BiomeLogic
Public framework audit

The evidence behind the Host Capacity Model

When colonocyte bioenergetic capacity falls, the colonic oxygen gradient destabilises, facultative anaerobes expand, barrier integrity weakens, and downstream immune, mast-cell, and metabolic systems amplify. The Host Capacity Model proposes that in a subset of complex chronic cases — recurrent SIBO, MCAS-pattern symptoms, post-viral gut dysfunction — host substrate capacity is the dominant leverage point, not the microbe.

This page exists so the framework can be argued with. Each claim below is stated separately, graded on five independent dimensions, and paired with the strongest objection to it and the finding that would overturn it.

Last reviewed: 2026-05-12

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Audit snapshot

Every claim the Host Capacity Model rests on is listed below and graded on five independent dimensions. Grades reflect the state of the evidence, not confidence in the framework. Last reviewed 2026-05-12.

Claims audited
9
Distinct evidence types
6
High or medium confidence
6 of 9
Low or insufficient evidence
3 of 9

Distribution by evidence type

  • Established biology1 of 9 claims (11%)
  • Literature-supported mechanism2 of 9 claims (22%)
  • Mechanistic inference1 of 9 claims (11%)
  • Clinical-pattern observation2 of 9 claims (22%)
  • HCM interpretation1 of 9 claims (11%)
  • Testable hypothesis2 of 9 claims (22%)
How these grades are assigned

The five dimensions are independent. A claim can be foundational to the model and still carry low confidence — that combination is stated openly rather than smoothed over.

Evidence type
What kind of claim is this?
Confidence
How strongly does the current evidence support it?
Residual uncertainty
How much remains unresolved?
Framework role
How important is it to the Host Capacity Model?
Applicability
How broadly can it reasonably be generalized?
Established biology
Replicated, broadly accepted physiology described consistently across independent peer-reviewed work.
Literature-supported mechanism
A mechanism described in published research, typically with strong animal or in vitro support and less human consensus.
Mechanistic inference
A step that follows logically from established mechanisms but has not been measured directly in the population described.
Clinical-pattern observation
A pattern repeatedly observed in case material or reported in clinical literature, without controlled causal evidence.
HCM interpretation
A reading specific to the Host Capacity Model: how BiomeLogic organizes existing findings, not an external consensus position.
Testable hypothesis
A proposal stated precisely enough that a study could support or contradict it, but which is not yet supported enough to rely on.
Speculative or emerging
Plausibility-level reasoning at the edge of the available evidence, retained because it is useful to state openly.
High confidence
High confidence: replicated findings from independent groups support the claim, and the main alternative explanations have been addressed.
Medium confidence
Medium confidence: multiple relevant findings support the claim, but important limitations, indirect evidence, or insufficient human replication remain.
Low confidence
Low confidence: the claim is consistent with available data, but the supporting evidence is sparse, indirect, or open to several readings.
Insufficient evidence
Insufficient evidence: the claim has not been tested adequately enough for a confidence judgement to be meaningful.

Claim explorer

Each card states one claim, how it is graded, what supports it, where it is weak, and what would change the grade. Expand a card to read the full assessment.

Showing 9 of 9 claims.

  • Bioenergetics

    Colonocyte butyrate oxidation shapes physiologic epithelial hypoxia

    Colonocytes burn butyrate as their main fuel, and that oxygen consumption is a major reason the healthy colonic surface stays low in oxygen.

    Replicated, broadly accepted physiology described consistently across independent peer-reviewed work.High confidence: replicated findings from independent groups support the claim, and the main alternative explanations have been addressed.Limited uncertainty: the open questions concern detail and magnitude rather than whether the effect exists.Foundational means the rest of the model depends on this claim being approximately right. It does not mean the claim is proven.Broadly applicable: expected to hold across most people, independent of the specific case pattern.

  • Bioenergetics

    Inflammation disrupts epithelial mitochondrial metabolism

    Inflammatory signaling can impair mitochondrial function in gut epithelial cells, which reduces the cell's capacity to burn butyrate.

    A mechanism described in published research, typically with strong animal or in vitro support and less human consensus.Medium confidence: multiple relevant findings support the claim, but important limitations, indirect evidence, or insufficient human replication remain.Meaningful uncertainty: direction of causation, size of effect, or relevance to humans is still genuinely unsettled.Integrative: connects two otherwise separate parts of the model to each other.Conditionally applicable: expected to hold only in cases matching the pattern described, not as a general rule.

  • Microbial ecology

    Oxygen-gradient instability favors facultative anaerobes

    When the low-oxygen environment at the mucosal surface is lost, organisms that tolerate oxygen gain a competitive advantage over strict anaerobes.

