Dual-Sugar Ingestion
Two inert sugars probe gut barrier integrity at once.
- 342 Da: Lactulose size (disaccharide, non-absorbed)
- 182 Da: Mannitol size (small monosaccharide)
- 10g / 5g: Typical dose (lactulose / mannitol)
- 0–6 h: Urine collected over (timed window)
Why two sugars
Paired probes control for gastric emptying and renal handling.
Neither sugar is metabolized
Both pass unchanged into urine, only gut wall gates entry.
Non-metabolized markers isolate barrier function alone.
Baseline void
Patient empties bladder before dosing to zero background.
Mannitol Absorption
Mannitol slips through pores in the cell membrane itself.
- Transcellular: Absorption route (through cell, not between)
- 14–24%: Healthy recovery (of ingested dose)
- ~0.4 nm: Molecular radius (fits membrane pores)
- Yes: Independent of junctions (unaffected by leaky gut)
Transcellular pathway
Small mannitol diffuses directly through epithelial cell pores.
Internal control
Mannitol recovery reflects mucosal surface area, not leakiness.
Low mannitol recovery flags villous atrophy, not permeability.
Normalizes the ratio
Dividing lactulose by mannitol cancels out intake variability.
Lactulose Exclusion — Normal Barrier
Tight junctions seal the paracellular space against big molecules.
- Paracellular: Absorption route (between cells, junction-gated)
- <0.5%: Healthy recovery (of ingested dose)
- ~0.5 nm: Molecular radius (too large for tight pores)
- Claudins, occludin: Junction proteins (seal intercellular space)
Tight junction seal
Claudin strands clamp adjacent cells, blocking large solutes.
Minimal leak in health
Only trace lactulose crosses through rare junction pores.
Healthy gut keeps lactulose recovery near zero.
Ratio stays low
Low lactulose plus normal mannitol yields a low L:M ratio.
Increased Permeability Scenario
Widened junctions let large lactulose leak through abnormally.
- Crohn's, celiac: Trigger examples (inflammation, NSAIDs)
- >0.5–1%+: Elevated recovery (of ingested dose)
- Widened gaps: Junction change (claudin disassembly)
- Barrier compromise: Clinical signal (precedes symptoms)
Junction disruption
Inflammation loosens claudin strands, opening paracellular gaps.
Lactulose surge
Large sugar now slips through where it normally could not.
Rising lactulose recovery signals a compromised barrier.
Mannitol unaffected
Small-molecule route stays open regardless of junction state.
Urinary Ratio Calculated
The lactulose:mannitol ratio quantifies gut barrier integrity.
- %Lac ÷ %Man: Formula (urinary recovery ratio)
- <0.03: Normal ratio (intact barrier)
- >0.03–0.07+: Elevated ratio (increased permeability)
- 5–6 h: Sample window (urine collection complete)
Ratio cancels confounders
Dividing corrects for gastric emptying and renal clearance.
Clinical use
Flags leaky gut in IBD, celiac disease, critical illness.
A single urine collection quantifies barrier function non-invasively.
Limitations
Renal function and gut transit time can skew results.