HUMAN MICROBIOME
IN HEALTH & DISEASE
Dr/ Eman Ahmed Abd-Alrahman
Lecturer of Medical Microbiology and Immunology
Outcomes
Defining the term “microbiome” (and other related
terminology)
Current hypothesis around the ways we may be
acquiring our microbes; how it may be changed
due to lifetime exposures and how these
microbial profiles may be similar or vary between
individuals
Know that different body sites have unique
microbiomes
Appreciate the importance of studying the
microbiome (what are the clinical impacts).
• The human microbiome can be defined as the
“ecological community of commensal, symbiotic,
and pathogenic microorganisms that share our
body space.
• The microbiota includes helminths, fungi,
protozoa, viruses, bacteria, and archaea.
HUMAN MICROBIOME
HUMAN MICROBIOME
• The quantity of microbes in our
bodies number approximately 100
trillion cells, ten times more than
the number of human cells.
• Gut contains 70% of total
microbiota
We are more microbes than human.
Gastrointestinal Microbiota
> 1000 bacterial species
 each Individuals have > 160 species
– Firmicutes >250 genera
Lactobacillus, mycoplasma, bacillus, clostridium …
– Bacteroidetes ~ 20 genera
– Actinobacteria
Core Microbiome (18 species shared individuals)
Qin et al Nature 2010, 464:59-65 MetaHIT Consortium
90%
THE HUMAN MICROBIOME: MORE THAN
JUST THE GIT
Compositional differences in the microbiome by anatomic site Cho I. and Blaser M. Nat Rev Genet 2012 13(4): 260–270
A. González,1 Y. Vázquez-Baeza, R. Knight Cell 158 July 31 2014
MMHP: Million Microbiomes from Humans
Project
The Million Microbiomes from Humans Project
(MMHP) was officially launched at the 14th
International Conference on Genomics (ICG-14).
Scientists from China, Sweden, Denmark, France,
and Latvia agreed to collaborate on a large-scale
microbial metagenomic project, aiming to
sequence and analyze one million samples
from the intestine, mouth, skin, reproductive
tract, and other organs in the next three to five
years to construct a microbiome map of the
human body and build the world's largest
database of the human microbiome.
https://db.cngb.org/mmhp/
• Human microbiota
begins to be
established even
before birth.
1) Gestation
FACTORS AFFECTING THE ESTABLISHMENT
AND ALTERATION OF HUMAN MICROBIOME
Jiménez et al. (2008) Res Microbiol. 159(3):187-93; Jiménez E
et al. (2005). Curr Microbiol. 51(4):270-4
HOW THE HUMAN MICROBIOTA IS
STABLISHED AND ALTERED
 Prenatal antibiotic
treatment
 Maternal prenatal
stress
 Gestational duration
 Maternal diabetes
status
FACTORS AFFECTING THE ESTABLISHMENT
AND ALTERATION OF HUMAN MICROBIOME
• One of the largest influences on the establishment of the
infant’s microbiota is the mode of delivery ,whether the
baby is delivered vaginally or not .
2) Mode of delivery
FACTORS AFFECTING THE ESTABLISHMENT
AND ALTERATION OF HUMAN MICROBIOME
FACTORS AFFECTING THE ESTABLISHMENT
AND ALTERATION OF HUMAN MICROBIOME
Lactobacillus
& Prevotella Corynebacte
rium,
& Propioniba
cterium
FACTORS AFFECTING THE ESTABLISHMENT
AND ALTERATION OF HUMAN MICROBIOME
3) Breast feeding
• Lactobacillus and Bifidobacterium
species are more dominant in
breast feeding infants that
essential for the breakdown of
maternal milk oligosaccharides into
short-chain fatty acids.
• short-chain fatty acids is essential
for the immune system maturation
and integrity of gut
Low
er fecal
diversity
in
breast-fed
infants
Bifidobacterim
Ma, J., Li, Z., Zhang, W. et al. Comparison of gut microbiota in exclusively breast-fed and
formula-fed babies: a study of 91 term infants. Sci Rep 10, 15792 (2020).
• The gut microbiota has essential roles in degradation of
dietary components, producing compounds that support
host nutrition, the maturation of the immune system, and
the prevention of colonization of invading pathogens.
FACTORS AFFECTING THE ESTABLISHMENT
AND ALTERATION OF HUMAN MICROBIOME
4) Dietary content
Dietary shifts, including the
introduction of high-fat, low-fibre
diets, have a significant impact
on microbiota composition,
metabolome and diversity.
Low-fibre diets lacking complex
polysaccharides impair the
protective barrier functions
conferred by the microbiota
against pathogens. .
FACTORS AFFECTING THE ESTABLISHMENT
AND ALTERATION OF HUMAN MICROBIOME
FACTORS AFFECTING THE ESTABLISHMENT
AND ALTERATION OF HUMAN MICROBIOME
5) Antibiotic intake
The antibiotics has a
compromising effect on microbial
community and leading to changes
in host health.
These impacts can be transient or
permanent, causing irreversible
damage to gut microbiota.
