This document discusses the role of the human microbiome and its interaction with the immune system. It notes that humans are composed of both human and microbial cells that co-evolve and interact. The microbiome plays a key role in immune system development and homeostasis. The microbes inhabit all barrier surfaces of the body and outnumber human cells. They have a significant impact on local and systemic immunity and inflammation, as well as diseases like cancer, metabolic disorders, and neurological/behavioral functions. The microbiome composition is shaped by various environmental factors and can be modulated to impact health outcomes.
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.
The Human Microbiome in Sports Performance and Healthctorgan
Because our knowledge of the human microbiome is moving so rapidly, we turned our presentation at this conference into a discussion session so experts in the audience could share their professional knowledge and personal experience. By the end of the session, it was clear that we had barely scratched the surface of the importance of our microscopic kin to our health, to sports performance, and to how we need to think about designing research studies. A list of recommended resources is available at: www.caroltorgan.com/microbiome-sports/. We welcome your input!
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.
The Human Microbiome in Sports Performance and Healthctorgan
Because our knowledge of the human microbiome is moving so rapidly, we turned our presentation at this conference into a discussion session so experts in the audience could share their professional knowledge and personal experience. By the end of the session, it was clear that we had barely scratched the surface of the importance of our microscopic kin to our health, to sports performance, and to how we need to think about designing research studies. A list of recommended resources is available at: www.caroltorgan.com/microbiome-sports/. We welcome your input!
Dr. Heather Allen - The Swine Gut Microbiota: Status and OutlookJohn Blue
The Swine Gut Microbiota: Status and Outlook - Dr. Heather Allen, National Animal Disease Center, USDA, from the 2016 Allen D. Leman Swine Conference, September 17-20, 2016, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2016-leman-swine-conference-material
Hervé Blottiere-El impacto de las ciencias ómicas en la medicina, la nutrició...Fundación Ramón Areces
El 29 de marzo de 2016 celebramos un Simposio Internacional sobre el 'Impacto de las ciencias ómicas en la medicina, nutrición y biotecnología'. Organizado por la Fundación Ramón Areces en colaboración con la Real Academia Nacional de Medicina y BioEuroLatina, abordó cómo un mejor conocimiento del genoma humano está permitiendo notables avances hacia una medicina de precisión.
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.
Power Point for research paper presentation by Kevin Hugins.
Through microbial endocrinology other treatments may be developed. As this paper has discussed, application of these techniques may one day provide a treatment for pathogens other than the traditional antibiotics. It may lead to techniques for dealing with auto-immune diseases. Considering the sheer numbers of microorganisms in our microbiota and all we have yet to learn on the molecular level, this field of research may answer questions we do not even know we have yet.
This presentation include microbiome involve in human health and disease. classification and categorization of microbiota is aslo given.Anatomical area in which these microbes present.
Dr. Tom Burkey - Host-Microbe Interactions: Effects on nutrition and physiologyJohn Blue
Host-Microbe Interactions: Effects on nutrition and physiology - Dr. Tom Burkey, University of Nebraska-Lincoln, from the 2014 Allen D. Leman Swine Conference, September 15-16, 2014, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2014-leman-swine-conference-material
Human nutrition, gut microbiome and immune system S'eclairer
Dr Zahida Chaudnary talks with the students about nutrition, gut microbiomes, and nutrition as we look at diseases and how your body reacts to what you eat.
Check out the slideshow by itself here.
Want an audio version? Subscribe to our Podcast on iTunes!
Want to join us for the live discussion? Check out our Social Media in the noon hour every Monday as we sit down on Google Hangout OnAir! Follow us on Twitter, Facebook, or Google+ to get updated with the link when we start!
Dr. Heather Allen - The Swine Gut Microbiota: Status and OutlookJohn Blue
The Swine Gut Microbiota: Status and Outlook - Dr. Heather Allen, National Animal Disease Center, USDA, from the 2016 Allen D. Leman Swine Conference, September 17-20, 2016, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2016-leman-swine-conference-material
Hervé Blottiere-El impacto de las ciencias ómicas en la medicina, la nutrició...Fundación Ramón Areces
El 29 de marzo de 2016 celebramos un Simposio Internacional sobre el 'Impacto de las ciencias ómicas en la medicina, nutrición y biotecnología'. Organizado por la Fundación Ramón Areces en colaboración con la Real Academia Nacional de Medicina y BioEuroLatina, abordó cómo un mejor conocimiento del genoma humano está permitiendo notables avances hacia una medicina de precisión.
