Transcript Gut Microbiota

The Microbiome and Probiotics:
Fact and Fiction
Ameet Parikh, MD
Microbiome
Human Gut microbiome
- What is it
- What role does it play in health and in disease
- Modification of the microbiome to maintain
health or treat disease
Microbiome
Microbiota
• The microorganisms that live in an established
environment
Microbiome
• The full complement of microbes, their genes, and
genomes in a particular environment
The Gut Microbiota
- Complex community of microbes – estimated
to contain 200 trillion cells
- > 1000 diverse microbial species
- 10 x the number of human cells in our body
- Gut microbiome is 150 x larger than the human
genome
Gut Microbiota
Gut Microbiota
Bacteroidetes and Firmicutes make up around 90% of
the gut microbiota
Each individual harbors his/her own distinctive
pattern of gut microbial communities
For a given individual, the fecal microbiota remains
remarkably stable over a person’s lifetime
Gut Microbiota - Functions
Prevents colonization by pathogens
“Educates the immune system”
Metabolic role
- Caloric salvage
- Produces
• SCFA
• Vit K and folate
Participates in drug metabolism
• Activates 5-ASA
Deconjugates bile acids
Gut Microbiota
Colonization of the gastrointestinal tract begins
immediately after birth
Initial bacterial colonization (normal) starts from a “Germ
free” intrauterine environment and is populated through
maternal vaginal/fecal flora and oral feeding (breast milk
vs formula)
Complete adult colonization : by 3 yrs of life
Factors affecting Gut Microbiome
Microbiome
Alterations in gut microbiota have been
linked with
FBD
IBD
CDI
Celiac disease
Allergies
Autism
Metabolic diseases
Obesity
Malignancy
Type I DM
NASH
Depression
Gut Microbiota
Does the intestinal microbiota differ in patients
with specific disorders (IBS/IBD) from healthy
subjects?
If the microbiota does differ, is it an important
factor in the pathogenesis of the disorder?
Gut Microbiota - IBD
Pathogenesis – linked to inappropriate activation of GI
immune system toward the gut microbiota in genetically
susceptible hosts &under the influence of environmental
factors
Gut Microbiota - IBD
Gut Microbiota - FBD
IBS, functional bloating/constipation/diarrhea
Change in gut microbiota – cause abn fermentation of
dietary substrates
elicit excess stimulation of the mucosal immune system
through a ‘leaky gut’ – leads to low grade inflammation,
affects gut motor responses & elicits visceral
hypersensitivity
Decreased Bifidobacterium and Lactobacillus in IBS
Gut Microbiota - CDI
Gut Microbiota
- Diet
- Antibiotics
- Prebiotics
- Probiotics
- Symbiotics
- FMT
Probiotics
Global sales of Probiotics – 21.6 billion dollars
in 2010, expected to reach 31.1 billion in 2015
Fastest growing segment of the global dietary
supplement & functional food industries
People are looking for ‘natural’ or non-drug
ways to maintain health or treat disease
Probiotics
First described by
Metchnikoff in 1907
Probiotics
Probiotics
Live microorganisms which, when administered
in adequate amounts, confer a health benefit on
the host
Prebiotics
Nondigestible substances that provide a
beneficial physiological effect for the host by
selectively stimulating the favorable growth or
activity of a limited number of indigenous
bacteria
Probiotics
Synbiotics
Products that contain both probiotics and
prebiotics
Probiotics in the Treatment of Gastrointestinal
Disorders
Diarrhea
Acute infectious
Antibiotic-associated
C. difficile
H. pylori
Eradication
IBD
Ulcerative
colitis
Crohn’s
disease
Pouchitis
Lactose
Intolerance
FBD
Probiotics
Characteristics of Effective Probiotics
• Able to survive the passage through the digestive
system.
• Able to attach to the intestinal epithelia and colonize.
• Able to maintain good viability.
• Able to utilize the nutrients and substrates in a
normal diet.
• Non pathogenic and non toxic.
• Capable of exerting a beneficial effect on the host.
• Stability of desired characteristics during processing,
storage and transportation.
Probiotics – Diarrheal Diseases
Probiotics - AAD
Antibiotic Associated Diarrhea
Antibiotic Associated Diarrhea
Antibiotic Associated Diarrhea
Probiotics - FBD
10 – 15% of population has IBS
pathogenesis – dysmotility, visc hypersensitivity,
disturbances in GI flora, and chronic immune activation
leading to low grade mucosal inflammation have all
been implicated
Probiotics - CDAD
FMT – LGI experience
• First Transplant was in November 2013
• Performed 62 transplants to date for recurrent CDI
• Of the elective cases we have had sustained cures in
57/62 first time FMT- 5 relapses occurred
• 3/5 relapses needed antibiotics after FMT
• 3 competed 2nd FMT, no continued issues to date
• 2 treated with Vanco or Dificid and did not require 2nd
FMT
Probiotics - IBD
FMT - IBD
FMT - IBD
FMT - IBD
Much work remains:
•
Is FMT effective and safe in IBD?
- Adequately powered trials
•
Ideal recipient?
- Genotype
- Phenotype: Pouchitis, Proctitis, Post-op prophylaxis,
ileal Crohn’s, maintenance of remission, Microbiome
- Concomitant meds
- Can FMT make some patients worse?
FMT
Great success story for recurrent CDI
Being studied for multiple other conditions – IBD, IBS, Obesity
Autism, NASH/Met synd, reversal of multidrug resistance to abx
IBD is associated with dysbiosis
–More complicated than C. difficile
Patients are eager for alternative therapies
FMT appears generally “pretty safe”
– Infections and disease flares have been reported
Therapeutic Manipulation of gut microbiota holds promise & may
eventually prove beneficial for other conditions
– We must not be overly enthusiastic and remember that this is
experimental and unproven therapy.
Microbiome - Future
Lachnospiraceae family
Faecalibacterium prausnitzii
Akkermansia muciniphila
Probiotic ecosystems
Gut Microbiome
“All disease begins in the gut”
Hippocrates 460 BC – 370BC
“Health is determined by the microbiota in our
gut”
Hippocrates
Gut Microbiome
Thank You