Gut permeability and its clinical relevance in schizophrenia

• Published in: Neuropsychopharmacology reports Vol. 42; no. 1; pp. 70 - 76
• Main Authors: Ishida, Ikki, Ogura, Jun, Aizawa, Emiko, Ota, Miho, Hidese, Shinsuke, Yomogida, Yukihito, Matsuo, Junko, Yoshida, Sumiko, Kunugi, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2022; John Wiley and Sons Inc; Wiley
• Subjects: Adult; Body mass index; Cognition & reasoning; Cognitive ability; cognitive function; Executive function; Female; gut permeability; Humans; Intestine, Small; Lactulose; lactulose‐mannitol test; Male; Mannitol; Mental disorders; Middle Aged; natural killer cell activity; Normal distribution; Original; Pathophysiology; Permeability; Psychotropic drugs; Schizophrenia; Schizophrenia - diagnosis; Small intestine; Women; cognitive function; natural killer cell activity; schizophrenia; gut permeability; lactulose-mannitol test
• ISSN: 2574-173X; 2574-173X
• DOI: 10.1002/npr2.12227

Aim We aimed to examine the gut permeability in patients with schizophrenia and its relevance to schizophrenia symptoms, medication, cognitive functions, and blood immune markers. Methods We selected 22 patients with schizophrenia (mean age: 37.9 ± 10.5 years) comprising 9 men and 13 women. Furthermore, we included 86 healthy controls (mean age: 43.5 ± 11.0 years) comprising 41 men and 45 women. All participants were biologically unrelated and of Japanese descent. We used the Positive and Negative Syndrome Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS) to measure the severity of schizophrenia symptoms and cognitive functions, respectively. The lactulose‐mannitol loading test was used to measure the permeability of the small intestine. Furthermore, we used the lactulose to mannitol ratio (LMR) as an index of gut permeability. We measured the C‐reactive protein and natural killer (NK) cell activity in the blood as highly sensitive immune markers. Results The patients had a significantly higher rate of “leaky gut” (defined as LMR ≥ 0.1) compared to the control group (22.7% vs. 5.8%, odds ratio: 4.8 [95% confidence interval, 1.2‐18.3], Fisher's exact test, P = 0.03). There was no significant correlation between the LMR and PANSS scores or in the daily antipsychotic dose. In addition, the LMR was negatively correlated with the total Z‐score of the BACS and NK cell activity in the patients. Conclusions Our results suggest a higher rate of abnormally increased gut permeability in patients with schizophrenia than in controls. Moreover, gut permeability may be related to the cognitive and cellular immunity function of patients with schizophrenia. Frequency of “leaky gut” was increased in patients with schizophrenia. Gut permeability showed a negative correlation with cognitive function in patients. Gut permeability correlated negatively with natural killer cell activity in patients.