The document summarizes a presentation on the gut-brain axis and probiotics. It provides an overview of the gut-brain axis as an integrative bidirectional system involving the brain, gut microbiota, neuroanatomical pathways, the neuroendocrine HPA axis, the gut immune system, gut microbiota and metabolism, and intestinal and blood-brain barriers. It discusses evidence from preclinical studies using germ-free mice models and human studies such as those linking gut microbiota to HPA axis response and evidence from fMRI studies showing probiotic consumption can decrease brain reactivity to negative stimuli.
Bacterial colonisation of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signaling. Regulation of the microbiota-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. Moreover, there is now expanding evidence for the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. Research has focused on how the microbiota communicates with the central nervous system (CNS) and thereby influences brain function. The routes of this communication are not fully elucidated but include neural, humoral, immune and metabolic pathways. This view is underpinned by studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotic agents which indicate a role for the gut microbiota in the regulation of mood, cognition, pain and obesity. Thus the concept of a microbiota-gut brain axis is emerging which suggests that modulation of the gut microflora may be a tractable strategy for developing novel therapeutics for complex stress-related CNS disorders where there is a huge unmet medical need.
The Gut-Brain Connection: An Inside Look at DepressionAugustin Bralley
During a recent Metametrix sponsored breakfast at the IFM Symposium in Hollywood, Florida, Dr. Todd LePine gave a compelling presentation entitled The Gut-Brain Connection: An Inside Look at Depression.
Bacterial colonisation of the intestine has a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signaling. Regulation of the microbiota-gut-brain axis is essential for maintaining homeostasis, including that of the CNS. Moreover, there is now expanding evidence for the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. Research has focused on how the microbiota communicates with the central nervous system (CNS) and thereby influences brain function. The routes of this communication are not fully elucidated but include neural, humoral, immune and metabolic pathways. This view is underpinned by studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotic agents which indicate a role for the gut microbiota in the regulation of mood, cognition, pain and obesity. Thus the concept of a microbiota-gut brain axis is emerging which suggests that modulation of the gut microflora may be a tractable strategy for developing novel therapeutics for complex stress-related CNS disorders where there is a huge unmet medical need.
The Gut-Brain Connection: An Inside Look at DepressionAugustin Bralley
During a recent Metametrix sponsored breakfast at the IFM Symposium in Hollywood, Florida, Dr. Todd LePine gave a compelling presentation entitled The Gut-Brain Connection: An Inside Look at Depression.
What is gut microbiota? What is the influence of diet on the proper functioning of our gut microbiota? How does the gut-brain axis (GBA) influence the emotional and cognitive centers of the brain? Tune into this webinar to find out more about this timely topic.
Learning Objectives:
List the neurological and physiological connections that enable the bidirectional communication between the gut and the brain
Identify lifestyle, dietary, and microbial influences on the flow and function of signaling molecules along the gut-microbiota-brain axis
Implement dietary regimens that target the gut and gastrointestinal microbiota to improve or maintain optimal physical and mental health
RDNs earn 1.0 CEU
Moving into the Post-MetagenomicEra of Gut Microbiome ResearchJonathan Clarke
Julian Marchesi's presentation slides from our previous Microbiome R&D and Business Collaboration Forum. For information about this years event please visit http://www.globalengage.co.uk/microbiota.html
Gasbarrini A. Microbiota, Antibiotici e Probiotici in Gastroenterologia. ASMa...Gianfranco Tammaro
PROF. ANTONIO GASBARRINI - 3° Giornata Master ECM in Gastroenterologia 2016 (25/11/2016) - Fondazione Santa Lucia - Sala Congressi - Roma
Sito: www.asmad.net
Canale Youtube: https://youtu.be/ouYcXg_ZtJM
Why is the gut our second brain? Robert-J M BrummerValio
Robert-J M Brummer MD PhD
Professor of Gastroenterology and Clinical Nutrition, director Nutrition-Gut-Brain Interactions Research Centre
Pro-Vice-Chancellor, Örebro University, Sweden
Helsinki, June 15, 2016
Recent research suggests that a variety of lifestyle - especially dietary - changes influencing the integrity of gastrointestinal function may be driving at least some portion of the increased prevalence of illnesses of civilization, including neuropsychiatric problems, such as autism, attention-deficit-hyperactivity disorder, major depression, obsessive-compulsive disorder and Alzheimer disease. One area of interest involves the relationship between the gut's microbiome (as well as the related functional integrity of the gastrointestinal tract) and mental health.
