Biomelogic
Mechanistic reasoning infrastructure

Explore the reasoning behind the Host Capacity Model

Causal chains, competing hypotheses, and mechanistic state maps. Each item is labelled by evidence level. Educational only — not medical advice.

Causal chains

  • Evidence floor: mechanistic-inference

    Oxygen-leak → facultative-anaerobe expansion → mucosal inflammation

    Loss of colonocyte β-oxidation raises mucosal oxygen tension, lifting the obligate-anaerobe advantage and allowing facultative-anaerobe expansion that further amplifies inflammation.

    7 steps

    Linked claims

    Chain evidence floor is mechanistic-inference; the chain is only as strong as its weakest of 7 steps.

    Unresolved contradiction

    1 competing chain offer alternative routes: motility-first-cascade.

    State map

    Realised in 3 state maps: Epithelial energy failure state; Mucosal oxygen leak state; Post-viral metabolic stall state.

  • Evidence floor: hypothesis

    Excess H₂S → colonocyte energy stall → SIBO + MCAS amplification

    Hydrogen sulfide inhibits short-chain acyl-CoA dehydrogenase and complex IV in colonocytes, stalling β-oxidation and OXPHOS, plausibly producing the same downstream oxygen-leak cascade *and* sensitising mucosal mast cells via TRPA1.

    5 steps

    Linked claims

    Chain evidence floor is hypothesis; the chain is only as strong as its weakest of 5 steps.

    Unresolved contradiction

    1 competing chain offer alternative routes: independent-cooccurrence-chain.

    State map

    Realised in 3 state maps: Epithelial energy failure state; Sulfide-overload state; Mast-cell amplification state.

  • Evidence floor: hypothesis

    Gut LPS → granulosa TLR4 → follicular aromatase suppression

    LPS translocation activates TLR4 on granulosa cells; locally produced TNF-α and IL-1β suppress FSH-driven CYP19A1, lowering intra-follicular estrogen even when serum estradiol appears normal.

    5 steps

    Linked claims

    Chain evidence floor is hypothesis; the chain is only as strong as its weakest of 5 steps.

    Unresolved contradiction

    1 competing chain offer alternative routes: primary-ovarian-aging-chain.

    State map

    Realised in 1 state map: Inflammatory dominance state.

  • Evidence floor: established

    Bile-acid pool failure → proximal small-bowel overgrowth

    Conjugated bile acids exert direct antimicrobial activity in the proximal small bowel; impaired conjugation, accelerated deconjugation, or reduced flow lifts that microbial brake.

    3 steps

    Linked claims

    Chain evidence floor is established; the chain is only as strong as its weakest of 3 steps.

    State map

    Realised in 1 state map: Bile-acid dysregulation state.

  • Evidence floor: emerging

    (Competing) Motility failure → stagnation → microbial overgrowth → barrier stress

    Conventional view: MMC dysfunction (post-infectious autoimmunity, neuropathy, structural) is the primary lesion; ecological and bioenergetic changes are secondary.

    3 steps

    Linked claims

    Chain evidence floor is emerging; the chain is only as strong as its weakest of 3 steps.

    Unresolved contradiction

    1 competing chain offer alternative routes: oxygen-leak-cascade.

  • Evidence floor: mechanistic-inference

    (Competing) SIBO + MCAS as independently co-occurring, not shared-driver

    Alternative to the H₂S-shared-driver hypothesis: barrier failure independently sets up both conditions; no single molecular driver is required.

    3 steps

    Linked claims

    Chain evidence floor is mechanistic-inference; the chain is only as strong as its weakest of 3 steps.

    Unresolved contradiction

    1 competing chain offer alternative routes: h2s-shared-driver-chain.

  • Evidence floor: established

    (Competing) Primary ovarian aging / mtDNA damage explains poor egg quality

    Conventional view: oocyte mitochondrial DNA damage and follicle-pool depletion drive declining egg quality independently of any gut-derived inflammation.

    2 steps

    Linked claims

    Chain evidence floor is established; the chain is only as strong as its weakest of 2 steps.

    Unresolved contradiction

    1 competing chain offer alternative routes: lps-aromatase-paradox.

Competing hypotheses

  • Is dysbiosis a primary lesion or an adaptive response to host failure?