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.
Power Point for research paper presentation by Kevin Hugins.
Through microbial endocrinology other treatments may be developed. As this paper has discussed, application of these techniques may one day provide a treatment for pathogens other than the traditional antibiotics. It may lead to techniques for dealing with auto-immune diseases. Considering the sheer numbers of microorganisms in our microbiota and all we have yet to learn on the molecular level, this field of research may answer questions we do not even know we have yet.
This presentation include microbiome involve in human health and disease. classification and categorization of microbiota is aslo given.Anatomical area in which these microbes present.
Dr. Tom Burkey - Host-Microbe Interactions: Effects on nutrition and physiologyJohn Blue
Host-Microbe Interactions: Effects on nutrition and physiology - Dr. Tom Burkey, University of Nebraska-Lincoln, from the 2014 Allen D. Leman Swine Conference, September 15-16, 2014, St. Paul, Minnesota, USA.
More presentations at http://www.swinecast.com/2014-leman-swine-conference-material
Human nutrition, gut microbiome and immune system S'eclairer
Dr Zahida Chaudnary talks with the students about nutrition, gut microbiomes, and nutrition as we look at diseases and how your body reacts to what you eat.
Check out the slideshow by itself here.
Want an audio version? Subscribe to our Podcast on iTunes!
Want to join us for the live discussion? Check out our Social Media in the noon hour every Monday as we sit down on Google Hangout OnAir! Follow us on Twitter, Facebook, or Google+ to get updated with the link when we start!
A review report on detailed study of research endeavours, undertaken on Human Microbiome, its composition, its implications, applications, disease and other role.
The diversity of microbial species in a metagenomic study is commonly assessed using 16S rRNA gene sequencing. With the rapid developments in genome sequencing technologies, the focus has shifted towards the sequencing of hypervariable regions of 16S rRNA gene instead of full length gene sequencing. Therefore, 16S Classifier is developed using a machine learning method, Random Forest, for faster and accurate taxonomic classification of short hypervariable regions of 16S rRNA sequence. It displayed precision values of up to 0.91 on training datasets and the precision values of up to 0.98 on the test dataset. On real metagenomic datasets, it showed up to 99.7% accuracy at the phylum level and up to 99.0% accuracy at the genus level. 16S Classifier is available freely at http://metagenomics.iiserb.ac.in/16Sclassifier and http://metabiosys.iiserb.ac.in/16Sclassifier.
International conference «Actual approaches to the extremely preterm babies: International experience and Ukrainian realities» (Kyiv, Ukraine, March 5-6, 2013)
Human Microbiome is the current project in Research field. The importance of Microorganisms in the human body, the importance and novel roe of the microorganisms on a human body is very effective and helpful. Fecal Transplantation is a unique and helpful technique to cure a dreadful disease naturally by means of microorganisms or introducing the normal flora in to the body again.
Microbiota, leaky gut syndrome and gut-related diseasesMaurizio Salamone
Lecture on "Microbiota, Leaky gut Syndrome and gut-related disease" at the 7° International workshop on Immunonutrition "Eating for preventing" Carovigno (BA) May 1st-3th 2014
the paper is a review paper for the MSc courses in animal science biotechnology course. Basically it shows the genetic based disease resistance of indigenous livestock breeds.
The ultimate goal of endodontic treatment is to remove as many micro-organisms and their byproducts from the root canal space by using various antimicrobial agents to provide a environment free of micro-organisms . Antibiotics have revolutionized the entire health care system including both medicine and dentistry.
3rd GRF One Health Summit 2015
Keynote V: AMR – There is a lot going on, but not enough One Health
Peter BORRIELLO, Professor, Chief Executive Officer, Veterinary Medicines Directorate VMD, Surrey, United Kingdom
Antibiotic selection /certified fixed orthodontic courses by Indian dental ...Indian dental academy
Welcome to Indian Dental Academy
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.