What is gut microbiota? What is the influence of diet on the proper functioning of our gut microbiota? How does the gut-brain axis (GBA) influence the emotional and cognitive centers of the brain? Tune into this webinar to find out more about this timely topic.
Learning Objectives:
List the neurological and physiological connections that enable the bidirectional communication between the gut and the brain
Identify lifestyle, dietary, and microbial influences on the flow and function of signaling molecules along the gut-microbiota-brain axis
Implement dietary regimens that target the gut and gastrointestinal microbiota to improve or maintain optimal physical and mental health
RDNs earn 1.0 CEU
Moving into the Post-MetagenomicEra of Gut Microbiome ResearchJonathan Clarke
Julian Marchesi's presentation slides from our previous Microbiome R&D and Business Collaboration Forum. For information about this years event please visit http://www.globalengage.co.uk/microbiota.html
Gasbarrini A. Microbiota, Antibiotici e Probiotici in Gastroenterologia. ASMa...Gianfranco Tammaro
PROF. ANTONIO GASBARRINI - 3° Giornata Master ECM in Gastroenterologia 2016 (25/11/2016) - Fondazione Santa Lucia - Sala Congressi - Roma
Sito: www.asmad.net
Canale Youtube: https://youtu.be/ouYcXg_ZtJM
Why is the gut our second brain? Robert-J M BrummerValio
Robert-J M Brummer MD PhD
Professor of Gastroenterology and Clinical Nutrition, director Nutrition-Gut-Brain Interactions Research Centre
Pro-Vice-Chancellor, Örebro University, Sweden
Helsinki, June 15, 2016
Recent research suggests that a variety of lifestyle - especially dietary - changes influencing the integrity of gastrointestinal function may be driving at least some portion of the increased prevalence of illnesses of civilization, including neuropsychiatric problems, such as autism, attention-deficit-hyperactivity disorder, major depression, obsessive-compulsive disorder and Alzheimer disease. One area of interest involves the relationship between the gut's microbiome (as well as the related functional integrity of the gastrointestinal tract) and mental health.
There are so many choices that you can consider when you look at probiotics and choosing a probiotic is very difficult. There are criteria you should look for when you choose a probiotic.
Medical considerations in dental treatment of patients with liver disease. Main types of liver disease, clinical manifestations, lab tests, treatment considerations.
The storyline behind the modern epidemic of inflammation driven disease goes as follows:
• Chronic degenerative conditions (Diseases of Civilization – DOCs) are on the rise and have overtaken infections as the major source of death and illness.
• This epidemiological transition is due, at least in part, to environmental changes that have increased the disease liability of genetic profiles that were previously benign.
• These DOCs are associated with increased systemic inflammation stemming from inappropriate stressor-response mechanisms.
• Much of this inflammation is generated and/or perpetuated by the gut-brain axis.
• Gut-brain axis derived inflammation leads to disruptions in psycho-neuro-immunological (PNI) balances.
• Pathophysiological mediators of PNI disturbances can be measured and treated.
• A cornerstone of said treatment is the regular consumption of a high quality multi-strain probiotic.
The carefully selected strains in Tri-Flora have been shown to:
• Decrease pro-inflammatory cytokines;
• Increase anti-inflammatory cytokine IL-10;
• Stimulate regulatory immune cells;
• Inhibit immune response to LPS (lipopolysaccharide) transduction;
• Improve intestinal barrier function;
• Enhance mucosal and systemic immune responses;
• Produce and deliver neurotransmitters such as GABA and serotonin.
And in so doing accomplish some very intriguing clinical feats:
1. Lessen symptoms of chronic fatigue syndrome;
2. Act as an adjunct to standard care in the treatment of Major Depressive Disorder;
3. Improve anxiety and reduce brain cell death; and
4. Help women lose weight.
It is for reasons such as this, that my most commonly recommended supplement for most people is a high quality probiotic. Tri-Flora by IP Formulas is my new favorite.