    Conventional gastroenterology often treats dysbiosis as the lesion to be corrected (kill, replace, restore). The Host Capacity Model treats most clinically relevant dysbiosis as an ecologically rational adaptation to a hospitable habitat created by host bioenergetic failure.

    • treated-as-rival · emerging
      Dysbiosis as primary lesion

      An abnormal microbial composition is itself the disease driver; restoring composition restores function.

    • preferred · mechanistic-inference
      Dysbiosis as habitat adaptation (HCM)

      Most clinically observed dysbiosis is an ecologically rational response to a host habitat that has lost its O₂ gradient and SCFA-driven selection.

    Unresolved contradiction

    2 positions documented with explicit supporting and weakening evidence.

    Linked claims

    2 arbitrating experiments could discriminate between positions.

    Central to the model

    Touches 3 concepts: host-capacity-model, dysbiosis-ecology, oxygen-gradient-failure.

  • Is exogenous butyrate always beneficial in chronic gut disease?

    Default narrative: butyrate is fuel, give more. Mechanistic concern: in epithelium with impaired β-oxidation (low SIRT3, H₂S burden, mitochondrial damage), exogenous butyrate may not be oxidised efficiently and could plausibly worsen symptoms.

    • treated-as-rival · emerging
      Butyrate is universally beneficial

      Increasing colonic butyrate availability improves epithelial function and reduces inflammation across patient groups.

    • preferred · hypothesis
      Butyrate is context-dependent

      In epithelium with impaired β-oxidation capacity, exogenous butyrate may accumulate as an unprocessed substrate and worsen symptoms; benefit requires intact mitochondrial throughput.

    Unresolved contradiction

    2 positions documented with explicit supporting and weakening evidence.

    Linked claims

    1 arbitrating experiment could discriminate between positions.

    Central to the model

    Touches 2 concepts: butyrate-oxidation, colonocyte-bioenergetics.

  • Are lactulose / glucose breath tests a valid diagnostic for SIBO?

    Breath testing dominates clinical practice but has poor specificity against jejunal aspirate culture. The disagreement is whether they remain useful as pattern-recognition tools or should be abandoned.

    • considered-plausible · emerging
      Breath tests remain clinically useful

      Despite imperfect operating characteristics, gas patterns (H₂, CH₄) discriminate clinically meaningful subgroups and guide therapy.

    • preferred · hypothesis
      Breath tests are mechanistically misleading

      Breath tests measure microbial fermentation kinetics, not overgrowth per se; they entrench composition-first thinking and miss the host-bioenergetic lesion.

    Unresolved contradiction

    2 positions documented with explicit supporting and weakening evidence.

    Linked claims

    1 arbitrating experiment could discriminate between positions.

    Central to the model

    Touches 1 concept: sibo-host-capacity-model.

  • Is MCAS a primary mast-cell disorder or a downstream amplification of candidate upstream mechanisms?

    Whether mast-cell activation is the disease or a symptom of barrier/sulfide/autonomic candidate upstream mechanisms has direct treatment implications.

    • considered-plausible · emerging
      MCAS as primary mast-cell disorder

      An intrinsic mast-cell hyperactivation tendency is the lesion; mast-cell stabilisation is therefore disease-modifying.

    • preferred · hypothesis
      MCAS as downstream amplification (HCM lens)

      In the recurrent-SIBO/post-viral population, mast-cell activation is amplification driven by barrier failure, sulfide burden, autonomic dysregulation, or histamine clearance failure.

    Unresolved contradiction

    2 positions documented with explicit supporting and weakening evidence.

    Linked claims

    1 arbitrating experiment could discriminate between positions.

    Central to the model

    Touches 1 concept: mcas-histamine-patterns.

Mechanistic state maps

  • Epithelial energy failure state

    Colonocyte mitochondrial throughput drops below the rate needed to oxidise available SCFA and consume luminal O₂.

    Spatial: colonocyte, mitochondria, epithelial layer · Phase: chronic, collapse

    State map

    Spatial focus: colonocyte, mitochondria, epithelial layer. Temporal phases: chronic, collapse.

    Linked claims

    Realises 2 causal chains: oxygen-leak-cascade, h2s-shared-driver-chain.

