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PROBIOTICI E PREBIOTICI PER IL MICROBIOTA UMANO
Patrizia BrigidiDept. Pharmacy and Biotechnology
University of [email protected]
THE HUMAN INTESTINAL MICROBIOTA
the 1014 bacterial mutualists (10 x our total cell number) which inhabit our GIT constitute the human intestinal microbiota
• 1012 CFU/g• up to 1.5 kg
the most dense bacterial ecosystem on our planet
> 1000 species
5 (out of 100) bacterial phyla•Firmicutes (65%), Bacteroidetes (25%)•Actinobacteria (5%), Proteobacteria (<8%), Fusobacteria (1%) and Verrucomicrobia (1%)
PHYLOGENETIC STRUCTURE
FUNCTIONAL DIVERSITY
MICROBIOME 106 GENES
58% KNOWN 42% UNKNOWN • carbohydrate metabolism (CAZymes)• energy metabolism• amino acid metabolism• biosynthesis of secondary metabolites• metabolism of cofactors and vitamins
MICROBIOTA-HOST MUTUALISM, ECOLOGICAL SERVICES
our bacterial counterpart provides essential features we have not evolved
IMPACT ON HOST NUTRITION
indigestible plant polysaccharides (xylan, pectin, arabinose containing-dietary carbohydrates as plant-derived pectin, cellulose, hemicellulose, resistant starches)
reach unchanged the colon where they are metabolized by the intestinal microorganisms
equipped with a real arsenal of CAZymes – absent in human genome –intestinal microorganisms degrade plant polysacchar ides to SCFA
SCFAkey microbiota metabolites
regulating the host nutritional status
indigestible plant polysaccharides
SCFA, MICROBIAL METABOLITES WITH A KEY MULTIFACTORIAL ROLE IN HOST NUTRITION
energy source for the colonic epithelium
leptin productionpyy expression
SCFA: butyrate - acetate - propionate
lipid synthesis in the liver gluconeogenesis
energy extraction
energy storageAppetite control
insulin secretion
SCFA also possess immunomodulating and antimicrobial properties and regulate host epigenome
123
5-15% of the total energy required
EPIGENOME REGULATION
INHIBITING HISTONE DEACETYLASE, SCFA CAN MODULATE HOST EPIGENOME
MODULATION OF GENE EXPRESSION IN COLONIC EPITHELIAL CELLS
INTER-INDIVIDUAL PHYLOGENETIC VARIABILITY
THE INDIVIDUAL MICROBIOTA SHOWS AN ASTONISHING LEVEL OF
INTER-INDIVIDUAL VARIABILITY
MICROBIAL FINGERPRINT
• 70% of species phylotypes are subject specific
• no phylotype is present at more than 0.5% of abundance in all subjects
EACH HEALTHY SUBJECT POSSESSES A SPECIFIC AND DYNAMIC SUBSET OF HUNDREDS OF SPECIES
MICROBIOTA PLASTICITY
THE INDIVIDUAL MICROBIOTA COMPOSITION CONTINUOUSLY CHANGES IN RESPONSE TO EXTRINSIC AND
INTRINSIC VARIABLES
DIET
HOST GENETICS
MICROBIOTA MAKE-UP
GIT ENVIRONMENT
(inflammation-disease)
ENV. FACTORS
(env. microbes-geography-climatesanitization-medication)
AGE
DIET SHAPES THE MICROBIOTA AND ITS VAST COLLECTION OF GENES IN A DRAMATIC AND REPRODUCIBLE WAY
•FAST: dietary changes occur and reverse in 1-3 days
•INDIVIDUAL MICROBIOTA SPECIFIC: response to dietary changes is influenced by the initial species composition of the individual microbiota
•SHORT-TERM AND LONG-TERM RESPONDERS: while some bacterial groups respond rapidly to diet, others are modulated exclusively by long-term dietary changes (enterotypes)
HOW MICROBIOTA RESPONDS TO DIET
THE INTESTINAL MICROBIOTA CONFIGURES ITS PHYLOGENET IC PROFILE TO OPTIMIZE ITS CAPACITY TO METABOLIZE DIET ARY
COMPONENTS
MUTUALISM BREAKDOWN
INFLAMMATION AND MICROBIOTAA NON-CONTROLLED PRO-INFLAMMATORY PATHWAY CAN
DRAMATICALLY IMPACT ON THE COMPOSITION OF THE INTESTINAL MICROBIOTA
SUSCEPTIBLE HOST- GENETICS- ENV. FACTORS
CHRONIC GIT INFLAMMATION
MICROBIOTA DYSBIOSIS
RAISE IN PATHOBIONTS
PRO-INFLAMMATORY LOOP
PRO-INFLAMMATORY INTESTINAL MICROBIAL COMMUNITY
DECREASE OF IMMUNO
MODULATORY GROUPS
MANIPULATION OF THE HUMAN INTESTINAL MICROBIOTA
A LIVE MICROBIAL FEED SUPPLEMENT
WHICH BENEFICIALLY AFFECTS THE HOST
PROBIOTICS SHOULD BE ABLE TO SURVIVE AND MULTIPLY IN THE HOST GI TRACT BUT RAPIDLY DISAPPEAR WHEN ORAL ADMINISTRATION IS STOPPED
USE: FUNCTIONAL FOODS (FERMENTED MILKS, INFANT FORMULA, FRUIT DRINKS)
PHARMACEUTICAL PREPARATION (DRIED SUPPLEMENTS)
PROBIOTICS
MOST COMMONLY USED PROBIOTICS
LACTIC ACID BACTERIA
LACTOBACILLUS (L. acidophilus, L. casei,L. delbrueckii,L. gasseri, L. rhamnonsus, L. cellobiosus, L. curvatus, L. fermentum, L. lactis, L. plantarum, L.