Many are confused what is the difference between prebiotics and probiotics. They are always surprised when they find out that they are completely different, but they complement each other very well.
dkNET Webinar: Population-Based Approaches to Investigate Endocrine Communica...dkNET
Abstract
Mechanisms of inter-organ signaling have been established as hallmarks of nearly every pathophysiologic condition, where many exist as related and complex diseases. While significant work has been focused on understanding how individual cell types contribute and respond to specific perturbations related to common, complex disease, an equally-important but relatively less-explored question involves how relationships between organs are altered in the context of an integrated living organism. Current technical advances, such as proteomic analysis of plasma or conditioned media, have allowed for a more unbiased visualization and discovery of additional inter-tissue signaling molecules. However, one important feature which is lacking from these approaches is the ability to gain insight as to the function, mechanisms of action and target tissue(s) of relevant molecules. To begin to address these constraints, we initially developed a correlation-based bioinformatics framework which uses multi-tissue gene expression and/or proteomic data, as well as publicly available resources to statistically rank and functionally annotate endocrine proteins involved in tissue cross-talk. Using this approach, we identified many known and experimentally validated several novel inter-tissue circuits. This was this first study to directly link an endocrine-focused bioinformatics pipeline from population data directly to experimentally-validated mechanisms of inter-tissue communication. While these validations provide strong support for exploiting natural variation to discover new modes of communication, these serve as simple proof-of-principle studies and, thus, have promising potential for expansion. Some of these will be discussed during the presentation.
Presenter: Marcus Seldin, Ph.D. Assistant Professor, Biological Chemistry, University of California Irvine
Upcoming webinars schedule: https://dknet.org/about/webinar
Nutrigenomics is the science that examines the response of individuals to food compounds using post-genomic and related technologies (e.g. genomics, transcriptomics, proteomics, metabol/nomic etc.). The long-term aim of nutrigenomics is to understand how the whole body responds to real foods using an integrated approach termed 'systems biology'. The huge advantage in this approach is that the studies can examine people (i.e. populations, sub-populations - based on genes or disease - and individuals), food, life-stage and life-style without preconceived ideas.
During the 5th Yogurt Summit, held in Buenos Aires during ICN2017, Professor Sharon Donovan (University of California, Davis, USA) explained why gut microbiota are recognised today as the intersection between diet and health.
ORIGINAL INVESTIGATIONPrebiotic intake reduces the waking .docxgerardkortney
ORIGINAL INVESTIGATION
Prebiotic intake reduces the waking cortisol response
and alters emotional bias in healthy volunteers
Kristin Schmidt & Philip J. Cowen & Catherine J. Harmer &
George Tzortzis & Steven Errington & Philip W. J. Burnet
Received: 23 July 2014 /Accepted: 10 November 2014 /Published online: 3 December 2014
# The Author(s) 2014. This article is published with open access at Springerlink.com
Abstract
Rationale There is now compelling evidence for a link be-
tween enteric microbiota and brain function. The ingestion of
probiotics modulates the processing of information that is
strongly linked to anxiety and depression, and influences the
neuroendocrine stress response. We have recently demonstrat-
ed that prebiotics (soluble fibres that augment the growth of
indigenous microbiota) have significant neurobiological ef-
fects in rats, but their action in humans has not been reported.
Objectives The present study explored the effects of two
prebiotics on the secretion of the stress hormone, cortisol
and emotional processing in healthy volunteers.
Methods Forty-five healthy volunteers received one of two
prebiotics (fructooligosaccharides, FOS, or Bimuno®-galacto-
oligosaccharides, B-GOS) or a placebo (maltodextrin) daily for
3 weeks. The salivary cortisol awakening response was sam-
pled before and after prebiotic/placebo administration. On the
final day of treatment, participants completed a computerised
task battery assessing the processing of emotionally salient
information.
Results The salivary cortisol awakening response was signif-
icantly lower after B-GOS intake compared with placebo.
Participants also showed decreased attentional vigilance to
negative versus positive information in a dot-probe task after
B-GOS compared to placebo intake. No effects were found
after the administration of FOS.
Conclusion The suppression of the neuroendocrine stress
response and the increase in the processing of positive
versus negative attentional vigilance in subjects supple-
mented with B-GOS are consistent with previous find-
ings of endocrine and anxiolytic effects of microbiota
proliferation. Further studies are therefore needed to test
the utility of B-GOS supplementation in the treatment
of stress-related disorders.
Keywords Cortisol . Hypothalamic-pituitary-adrenal axis .