Indian dental academy has a unique training program & curriculum that provides students with exceptional clinical skills and enabling them to return to their office with high level confidence and start treating patients
State of the art comprehensive training-Faculty of world wide repute &Very affordable.
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.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
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.
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.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
For more information, visit-www.vavaclasses.com
Embracing GenAI - A Strategic ImperativePeter 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. Humans have co-evolved with microbial partners
• We are a composite of species: bacteria,
fungi, viruses, bacteriophages
• Microorganisms inhabit all barrier surfaces of
the organism and outnumber the human
cells by about 10 fold
• The total microbial DNA in our body (the
microbiome) contains 100 times more genes
than our ‘own’ human genome
• The microbiome is an integral part of our
genetic landscape and plays a central role in
the maintenance and control of host
homeostasis
• The development of the immune system is
dependent on interactions with the
commensal microbiota
OOeessoopphhaagguuss
SSttoommaacchh
VVaaggiinn
aa
MMoouutthh
SSkkiinn
CCoolloonn
Firmicutes
Bacteroidetes
Actinobacteria
Proteobacteria
Other phyla
3. Microorganisms inhabit all barrier surfaces of the organism
Nat Immunol. 2013 Jul;14(7
Compartmentalized and systemic control of tissue immunity by commensals.
Belkaid Y, Naik S.
5. Development of the microbiota from the first inoculum as an infant
through continuous change, modified by diet, genetics and the
environment, through life
• Changes in the last
trimester of pregnancy
Dominguez-Bello MG, Blaser MJ, Ley RE, Knight R.
Development of the human gastrointestinal microbiota and insights from high-throughput sequencing.
Gastroenterology. 2011;140:1713-9.
7. Microbiota-induced maturation of the mouse gastrointestinal tract
Sommer F, Bäckhed F.
The gut microbiota--masters of host development and physiology.
Nat Rev Microbiol. 2013;11:227-38.
8. Modulation of adaptive immune responses in the gut by the
Nadine Cerf-Bensussan and Valerie Gaboriau-Routhiau
The immune system and the gut: friends or foes?
Nature Reviews Immunology 10:735 (2010)
commensal microbiota
9. The intestinal microbiota enhances colonization resistance to intestinal
pathogens by both direct and indirect (immune-mediated) mechanisms of
action.
Charlie G. Buffie & Eric G. Pamer1
Microbiota-mediated colonization resistance against intestinal pathogens
Nature Reviews Immunology 13:790 (2013)
11. IL-17A production in skin tissue is not impacted by distinct
gut commensal populations
8 Taconic
7
6
5
4
3
2
1
0 Gut Skin
Jackson
% IL-17A+ CD45+
NS
Science 337, 1115 (2012)
Taconic
Farms
SFB
Jackson Labs
8
7
CD45+
6
5
17A+ 4
3
IL-2
% 1
0 Gut
Taconic
Jackson
12. Altered T cell inflammatory and regulatory
profile in skin tissue of germ free mice.
Skin
12 **
Germ
free
SPF GF
8
4
32
24
16
8
0
25 **
SPF GF
20
15
10
5
70
60
50
40
30
20
10
0
% IL-17A+ gd T Cells
% IFNg+ ab T Cells
% IL-17A+ab T Cells
% Foxp3+ Tregs
SPF GF
0
SPF GF
0
* **
SPF- Specific Pathogen Free GF- Germ Free
4 weeks
Oral Antibiotic
(ATB)
Ampicillin
Metronidazole
Neomycin
Vancomycin
GUT ***
% IL-17A+CD45+ % IL-17A+CD45+
25
20
15
10
5
0
30
20
10
0
% IFNg+ ab T Cells % IFNg+ ab T Cells
**
8
6
4
2
0
5
4
3
2
1
0
SKI
N
Vehicle
ATB
18. MMiiccrroobbiioottaa MMiiccrroobbiioottaa
PPaatthhoobbiioonnttss
PPaatthhooggeennss
Mets
GGeennoommiicc
mmuuttaattiioonnss
TTuummoorr
pprroommoottiioonn
CChhrroonniicc
iinnffllaammmmaattiioonn
((iinnffeeccttiioonnss,,
aasseeppttiicc))
IInnttrriinnssiicc //
oonnccooggeennee
iinndduucceedd
iinnffllaammmmaattiioonn
PPrreeddiissppoossiinngg ccoonnddiittiioonnss
((oobbeessiittyy,, mmeettaabboolliicc ssyynnddrroommee))
CCaanncceerr
aassssoocciiaatteedd
iinnffllaammmmaattiioonn
TTuummoorr ggrroowwtthh
AAnnggiiooggeenneessiiss
TTiissssuuee rreemmooddeelliinngg
IInnffiillttrraattiioonn aanndd
MMeettaassttaassiiss
IImmmmuunnoo
eevvaassiioonn
CCoo--mmoorrbbiiddiittiieess
RReessppoonnssee ttoo
tthheerraappyy
AAnnttii--ccaanncceerr
iimmmmuunnee
rreessppoonnssee
PPrriimmaarryy
ttuummoorr
MMiiccrroobbiioottaa
A Dzutsev, RS Goldszmid, S Viaud, L Zitvogel, G
Trinchieri. The role of the microbiota in
inflammation, carcinogenesis and cancer
therapy. Eur J Immunol 2014 Oct 18 DOI:
10.1002/eji.201444972
19. Is the response to cancer therapy regulated by the
commensal bacteria?