reuteri, L. salivarius, L. brevis)
BIFIDOBACTERIUM (B. longum, B. bifidum, B. adolescentis, B. infantis, B. breve, B. animalis, B. lactis )
ENTEROCOCCUS (E. faecalis, E. faecium)
PROBIOTICS OTHER THAN LAB
BACILLUS SPORES (B. cereus, B. clausii, B. subtilis)
SACCHAROMYCES (S. boulardii, S. cerevisiae)
HEALTH PROMOTING EFFECTS OF PROBIOTICS
PROBIOTICS: FROM RESEARCH TO APPLICATION
� Isolation (strain origin)
� Identification/characterization (physiological and genotypic characteriziation)
� Strain screening- Safety: AB-resistance profile
undesidered properties (hemolysis, mucus degradation, production of biogenic amines, etc)
- Efficacy (in vivo functionality, mechanism of action)
- Documentation (safety and efficacy)
� Growth medium
� Fermentation
� Filtration
� Encapsulation (delivery system)
� Drying
� Product formulation
� Packaging functionality
� Supply chain distribution
� Consumer benefit communication
IMPIEGO DEI PROBIOTICIMalattie infiammatorie croniche intestinali
Diarrea da antibiotici
Diarrea del viaggiatore
Colite da C. difficile
Infezione da H. pylori
Disordini funzionali gastrointestinali
Allergie alimentari
Intolleranza al lattosio
Patologie epatiche croniche (steatosi, cirrosi)
Gastroenterite acuta infettiva (Rotavirus)
Coliche gassose
Enterocolite necrotizzante
Faecalibacterium prausnitzii
Roseburia
Bacteroides
NEXT GENERATION PROBIOTICS
‘Non digestible food ingredients that selectively stimulate a limited number of bacteria in the colon, to improve host
health’
PREBIOTICS
• Fructooligosaccharides (tested in humans)• Lactulose (tested in humans) • Trans-galactooligosaccharides
Present in: bananas, artichoke, leeks, onions, garl ic, asparagus, chicory
Application of prebiotics : Beverages and fermented milks, Health drinks, Infant formulae and weaning foods, Cereals, Biscuits, Confectionery, Cakes, Food supplements,
Pet food, Farm animals
PREBIOTICS FERMENTATION IN HUMAN GUT
THANK YOU FOR YOUR ATTENTION
WESTERN DIET
• HIGH FAT• HIGH PROTEIN• HIGH SUGAR• FOOD PROCESSING• FOOD STORING
• LOW FAT• STARCH AND PLANT
POLYSACCHARIDE-RICH• CONTAMINATED• HOMEMADE• PROMPTLY CONSUMED• LOCALLY PRODUCED
MICROBIOTA MAKE-UP
+ Firmicutes+ Proteobacteria
LOW FUNCTIONAL AND PHYLOGENETIC
DIVERSITY
+ Bacteroidetes+ Actinobacteria
HIGH FUNCTIONAL AND PHYLOGENETIC
DIVERSITY
WESTERN DIET RURAL AFRICAN DIET
The continuous immunological cross-talk between the intestinal microbiota and the gut immune system is a vital factor for its
• DEVELOPMENT
• EDUCATION TO TOLERANCE AND RESPONSIVENESS
• FUNCTION/REGULATION
GALT EDUCATION
HUMAN GENOME DOES NOT ENCODE FOR ALL FUNCTIONS REQUIRED FOR IMMUNOLOGICAL DEVELOPMENT BUT
DEPENDS ON THE CRITICAL INTERACTION WITH MICROBIOME
• BIOSYNTHESIS OF NEURO-ACTIVE METABOLITES (lactic acid, propionic acid, 5-hydroxytryptamine)
• REGULATION OF NEUROTRANSMITTER PRODUCTION (GABA, noradrenaline, dopamine, acetylcholine)
• DIRECT NEURONAL ACTIVATION OF STRESS CIRCUITS (modulation of the host inflammatory response)
SYNAPTOGENESIS; PITUITARY-ADRENAL AXIS PROGRAMMING; STRESS REACTIVITY; ANXIETY-
LIKE BEHAVIOR
CENTRAL NERVOUS SYSTEM FUNCTION AND BEHAVIOR