Gut microbiota . Prebiotics . Anxiety . Attention . Emotional
processing
Introduction
The adult human gut microbiota comprises over 1000
species and 7000 bacterial strains and is characterised
by a balanced compositional signature with moderate
inter-individual variability (Gareau et al. 2010; Cryan
and Dinan 2012). Probiotic strains, which have the
ability to confer beneficial effects upon the host, have
received renewed attention in recent years (e.g. Forsythe
and Kunze 2013). A particular focus has been put on
their ability to influence neural and endocrine systems
and behavioural phenotypes (Cryan and O’Mahony
2011; Dinan and Cryan 2012). Their potentia.
Remodeling of Pancreatic Innervation in DiabetesInsideScientific
The pancreas is densely innervated, and neural signals play a significant role in glucose regulation by modulating pancreatic hormone release. However, relatively little is known about the anatomical relationships between islets and nerves across the whole pancreas. In this webinar, Dr. Sarah Stanley and Dr. Alexandra Alvarsson will discuss their research using tissue clearing and whole organ imaging of the pancreas to identify the 3D structure of pancreatic nerves and islets.
In particular, they will provide an overview of their methodology, which provides detailed information and quantification of pancreatic innervation in healthy pancreas, in canonical models of diabetes and in samples from nondiabetic and diabetic donors. They will also present their findings, demonstrating greatly enriched innervation in the islets with regional variations. They will also discuss beta cell innervation in mouse models of diabetes and in pancreata from human donors with type 2 diabetes.
Key Topics Include:
- Tissue clearing and 3D imaging to allow the mapping of nerves in peripheral organs
- Innervation of peripheral organs such as the pancreas
- How pancreatic nerves are remodeled in diabetes
Microbiota and Gut-Brain Axis in HealthSindhBiotech
This lecture is presented by our volunteer Hina Nawaz, she is from Karachi, Pakistan, and she is covering "Microbiota and Gut-Brain Axis in Health"
For video: https://youtu.be/W2hfl5_FaF8
Summary
Neurodevelopment is a complex process governed by both intrinsic and extrinsic signals. While historically studied by researching the brain, inputs from the periphery impact many neurological conditions. Indeed, emerging data suggests communication between the gut and the brain in anxiety,
depression, cognition and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut. These cues largely originate from the microbiome, the consortium of symbiotic bacteria that reside within all animals. Research over the past few years reveals that the gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brainbarrier, myelination, neurogenesis, and microglia maturation, and also modulates many aspects of animal behavior. Herein, we discuss the biological intersection of neurodevelopment and the microbiome, and explore the hypothesis that gut bacteria are integral contributors to development and function of the nervous system, and the balance between mental health and disease.
Physiology means study of functions. It is a subject that include everything about how organisms work and how they coordinate within their own bodies and also how they respond to the ever-changing environment.
Welcome to the wonderful world of physiology.
VHIR Seminar led by Joel Doré. Research Director. Institut National de la Recherche Agronomique (INRA). Jouy-en-Josas, France.
Abstract: The human intestinal tract harbours a complex microbial ecosystem which plays a key role in nutrition and health. Interactions between food constituents, microbes and the host organism derive from a long co-evolution that resulted in a mutualistic association.
Current investigations into the human faecal metagenome are delivering an extensive gene repertoire representative of functional potentials of the human intestinal microbiota. The most redundant genomic traits of the human intestinal microbiota are identified and thereby its functional balance. These observation point towards the existence of enterotypes, i.e. microbiota sharing specific traits but yet independent of geographic origin, age, sex etc.. It also shows a unique segregation of the human population into individuals with low versus high gene-counts. In the end, it not only gives an unprecedented view of the intestinal microbiota, but it also significantly expands our ability to look for specificities of the microbiota associated with human diseases and to ultimately validate microbial signatures of prognostic and diagnostic value in immune mediated diseases.
Metagenomics of the human intestinal tract was applied to specifically compare obese versus lean individuals as well as to explore the dynamic changes associated with a severe calory-restricted diet. Microbiota structure differs with body-mass index and a limited set of marker species may be used as diagnostic model with a >85% predictive value. Among obese subjects; the overall phenotypic characteristics are worse in individuals with low gene counts microbiota, including a worse evolution of morphometric parameters over a period of 10 years, a low grade inflammatory context also associated with insulin-resistance, and the worst response to dietary constraints in terms of weight loss or improvement of biological and inflammatory characteristics. Low gene count microbiota is also associated with less favourable conditions in inflammatory bowel disease, such as higher relapse rate in ulcerative colitis patients.