SSyysstteemmiicc aannttii--IILL--1100RR ++ IInnttrraattuummoorr CCppGG--OOGGNN iimmmmuunnootthheerraappyy
PPllaattiinnuumm ccoommppoouunndd ((ooxxaalliippllaattiinn,, cciissppllaattiinn)) cchheemmootthheerraappyy
IInntteessttiinnaall mmiiccrroobbiioottaa
SStteerriillee ssuubbccuuttaanneeoouuss
ttrraannssppllaanntteedd
ttuummoorr
AANNTTIIBBIIOOTTIICCSS
NNeeoommyycciinn
VVaannccoommyycciinn
IImmiippeenneemm
oorr GGeerrmm--ffrreeee mmiiccee
Noriho Iida, Amiran Dzutsev, C. Andrew Stewart, ……… Giorgio
Trinchieri, Romina S. Goldszmid
Commensal bacteria control cancer response to therapy by
modulating the tumor microenvironment
Science, 2013; 342:967-70
21. Response to Cancer Immunotherapy and Chemotherapy
Requires the Commensal Microbiota
CpG-CyclophosphamidCpG-OGN Oxaliplatin Cisplatin Cyclophosphamidee
Days after treatment
Tx
Tx + Antibiotics
Untreated
Noriho Iida, Amiran Dzutsev, C. Andrew Stewart, ………
Giorgio Trinchieri, Romina S. Goldszmid
Commensal bacteria control cancer response to therapy by
modulating the tumor microenvironment
Science, 2013; 342:967-70
Sophie Viaud, ……….and Laurence Zitvogel
The intestinal microbiota modulates the anticancer
immune effects of cyclophosphamide
Science, 2013, 342:9671-74
Sterile subcutaneous mouse
transplantable tumors
22. Antibiotics (ABX) suppress TNF-mediated early necrosis of the tumor and
decrease inflammatory cytokine production following anti-IL-10R/CpG
WT (BL6Ncr) TNFKO
H2O
untreated
H2O
aIL-10R
CpG
ABX
aIL-10R
CpG
1 cm
1 ABX decrease TNF and IL-122 pprroodduuccttiioonn bbyy ttuummoorr--
iinnffiillttrraattiinngg mmyyeellooiidd cceellllss ffoolllloowwiinngg aaIILL--1100RR//CCppGG
H2O aIL-10R/CpG
ABX aIL-10R/CpG
ABX untreated
H2O untreated
Most inflammatory but not anti-inflammatory (e.g. IL10)
genes are lower in ABX treated mice
MC38 tumor, 72 h after CpG treatment
23. Oral LPS partially restores the TNF production impaired
by ABX and TLR4 signaling is required for the effective
Cytokine production by tumor
infiltrating myeloid cells
** P=0.05
anti-tumor response
aIL-10R/CpG
25mg/kg BW of LPS was orally administered 3 times/week,
2 weeks prior and 1week after tumor injection
Tlr4-/- mice fail to respond to aIL-10R/CpG
24. Composition of fecal microbiota can be used to segregate mice
with high and low intratumoral TNF in response to CpG
High TNF
Low TNF
Unweighted Unifrac
H2O- drinking mice
PCA1
PCA2
PCA3
PCA1
16S rDNA analysis using 454 pyrosequencing
25. Identification of bacterial genera positively correlating with intratumoral
TNF levels after CpG in microbiota perturbation experiments
AA.. sshhaahhiiii
SSiinnggllee
uunnccllaassssiiffiieedd
OOTTUU
Alistipes (Gram-)
Ruminococcus (Gram+)
26. Identification of bacterial genera negatively correlating with intratumoral
TNF levels after CpG in microbiota perturbation experiments
L. murinum
L. intestinalis
LL.. ffeerrmmeennttuumm
