GUT MICROFLORA HAVE TO BE MODERNLY CONSIDERED A

1

• GUT MICROFLORA HAVE TO BE MODERNLY CONSIDERED A
  MICROMIAL ORGAN PLACED WITHIN A HOST ORGAN.

2

• 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 concentrations
  of up to 1012or 1013 cells/g of luminal contents.
  Simon GL. Gastroenterology 1984

3
Czarniecki M. J Med Chem 2008
4
(No Transcript)
5

• 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.

6

• 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. Ohara AM. Sci World J 2007

7

• 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

8

• 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

9

• 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.

10

• 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.

11

• 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
82(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 Jul38 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 ii1984-85
12

• IN THE ERA OF METAGENOMICS FECAL TRANSPLANT AND
  SYNTHETIC MICROBIOME TRANSPLANT MIGHT BE VERY
  PROMISING THERAPIES FOR DYSBIOSIS-ASSOCIATED
  DISEASES.

13

• FUTURE OF MICROBIOME STUDIES
• NEED FOR STANDARDIZATION
• NEED FOR LARGE PROSPECTIVE COHORTS
• NEED FOR HOLISTIC APPROACH
• NEED FOR AN ECOLOGICAL UNDERSTANDING

14

• 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.

15

• 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.

16

• WHAT IS MORE IMPORTANT IN INDUCING INFLAMMATORY
  AND CANCEROUS CHANGES?
• - A GENERAL DESTRUCTURATION OF THE ECOSYSTEM
• - SOME SPECIFIC BACTERIA

17

• 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

18
(No Transcript)
19
(No Transcript)
20

• 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