Finally, microbiota transplantation has seen a regain of interest with applications expanding from Clostridium difficile infections to immune mediated and metabolic diseases.
The human intestinal microbiota should hence be regarded as a true organ, amenable to rationally designed modulation for human health.
Richard Frye, MD, PhD, FAAP, FAAN, CPI, will discuss:
*The enteric (gut) microbiome has an important influence on health and disease states in humans.
* The enteric microbiome influences the human host using chemical mediators, some of which can directly affect mitochondrial function
* Short chain fatty acids produced by gut bacteria not only modulate mitochondrial function and cellular regulatory pathways, but can also be used as mitochondrial fuels.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
A Strategic Approach: GenAI in EducationPeter Windle
Artificial Intelligence (AI) technologies such as Generative AI, Image Generators and Large Language Models have had a dramatic impact on teaching, learning and assessment over the past 18 months. The most immediate threat AI posed was to Academic Integrity with Higher Education Institutes (HEIs) focusing their efforts on combating the use of GenAI in assessment. Guidelines were developed for staff and students, policies put in place too. Innovative educators have forged paths in the use of Generative AI for teaching, learning and assessments leading to pockets of transformation springing up across HEIs, often with little or no top-down guidance, support or direction.
This Gasta posits a strategic approach to integrating AI into HEIs to prepare staff, students and the curriculum for an evolving world and workplace. We will highlight the advantages of working with these technologies beyond the realm of teaching, learning and assessment by considering prompt engineering skills, industry impact, curriculum changes, and the need for staff upskilling. In contrast, not engaging strategically with Generative AI poses risks, including falling behind peers, missed opportunities and failing to ensure our graduates remain employable. The rapid evolution of AI technologies necessitates a proactive and strategic approach if we are to remain relevant.
2. Gut-Brain Axis is more than an emerging concept
Social
Networks
Personal
Development Press
International
Best Seller
Academic
Press
Scientific
Press
Biomedical
Publications
GUT-BRAIN AXIS| R. MORIEZ
3. To have in mindbefore the presentation….
• Gut-Brain axis - a misleading term differentially used to named:
=> Neuroanatomical pathways between Gastrointestinal tract & brain [pathway of visceral
pain…]
=> Neuro -endocrine -immune communications between GI tract & brain...
• Gut-Brain axis is more complex, and is an INTEGRATIVE SYSTEM,
BIDIRECTIONAL that integrates all dimensions of the host and of it’s
microbiota
Brain-Gut Axis
Brain-Gut-Intestinal Microbiota Axis
GUT-BRAIN AXIS| R. MORIEZ
4. • Introduction to the Gut-Brain axis with preclinical and clinical
data
• Probiotics are an interesting route to consider in the
management of syndromes/pathologies associated with Gut-
Brain axis dysfunction
TODAY’sTALK
GUT-BRAIN AXIS| R. MORIEZ
5. ❸ Neuroanatomical
pathway of gut-brain
axis
❹
Neuroendocrine
HPA axis
pathway
❺Gut immune
system &
neuroimmune
pathways
❻ Gut
microbiota &
metabolism
system
❼ Intestinal
barrier
& blood brain
barrier
❷ Gut microbiota
❶ Brain
How the Gut-Brain Axis works
GUT-BRAIN AXIS| R. MORIEZ
6. • enteric NS
• parasympathetic NS
• sympathetic NS
• CRF, ACTH, cortisol • mast cells,
macrophages..
• Cytokines, PGs…
• Proteases
• GABA, Dopamine,
serotonin…
• LPS, SCFA…
• Epithelial/Enteroendocr
ne cells
• Tight Jcts/permeability
How the Gut-Brain Axis works– The key Actors
❸ Neuroanatomical
pathway of gut-brain
axis
❹
Neuroendocrine
HPA* axis
pathway
❺Gut immune
system &
neuroimmune
pathways
❻ Gut
microbiota &
metabolism
system
❼ Intestinal
barrier
& blood brain
barrier
❷ Gut microbiota
❶ Brain
*Hypothalamic–pituitary–adrenal
GUT-BRAIN AXIS| R. MORIEZ
7. life style diet dietary proteins antibiotic xenobiotic food allergies infections
How the Gut-Brain Axis works– The key Actors & Modulators
❷ gut microbiota
❶ brain
❸ neuroanatomical
pathway of gut-brain axis
❹ neuroendocrine
HPA axis pathway
❺gut immune system &
neuroimmune pathways
❻ gut microbiota
& metabolism
system
❼ intestinal barrier
& blood brain barrier
life style stress hormones aging genetic diet infections / chronic pathologies & treatments
• enteric NS
• parasympathetic NS
• sympathetic NS
• CRF, ACTH, cortisol • mast cells, macrophages..