28. Antibiotics (ABX) impair oxaliplatin chemotherapy bbyy pprreevveennttiinngg RROOSS
pprroodduuccttiioonn ffrroomm NNOOXX22 ((CCyybbbb)) eexxpprreessssiinngg mmyyeellooiidd cceellllss
Oxaliplatin induces ROS
production in tumors of control
but not ABX-treated mice
EL4 tumors-bearing B6 mice were treated with 10mg/kg
oxaliplatin
ROS-induced bioluminescence using the L-012 probe was
analyzed 24 hours after oxaliplatin injection
MFI ROS x 10-3
80
60
40
20
0
Oxaliplatin induces NOX2 (Cybb)-
mediated ROS production in
tumor-associated myeloid cells
WT Cybb-/-
Ctrl Oxp Ctrl Oxp
H2O
ABX
Ctrl Oxp
H2O
ROS+ Gr1hi
(neutrophils)
60
40
20
0
ROS+ Ly6C+F4/80+
(monocyte-derived)
WT Cybb-/-
Ctrl Oxp Ctrl Oxp
H2O
ABX
Ctrl Oxp
ROS- production analyzed by flow cytofluorimetry in EL-4 tumor-infiltrating
H2O
myeloid cells ex-vivo 24 hours after oxaliplatin injection
29. Cyclophosphamide (CTX) induces mucosal bacterial translocation
that is required for anti-tumor Th17 response
Sophie Viaud, ……….and Laurence Zitvogel
The intestinal microbiota modulates the
anticancer immune effects of cyclophosphamide
Science, 2013, in press
30. Microbial translocation following total body irradiation augments the
function of adoptively transferred tumor-specific CD8+ T cells
Paulos CM …..Restifo NP.
Microbial translocation augments the function of adoptively
transferred self/tumor-specific CD8+ T cells via TLR4 signaling.
Adoptive transfer of pmel-1 tumor reactive CD8+ T
cells into animal bearing established B16F10
melanoma tumors
TBI leads to: Destruction of
established
tumors
Enhanced autoimmune
vitiligo
Increased pmel-1 T
cells cytokine
production 5 days after
transfer
31. Microbial translocation following total body irradiation augments the
function of adoptively transferred tumor-specific CD8+ T cells
Paulos CM …..Restifo NP.
Microbial translocation augments the function of adoptively
TBI causes mucosal barrier injury resulting in
bacteria translocation, increased serum LPS and
activation of innate immune response.
ABX leads to: Reduced systemic
LPS level
Impairedactivation of
antigen presenting cells
Reduced effectiveness
of adoptive cell
transfer therapy
32. CpG-ODN +
anti-IL-10R TNF
MyD88, Cybb
TBI and
adoptive T cell
transfer
Myeloid cell Tumor
CTL
CTX
Th17 CTL
Gut
microbiota
TBI or CTX induced transmucosal
bacterial translocation
ROS
Oxaliplatin
Iida N, Dzutsev A, Stewart CA ……, Trinchieri G,
Goldszmid RS.
Commensal bacteria control cancer response to
therapy by modulating the tumor microenvironment.
Science. 2013;342:967-70
Paulos CM …..Restifo NP.
Microbial translocation augments the function
of adoptively transferred self/tumor-specific
CD8+ T cells via TLR4 signaling.
J Clin Invest. 2007;117:2197-204
Viaud S …….. Zitvogel L.
The intestinal microbiota modulates the anticancer
immune effects of cyclophosphamide.
Science. 2013;342:971-6
Modified from:
Goldszmid R.S., Dzutsev A., Trinchieri G.
