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Article ; Online: Gut-Brain Axis and Behavior.

Martin, Clair R / Mayer, Emeran A

Nestle Nutrition Institute workshop series

2017 Volume 88, Page(s) 45–53

Abstract: In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food ... ...

Abstract	In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake. Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function. Converging evidence suggests that the brain and the gut microbiota are in bidirectional communication. Observed dysbiotic states in depression, chronic stress, and autism may reflect altered brain signaling to the gut, while altered gut microbial signaling to the brain may play a role in reinforcing brain alterations. On the other hand, primary dysbiotic states due to Western diets may signal to the brain, altering ingestive behavior. While studies performed in patients with depression and rodent models generated by fecal microbial transfer from such patients suggest causation, evidence for an influence of acute gut microbial alterations on human behavioral and clinical parameters is lacking. Only recently has an open-label microbial transfer therapy in children with autism tentatively validated the gut microbiota as a therapeutic target. The translational potential of preclinical findings remains unclear without further clinical investigation.
MeSH term(s)	Animals ; Autistic Disorder/microbiology ; Behavior/physiology ; Brain/physiology ; Depression/microbiology ; Dysbiosis/psychology ; Fecal Microbiota Transplantation ; Feeding Behavior ; Gastrointestinal Microbiome/physiology ; Gastrointestinal Tract/physiology ; Humans ; Irritable Bowel Syndrome/microbiology ; Prebiotics/administration & dosage ; Probiotics/therapeutic use
Chemical Substances	Prebiotics
Language	English
Publishing date	2017-03-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	1664-2155
ISSN (online)	1664-2155
DOI	10.1159/000461732
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Gut Microbiome and Modulation of CNS Function.

Osadchiy, Vadim / Martin, Clair R / Mayer, Emeran A

Comprehensive Physiology

2019 Volume 10, Issue 1, Page(s) 57–72

Abstract: Preclinical evidence strongly suggests a role for the gut microbiome in modulating the host central nervous system function and behavior. Several communication channels have been identified that enable microbial signals to reach the brain and that enable ...

Abstract	Preclinical evidence strongly suggests a role for the gut microbiome in modulating the host central nervous system function and behavior. Several communication channels have been identified that enable microbial signals to reach the brain and that enable the brain to influence gut microbial composition and function. In rodent models, endocrine, neural, and inflammatory signals generated by gut microbes can alter brain structure and function, while autonomic nervous system activity can affect the microbiome by modulating the intestinal environment and by directly regulating microbial behavior. The amount of information that reaches the brain is dynamically regulated by the blood-brain barrier and the intestinal barrier. In humans, associations between gut microbial composition and function and several brain disorders have been reported, and fecal microbial transplants from patient populations into gnotobiotic mice have resulted in the reproduction of homologous features in the recipient mice. However, in contrast to preclinical findings, there is little information about a causal role of the gut microbiome in modulating human central nervous system function and behavior. Longitudinal studies in large patient populations with therapeutic interventions are required to demonstrate such causality, which will provide the basis for future clinical trials. © 2020 American Physiological Society. Compr Physiol 10:57-72, 2020.
MeSH term(s)	Animals ; Autonomic Nervous System ; Brain/physiology ; Feeding Behavior ; Gastrointestinal Microbiome/physiology ; Gastrointestinal Motility ; Humans ; Obesity
Language	English
Publishing date	2019-12-18
Publishing country	United States
Document type	Journal Article
ISSN	2040-4603
ISSN (online)	2040-4603
DOI	10.1002/cphy.c180031
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Article ; Online: Proteolysis of fibrillin-2 microfibrils is essential for normal skeletal development.

Mead, Timothy J / Martin, Daniel R / Wang, Lauren W / Cain, Stuart A / Gulec, Cagri / Cahill, Elisabeth / Mauch, Joseph / Reinhardt, Dieter / Lo, Cecilia / Baldock, Clair / Apte, Suneel S

eLife

2022 Volume 11

Abstract: The embryonic extracellular matrix (ECM) undergoes transition to mature ECM as development progresses, yet few mechanisms ensuring ECM proteostasis during this period are known. Fibrillin microfibrils are macromolecular ECM complexes serving structural ... ...