• Cytokines, PGs…
• Proteases
• GABA, Dopamine,
serotonin…
• LPS, SCFA…
• Epithelial/Enteroendocrine
cells
• Tight Jcts/permeability
GUT-BRAIN AXIS| R. MORIEZ
8. Differents approaches to demonstrate Gut-Brain axis interaction
PreclinicalResearch
Cryan & Dinan, Nature Neurosci Rev (2012)
GUT-BRAIN AXIS| R. MORIEZ
9. Differents approaches to demonstrate Gut-Brain axis interaction
PreclinicalResearch
Cryan & Dinan, Nature Neurosci Rev (2012)
GUT-BRAIN AXIS| R. MORIEZ
10. • Research using GF mice has arguably provided the most convincing
evidence for a role of microbiota in gut-brain signaling
• One of the main advantages of the GF model is that identical strains of
bacteria can be introduced and GF mice can be « humanized » by
transplanting fecal microbiota from human patients with different
diseases.
Differents approaches to demonstrate Gut-Brain axis interaction
PreclinicalResearch
GUT-BRAIN AXIS| R. MORIEZ
11. HPA axis responseis influence bygut microbiotacomposition
Germ Free [GF] Specific Pathogen
Free [SPF]
Germ Free [GF]
Germ Free [GF]
B. infantis EPEC Mutant EPEC Tir
[SPF]
GERM FREE vs. SPECIFIC PATHOGEN FREE MONOASSOCIATED FLORA FECAL TRANSPLANTATION
vs.
Acute Restraint Stress [1h] => measure of plasmatic corticosterone
Sudo et al., J Physiol (2004)*Tir (translocated intimin receptor) is an essential component in the adherence of E.coli
*
PreclinicalResearch
GUT-BRAIN AXIS| R. MORIEZ
12. The body of Evidence of Gut-Brain axis interaction in GF models
Luczynski P et al., Int J.of Neuropsychopharmacology (2016)
PreclinicalResearch
GUT-BRAIN AXIS| R. MORIEZ
13. Can we transposepreclinical data to humans?
? Experimentally, Technically & Ethically
difficult to investigate Gut brain
mechanism and its components
[microbiota, GIT & brain biopsy….]
Brain structure, microbiota composition
is different in humans compared to
animal models…
No direct evidence of a gut-brain-
microbiota interaction in human [How it
works], but a robust and coherent level of
indirect evidence
GUT-BRAIN AXIS| R. MORIEZ
14. ❸ neuroanatomical
pathway of gut-brain axis
❹ neuroendocrine
HPA axis pathway
❺gut immune system &
neuroimmune pathways
❻ gut microbiota
& metabolism
system
❼ intestinal barrier
& blood brain barrier
❷ gut microbiota
❶ brain
Gut-Brain Axis in Human– IBS as model of evidence
GUT-BRAIN AXIS| R. MORIEZ
15. ❸ neuroanatomical
pathway of gut-brain axis
❹ neuroendocrine
HPA axis pathway
❺gut immune system &
neuroimmune pathways
❻ gut microbiota
& metabolism
system
❼ intestinal barrier
& blood brain barrier
❷ gut microbiota
❶ brain
Gut-Brain Axis in Human– IBS as model of evidence
Enck P et al., Nature Reviews I Disease Primers (2016)
GUT-BRAIN AXIS| R. MORIEZ
16. ❸ neuroanatomical
pathway of gut-brain axis
❹ neuroendocrine
HPA axis pathway
❺gut immune system &
neuroimmune pathways
❻ gut microbiota
& metabolism
system
❼ intestinal barrier
& blood brain barrier
❷ gut microbiota
❶ brain
The other Troubles & Pathologies where Gut-Brain is altered
Stress
StressStress Stress
Stress
Autism
Autism
Autism
Autism
Autism
Autism
Autism
mood disorders
psychiatric diseases
metabolic disorders
Obesity
T2DM
Obesity
T2DM
Obesity
T2DM
Obesity
T2DM
Obesity
T2DM
Obesity
T2DM
GI diseasesIBD
IBD
IBD
IBD
IBD IBD
GUT-BRAIN AXIS| R. MORIEZ
17. ❸ neuroanatomical
pathway of gut-brain axis
❹ neuroendocrine
HPA axis pathway
❺gut immune system &
neuroimmune pathways
❻ gut microbiota
& metabolism
system
❼ intestinal barrier
& blood brain barrier
❷ gut microbiota
❶ brain
Gut-Brain Interaction - Impact on Health ?
