The microbiota-gut-inflammasome-brain (MGIB) axis

Antonio Inserra, Ma-Li Wong, Martin Lewis, Claudio A. Mastronardi, Lex Leong, Jocelyn Choo, Stephen J. Kentish, P. Xie, M. Morrison, Steven Wesselingh, Geraint Rogers, Julio Licinio

Research output: Contribution to conferencePoster

Abstract

Increasing evidence suggests the involvement of neuroinflammatory pathways and gut microbiota in major depressive disorder and in antidepressant response. Inflammasome activation triggered by psychosocial stress results in the maturation of caspase-1 and activation of interleukin (IL)-1ß and IL-18, two pro-inflammatory cytokines involved in HPA axis activation and stress-coping pathways. The microbiota-gut-brain (MGB) axis is a multi-organ bidirectional signaling system between the gut microbiota and the CNS that plays fundamental roles in host homeostasis, behavior and stress response. Caspase-1 KO and minocycline-treated mice were screened for anxiety-like, depressive-like and locomotor activity at baseline and following chronic stress. Moreover, gut microbiota was studied through 16S sequencing in chronically stressed and control wild-type mice with or without pharmacological inhibition of caspase-1. Caspase-1 deficiency decreased depressive- and anxiety-like behaviours at baseline, and increased locomotor activity and locomotor skills. Moreover, caspase-1 genetic deletion decreased the exacerbation of anxiety- and depressive- like behaviours following stress. Furthermore, caspase-1 antagonism with minocycline decreased stress-induced rise in depressive-like behaviour. Gut microbiota composition of stressed mice showed alterations of the Firmicutes/Bacteroidetes ratio, decreased Bifidobacterium spp. as well as increased Lactobacillus spp., changes associated with increased inflammasome activation and increased NF-kB activity. When restrained mice were treated with minocycline, evidence of both synergistic and antagonistic effects on microbiota composition was detected. For example, Blautia, Akkermansia and a member of the Lachnospiraceae family were increased. This effect is relevant to stress-responses given that Akkermansia attenuates inflammation in adipose tissue via induction of Foxp3 regulatory T-cells, and suppression of IL-6- and IL-1ß-mediated pathways. Caspase-1 inhibition exerts protective effects via modulating the interface between stress response and microbiota composition. We propose the novel concept of a “microbiota-gut-inflammasome-brain (MGIB) axis”, in which the gut microbiota through inflammasome signalling modulates inflammatory pathways that modulate brain function and affect anxiety- and depressive-like behaviours.

Conference

Conference14th Annual Meeting of Asian-Pacific Society for Neurochemistry 2016
CountryMalaysia
CityKuala Lumpur
Period27/08/1630/08/16
Internet address

