The gut produces approximately 90% of the body's serotonin and hosts the enteric nervous system — sometimes called the "second brain." The gut-brain axis is a bidirectional communication network, meaning chronic gut dysfunction directly impacts cognitive function and mood. Here are the supplements with the most credible evidence for supporting this system.
Ashwagandha KSM-66 Root Extract
AdaptogenChronic stress is one of the most damaging factors for gut barrier integrity — cortisol increases intestinal permeability and disrupts the microbiome composition within days. KSM-66 is the most studied ashwagandha extract, with multiple RCTs showing significant reductions in cortisol levels and perceived stress. Targeting the stress axis is therefore one of the most direct ways to support gut health in chronically stressed individuals. KSM-66 specifically — not generic ashwagandha root powder.
Pros
- Multiple RCTs showing measurable cortisol reduction
- Addresses one of the primary drivers of gut barrier disruption
- KSM-66 is the most bioavailable and studied extract form
Cons
- Not suitable during pregnancy or with thyroid conditions
- Effects are cumulative — takes 4–8 weeks of consistent use
L-Glutamine Powder (Pharmaceutical Grade)
Amino AcidGlutamine is the primary fuel source for enterocytes — the cells lining the intestinal wall. During periods of gut stress, illness, or intense exercise, glutamine becomes conditionally essential: the body's demand exceeds what can be synthesised. Supplemental glutamine at 5g daily has evidence for supporting intestinal permeability markers and is widely used in clinical nutrition for gut recovery. Buy unflavoured pharmaceutical-grade powder — not the flavoured sports versions which contain unnecessary additives.
Pros
- Primary fuel source for gut lining cells — direct mechanism of action
- Evidence for intestinal permeability support in clinical settings
- Excellent value — pharmaceutical-grade powder costs very little per dose
Cons
- Unflavoured powder needs mixing into liquid or food
- Not suitable for those with kidney disease or certain neurological conditions
Magnesium Glycinate 400mg
MineralMagnesium is required for over 300 enzymatic processes in the body and is deficient in an estimated 70% of UK adults. Its relevance for the gut-brain axis is threefold: it supports the enteric nervous system directly, regulates the stress response via the HPA axis, and has evidence for improving sleep quality — and poor sleep is one of the fastest ways to disrupt the microbiome. Glycinate is the form with the highest bioavailability and the least laxative effect at therapeutic doses. Avoid magnesium oxide — it's poorly absorbed and primarily used as a laxative.
Pros
- Glycinate form is highly bioavailable with minimal laxative effect
- Supports the enteric nervous system, stress response, and sleep simultaneously
- Addresses a widespread deficiency — most UK adults are under-consuming magnesium
Cons
- Glycinate capsules are large and require taking multiple per day
- Effects on sleep are clearer than direct gut effects in the evidence base