Open mechanistic questions
Unanswered questions, candidate experiments, and partially-answered problems the BiomeLogic framework is actively tracking.
- Actively tracked
Do colonic bioenergetic markers (mucosal SIRT3, lactate/pyruvate, stool SCFA) prospectively predict relapse risk in functional gut disease?
If they do, the Host Capacity Model gains a clinically actionable readout for staging recovery and timing intervention.
Candidate experiments
- Prospective cohort with serial mucosal biopsies + SCFA before / after relapse.
- Bioenergetic-stratified RCT comparing intervention orders.
- Open
Does restoring colonocyte bioenergetics shift microbial ecology back toward obligate-anaerobe dominance without targeted antimicrobials?
Direct test of dysbiosis-as-adaptation versus dysbiosis-as-primary-lesion.
Candidate experiments
- Bioenergetic-only intervention arm with longitudinal 16S + metabolomics.
- Open
Under what bioenergetic conditions does exogenous butyrate help, do nothing, or worsen mucosal stress?
Resolves a clinically common contradiction and lets clinicians stop using butyrate empirically.
Candidate experiments
- Stratified trial by baseline mucosal β-oxidation capacity.
- Actively tracked
Is MCAS-pattern symptomatology a primary mast-cell disorder or a downstream amplification of upstream gut, mitochondrial, or connective-tissue lesions?
Determines whether mast-cell stabilisation is curative or merely symptomatic in most cases.
Candidate experiments
- Sequential intervention trial: upstream-first vs. mast-cell-first.
- Partially answered
Are lactulose / glucose breath tests clinically useful as a stand-alone SIBO diagnostic, or only when combined with mechanistic context?
Has direct implications for over- and under-treatment of suspected SIBO.
Candidate experiments
- Blinded comparison of test result vs. mechanism-grounded clinical pattern.
- Open
Does aromatase / oestrogen modulation measurably affect MCAS-pattern severity in humans?
Mechanistically plausible but human evidence is still thin; confirmation would justify a hormonal axis in MCAS staging.
Candidate experiments
- Cycle-phased symptom tracking with concurrent oestrogen + tryptase profiles.
- Open
Does sulfide (H₂S) burden gate colonocyte recovery independently of SCFA supply?
If yes, sulfide-targeted strategies become a parallel axis to SCFA-restoration in HCM.
Candidate experiments
- Sulfide-stratified bioenergetic recovery trial.
- Actively tracked
Does intestinal mitochondrial dysfunction propagate systemically to skeletal muscle and immune compartments in chronic gut disease?
Would unify post-viral / ME-CFS / chronic-gut overlap under a shared bioenergetic frame.
Candidate experiments
- Multi-tissue mitochondrial-function profiling in cohorts with gut + systemic symptoms.
- Open
Do shifts in primary/secondary bile-acid ratios track recovery from host-capacity failure independently of microbial composition?
Bile-acid signalling is a candidate readout that's cheaper than mucosal biopsies.
Candidate experiments
- Longitudinal bile-acid profiling alongside bioenergetic markers.
- Open
Is increased intestinal permeability a primary lesion or a downstream consequence of bioenergetic failure?
Determines whether barrier-targeted therapies should sit upstream or downstream of bioenergetic restoration.
Candidate experiments
- Permeability + bioenergetic co-measurement across recovery timepoints.