These changes in the gut microbial
are various between individuals
depending on its duration, the
number of doses, antibiotic class,
host age, genetic susceptibility, and
lifestyle.
CONSEQUENCES OF ANTIBIOTIC-INDUCED
MICROBIOTA CHANGES FOR HEALTH AND DISEASE
Surrounding environment (e.g., sanitation, urban vs.
rural, geographic factors)
Caregiving structure (e.g., extended family
involvement).
 Ethnicity and cultural practices.
FACTORS AFFECTING THE ESTABLISHMENT
AND ALTERATION OF HUMAN MICROBIOME
5) Others
Relationship between Host and Microbes
(beneficial to both)
Germ free mouse models( complete absence bacteria in the
gut )
Defective gut associated/mesenteric lymphoid tissue, low
levels IgA.
• Immune response devolopment
• Cover body spaces.
• Mitigate intestinal pathogens
• Maintain tissue homeostasis
• Facilitate fermentation of dietary fiber (inulin, pectin…)
• Metabolic end products and therapeutic drug processing
• Signaling among cells and organ systems
• Butyrate: Energy for gut epithelial cells
• Acetate and Propionate: Lipogenesis and Gluconeogenesis
Does a compromised Microbiome lead to
Disease?
Koch’s Postulates
Be present in all cases of
the disease.
Be isolated from diseased
patients .
Cause disease when
reintroduced to a healthy
susceptible animal model.
Be isolated again from the new
host.
V.P. Singh et al. / Clinical Microbiology and Infection
(2016)
Microbiome and disease
Modification of gut microbiota
• Prebiotic: Chemical that induces the growth or activity of
microorganisms that potentially contribute to well-being of
the host (HMOs in infants) – Increase number or activity
of bifidobacteria.
– Bran sources
– Raw foods:raw garlic, leek, onion, chicory root and
banana
• Probiotic: Ingested microorganism(s) associated with
beneficial effects to humans and animals
– Lacctobacillus (50 species), Bifidobacteria (30 species),
Sacchoaroyces boulardii, Streptococcus thermophilus&
Enterococcus faecium
Fecal Microbial Transplantation
Fecal Microbial Transplantation durably alters gut
microbiota
Goal: Restore phylogenetic diversity
C. difficile infection
– Severe or recurrent infection
– Mean cure rate 80-90% (>500 cases)
119 FMT clinical trials (mostly C. diff) have been submitted
to FDA Kelly et al Gastroenterology 2015;149:223 –237
November 30, 2022
Assessment of microbial community profiling
using 16S rRNA gene sequencing
Gut microbiome.pptx for medical students

Gut microbiome.pptx for medical students

  • 1.
    HUMAN MICROBIOME IN HEALTH& DISEASE Dr/ Eman Ahmed Abd-Alrahman Lecturer of Medical Microbiology and Immunology
  • 3.
    Outcomes Defining the term“microbiome” (and other related terminology) Current hypothesis around the ways we may be acquiring our microbes; how it may be changed due to lifetime exposures and how these microbial profiles may be similar or vary between individuals Know that different body sites have unique microbiomes Appreciate the importance of studying the microbiome (what are the clinical impacts).
  • 4.
    • The humanmicrobiome can be defined as the “ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body space. • The microbiota includes helminths, fungi, protozoa, viruses, bacteria, and archaea. HUMAN MICROBIOME
  • 5.
    HUMAN MICROBIOME • Thequantity of microbes in our bodies number approximately 100 trillion cells, ten times more than the number of human cells. • Gut contains 70% of total microbiota We are more microbes than human.
  • 6.
    Gastrointestinal Microbiota > 1000bacterial species  each Individuals have > 160 species – Firmicutes >250 genera Lactobacillus, mycoplasma, bacillus, clostridium … – Bacteroidetes ~ 20 genera – Actinobacteria Core Microbiome (18 species shared individuals) Qin et al Nature 2010, 464:59-65 MetaHIT Consortium 90%
  • 7.
    THE HUMAN MICROBIOME:MORE THAN JUST THE GIT Compositional differences in the microbiome by anatomic site Cho I. and Blaser M. Nat Rev Genet 2012 13(4): 260–270
  • 8.
    A. González,1 Y.Vázquez-Baeza, R. Knight Cell 158 July 31 2014
  • 9.
    MMHP: Million Microbiomesfrom Humans Project The Million Microbiomes from Humans Project (MMHP) was officially launched at the 14th International Conference on Genomics (ICG-14). Scientists from China, Sweden, Denmark, France, and Latvia agreed to collaborate on a large-scale microbial metagenomic project, aiming to sequence and analyze one million samples from the intestine, mouth, skin, reproductive tract, and other organs in the next three to five years to construct a microbiome map of the human body and build the world's largest database of the human microbiome. https://db.cngb.org/mmhp/
  • 10.
    • Human microbiota beginsto be established even before birth. 1) Gestation FACTORS AFFECTING THE ESTABLISHMENT AND ALTERATION OF HUMAN MICROBIOME
  • 11.