Abstract	The embryonic extracellular matrix (ECM) undergoes transition to mature ECM as development progresses, yet few mechanisms ensuring ECM proteostasis during this period are known. Fibrillin microfibrils are macromolecular ECM complexes serving structural and regulatory roles. In mice,
MeSH term(s)	ADAMTS Proteins/chemistry ; ADAMTS Proteins/genetics ; ADAMTS Proteins/metabolism ; Animals ; Fibrillin-1/genetics ; Fibrillin-2/metabolism ; Fibrillins/metabolism ; Mice ; Microfibrils/metabolism ; Proteolysis
Chemical Substances	Fibrillin-1 ; Fibrillin-2 ; Fibrillins ; ADAMTS Proteins (EC 3.4.24.-) ; ADAMTS10 protein, mouse (EC 3.4.24.-)
Language	English
Publishing date	2022-05-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.71142
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Article: Studying Process and Proximal Outcomes of Supervision for Motivational Interviewing.

Stein, L A R / Clair, Mary / Soenksen, Shayna / Martin, Rosemarie A / Clarke, Jennifer G

Training and education in professional psychology

2015 Volume 9, Issue 2, Page(s) 175–182

Language	English
Publishing date	2015-05-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2260442-X
ISSN	1931-3926 ; 1931-3918
ISSN (online)	1931-3926
ISSN	1931-3918
DOI	10.1037/tep0000073
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Article ; Online: The Gut-Brain Axis and the Microbiome: Mechanisms and Clinical Implications.

Osadchiy, Vadim / Martin, Clair R / Mayer, Emeran A

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2018 Volume 17, Issue 2, Page(s) 322–332

Abstract: Background & aims: Based largely on results from preclinical studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome, and the nervous system. Limited data obtained ... ...

Abstract	Background & aims: Based largely on results from preclinical studies, the concept of a brain gut microbiome axis has been established, mediating bidirectional communication between the gut, its microbiome, and the nervous system. Limited data obtained in human beings suggest that alterations in these interactions may play a role in several brain gut disorders. Methods: We reviewed the preclinical and clinical literature related to the topic of brain gut microbiome interactions. Results: Well-characterized bidirectional communication channels, involving neural, endocrine, and inflammatory mechanisms, exist between the gut and the brain. Communication through these channels may be modulated by variations in the permeability of the intestinal wall and the blood-brain barrier. Brain gut microbiome interactions are programmed during the first 3 years of life, including the prenatal period, but can be modulated by diet, medications, and stress throughout life. Based on correlational studies, alterations in these interactions have been implicated in the regulation of food intake, obesity, and in irritable bowel syndrome, even though causality remains to be established. Conclusions: Targets within the brain gut microbiome axis have the potential to become targets for novel drug development for brain gut disorders.
MeSH term(s)	Biological Factors/metabolism ; Brain/drug effects ; Brain/physiology ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Host Microbial Interactions ; Humans ; Microbiota
Chemical Substances	Biological Factors
Language	English
Publishing date	2018-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2018.10.002
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Article ; Online: A randomized clinical trial of motivational interviewing plus skills training vs. Relaxation plus education and 12-Steps for substance using incarcerated youth: Effects on alcohol, marijuana and crimes of aggression.

Stein, L A R / Martin, Rosemarie / Clair-Michaud, Mary / Lebeau, Rebecca / Hurlbut, Warren / Kahler, Christopher W / Monti, Peter M / Rohsenow, Damaris

Drug and alcohol dependence

2019 Volume 207, Page(s) 107774

Abstract: Background: Motivational Interviewing plus Cognitive Behavior Therapy (MI/CBT) has been used to reduce adolescent substance use, but has rarely been applied in youth correctional settings. This trial compared MI/CBT against Relaxation Training plus ... ...

