Background: Increased intestinal permeability with heightened translocation of Gramnegative
bacteria, also known as “leaky gut”, is associated with the pathophysiology of neuroimmune
disorders, such as Major Depressive Disorder (MDD), Chronic Fatigue Syndrome (CSF) and (deficit)
schizophrenia, as well as with general medical disorders, including irritable bowel syndrome. This review
aims to summarize clinical biochemistry and molecular immunology tests that may aid in the recognition
of leaky gut in clinical practice.
Methods: We searched online libraries, including PubMed/MEDLINE, Google Scholar and Scopus, with
the key words “diagnosis” or “biomarkers” and “leaky gut”, “bacterial translocation”, and “intestinal
permeability” and focused on papers describing tests that may aid in the clinical recognition of leaky gut.
Results: To evaluate tight junction barrier integrity, serum IgG/IgA/IgM responses to occludin and zonulin
and IgA responses to actomyosin should be evaluated. The presence of cytotoxic bacterial products in
serum can be evaluated using IgA/IgM responses to sonicated samples of common Gram-negative gut
commensal bacteria and assays of serum lipopolysaccharides (LPSs) and other bacterial toxins, including
cytolethal distenting toxin, subunit B. Major factors associated with increased gut permeability, including
gut dysbiosis and yeast overgrowth, use of NSAIDs and alcohol, food hypersensitivities (IgE-mediated),
food intolerances (IgG-mediated), small bacterial overgrowth (SIBO), systemic inflammation, psychosocial
stressors, some infections (e.g., HIV) and dietary patterns, should be assessed. Stool samples can be
used to assay gut dysbiosis, gut inflammation and decreased mucosal defenses using assays of fecal
growth of bacteria, yeast and fungi and stool assays of calprotectin, secretory IgA, β-defensin, α-
antitrypsin, lysozyme and lactoferrin. Blood and breath tests should be used to exclude common causes
of increased gut permeability, namely, food hypersensitivities and intolerances, SIBO, lactose intolerance
and fructose malabsorption.
Discussion: Here, we propose strategies to recognize “leaky gut” in a clinical setting using the most adequate
clinical chemistry and molecular immunology assays.