    A mechanism described in published research, typically with strong animal or in vitro support and less human consensus.Medium confidence: multiple relevant findings support the claim, but important limitations, indirect evidence, or insufficient human replication remain.Meaningful uncertainty: direction of causation, size of effect, or relevance to humans is still genuinely unsettled.Foundational means the rest of the model depends on this claim being approximately right. It does not mean the claim is proven.Conditionally applicable: expected to hold only in cases matching the pattern described, not as a general rule.

  • Bioenergetics

    Elevated hydrogen sulfide can inhibit cytochrome c oxidase, linking microbial output to host respiration

    At raised concentrations, hydrogen sulfide inhibits a core enzyme of the mitochondrial respiratory chain, which is a candidate route from microbial metabolism back to host energy capacity.

    A step that follows logically from established mechanisms but has not been measured directly in the population described.Medium confidence: multiple relevant findings support the claim, but important limitations, indirect evidence, or insufficient human replication remain.Substantial uncertainty: competing explanations remain fully viable and the claim could be substantially revised.Integrative: connects two otherwise separate parts of the model to each other.Conditionally applicable: expected to hold only in cases matching the pattern described, not as a general rule.

  • Microbial ecology

    Dysbiosis may be adaptive to host-state change in some cases

    In a subset of cases the microbial shift is better read as a response to a changed habitat than as the primary disturbance.

    A reading specific to the Host Capacity Model: how BiomeLogic organizes existing findings, not an external consensus position.Medium confidence: multiple relevant findings support the claim, but important limitations, indirect evidence, or insufficient human replication remain.Substantial uncertainty: competing explanations remain fully viable and the claim could be substantially revised.Foundational means the rest of the model depends on this claim being approximately right. It does not mean the claim is proven.Conditionally applicable: expected to hold only in cases matching the pattern described, not as a general rule.

  • Immune and mast cell

    MCAS-pattern symptoms may amplify from gut-barrier and metabolite stress

    In cases where no primary mast-cell cause is identified, barrier permeability and microbial metabolites are a candidate source of ongoing mast-cell activation.

    A pattern repeatedly observed in case material or reported in clinical literature, without controlled causal evidence.Low confidence: the claim is consistent with available data, but the supporting evidence is sparse, indirect, or open to several readings.Substantial uncertainty: competing explanations remain fully viable and the claim could be substantially revised.Supporting: strengthens the model's account but the framework survives without it.Narrowly applicable: relevant to a small subset of cases and should not be generalized beyond them.

  • Recurrence

    SIBO recurrence may reflect unresolved epithelial bioenergetic capacity

    Repeated recurrence after antimicrobial cycles is read as evidence that the conditions permitting overgrowth were never addressed.

    A pattern repeatedly observed in case material or reported in clinical literature, without controlled causal evidence.Medium confidence: multiple relevant findings support the claim, but important limitations, indirect evidence, or insufficient human replication remain.Meaningful uncertainty: direction of causation, size of effect, or relevance to humans is still genuinely unsettled.Predictive: states what should be observed if the model is right, and is therefore the easiest kind of claim to test.Conditionally applicable: expected to hold only in cases matching the pattern described, not as a general rule.

  • Synthesis

    Recurrent SIBO, MCAS-pattern symptoms, and long COVID may share an upstream host-capacity substrate

    The most integrative and least supported claim in the model: that these presentations overlap because they sit downstream of a common capacity failure.

    A proposal stated precisely enough that a study could support or contradict it, but which is not yet supported enough to rely on.Low confidence: the claim is consistent with available data, but the supporting evidence is sparse, indirect, or open to several readings.Substantial uncertainty: competing explanations remain fully viable and the claim could be substantially revised.Integrative: connects two otherwise separate parts of the model to each other.Narrowly applicable: relevant to a small subset of cases and should not be generalized beyond them.

  • Recurrence

    Restoring epithelial bioenergetic capacity may be more durable than repeated antimicrobial cycles in this subset

    The model's central practical proposal, and one that has not been tested against the comparator it names.

    A proposal stated precisely enough that a study could support or contradict it, but which is not yet supported enough to rely on.Insufficient evidence: the claim has not been tested adequately enough for a confidence judgement to be meaningful.Substantial uncertainty: competing explanations remain fully viable and the claim could be substantially revised.Predictive: states what should be observed if the model is right, and is therefore the easiest kind of claim to test.Narrowly applicable: relevant to a small subset of cases and should not be generalized beyond them.

Counterarguments to the framework as a whole

These are objections to the model overall, distinct from the per-claim counterarguments in the explorer above. None of them has been resolved.

  • Dysbiosis may be primary in some cases; treating the microbe first may be sufficient.
  • MCAS may be primarily mast-cell-intrinsic, genetic, structural, or post-trauma — independent of gut state.
  • Post-COVID symptoms may be primarily vascular, neurological, or autoimmune rather than gut-mediated.
  • Some patients durably resolve recurrent SIBO with antimicrobials alone; the model does not explain those cases.
  • Normal stool testing in some cases challenges the centrality of dysbiosis in the framework.