Abstract	Background: Motivational Interviewing plus Cognitive Behavior Therapy (MI/CBT) has been used to reduce adolescent substance use, but has rarely been applied in youth correctional settings. This trial compared MI/CBT against Relaxation Training plus Substance-Education/12-Steps (RT/SET) to reduce substance use and crime among incarcerated youth. Methods: Participants (N = 199) were incarcerated juveniles (64.8 % non-White, 10.1 % girls, mean age of 17.1 years). Two individual sessions of MI (or RT) were followed by 10 group sessions of CBT (or SET). Youth were randomized to condition with follow-ups at 3- and 6-months after release. Major outcomes included alcohol, marijuana and crimes involving aggression. Results: A marginal treatment by time interaction was found for percent heavy drinking days, with follow-up tests indicating less alcohol use in RT/SET than MI/CBT at 6 months, and increased use within MI/CBT from 3 to 6 months. A significant treatment by time interaction was found for alcohol-related predatory aggression, with follow-up tests indicating fewer youth engaged in this behavior from 3 to 6 months within RT/SET, and weak evidence favoring MI/CBT over RT/SET at 3 months. General predatory aggression decreased from 3 to 6-months for both treatments. Conclusions: Although weak evidence was found favoring MI/CBT with respect to alcohol-related predatory aggression, results generally support RT/SET in reducing percent heavy drinking days.
MeSH term(s)	Adolescent ; Aggression/psychology ; Alcohol Drinking/epidemiology ; Alcohol Drinking/psychology ; Alcohol Drinking/therapy ; Cognitive Behavioral Therapy/methods ; Combined Modality Therapy/methods ; Crime/psychology ; Female ; Follow-Up Studies ; Humans ; Male ; Marijuana Use/epidemiology ; Marijuana Use/psychology ; Marijuana Use/therapy ; Motivational Interviewing/methods ; Patient Education as Topic/methods ; Prisoners/psychology ; Relaxation Therapy/methods ; Relaxation Therapy/psychology ; Substance-Related Disorders/epidemiology ; Substance-Related Disorders/psychology ; Substance-Related Disorders/therapy ; Young Adult
Language	English
Publishing date	2019-12-13
Publishing country	Ireland
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
ZDB-ID	519918-9
ISSN	1879-0046 ; 0376-8716
ISSN (online)	1879-0046
ISSN	0376-8716
DOI	10.1016/j.drugalcdep.2019.107774
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Article ; Online: The Trypanosoma brucei MISP family of invariant proteins is co-expressed with BARP as triple helical bundle structures on the surface of salivary gland forms, but is dispensable for parasite development within the tsetse vector.

Casas-Sanchez, Aitor / Ramaswamy, Raghavendran / Perally, Samïrah / Haines, Lee R / Rose, Clair / Aguilera-Flores, Marcela / Portillo, Susana / Verbeelen, Margot / Hussain, Shahid / Smithson, Laura / Yunta, Cristina / Lehane, Michael J / Vaughan, Sue / van den Abbeele, Jan / Almeida, Igor C / Boulanger, Martin J / Acosta-Serrano, Álvaro

PLoS pathogens

2023 Volume 19, Issue 3, Page(s) e1011269

Abstract: Trypanosoma brucei spp. develop into mammalian-infectious metacyclic trypomastigotes inside tsetse salivary glands. Besides acquiring a variant surface glycoprotein (VSG) coat, little is known about the metacyclic expression of invariant surface antigens. ...

Abstract	Trypanosoma brucei spp. develop into mammalian-infectious metacyclic trypomastigotes inside tsetse salivary glands. Besides acquiring a variant surface glycoprotein (VSG) coat, little is known about the metacyclic expression of invariant surface antigens. Proteomic analyses of saliva from T. brucei-infected tsetse flies identified, in addition to VSG and Brucei Alanine-Rich Protein (BARP) peptides, a family of glycosylphosphatidylinositol (GPI)-anchored surface proteins herein named as Metacyclic Invariant Surface Proteins (MISP) because of its predominant expression on the surface of metacyclic trypomastigotes. The MISP family is encoded by five paralog genes with >80% protein identity, which are exclusively expressed by salivary gland stages of the parasite and peak in metacyclic stage, as shown by confocal microscopy and immuno-high resolution scanning electron microscopy. Crystallographic analysis of a MISP isoform (MISP360) and a high confidence model of BARP revealed a triple helical bundle architecture commonly found in other trypanosome surface proteins. Molecular modelling combined with live fluorescent microscopy suggests that MISP N-termini are potentially extended above the metacyclic VSG coat, and thus could be tested as a transmission-blocking vaccine target. However, vaccination with recombinant MISP360 isoform did not protect mice against a T. brucei infectious tsetse bite. Lastly, both CRISPR-Cas9-driven knock out and RNAi knock down of all MISP paralogues suggest they are not essential for parasite development in the tsetse vector. We suggest MISP may be relevant during trypanosome transmission or establishment in the vertebrate's skin.
MeSH term(s)	Animals ; Mice ; Trypanosoma brucei brucei/genetics ; Parasites ; Membrane Proteins ; Alanine ; Proteomics ; Salivary Glands/parasitology ; Trypanosoma ; Mammals ; Membrane Glycoproteins
Chemical Substances	Membrane Proteins ; Alanine (OF5P57N2ZX) ; BARP protein, mouse ; Membrane Glycoproteins
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011269
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Article ; Online: Proteolysis of fibrillin-2 microfibrils is essential for normal skeletal development

