim: Veillonella performance link.

  • Fact-Check: Verified. The study published in Nature Medicine (2019) confirmed Veillonella expansion post-marathon and showed increased treadmill runtime in mice treated with Veillonella atypica. Link to Nature Medicine

  • Claim: Firmicutes/Bacteroidetes ratio is unreliable.

  • Fact-Check: Consistent with current science. Large-scale meta-analyses have shown that this ratio is often inconsistent across different populations and study designs. Link to Nutrients Review


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I had not heard of this before, so wanted to research it a bit more: Veillonella specifically, and “Veillonella improves athletic endurance”.

What are validated strategies and tactics for increasing Veillonella in a person’s microbiome?

Strategy Tactical Approach Scientific Evidence
Lactate Induction HIIT / Sprinting / Heavy Lifting Strong. Confirmed in Nature Medicine (Scheiman et al., 2019).
GOS/FOS Prebiotics 5-10g/day of chicory or legumes Informed Speculation. Based on known cross-feeding pathways.
Direct Probiotics Lactobacillus species Moderate. Probiotics increase lactate, but host retention varies.
Direct Supplementation Taking Veillonella as a pill Weak/Experimental. Not currently available as a commercial probiotic.

Full Gemini response: https://gemini.google.com/share/8e81c2301301

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I also suggest running reports through a different AI chat in the same AI or a different one, and asking it to critique, and then working on the critique items to build a final product.

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One thing worth mentioning is that, because hunter gatherers tend to have exceptionally high fiber intake (both soluble and insoluble), their gut bacteria likely produces a lot of butyrate. I’m guessing it had and has some health benefits for them, yet it can’t be that impressive due to the fact that hunter gatherers experience age-related declines of things like grip strength:

This is true for many supplements (or e.g. molecules produced by gut bacteria), because hunter gatherers had high intakes of most of them – including omega-3s, niacin, potassium, magnesium, vitamin D (as measured in the body, not necessarily taken up by diet), choline, taurine, anthocyanins, and much more. So, if some supplement is going to profoundly slow aging (raising median lifespan to 90 or higher, say), then it’s got to either be due to much higher intake than that of hunter gatherers or else it’s got to be some molecule they don’t get in their diets in high quantities. Some candidates for the latter would be AKG and melatonin, since these generally don’t occur in food in high quantities; niacin (or nicotinamide, NR, NMN, etc.), say, in high doses (much higher than hunter gatherers) is an example candidate for the former.

First of all… note that you don’t want the regular “Clostridium Buyricum” product. See below:

Gemini Comparison of versions of Clostridium butyricum

The distinction between Clostridium butyricum MIYAIRI 588 (CBM 588) and “regular” or wild-type Clostridium butyricum is critical. While they share the same species name, they are vastly different in terms of safety and biological activity.

The short answer: CBM 588 is a specific, non-toxic therapeutic strain. “Regular” Clostridium butyricum includes wild strains that can be pathogenic and fatal.

Here is the breakdown of the scientific and clinical differences.

1. Safety: The Neurotoxin Risk (Critical)

The most significant difference is safety.

  • Regular Clostridium butyricum : Some wild strains of C. butyricum carry the gene for type E botulinum neurotoxin . These strains have been identified as causative agents in cases of infant botulism (a potentially fatal paralytic illness) and necrotizing enterocolitis (NEC) in premature infants. You cannot assume a generic C. butyricum is safe.
  • CBM 588: This specific strain has been genomically sequenced and proven to lack the genes for botulinum neurotoxins (types A, B, E, and F) and other virulence factors. It is one of the few strains authorized for human use by regulatory bodies (like the EU’s EFSA and Japan’s Ministry of Health) specifically because it is confirmed non-toxigenic.

2. Mechanism of Action: Unique Pathways

While all Clostridium butyricum strains ferment fiber to produce butyrate (a beneficial short-chain fatty acid), CBM 588 possesses specific immunomodulatory traits that are not guaranteed in generic strains.

Feature CBM 588 (Therapeutic Strain) Regular C. butyricum (Wild Type)
Protectin D1 Induction Proven. CBM 588 specifically triggers the gut to produce Protectin D1, a rare molecule that actively “resolves” inflammation and speeds up tissue repair. Unknown/Unverified. This complex signaling pathway has not been established as a general trait of the species.
IL-10 Upregulation Proven. It potently stimulates regulatory T-cells (Tregs) to release Interleukin-10 (anti-inflammatory) in the colon. Variable. Some wild strains may actually provoke inflammation or aggravate conditions like NEC (necrotizing enterocolitis) rather than soothe them.
Spore Resistance Optimized. CBM 588 spores are highly resistant to gastric acid and heat, ensuring they reach the lower colon alive. Variable. Wild strains vary wildly in their ability to survive the stomach’s acidity.