Competing frameworks that explain the same observations

  • Bile-acid-first models propose bile signaling as the dominant upstream lever.
  • Vagal/autonomic-first models propose autonomic dysfunction as the upstream node.
  • Connective-tissue-first models (hEDS-spectrum) propose tissue laxity as the upstream substrate.
  • Genetic mast-cell disorders propose mast cells themselves as the primary lesion.

What would falsify this model

Findings that would require the framework to be substantially revised or abandoned. They are written to be checkable, not rhetorical.

  1. 01A controlled human trial showing durable resolution of recurrent SIBO with antimicrobial-only strategies in cases with documented bioenergetic impairment.
  2. 02A cohort study showing that targeted restoration of colonocyte bioenergetics alone fails to reduce SIBO/MCAS/post-viral burden across reasonable timeframes.
  3. 03Direct human evidence that mucosal hypoxia is preserved despite chronically suppressed colonocyte β-oxidation.
  4. 04Demonstration that the SIBO/MCAS/long-COVID overlap is fully accounted for by shared genetic risk or ascertainment bias.

Where this model does not apply

  • Acute infection requiring medical care.
  • Structural GI disease (strictures, fistulae, neoplasia).
  • Primary immunodeficiency.
  • Symptoms primarily driven by medication.
  • Severe endocrine disorders (untreated thyroid, adrenal, pituitary disease).
  • Pregnancy emergencies and pediatric emergencies.
  • Cases where microbial-directed intervention has produced durable remission.
  • MCAS that appears clearly independent of gut dysfunction.

Clinical-scope boundaries

  • BiomeLogic does not diagnose, treat, prescribe, or guarantee outcomes.
  • All work is educational systems-biology analysis intended to be discussed with the client's licensed medical team.
  • Engagement is declined when a case is outside the model's scope or appears to require urgent clinical care.

References

Each entry was checked against its PubMed record: the title, journal, year, and authors below match the paper the link resolves to.

  1. Donohoe 2011 · Primary research

    The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon

    Donohoe DR, Garge N, Zhang X, et al. · Cell Metabolism · 2011

    Primary support for treating butyrate as the dominant energy substrate of the colonocyte, which is the starting point of the model.

    Cited by: Colonocyte butyrate oxidation shapes physiologic epithelial hypoxia, Inflammation disrupts epithelial mitochondrial metabolism

  2. Byndloss 2017 · Primary research

    Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion

    Byndloss MX, Olsan EE, Rivera-Chávez F, et al. · Science · 2017

    Links colonocyte metabolism to epithelial oxygen availability and to the expansion of facultative anaerobes in a murine model.

    Cited by: Colonocyte butyrate oxidation shapes physiologic epithelial hypoxia, Oxygen-gradient instability favors facultative anaerobes

  3. Litvak 2018 · Review

    Colonocyte metabolism shapes the gut microbiota

    Litvak Y, Byndloss MX, Bäumler AJ · Science · 2018

    Review that frames host epithelial metabolism, rather than the microbe itself, as a determinant of microbial community structure.

    Cited by: Oxygen-gradient instability favors facultative anaerobes, Dysbiosis may be adaptive to host-state change in some cases

  4. Pimentel 2011 · Primary research

    Rifaximin therapy for patients with irritable bowel syndrome without constipation

    Pimentel M, Lembo A, Chey WD, et al. · New England Journal of Medicine · 2011

    Documents both the benefit and the incomplete durability of an antimicrobial-only strategy, which is the clinical observation the recurrence claim rests on.

    Cited by: Dysbiosis may be adaptive to host-state change in some cases, SIBO recurrence may reflect unresolved epithelial bioenergetic capacity, Restoring epithelial bioenergetic capacity may be more durable than repeated antimicrobial cycles in this subset

The reference list is deliberately short. It names the sources the audited claims actually rest on rather than every paper consulted; 9 claims are audited above, and those without a citation are marked as inference, observation, or hypothesis for that reason.

Questions about this audit

Why publish a framework audit at all?
A framework that is never stated precisely cannot be checked. Publishing the claims, their grades, and the counterarguments lets a reader — or a clinician a client shares this with — judge the reasoning rather than take it on trust.
Does a high-confidence grade mean the claim is proven?
No. High confidence means replicated findings from independent groups support the claim and the main alternative explanations have been addressed. It remains open to revision, and the audit records what would revise it.
Can a foundational claim have low confidence?
Yes, and several do. Framework role and confidence are independent dimensions. A claim can be load-bearing for the model while the evidence for it remains thin — that combination is stated here rather than hidden.
Is this medical advice?
No. BiomeLogic does not diagnose, treat, prescribe, or guarantee outcomes. Everything here is educational systems-biology analysis intended to be discussed with a client's licensed medical team.
How often is the audit updated?
Claims are reviewed on a rolling basis and each card carries its own review date. The current review cycle completed on 2026-05-12.
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Hard questions about this framework

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