Timothy J Mead / Daniel R Martin / Lauren W Wang / Stuart A Cain / Cagri Gulec / Elisabeth Cahill / Joseph Mauch / Dieter Reinhardt / Cecilia Lo / Clair Baldock / Suneel S Apte

eLife, Vol

2022 Volume 11

Abstract	The embryonic extracellular matrix (ECM) undergoes transition to mature ECM as development progresses, yet few mechanisms ensuring ECM proteostasis during this period are known. Fibrillin microfibrils are macromolecular ECM complexes serving structural and regulatory roles. In mice, Fbn1 and Fbn2, encoding the major microfibrillar components, are strongly expressed during embryogenesis, but fibrillin-1 is the major component observed in adult tissue microfibrils. Here, analysis of Adamts6 and Adamts10 mutant mouse embryos, lacking these homologous secreted metalloproteases individually and in combination, along with in vitro analysis of microfibrils, measurement of ADAMTS6-fibrillin affinities and N-terminomics discovery of ADAMTS6-cleaved sites, identifies a proteostatic mechanism contributing to postnatal fibrillin-2 reduction and fibrillin-1 dominance. The lack of ADAMTS6, alone and in combination with ADAMTS10 led to excess fibrillin-2 in perichondrium, with impaired skeletal development defined by a drastic reduction of aggrecan and cartilage link protein, impaired BMP signaling in cartilage, and increased GDF5 sequestration in fibrillin-2-rich tissue. Although ADAMTS6 cleaves fibrillin-1 and fibrillin-2 as well as fibronectin, which provides the initial scaffold for microfibril assembly, primacy of the protease-substrate relationship between ADAMTS6 and fibrillin-2 was unequivocally established by reversal of the defects in Adamts6-/- embryos by genetic reduction of Fbn2, but not Fbn1.
Keywords	extracellular matrix ; Protease ; ADAMTS ; proteolysis ; fibrillin ; skeletal development ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The Brain-Gut-Microbiome Axis.

Martin, Clair R / Osadchiy, Vadim / Kalani, Amir / Mayer, Emeran A

Cellular and molecular gastroenterology and hepatology

2018 Volume 6, Issue 2, Page(s) 133–148

Abstract: Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and ... ...

Abstract	Preclinical and clinical studies have shown bidirectional interactions within the brain-gut-microbiome axis. Gut microbes communicate to the central nervous system through at least 3 parallel and interacting channels involving nervous, endocrine, and immune signaling mechanisms. The brain can affect the community structure and function of the gut microbiota through the autonomic nervous system, by modulating regional gut motility, intestinal transit and secretion, and gut permeability, and potentially through the luminal secretion of hormones that directly modulate microbial gene expression. A systems biological model is proposed that posits circular communication loops amid the brain, gut, and gut microbiome, and in which perturbation at any level can propagate dysregulation throughout the circuit. A series of largely preclinical observations implicates alterations in brain-gut-microbiome communication in the pathogenesis and pathophysiology of irritable bowel syndrome, obesity, and several psychiatric and neurologic disorders. Continued research holds the promise of identifying novel therapeutic targets and developing treatment strategies to address some of the most debilitating, costly, and poorly understood diseases.
Language	English
Publishing date	2018
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2352-345X
ISSN	2352-345X
DOI	10.1016/j.jcmgh.2018.04.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Observational study investigating Tolerance Of Anticancer Systemic Therapy In the Elderly (TOASTIE)

Sarah Taylor / Eleanor Smith / Christopher Mark Jones / Daniel Swinson / Mark A Baxter / Fiona Smith / R D Petty / Helen Dearden / Sally Martin / Michael Rowe / Kieran Zucker / Anna C Olsson-Brown / Clair Brunner / Anna Lewis / Lisa Rodgers / Anthea Cree

BMJ Open, Vol 11, Iss

a protocol

2021 Volume 9

Keywords	Medicine ; R
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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