The study evaluating the effect of probiotic supplementation on the mental status, inflammation, and intestinal barrier in major depressive disorder patients using gluten-free or gluten-containing diet (SANGUT study): a 12-week, randomized, double-blind, and placebo-controlled clinical study protocol

Nutr J. 2019 Aug 31;18(1):50. doi: 10.1186/s12937-019-0475-x.


Background: Current treatment of major depressive disorder (MDD) often does not achieve full remission of symptoms. Therefore, new forms of treatment and/or adjunct therapy are needed. Evidence has confirmed the modulation of the gut-brain-microbiota axis as a promising approach in MDD patients. The overall purpose of the SANGUT study-a 12-week, randomized, double-blind, and placebo-controlled Study Evaluating the Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet - is to determine the effect of interventions focused on the gut-brain-microbiota axis in a group of MDD patients.

Methods: A total of 120 outpatients will be equally allocated into one of four groups: (1) probiotic supplementation+gluten-free diet group (PRO-GFD), (2) placebo supplementation+ gluten-free diet group (PLA-GFD), (3) probiotic supplementation+ gluten containing diet group (PRO-GD), and (4) placebo supplementation+gluten containing diet group (PLA-GD). PRO groups will receive a mixture of psychobiotics (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175), and GFD groups will follow a gluten-free diet. The intervention will last 12 weeks. The primary outcome measure is change in wellbeing, whereas the secondary outcome measures include physiological parameters.

Discussion: Microbiota and its metabolites have the potential to influence CNS function. Probiotics may restore the eubiosis within the gut while a gluten-free diet, via changes in the microbiota profile and modulation of intestinal permeability, may alter the activity of microbiota-gut-brain axis previously found to be associated with the pathophysiology of depression. It is also noteworthy that microbiota being able to digest gluten may play a role in formation of peptides with different immunogenic capacities. Thus, the combination of a gluten-free diet and probiotic supplementation may inhibit the immune-inflammatory cascade in MDD course and improve both psychiatric and gut barrier-associated traits.

Trial registration: NCT03877393 .

Keywords: Depression; EEG functional connectivity; Gluten-free diet; Gut microbiota; Gut permeability; Gut-brain axis; Inflammation; Intervention study; Probiotics; Study protocol.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Depressive Disorder, Major / physiopathology*
  • Depressive Disorder, Major / psychology*
  • Diet / methods*
  • Diet, Gluten-Free / methods
  • Double-Blind Method
  • Female
  • Gastrointestinal Microbiome
  • Glutens / administration & dosage
  • Humans
  • Inflammation / physiopathology
  • Inflammation / prevention & control*
  • Intestines / microbiology*
  • Male
  • Probiotics / administration & dosage
  • Probiotics / pharmacology*
  • Prospective Studies


  • Glutens

Associated data