Host immune response to infection and
cancer: unexpected commonalities
Cell Host & Microbe, 15, 295-305, 2014
TLR4
TLR4
MyD88
33. IImmmmuunnootthheerraappyy
CChheemmootthheerraappyy
RReessoolluuttiioonn ooff
IInnffeeccttiioonn,,
IInnffllaammmmaattiioonn
aanndd IImmmmuunniittyy
IInnffeeccttiioonn
((aaccuuttee
iinnffllaammmmaattiioonn))
TTuummoorr
((cchhrroonniicc
iinnffllaammmmaattiioonn))
Modified from:
Goldszmid R.S., Dzutsev A., Trinchieri G.
Host immune response to infection and cancer:
unexpected commonalities
Cell Host & Microbe, 15, 295-305, 2014
34. Commensal bacteria calibrate the activation threshold of innate antiviral immunity.
Abt MC, Osborne LC, Monticelli LA, Doering TA, Alenghat T, Sonnenberg GF, Paley MA,
Antenus M, Williams KL, Erikson J, Wherry EJ, Artis D.
Priming of natural killer cells by nonmucosal mononuclear
phagocytes requires instructive signals from commensal microbiota.
Ganal SC, Sanos SL, Kallfass C, Oberle K, Johner C, Kirschning C,
Lienenklaus S, Weiss S, Staeheli P, Aichele P, Diefenbach A.
IImmmmuunniittyy
JJuullyy 22001122
Resistance to
respiratory viral
infection
Gut microbiota
35. Intestinal microbiota regulates granulocytosis, neutrophil
homeostasis and resistance to sepsis in neonates
Ajitha Thanabalasuriar & Paul Kubes
Neonates, antibiotics and the microbiome
Nature Medicine 20, 469–470 (2014)
Hitesh S Deshmukh, Yuhong Liu, Ogechukwu R Menkiti,
Junjie Mei, Ning Dai, Claire E O'Leary,Paula M Oliver, Jay K
Kolls, Jeffrey N Weiser & G Scott Worthen
The microbiota regulates neutrophil homeostasis and host
resistance to Escherichia coli K1 sepsis in neonatal mice
36. Gut microbes impact myelopoiesis and promote host resistance to
systemic bacterial infection
Gut Microbiota Promote Hematopoiesis to Control Bacterial Infection.
Arya Khosravi , Alberto Yáñez , Jeremy G. Price , Andrew Chow , Miriam Merad ,
Helen S. Goodridge , Sarkis K. Mazmanian.
Cell Host & Microbe, Volume 15, Issue 3, 2014, 374 - 381
37. Role of the microbiome in GVHD
The primary target organs of acute GVHD (i.e. G.I. tract, skin, lung and
liver) are in constant interaction with commensal and pathogenic bacteria
TBI and/or chemotherapy
38.
39. The effects of intestinal tract bacterial diversity on mortality following
allogeneic hematopoietic stem cell transplantation
Taur Y, Jenq RR, Perales MA, Littmann ER, Morjaria S, Ling L, No D, Gobourne A,
Viale A, Dahi PB, Ponce DM, Barker JN, Giralt S, van den Brink M, Pamer EG.Ying
Blood, 2014.
Key Points
Intestinal diversity is predictive of mortality in allo-HSCT.
Abstract
Highly diverse bacterial populations inhabit the gastrointestinal tract and modulate host inflammation and
promote immune tolerance. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the
gastrointestinal mucosa is damaged, and colonizing bacteria are impacted, leading to an impaired intestinal
microbiota with reduced diversity. We examined the impact of intestinal diversity on subsequent mortality
outcomes following transplantation. Fecal specimens were collected from 80 recipients of allo-HSCT at the
time of stem cell engraftment. Bacterial 16S rRNA gene sequences were characterized, and microbial diversity
was estimated using the inverse Simpson index. Subjects were classified into high, intermediate, and low
diversity groups and assessed for differences in outcomes. Mortality outcomes were significantly worse in
patients with lower intestinal diversity; overall survival at 3 years was 36%, 60%, and 67% for low,
intermediate, and high diversity groups, respectively (P = .019, log-rank test). Low diversity showed a strong
effect on mortality after multivariate adjustment for other clinical predictors (transplant related mortality:
adjusted hazard ratio, 5.25; P = .014). In conclusion, the diversity of the intestinal microbiota at engraftment is
an independent predictor of mortality in allo-HSCT recipients. These results indicate that the intestinal
microbiota may be an important factor in the success or failure in allo-HSCT.
