Transcript Flora batterica intestinale in salute e malattia

GUT MICROFLORA HAVE TO
BE MODERNLY CONSIDERED
A “MICROMIAL ORGAN”
PLACED WITHIN A HOST
ORGAN.
• The intestinal habitat of an individual
contains 300-500 different species of
bacteria, and the number of microbial cells
within the gut lumen is about 10 times
larger than the number of eukariotic cells
in the human body. Bengmark S. Gut 1998
• Gastric acid, bile and pancreatic secretion
kill most ingested microorganisms.
• The large intestine contains a complex and
dynamic microbial ecosystem with high
densities of living bacteria which achieve
12
13
concentrations of up to 10 or 10 cells/g of
luminal contents. Simon GL. Gastroenterology 1984
Czarniecki M. J Med Chem 2008
• A large proportion of the faecal mass
consists of bacteria (around 60%).
Stephen AM,
Cummings JH. J.Med.Microbiol.
• Some of these bacteria are potential
pathogens. However, the presence of
bacterial competition and the constant
interation between the host and its
microbial guests can infer important health
benefits to the human host. Salminen S et al. Br J
Nutr1998.
COMPOSITION OF THE FLORA
-Colonization of the gastrointestinal tract starts
immediately after birth, occurs within a few days,
and it is linked to the type of delivery, the type of
diet and environmental factors.
-Pioneer bacteria can modulate expression of genes
in host epithelial cells, thus creating a favourable
habitat for themselves, and can prevent growth of
other bacteria in the ecosystem. The initial
colonisation is therefore very relevant to the final
composition of the permanent flora. Hooper LV et al.
Science 2001
-Resident bacteria deliver regulatory signals to the
epithelium and instruct mucosal immune response.
O’hara AM. Sci World J 2007
• Anaerobic bacteria outnumber aerobic bacteria by a
factor of 100-1000. The genera bacterioides,
bifidobacterium, eubacterium, clostridium,
peptococcus,peptostreptococcus, and ruminococcus
are predominant in human beings, whereas
aerobes(facultative anaerobe) such as escherichia,
enterobacter, enterococcus, klebsiella, lactobacillus,
proteus, etc are among the subdominant genera.
Salminen S. Br J Nutr 1998
• Every individual presents a particular combination
•
of predominant species that is distinct from that
found in other individuals.
Although bacterial composition can fluctuate under
some circumstances (acute diarrhoeal illnesses,
antibiotic treatment, dietary interventions),
individuals’ flora composition pattern usually remain
constant. Willson kh. Appl Environ Microbiol 1996
• Several bacteria that can be seen by direct
microscopic examination of diluted faecal
specimens cannot be grown in culture
media: 40-80% of total microscopic counts
are not recoverable by culture, although
estimates vary between individuals and
between studies. Suau A et al. Appl Environ Microbiol 1999
• Molecular biological procedures can now be
used to investigate the microbial ecology in
the colon. Many DNA sequences correspond
to previously undescribed bacteria and data
suggest that every individual has unique
strains of bacteria. Tannock GW. Am J Clin Nutr 2001
• LA METAGENOMICA E' UN APPROCCIO BASATO SULL'UTILIZZO DI
TECNICHE GENOMICHE MODERNE PER LO STUDIO DI COMUNITA'
MICROBICHE DIRETTAMENTE NEL LORO AMBIENTE NATURALE,
EVITANDO IL PRELIEVO E LA COLTURA IN LABORATORIO.
SI BASA SUL SEQUENZIAMENTO DEL GENOMA DI MICROORGANISMI
LA CUI ANALISI NEL LORO HABITAT NATURALE VIENE DEFINITA
METAGENOMA.
• LA METAGENOMICA HA MESSO IN EVIDENZA UNA DIVERSITA'
SENZA PRECEDENTI NELLA COMPOSIZIONE DELLE COMUNITA'
MICROBICHE CON UNA LARGHISSIMA PROPORZIONE DI NUOVI
GENI.
• THE HUMAN GUT HOSTS MORE THAN 100 TRILLION
BACTERIA, WHICH TOGETHER MAKE UP THE GUT
MICROBIOTA. THE GUT MICROBIOTA CO-EVOLVED
WITH HUMANS TO ACHIEVE A SYMBIOTIC
RELATIONSHIP LEADING TO PHYSIOLOGICAL
HOMEOSTASIS.