Cite this

Inserra, A., Wong, M-L., Lewis, M., Mastronardi, C. A., Leong, L., Choo, J., ... Licinio, J. (2016). The microbiota-gut-inflammasome-brain (MGIB) axis. Poster session presented at 14th Annual Meeting of Asian-Pacific Society for Neurochemistry 2016, Kuala Lumpur, Malaysia.
Inserra, Antonio ; Wong, Ma-Li ; Lewis, Martin ; Mastronardi, Claudio A. ; Leong, Lex ; Choo, Jocelyn ; Kentish, Stephen J. ; Xie, P. ; Morrison, M. ; Wesselingh, Steven ; Rogers, Geraint ; Licinio, Julio. / The microbiota-gut-inflammasome-brain (MGIB) axis. Poster session presented at 14th Annual Meeting of Asian-Pacific Society for Neurochemistry 2016, Kuala Lumpur, Malaysia.
@conference{05af8b3f926d4698a60b3bf26fce63c8,
title = "The microbiota-gut-inflammasome-brain (MGIB) axis",
abstract = "Increasing evidence suggests the involvement of neuroinflammatory pathways and gut microbiota in major depressive disorder and in antidepressant response. Inflammasome activation triggered by psychosocial stress results in the maturation of caspase-1 and activation of interleukin (IL)-1{\ss} and IL-18, two pro-inflammatory cytokines involved in HPA axis activation and stress-coping pathways. The microbiota-gut-brain (MGB) axis is a multi-organ bidirectional signaling system between the gut microbiota and the CNS that plays fundamental roles in host homeostasis, behavior and stress response. Caspase-1 KO and minocycline-treated mice were screened for anxiety-like, depressive-like and locomotor activity at baseline and following chronic stress. Moreover, gut microbiota was studied through 16S sequencing in chronically stressed and control wild-type mice with or without pharmacological inhibition of caspase-1. Caspase-1 deficiency decreased depressive- and anxiety-like behaviours at baseline, and increased locomotor activity and locomotor skills. Moreover, caspase-1 genetic deletion decreased the exacerbation of anxiety- and depressive- like behaviours following stress. Furthermore, caspase-1 antagonism with minocycline decreased stress-induced rise in depressive-like behaviour. Gut microbiota composition of stressed mice showed alterations of the Firmicutes/Bacteroidetes ratio, decreased Bifidobacterium spp. as well as increased Lactobacillus spp., changes associated with increased inflammasome activation and increased NF-kB activity. When restrained mice were treated with minocycline, evidence of both synergistic and antagonistic effects on microbiota composition was detected. For example, Blautia, Akkermansia and a member of the Lachnospiraceae family were increased. This effect is relevant to stress-responses given that Akkermansia attenuates inflammation in adipose tissue via induction of Foxp3 regulatory T-cells, and suppression of IL-6- and IL-1{\ss}-mediated pathways. Caspase-1 inhibition exerts protective effects via modulating the interface between stress response and microbiota composition. We propose the novel concept of a “microbiota-gut-inflammasome-brain (MGIB) axis”, in which the gut microbiota through inflammasome signalling modulates inflammatory pathways that modulate brain function and affect anxiety- and depressive-like behaviours.",
author = "Antonio Inserra and Ma-Li Wong and Martin Lewis and Mastronardi, {Claudio A.} and Lex Leong and Jocelyn Choo and Kentish, {Stephen J.} and P. Xie and M. Morrison and Steven Wesselingh and Geraint Rogers and Julio Licinio",
year = "2016",
month = "8",
day = "27",
language = "English",
note = "14th Annual Meeting of Asian-Pacific Society for Neurochemistry 2016 ; Conference date: 27-08-2016 Through 30-08-2016",
url = "http://www.apsneurochem.org/14th-annual-meeting-of-asian-pacific-society-for-neurochemistry-2016/",

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Inserra, A, Wong, M-L, Lewis, M, Mastronardi, CA, Leong, L, Choo, J, Kentish, SJ, Xie, P, Morrison, M, Wesselingh, S, Rogers, G & Licinio, J 2016, 'The microbiota-gut-inflammasome-brain (MGIB) axis' 14th Annual Meeting of Asian-Pacific Society for Neurochemistry 2016, Kuala Lumpur, Malaysia, 27/08/16 - 30/08/16, .

The microbiota-gut-inflammasome-brain (MGIB) axis. / Inserra, Antonio; Wong, Ma-Li; Lewis, Martin; Mastronardi, Claudio A.; Leong, Lex; Choo, Jocelyn; Kentish, Stephen J.; Xie, P.; Morrison, M.; Wesselingh, Steven; Rogers, Geraint; Licinio, Julio.

2016. Poster session presented at 14th Annual Meeting of Asian-Pacific Society for Neurochemistry 2016, Kuala Lumpur, Malaysia.

Research output: Contribution to conferencePoster

TY - CONF

T1 - The microbiota-gut-inflammasome-brain (MGIB) axis

AU - Inserra, Antonio

AU - Wong, Ma-Li

AU - Lewis, Martin

AU - Mastronardi, Claudio A.

AU - Leong, Lex

AU - Choo, Jocelyn

AU - Kentish, Stephen J.

AU - Xie, P.

AU - Morrison, M.