    Central to the model

    Anchored in 3 concepts: colonocyte-bioenergetics, butyrate-oxidation, mitochondrial-dysfunction.

  • Mucosal oxygen leak state

    Loss of physiological epithelial hypoxia raises mucosal O₂, allowing facultative anaerobes to expand and obligate anaerobes to contract.

    Spatial: mucus layer, epithelial layer, lumen · Phase: compensatory, chronic

    State map

    Spatial focus: mucus layer, epithelial layer, lumen. Temporal phases: compensatory, chronic.

    Linked claims

    Realises 1 causal chain: oxygen-leak-cascade.

    Central to the model

    Anchored in 3 concepts: oxygen-gradient-failure, nitrate-respiration, dysbiosis-ecology.

  • Inflammatory dominance state

    TLR4/NF-κB tone is elevated, mast cells primed, and the mucosal cytokine milieu shifts toward TNF-α / IL-1β / IL-6.

    Spatial: lamina propria, mucosal mast cells, submucosa · Phase: acute, chronic

    State map

    Spatial focus: lamina propria, mucosal mast cells, submucosa. Temporal phases: acute, chronic.

    Linked claims

    Realises 1 causal chain: lps-aromatase-paradox.

    Central to the model

    Anchored in 2 concepts: gut-barrier-dysfunction, mcas-histamine-patterns.

  • Sulfide-overload state

    Expansion of sulfate-reducing organisms raises luminal H₂S beyond the colonocyte's mitochondrial sulfide-oxidising capacity.

    Spatial: colonocyte, mitochondria · Phase: chronic

    State map

    Spatial focus: colonocyte, mitochondria. Temporal phases: chronic.

    Linked claims

    Realises 1 causal chain: h2s-shared-driver-chain.

    Central to the model

    Anchored in 2 concepts: colonocyte-bioenergetics, mcas-histamine-patterns.

  • Bile-acid dysregulation state

    Disruption of bile-acid synthesis, conjugation, transport, or microbial deconjugation alters FXR signalling and proximal antimicrobial pressure.

    Spatial: proximal small intestine, ileum, hepatocyte · Phase: chronic

    State map

    Spatial focus: proximal small intestine, ileum, hepatocyte. Temporal phases: chronic.

    Linked claims

    Realises 1 causal chain: bile-acid-proximal-overgrowth.

    Central to the model

    Anchored in 2 concepts: bile-acid-dysfunction, sibo-host-capacity-model.

  • Mast-cell amplification state

    Mucosal mast cells become hyper-responsive, lowering activation thresholds and amplifying gut–brain symptoms.

    Spatial: mucosal mast cells, lamina propria, enteric nervous system · Phase: acute, chronic, compensatory

    State map

    Spatial focus: mucosal mast cells, lamina propria, enteric nervous system. Temporal phases: acute, chronic, compensatory.

    Linked claims

    Realises 1 causal chain: h2s-shared-driver-chain.

    Central to the model

    Anchored in 1 concept: mcas-histamine-patterns.

  • Post-viral metabolic stall state

    Persistent post-viral inflammation and mitochondrial dysfunction lock the system in a low-throughput, high-vigilance configuration.

    Spatial: mitochondria, epithelial layer, enteric nervous system · Phase: chronic, collapse

    State map

    Spatial focus: mitochondria, epithelial layer, enteric nervous system. Temporal phases: chronic, collapse.

    Linked claims

    Realises 1 causal chain: oxygen-leak-cascade.

    Central to the model

    Anchored in 2 concepts: mitochondrial-dysfunction, host-capacity-model.

  • Recovery / re-anchoring state

    Bioenergetic capacity returns; epithelial O₂ consumption rises; obligate-anaerobe advantage is restored; inflammatory tone falls.

    Spatial: colonocyte, mucus layer · Phase: recovery

    State map

    Spatial focus: colonocyte, mucus layer. Temporal phases: recovery.

    Central to the model

    Anchored in 2 concepts: host-capacity-model, colonocyte-bioenergetics.

Machine-readable
  • /api/public/v1/mechanism-chains
  • /api/public/v1/contradictions
  • /api/public/v1/state-maps
  • /api/public/v1/pathways
  • /api/public/v1/graph · /api/public/v1/claims · /api/public/v1/evidence-map

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