The area of the chart for each site represents the average number of distinct phylotypes (approximate species-level taxa, based on 16S rRNA gene-sequence analysis) per individual. (The mean number of phylotypes per individual is shown in parentheses; 3–11 individuals were studied per habitat.) The coloured wedges represent the proportion of phylotypes belonging to different phyla. More than 50 bacteria phyla exist, but human microbial communities are overwhelmingly dominated by the 4 that are shown. The relative abundance of these phyla at most sites tends to be consistent across individuals: for example, in almost all humans studied so far, Bacteroidetes and Firmicutes predominate in the colon. By contrast, the composition of the vaginal microbiota is more variable; most women have a preponderance of Firmicutes with few other representatives, whereas a minority of women have a preponderance of Actinobacteria with few other representatives. An estimated 20–80% of human-associated phylotypes (depending on habitat) are thought to have eluded cultivation so far. Data taken from refs 1, 2, 3, 4, 5, 6, 7.
Figure 1 Tissue-specific modes of host-commensal interactions at distinct barrier sites. The gastrointestinal tract has the most abundant commensal niches in the body. A thick mucus layer separates the intestinal epithelium from resident microbes. Certain commensal species such as segmented filamentous bacteria (SFB) can penetrate the intestinal mucosal layer and reside in intimate contact with epithelial cells and in Peyer’s patches. By virtue of their localization, these species are uniquely poised to influence immune functions. Commensal microorganisms reside on the surface of the skin and appendages, such as hair follicles, sebaceous glands and sweat glands. These appendages may be critical sites of interactions between immune cells and commensals in the skin. The oral cavity contains several microenvironments that house commensal microbes including buccal mucosa, saliva, teeth and gingiva. Individual teeth house bacteria, both above and below the gumline, that have been shown to modulate immunity in the surrounding gingiva; additionally, commensal bacteria constitutively form biofilm at this tissue site. In the respiratory tract, the composition of commensals is conserved across different geographical locations but the density of commensals is greatest in the upper airways and is less in the lower airways. The vaginal mucosa is dominantly colonized by Lactobacillus spp., but little is known about the precise localization of commensals in this niche and how fluctuations associated with sexual activity, menstrual cycle and pregnancy impact the microbiota in this site.
We speculated that some bacteria would be more important in regulating the response to therapy than other, due to close proximity to the surface of the gut or some other factors. Therefore we performed sequencing of the gut microbiota of fecal sample collected prior to the immunotherapy treatment. Interestingly, in several independent experiment we kept observing that composition of high and low producers of TNF is different.
16S rDNA data obtained from sequencing fecal samples from H2O-drinking mice collected prior to anti-IL-10R/CpG-ODN therapy was analyzed using unweighted Unifrac analysis and visualized using Principal Component Analysis (PCA). A gradient from blue to red represents relative mRNA Tnf levels from low to high respectively, Tnf levels were estimated using RT-PCR. Left panel shows PCA axis 1 vs axis 2 and right panel axis 1 vs axis 3. One representative of 3 experiments is shown.
Family level- p <0.05
Bacteria count normalized # bacteria (16S) per gram of feces
Correlation is Genus
We identified some species of Lacto (Lactobacillus plantarum, Lactobacillus johnsonii, Lactobacillus fermentum, Weissella confuse, Lactococcus raffinolactis, Lactococcus lactis) and first relative to Ruminococcaceae (same genus). It is unclassified Rumino. Lachnospiracae
Phylum
Class
Order
Family
Genus
Species
Strain
Family level- p <0.05
Bacteria count normalized # bacteria (16S) per gram of feces
Correlation is Genus
We identified some species of Lacto (Lactobacillus plantarum, Lactobacillus johnsonii, Lactobacillus fermentum, Weissella confuse, Lactococcus raffinolactis, Lactococcus lactis) and first relative to Ruminococcaceae (same genus). It is unclassified Rumino. Lachnospiracae
Phylum
Class
Order
Family
Genus
Species
Strain