Stress
StressStress Stress
Stress
Autism
Autism
Autism
Autism
Autism
Autism
mood disorders
Class of pathologies
psychiatric diseases
metabolic disorders
Obesity
T2DM
Obesity
T2DM
Obesity
T2DM
Obesity
T2DM
Obesity
T2DM
GI diseases
IBD
IBD
IBD
IBD
IBD
Gut
Brain
Gut Brain
vicious circle
Chicken or egg ?
stress, ATB
diet & life style…
HEALTHY Behavior changes
Syndromes
Pathologies
GUT-BRAIN AXIS| R. MORIEZ
18. Clinical studies with probioticsin the Gut-Brain Axis
• A growing wave of striking clinical studies mainly focused on response to
emotional attention tasks, mood disorders, stress, anxiety & depression.
• In order to evaluate levels of stress, brain activity and psychological symptoms in
clinical studies, several tools have been applied, including biomarkers (i.e. salivary
cortisol), brain MRI and validated psychological scales typically used for the
evaluation of anxiolytic drugs.
Pirbaglou M et al., Nutrition Research (2016)
GUT-BRAIN AXIS| R. MORIEZ
19. The evidence of a gut-brain interaction using FMRI*
*FMRI. Functional Magnetic Resonance Imaging
Objective:
To assess the effect of a 4-week consumption of Fermented Milk Product (FMP: 5 strains
of probiotics including B. animalis lactis DN 173 010B) (2x125g/day) on brain intrinsic
connectivity and responses to emotional attention task in healthy women.
Sample size: 36 subjects (ITT = Intention To Treat; 45 randomized)
12 in the FMP arm
11 in the CONTROL arm
13 in the NO INTERVENTION (NO IN) arm
Inclusion criteria:
Healthy women
Age 18-55
No chronic pain
No gastrointestinal symptoms
No psychiatric illness
Right handed
Tillisch K, Gastroenterology (2013)
GUT-BRAIN AXIS| R. MORIEZ
20. The evidence of a gut-brain interaction using FMRI*
Tillisch K, Gastroenterology (2013)
GUT-BRAIN AXIS| R. MORIEZ
21. The evidence of a gut-brain interaction using FMRI*
Assessment of regional cerebral activity at resting state and
following a negative emotional attention task
Emotional
Matching
Emotional
Matching
Matched
Emotion (ME)
Emotional
Matching
Emotion
Labellin
Emotional
Matching
Emotion
Labellin
Matched
Emotion (ME)
ID Emo
(IDE)
Co
1) Resting state: eyes closed for a 5 minutes
functional scan; no stimulation
2) Negative emotional attention task:
– Validated task probing attention to
negative context (Lieberman, 2007)
– Assess the brain response while
viewing human negative emotional
faces (angry or fearful expressions) and
matching shapes as a control
Tillisch K, Gastroenterology (2013)
GUT-BRAIN AXIS| R. MORIEZ
22. The evidence of a gut-brain interaction using FMRI*
Study Results: Emotional attention task - 1/2
• 4 week FMP consumption decreases reactivity to a negative emotional attention
task of a brain network receiving afferent signals from the gut:
– FMP group: decreased reactivity of a widely distributed brain network (insula,
somatosensory cortex, PAG) to the task (p<0.0001)
– Control group: no change in the reactivity of the brain network to the task
– No IN group: increased reactivity of the brain network to the task
No IN
FMPP
Emotional
Matching
Sha
Matc
Emotional
Labelling
Conditions
Emotional
Matching
Sha
Matc
Emotional
Labelling
Conditions
Matched
Emotion (ME)
Matc
Form
ID Emotion
(IDE)
nal
ng
Shape
Matching
Emotional
Labelling
Conditions
nal
ng
Shape
Matching
Emotional
Labelling
Conditions
d
n (ME)
Matched
Forms (MF)
ID Emotion
(IDE)
Conditions
(PAG)
Tillisch K, Gastroenterology (2013)
GUT-BRAIN AXIS| R. MORIEZ
23. The evidence of a gut-brain interaction using FMRI*
Emotional
Matching
Sha
Matc
Emotional
Labelling
Conditions
Emotional
Matching
Sha
Matc
Emotional
Labelling
