MICROBIOMA: basi e applicazionicnbbsv.palazzochigi.it/media/1868/brigidi.pdf · phylogenetic...
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MICROBIOMA: basi e applicazioni
Patrizia Brigidi
Dipartimento di Farmacia e Biotecnologia
Università di Bologna
ALL MACRO-ORGANISMS POPULATING OUR PLANET EXIST AS HOLOBIONTS
Holobionts are defined as animal,
plants or insect together with
associated microorganisms living on
it (including bacteria, fungi, and
viruses, known as microbiomes)
•1012 CFU/g• up to 1.5 kg
the most dense bacterial ecosystem on our planet
organized in a ecosystem of highly
interconnected microbes
we are 90% bacteria, 1013–1014 habits our body and the great majority of these microorganisms is hidden in the gastrointestinal tract
THE HOLOBIONTS MICROBIOME AS A KEY PROVIDER OF ESSENTIAL METABOLIC ACTIVITIES NOT EVOLVED BY THE HOST
Host-microbiome: a mutualistic agreement
Microorg-microorginteractions: syntrophic microbial networks
not accessible to the
human glycobiome !
HOST
POLYSACCHARIDES
STARCH PLANT CELL
WALL
celluloseSOLUBLE CELL WALL
POLYSACCHARIDES
Bacteroidetes
Ruminococci
Clostridium clusters
IV and XIVa
acetogensmethanogens
sulfate-reducing
bacteria
ACETATE
PROPIONATE BUTYRATE
SUCCINATE
H2
H2S
CH
4
ACETATE
ACETATE
Increase of energy harvest from diet; favor energy storage
processes; induction of post prandial satiety
GM IMPRINT ON HUMAN PHYSIOLOGY
reduction of anxiety and depression
Boost innate immune functions; favor of a tollerogenic layout of the
adaptive immune system
Turroni et al., JMC 2018
MICROBIOTA-HOST TRANSGENOMIC METABOLISM, BIOACTIVE MOLECULES FROM
THE INSIDE
Bioactive molecules from the inside:10% of the blood metabolites are derived from GM
HOW DO WE KNOW THIS?
Culture-based methods allow to recover
20-40% of total microscopic counts
MOSTLY UNCULTURED!
Culture-independent molecular survey:NGS
MICROBIOTA MOLECULAR ASSESSMENT: NEXT GENERATION SEQUENCING
whole genome
OTU compositionmetagenome
sequence
16S rDNAITS2 28S rDNA
next generation sequencing
phylogeneticstructure
rel. ab. of community members
rel. ab. of community
gene pathways
OMICS TECHNOLOGIES
MODULAR AND INTEGRATIVE BIOINFORMATICS ANALYSIS
Microbial community
characterization
Bacterial characterization
Functional characterization
Fungalcharacterization
Viral characterization
16S rRNA characterization
…other tools/softwaresMETADATA
andother OMICSIntegration of
the results
and deep
knowledge
of the
microbial
community
Network analysis
Machine learning
Deep learning
AI
central nervous system modulation
enhancement of the digestive efficiency and modulation of energetic homeostasis
competitive barrier against colonization/invasion
development, education and function of the immune system
vitamin synthesis
strengthening of the GIT epithelium impermeability
detoxification of xenobiotics
endocrine system modulation
Microbiome roles in humans
Microbiome roles in animals
Metabolism• Facilitate energy harvest
from the diet• Promote host adiposity
Behavior• Decreasing synaptic connectivity • Promoting anxiety-like behavior
and pain perception
Intestinal function- Gut-associated lymphoid
tissue (GALT) maturation,- Tissue regeneration- Motility - Barrier integrity
Intestinal vessels formationActivation of tissue factor pathways that influence vascular remodelling in the small intestine
Bone homeostasis - Decreasing bone mass by promoting the function of osteoclasts and increasing the numbers of pro-inflammatory Th17 cells.
Microbiome roles in plants
Climate change mitigation:• Reduced reliance on fossil fuel inputs in agriculture• Decreased N2O flux• Increased soil carbon storage
Increased agricultural sustainability and productivity:• Enhance plant nutrient uptake and
use efficiency• Enhance plant defense against
pathogens and pests• Increase plant water-use efficiency• Improve plant capacities to grow in
degraded habitats• Produce climate ready crops
Increases food quality• Produce higher nutritional quality
food• Reduce microbial contaminants • Suppress storage pathogens and
enhance food products’ shelf-life • Minimize allergens and toxins
Sustainable intensification of agriculture:• Maximize value of lands for food
production• Reduce reliance on external
nutrient and agrichemical inputs• Environmental sustainability• Food security• Poverty alleviation
Soil health and restoration:• Bioremediation of degraded or
contaminated habitats• Reduce soil desertification• Enhanced efficiency of water use in
agricultural systems• Enhanced soil carbon sequestration• Reduce loss of erosion of top soils
THE HOLOBIONTS MICROBIOME AS A KEY PROVIDER OF PHENOTYPIC PLASTICITY
HOLOBIONTS MICROBIOMES RESPOND RAPIDLY TO ENVIRONMENTAL
CHANGES, SUPPORTING AN HOST FAST ADAPTIVE RESPONSE
CHANGINGENVIRONMENT
ADAPTIVE MICROBIOME
VARIATION
ADAPTIVE HOST RESPONSE
IN A MUTUALISTIC CONTEXT, THE PLASTICITY OF THE HUMAN MICROBIOTA
GUARANTEES A RAPID ADAPTATION OF THE HOST IN RESPONSE TO DIET CHANGES,
AGE, ETC
MICROBIOTA PLASTICITY
THE MICROBIOTA COMPOSITION CONTINUOUSLY CHANGES IN RESPONSE
TO EXTRINSIC AND INTRINSIC VARIABLES (EXPOSOME)
MICROBIOME MODULATION
Therapeutic and preventive opportunities
DIETARY INTERVENTION NEXT GENERATION PROBIOTICS PREBIOTICS FECAL TRANSPLANTATION
THE ONE-HEALTH ECO-HEALTH PERSPECTIVE OF HUMAN GM VARIATION
Human microbiome variation needs to be viewed in the frame of the One Health Theory, determinants of variation need to be searched in
the total environment
Human microbiome reviewed at the connection between animals, plants, soil and oceans microbiomes, which are all challenged by
anthropic factors MICROBIOMES
PLANTSANIMALS
HUMANS ENVIRONMENT
ONE HEALTH