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3. Clinical Utility and Evidence

  • CBM 588: Almost all modern clinical trials regarding C. butyricum benefits (including the cancer immunotherapy trials mentioned previously) use the CBM 588 strain specifically.
  • Regular C. butyricum: There is virtually no clinical evidence supporting the use of “generic” C. butyricum. If a supplement label says Clostridium butyricum without specifying the strain (e.g., “MIYAIRI” or “CBM 588”), you are rolling the dice on its efficacy and safety profile.

Summary

To treat “regular” Clostridium butyricum as equivalent to CBM 588 is scientifically inaccurate.

  • CBM 588 is a pharmaceutical-grade, non-toxic probiotic with specific anti-inflammatory properties.
  • Regular C. butyricum is a broad category of bacteria found in soil and stool that includes potential pathogens capable of producing neurotoxins.

Recommendation

When sourcing this for longevity or gut health, you must verify the strain. Look specifically for “MIYAIRI 588,” “CBM 588,” or “Miyarisan.” Do not use products that simply list the species name without a strain identifier.

Measuring Results of your protocol:

Therefore, the most accurate way to measure success is to ignore the “Input” (butyrate levels) and measure the “Outcome” (Gut Barrier Integrity and Systemic Inflammation).

Here is the tiered approach to measurement, ranked by ease and accuracy.

1. The “Easiest” Method (Systemic & Subjective)

This combination costs <$50 and tells you if the gut protocol is translating to whole-body health.

  • Test: hs-CRP (High-Sensitivity C-Reactive Protein)
    • Why: Butyrate’s primary mechanism is sealing the gut lining to stop “Metabolic Endotoxemia” (LPS leaking into blood). If the protocol works, less LPS leaks, and your systemic inflammation (hs-CRP) will drop.
    • Target: You want to see hs-CRP drop below 1.0 mg/L (ideally <0.5 mg/L).
    • Timeline: Test at Day 0 and Day 45.
  • Tracker: The Bristol Stool Chart
    • Why: Clostridium butyricum and green banana flour normalize water absorption.
    • Target: You are aiming for Type 3 or Type 4 (smooth sausage). If you see Type 1 (constipation) or Type 6 (mushy), the fiber dose is incorrect.

2. The “Most Accurate” Method (The Barrier Panel)

If you want scientific proof that your gut lining is healing, you need specific fecal biomarkers. You will likely need to order a functional stool test (like GI-MAP, Genova, or Thorne).

  • Biomarker A: Fecal Calprotectin
    • What it is: A marker of neutrophil activation in the gut mucosa.
    • The Signal: Elevated levels (>50 µg/g) indicate active “fire” in the gut wall.
    • Success: Butyrate is a potent anti-inflammatory. If this protocol works, Calprotectin should plummet.
  • Biomarker B: Fecal Zonulin
    • What it is: The protein that regulates the “Tight Junctions” between your gut cells.
    • The Signal: High Zonulin = Leaky Gut.
    • Success: Green banana flour (resistant starch) specifically strengthens these junctions. A drop in Zonulin is the definitive proof that the barrier is sealed.

3. The “Engraftment” Check (Microbiome Sequencing)

If you specifically want to know if the Clostridium butyricum probiotic actually “moved in” (engrafted) rather than just passing through:

  • Test: 16S rRNA or Shotgun Metagenomic Sequencing (e.g., Thorne Gut Health, Tiny Health, Ombre).
  • The Metric: Look for the specific abundance of Clostridium clusters (specifically Cluster IV and XIVa) or the species C. butyricum.
  • Reality Check: Probiotics are often transient. Don’t be disappointed if the specific strain doesn’t permanently colonize. As long as Biomarkers A & B (above) improve, the protocol is a success.

Summary Protocol for Measurement

Method Biomarker Target Result Cost Accuracy
Blood (Easy) hs-CRP < 0.5 mg/L $ High (Systemic)
Stool (Deep) Calprotectin < 10 µg/g $$ Very High (Local Inflammation)
Stool (Deep) Zonulin Low Range $$ Very High (Permeability)
Observation Bristol Chart Type 4 Free Medium (Function)

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Actionable Recommendation: Start with the hs-CRP blood test. It is cheap and widely available. If your hs-CRP drops significantly over 6 weeks while on this stack, you can be 90% confident the gut barrier is healing without paying for expensive stool panels.

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