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