• THE HUMAN MICROBIOTA REMAINS GLOBALLY STABLE
OVER TIME IN HEALTHY CONDITIONS AND ABSENCE
OF PERTURBATION.
• APPLICATION OF METAGENOMICS TO THIS THIS
ENVIRONMENT MAY HELP IN DECIPHERING KEY
FUNCTIONS AND KEY BACTERIA INVOLVED IN HEALTH
AND DISEASE.
FAECAL BACTERIOTHERAPY:
AN UNTHINKABLE APPROACH
Faecal bacteriotherapy has a longstanding history in animal health. In
human beings it has been used in selected cases, especially as a
treatment of last resort for patients with severe Clostridium difficile
pseudomembranous colitis.
Schwan A, Sjölin S, Trottestam U, Aronsson B.
Relapsing clostridium difficile enterocolitis cured by rectal infusion of homologous faeces.
Lancet. 1983 Oct 8;2(8354):845.
Borody TJ, Warren EF, Leis SM, Surace R, Ashman O, Siarakas S.
Bacteriotherapy using fecal flora: toying with human motions.
J Clin Gastroenterol. 2004 Jul;38
Although it is unthinkable that this approach will gain the favour of the people, it could
indicate that the rectal infusion represents an alternative physiological administration
way of probiotics in selected clinical conditions.
Ricci N, Caselli M. Rectal infusion of bacterial preparations for intestinal
disorders. Lancet 1983; ii:1984-85
• IN THE ERA OF METAGENOMICS FECAL
TRANSPLANT AND SYNTHETIC
MICROBIOME TRANSPLANT MIGHT BE VERY
PROMISING THERAPIES FOR DYSBIOSISASSOCIATED DISEASES.
FUTURE OF MICROBIOME STUDIES
•
•
•
•
NEED FOR STANDARDIZATION
NEED FOR LARGE PROSPECTIVE COHORTS
NEED FOR HOLISTIC APPROACH
NEED FOR AN ECOLOGICAL UNDERSTANDING
UNDERSTANDING CO-EVOLUTION OF THE
MICROBIAL GENOMES AND HOST GENOME,
FROM GEOGRAPHICALLY AND CULTURALLY
DIVERSE POPULATIONS, WILL BE KEY FOR
FUTURE STRATEGIC PREVENTIVE
MEASURES THROUGHOUT THE LIFE-SPAN.
METABOLOMIC VIEW
METABOLOMIC APPROACHES, IN WHICH A LARGE NUMBER OF
SMALL MOLECULE METABOLITES CAN BE DEFINED IN A
BIOLOGICAL SAMPLE, OFFER A VERY PROMISING AND
POWERFUL AVENUE TO “FINGERPRINT” MICROBIOTA
FUNCTIONAL STATUS, WITH FUNCTIONAL
CHARACTERIZATION OF THE INTESTINAL MICROBIOTA
AND ITS INTERACTIONS WITH THE HOST.
WHAT IS MORE IMPORTANT IN INDUCING
INFLAMMATORY AND CANCEROUS
CHANGES?
- A GENERAL DESTRUCTURATION OF THE ECOSYSTEM
- SOME SPECIFIC BACTERIA
EXAMPLES OF EMERGIG SPECIFIC
BACTERIA:
-ENTEROTOXIGENIC BACTERIOIDES FRAGILIS
INVOLVED IN IBD AND COLORECTAL CANCER
-FUSOBACTERIA (NUCLEATUM, VARIUM, etc)
INVOLVED IN IBD AND COLORECTAL CANCER
-SEGMENTED FILAMENTOUS BACTERIA (SFB)
POSSIBLY INVOLVED IN AUTOIMMUNE DISEASES
PER CONOSCERE BENE LE COSE,
BISOGNA CONOSCERNE
I PARTICOLARI; E SICCOME
QUESTI SONO INFINITI,
LE NOSTRE CONOSCENZE SONO
SEMPRE SUPERFICIALI ED
IMPERFETTE.
Francois de La Rochefoucauld, 1665