    Jiménez et al.(2008) Res Microbiol. 159(3):187-93; Jiménez E et al. (2005). Curr Microbiol. 51(4):270-4 HOW THE HUMAN MICROBIOTA IS STABLISHED AND ALTERED
  • 12.
     Prenatal antibiotic treatment Maternal prenatal stress  Gestational duration  Maternal diabetes status FACTORS AFFECTING THE ESTABLISHMENT AND ALTERATION OF HUMAN MICROBIOME
  • 13.
    • One ofthe largest influences on the establishment of the infant’s microbiota is the mode of delivery ,whether the baby is delivered vaginally or not . 2) Mode of delivery FACTORS AFFECTING THE ESTABLISHMENT AND ALTERATION OF HUMAN MICROBIOME
  • 14.
    FACTORS AFFECTING THEESTABLISHMENT AND ALTERATION OF HUMAN MICROBIOME Lactobacillus & Prevotella Corynebacte rium, & Propioniba cterium
  • 15.
    FACTORS AFFECTING THEESTABLISHMENT AND ALTERATION OF HUMAN MICROBIOME 3) Breast feeding • Lactobacillus and Bifidobacterium species are more dominant in breast feeding infants that essential for the breakdown of maternal milk oligosaccharides into short-chain fatty acids. • short-chain fatty acids is essential for the immune system maturation and integrity of gut
  • 17.
    Low er fecal diversity in breast-fed infants Bifidobacterim Ma, J.,Li, Z., Zhang, W. et al. Comparison of gut microbiota in exclusively breast-fed and formula-fed babies: a study of 91 term infants. Sci Rep 10, 15792 (2020).
  • 19.
    • The gutmicrobiota has essential roles in degradation of dietary components, producing compounds that support host nutrition, the maturation of the immune system, and the prevention of colonization of invading pathogens. FACTORS AFFECTING THE ESTABLISHMENT AND ALTERATION OF HUMAN MICROBIOME 4) Dietary content
  • 20.
    Dietary shifts, includingthe introduction of high-fat, low-fibre diets, have a significant impact on microbiota composition, metabolome and diversity. Low-fibre diets lacking complex polysaccharides impair the protective barrier functions conferred by the microbiota against pathogens. . FACTORS AFFECTING THE ESTABLISHMENT AND ALTERATION OF HUMAN MICROBIOME
  • 22.
    FACTORS AFFECTING THEESTABLISHMENT AND ALTERATION OF HUMAN MICROBIOME 5) Antibiotic intake The antibiotics has a compromising effect on microbial community and leading to changes in host health. These impacts can be transient or permanent, causing irreversible damage to gut microbiota. These changes in the gut microbial are various between individuals depending on its duration, the number of doses, antibiotic class, host age, genetic susceptibility, and lifestyle.
  • 23.
    CONSEQUENCES OF ANTIBIOTIC-INDUCED MICROBIOTACHANGES FOR HEALTH AND DISEASE
  • 26.
    Surrounding environment (e.g.,sanitation, urban vs. rural, geographic factors) Caregiving structure (e.g., extended family involvement).  Ethnicity and cultural practices. FACTORS AFFECTING THE ESTABLISHMENT AND ALTERATION OF HUMAN MICROBIOME 5) Others
  • 27.
    Relationship between Hostand Microbes (beneficial to both) Germ free mouse models( complete absence bacteria in the gut ) Defective gut associated/mesenteric lymphoid tissue, low levels IgA. • Immune response devolopment • Cover body spaces. • Mitigate intestinal pathogens • Maintain tissue homeostasis • Facilitate fermentation of dietary fiber (inulin, pectin…) • Metabolic end products and therapeutic drug processing • Signaling among cells and organ systems • Butyrate: Energy for gut epithelial cells • Acetate and Propionate: Lipogenesis and Gluconeogenesis
  • 28.
    Does a compromisedMicrobiome lead to Disease? Koch’s Postulates Be present in all cases of the disease. Be isolated from diseased patients . Cause disease when reintroduced to a healthy susceptible animal model. Be isolated again from the new host. V.P. Singh et al. / Clinical Microbiology and Infection (2016)
  • 29.
  • 34.
    Modification of gutmicrobiota • Prebiotic: Chemical that induces the growth or activity of microorganisms that potentially contribute to well-being of the host (HMOs in infants) – Increase number or activity of bifidobacteria. – Bran sources – Raw foods:raw garlic, leek, onion, chicory root and banana • Probiotic: Ingested microorganism(s) associated with beneficial effects to humans and animals – Lacctobacillus (50 species), Bifidobacteria (30 species), Sacchoaroyces boulardii, Streptococcus thermophilus& Enterococcus faecium
  • 35.
    Fecal Microbial Transplantation FecalMicrobial Transplantation durably alters gut microbiota Goal: Restore phylogenetic diversity C. difficile infection – Severe or recurrent infection – Mean cure rate 80-90% (>500 cases) 119 FMT clinical trials (mostly C. diff) have been submitted to FDA Kelly et al Gastroenterology 2015;149:223 –237
  • 36.
  • 37.
    Assessment of microbialcommunity profiling using 16S rRNA gene sequencing