Conditions
Matched
Emotion (ME)
Matc
Form
ID Emotion
(IDE)
nal
ng
Shape
Matching
Emotional
Labelling
Conditions
nal
ng
Shape
Matching
Emotional
Labelling
Conditions
d
n (ME)
Matched
Forms (MF)
ID Emotion
(IDE)
Conditions
Study Results: Emotional attention task - 2/2
• Individual analyses of the regions from the identified network support previous
network results for the 3 groups
• 4 week FMP consumption decreases reactivity of interoceptive (mid-insula) and
somatosensory regions to a negative emotional attention task, compared to NO IN
(p<0.004; p<0.005) and CONTROL (p<0.03; p<0.02)
No IN > FMPP
Control > FMPP
Tillisch K, Gastroenterology (2013)
GUT-BRAIN AXIS| R. MORIEZ
24. The evidence of a gut-brain interaction using FMRI*
CONCLUSION.
• To our knowledge, this is the first demonstration in humans that chronic intake of a
fermented milk product with probiotic can modulate brain activity
• The findings suggest that regular intake of a fermented milk product with probiotic
can (i) affect brain regions concerned with the central processing of afferent signals
from the gut, and (ii) reduce the impact of the brain regions involved in emotional
arousal on the central processing of gut afferent signals
• Moreover, 4 week FMP consumption induced a shift away from an emotional arousal-
based resting state network towards a rationalization network
Tillisch K, Gastroenterology (2013)
GUT-BRAIN AXIS| R. MORIEZ
25. The evidence of a gut-brain interaction using BIOMARKER
Takada M, Neurogastroenterology & Motility (2016)
Objective:
Three double-blind, placebo-controlled trials were conducted to examine the effects of
of a 8-week consumption of Lactobacillus casei strain Shirota (once daily) on
psychological and physiological (BIOMARKER Cortisol) stress responses in healthy
medical students under academic examination stress.
Sample size: 140 subjects
70 in the placebo arm
70 in the LcS arm
GUT-BRAIN AXIS| R. MORIEZ
26. The evidence of a gut-brain interaction using BIOMARKER
Takada M, Neurogastroenterology & Motility (2016)
Study Results:
Ingestion of LcS suppressed stress-induced increases in glucocorticoids in an academic
stress model in healthy medical students
GUT-BRAIN AXIS| R. MORIEZ
27. How does it work ? Possible mechanisms.
B. longum strains on anxiety
=> vagus nerves, brain BDNF pathways
L. rhamnosus strains on anxiety & depression
GABA upregulation in brain
L. helveticus strains on anxiety
↘ neuroinflammation, ↘ serotonin
metabolism
B. Animalis strains properties
Inhibitor of Monoamine oxidase
(allow serotonin, dopamine..to remain in
Synaptic cleft ?) / scavenged free radicals
Exact mechanism of action of probiotics on Gut-Brain still remains to be established but
combining intrinsic properties of strains and the Preclinical & Clinical data we can
speculate that probiotics impact all the component of Gut-Brain axis (microbiota, barrier,
immune system, enteric nervous system, vagus nerves, brain).
GUT-BRAIN AXIS| R. MORIEZ
28. Conclusion
• A growing list of disorders – IBS, depression and autism
spectrum disorders - recently recognized as brain-gut
disorders
• Potential for novel therapeutic interventions at the
microbiome or at the gut level
• Probiotics have potential as agents to manage these
syndromes/pathologies associated with Gut-Brain axis
dysfunction
GUT-BRAIN AXIS| R. MORIEZ
29. “Let food be thy medicine and
medicine be thy food.”
Hippocrates (c. 460 BC – c. 370 BC)
GUT-BRAIN AXIS| R. MORIEZ
Editor's Notes
Probiotic supplementation in rodents has been shown to markedly change behaviour with correlated changes in neurochemistry