Elevated Systemic Levels of Markers Reflecting Intestinal Barrier Dysfunction and Inflammasome Activation Are Correlated in Severe Mental Illness
© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissionsoup.com..
BACKGROUND AND HYPOTHESIS: Gut microbiota alterations have been reported in severe mental illness (SMI) but fewer studies have probed for signs of gut barrier disruption and inflammation. We hypothesized that gut leakage of microbial products due to intestinal inflammation could contribute to systemic inflammasome activation in SMI.
STUDY DESIGN: We measured plasma levels of the chemokine CCL25 and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) as markers of T cell homing, adhesion and inflammation in the gut, lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP) as markers of bacterial translocation and gut barrier dysfunction, in a large SMI cohort (n = 567) including schizophrenia (SCZ, n = 389) and affective disorder (AFF, n = 178), relative to healthy controls (HC, n = 418). We assessed associations with plasma IL-18 and IL-18BPa and leukocyte mRNA expression of NLRP3 and NLRC4 as markers of inflammasome activation.
STUDY RESULTS: Our main findings were: (1) higher levels of sMAdCAM-1 (P = .002), I-FABP (P = 7.6E-11), CCL25 (P = 9.6E-05) and LBP (P = 2.6E-04) in SMI compared to HC in age, sex, BMI, CRP and freezer storage time adjusted analysis; (2) the highest levels of sMAdCAM-1 and CCL25 (both P = 2.6E-04) were observed in SCZ and I-FABP (P = 2.5E-10) and LBP (3) in AFF; and (3), I-FABP correlated with IL-18BPa levels and LBP correlated with NLRC4.
CONCLUSIONS: Our findings support that intestinal barrier inflammation and dysfunction in SMI could contribute to systemic inflammation through inflammasome activation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:49 |
|---|---|
| Enthalten in: |
Schizophrenia bulletin - 49(2023), 3 vom: 03. Mai, Seite 635-645 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Jensen, Søren B [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.05.2023 Date Revised 04.12.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1093/schbul/sbac191 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM349747180 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM349747180 | ||
| 003 | DE-627 | ||
| 005 | 20231226043349.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1093/schbul/sbac191 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1165.xml |
| 035 | |a (DE-627)NLM349747180 | ||
| 035 | |a (NLM)36462169 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Jensen, Søren B |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Elevated Systemic Levels of Markers Reflecting Intestinal Barrier Dysfunction and Inflammasome Activation Are Correlated in Severe Mental Illness |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.05.2023 | ||
| 500 | |a Date Revised 04.12.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissionsoup.com. | ||
| 520 | |a BACKGROUND AND HYPOTHESIS: Gut microbiota alterations have been reported in severe mental illness (SMI) but fewer studies have probed for signs of gut barrier disruption and inflammation. We hypothesized that gut leakage of microbial products due to intestinal inflammation could contribute to systemic inflammasome activation in SMI | ||
| 520 | |a STUDY DESIGN: We measured plasma levels of the chemokine CCL25 and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) as markers of T cell homing, adhesion and inflammation in the gut, lipopolysaccharide binding protein (LBP) and intestinal fatty acid binding protein (I-FABP) as markers of bacterial translocation and gut barrier dysfunction, in a large SMI cohort (n = 567) including schizophrenia (SCZ, n = 389) and affective disorder (AFF, n = 178), relative to healthy controls (HC, n = 418). We assessed associations with plasma IL-18 and IL-18BPa and leukocyte mRNA expression of NLRP3 and NLRC4 as markers of inflammasome activation | ||
| 520 | |a STUDY RESULTS: Our main findings were: (1) higher levels of sMAdCAM-1 (P = .002), I-FABP (P = 7.6E-11), CCL25 (P = 9.6E-05) and LBP (P = 2.6E-04) in SMI compared to HC in age, sex, BMI, CRP and freezer storage time adjusted analysis; (2) the highest levels of sMAdCAM-1 and CCL25 (both P = 2.6E-04) were observed in SCZ and I-FABP (P = 2.5E-10) and LBP (3) in AFF; and (3), I-FABP correlated with IL-18BPa levels and LBP correlated with NLRC4 | ||
| 520 | |a CONCLUSIONS: Our findings support that intestinal barrier inflammation and dysfunction in SMI could contribute to systemic inflammation through inflammasome activation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a affective disorder | |
| 650 | 4 | |a inflammasome | |
| 650 | 4 | |a intestinal fatty acid binding protein | |
| 650 | 4 | |a lipopolysaccharide binding protein | |
| 650 | 4 | |a mucosal vascular addressin cell adhesion molecule-1 | |
| 650 | 4 | |a schizophrenia | |
| 650 | 7 | |a Inflammasomes |2 NLM | |
| 700 | 1 | |a Sheikh, Mashhood A |e verfasserin |4 aut | |
| 700 | 1 | |a Akkouh, Ibrahim A |e verfasserin |4 aut | |
| 700 | 1 | |a Szabo, Attila |e verfasserin |4 aut | |
| 700 | 1 | |a O'Connell, Kevin S |e verfasserin |4 aut | |
| 700 | 1 | |a Lekva, Tove |e verfasserin |4 aut | |
| 700 | 1 | |a Engh, John A |e verfasserin |4 aut | |
| 700 | 1 | |a Agartz, Ingrid |e verfasserin |4 aut | |
| 700 | 1 | |a Elvsåshagen, Torbjørn |e verfasserin |4 aut | |
| 700 | 1 | |a Ormerod, Monica B E G |e verfasserin |4 aut | |
| 700 | 1 | |a Weibell, Melissa A |e verfasserin |4 aut | |
| 700 | 1 | |a Johnsen, Erik |e verfasserin |4 aut | |
| 700 | 1 | |a Kroken, Rune A |e verfasserin |4 aut | |
| 700 | 1 | |a Melle, Ingrid |e verfasserin |4 aut | |
| 700 | 1 | |a Drange, Ole K |e verfasserin |4 aut | |
| 700 | 1 | |a Nærland, Terje |e verfasserin |4 aut | |
| 700 | 1 | |a Vaaler, Arne E |e verfasserin |4 aut | |
| 700 | 1 | |a Westlye, Lars T |e verfasserin |4 aut | |
| 700 | 1 | |a Aukrust, Pål |e verfasserin |4 aut | |
| 700 | 1 | |a Djurovic, Srdjan |e verfasserin |4 aut | |
| 700 | 1 | |a Eiel Steen, Nils |e verfasserin |4 aut | |
| 700 | 1 | |a Andreassen, Ole A |e verfasserin |4 aut | |
| 700 | 1 | |a Ueland, Thor |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Schizophrenia bulletin |d 1974 |g 49(2023), 3 vom: 03. Mai, Seite 635-645 |w (DE-627)NLM000023388 |x 1745-1701 |7 nnns |
| 773 | 1 | 8 | |g volume:49 |g year:2023 |g number:3 |g day:03 |g month:05 |g pages:635-645 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1093/schbul/sbac191 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 49 |j 2023 |e 3 |b 03 |c 05 |h 635-645 | ||