AU - Wesselingh, Steven

AU - Rogers, Geraint

AU - Licinio, Julio

PY - 2016/8/27

Y1 - 2016/8/27

N2 - Increasing evidence suggests the involvement of neuroinflammatory pathways and gut microbiota in major depressive disorder and in antidepressant response. Inflammasome activation triggered by psychosocial stress results in the maturation of caspase-1 and activation of interleukin (IL)-1ß and IL-18, two pro-inflammatory cytokines involved in HPA axis activation and stress-coping pathways. The microbiota-gut-brain (MGB) axis is a multi-organ bidirectional signaling system between the gut microbiota and the CNS that plays fundamental roles in host homeostasis, behavior and stress response. Caspase-1 KO and minocycline-treated mice were screened for anxiety-like, depressive-like and locomotor activity at baseline and following chronic stress. Moreover, gut microbiota was studied through 16S sequencing in chronically stressed and control wild-type mice with or without pharmacological inhibition of caspase-1. Caspase-1 deficiency decreased depressive- and anxiety-like behaviours at baseline, and increased locomotor activity and locomotor skills. Moreover, caspase-1 genetic deletion decreased the exacerbation of anxiety- and depressive- like behaviours following stress. Furthermore, caspase-1 antagonism with minocycline decreased stress-induced rise in depressive-like behaviour. Gut microbiota composition of stressed mice showed alterations of the Firmicutes/Bacteroidetes ratio, decreased Bifidobacterium spp. as well as increased Lactobacillus spp., changes associated with increased inflammasome activation and increased NF-kB activity. When restrained mice were treated with minocycline, evidence of both synergistic and antagonistic effects on microbiota composition was detected. For example, Blautia, Akkermansia and a member of the Lachnospiraceae family were increased. This effect is relevant to stress-responses given that Akkermansia attenuates inflammation in adipose tissue via induction of Foxp3 regulatory T-cells, and suppression of IL-6- and IL-1ß-mediated pathways. Caspase-1 inhibition exerts protective effects via modulating the interface between stress response and microbiota composition. We propose the novel concept of a “microbiota-gut-inflammasome-brain (MGIB) axis”, in which the gut microbiota through inflammasome signalling modulates inflammatory pathways that modulate brain function and affect anxiety- and depressive-like behaviours.

AB - Increasing evidence suggests the involvement of neuroinflammatory pathways and gut microbiota in major depressive disorder and in antidepressant response. Inflammasome activation triggered by psychosocial stress results in the maturation of caspase-1 and activation of interleukin (IL)-1ß and IL-18, two pro-inflammatory cytokines involved in HPA axis activation and stress-coping pathways. The microbiota-gut-brain (MGB) axis is a multi-organ bidirectional signaling system between the gut microbiota and the CNS that plays fundamental roles in host homeostasis, behavior and stress response. Caspase-1 KO and minocycline-treated mice were screened for anxiety-like, depressive-like and locomotor activity at baseline and following chronic stress. Moreover, gut microbiota was studied through 16S sequencing in chronically stressed and control wild-type mice with or without pharmacological inhibition of caspase-1. Caspase-1 deficiency decreased depressive- and anxiety-like behaviours at baseline, and increased locomotor activity and locomotor skills. Moreover, caspase-1 genetic deletion decreased the exacerbation of anxiety- and depressive- like behaviours following stress. Furthermore, caspase-1 antagonism with minocycline decreased stress-induced rise in depressive-like behaviour. Gut microbiota composition of stressed mice showed alterations of the Firmicutes/Bacteroidetes ratio, decreased Bifidobacterium spp. as well as increased Lactobacillus spp., changes associated with increased inflammasome activation and increased NF-kB activity. When restrained mice were treated with minocycline, evidence of both synergistic and antagonistic effects on microbiota composition was detected. For example, Blautia, Akkermansia and a member of the Lachnospiraceae family were increased. This effect is relevant to stress-responses given that Akkermansia attenuates inflammation in adipose tissue via induction of Foxp3 regulatory T-cells, and suppression of IL-6- and IL-1ß-mediated pathways. Caspase-1 inhibition exerts protective effects via modulating the interface between stress response and microbiota composition. We propose the novel concept of a “microbiota-gut-inflammasome-brain (MGIB) axis”, in which the gut microbiota through inflammasome signalling modulates inflammatory pathways that modulate brain function and affect anxiety- and depressive-like behaviours.

M3 - Poster

ER -

Inserra A, Wong M-L, Lewis M, Mastronardi CA, Leong L, Choo J et al. The microbiota-gut-inflammasome-brain (MGIB) axis. 2016. Poster session presented at 14th Annual Meeting of Asian-Pacific Society for Neurochemistry 2016, Kuala Lumpur, Malaysia.