Transcript THE HUMAN MICROBIOME AND PROBIOTICS THE HUMAN MICROBIOME • The ecological community of commensal, symbiotic, and pathogenic microorganisms that share our body • Remember… You.

THE HUMAN MICROBIOME
AND PROBIOTICS
THE HUMAN MICROBIOME
• The ecological community of
commensal, symbiotic, and pathogenic
microorganisms that share our body
• Remember… You are made of 10x more
microbial cells than human cells
• Typical adult microbiome weighs
between 200 and 1,400 grams, with 400500 species of intestinal microflora
• Modern genetic analysis in the 1990’s led
to the discovery of microbiome; its
impact on human health is only
beginning to be understood
POSSIBLE EFFECTS OF THE
MICROBIOME
• Roles in auto-immune diseases like diabetes, rheumatoid arthritis, muscular
dystrophy, multiple sclerosis, fibromyalgia, some cancers and obesity
• Regulation of mood through the production of neurotransmitters involved in
schizophrenia, depression, bipolar disorder and other neuro-chemical
imbalances
• The microbes being discussed are generally non-pathogenic (do not cause
disease unless they grow abnormally); they exist in harmony and
symbiotically with their hosts
• Much of the human microbiome is composed of archaea
MICROBIOME EXPERIMENTAL
EVIDENCE
• Germ free mice have an exaggerated stress response and reduced
expression of brain-derived neurotrophic factor in the cortex and
hippocampus
• Treating maternally separated mice with a probiotic culture of
Bifodobacterium infantis minimizes weight loss, causes mice to swim longer
and increases the serotonin precursor tryptophan
• Human patients with depression are less able to properly digest fructose,
which is also associated with a reduction in tryptophan production
• Eliminating fructose from their diet improved depression in human test
subjects
HOLOGENOME THEORY OF
EVOLUTION
• All animals and plants establish symbiotic relationships with microorganisms
• Different host species contain different symbiont populations; individuals of the same
species may contain different symbiont populations
• Host organism + microbial community relationships affect both the host and its
microbiota
• Genetic info encoded by microorganisms can change under environmental
demands more rapidly and diversely than the genes encoded by the host organism
• The host genome can act in harmony with the genomes of the associated symbiotic
microorganisms to create a hologenome
• The holobiont with its hologenome should be considered as the unit of natural
selection in evolution
• If a given holobiont is to be considered a unit of natural selection the hologenome
must be heritable from generation to generation
COEVOLUTION OF THE
HOLOBIONT
• Holobiont = host + symbiotic
microbiota
• Coral reefs are examples of
holobionts – Oculina patagonia
– Mediterranean coral infected
by Vibrio bacteria – coral
developed resistance by
adaptive changes in
microbiota, not immune
response by O. patagonia
• The microbiome coevolves with
the immune system and controls
it – “germ free animals” possess
severely underdeveloped
immune systems
WHAT ARE PROBIOTICS?
• Dietary supplements or food products with viable microbe populations to alter the
microflora of the host with potential beneficial health effects
• 1877 – Pasteur – antagonistic relationships between bacteria suggested nonpathogenic microbes could be used to control pathogens
• 1907 - Elie Metchnikoff noticed lactic acid fermentation of milk stopped spoilage;
introduced the idea of eating lactic acid bacteria (LAB) to promote health;
attributed the longevity/health of populations in the Balkans to bacteria in their
traditional yogurt
• 1950’s researchers confirm the effects of antibiotics on beneficial intestinal microbes
• Fermentation effects are known to: improve digestion, produce amino acids and
vitamins, but the actual health benefits of probiotics are somewhat uncertain
THE MICROBIAL ECOSYSTEM OF
THE HUMAN GI TRACT
• Complexity and access of GI tract makes
research on probiotics difficult
• Human GI tract – 400 + species of bacteria
• Acidity of stomach destroys many potential
probiotics; acid/bile resistant strains of
Lactobacillus acidophilus and
Bifidobacterium have been isolated from
humans and used in yogurt cultures
COMMON PROBIOTIC GENERA
• Bifidobacterium – genus of non-motile, gram-positive anaerobes found in
human mouth, colon, and GI tract; common and ubiquitous human
endosymbiotic bacteria
• Some introduced through breastfeeding; babies with Bifidobacterium as
intestinal microflora were observed to suffer less from GI disorders
• Lactobacillus – Gram-positive facultative anaerobic or microaerophilic rodshaped bacteria
• Streptococcus
• Saccharomyces
PROBIOTICS
MANY POTENTIAL USES
• Infectious diarrhea and day care related illness
• Antibiotic Associated Diarrhea
• Clostridium difficile
• Inflammatory bowel disease
• Traveler’s diarrhea
• Prevention of NEC (necrotizing enterocolitus)
• Allergy
• Irritable Bowel Syndrome
Prevention of Diarrheal Illness
18 Week Therapy in French Children (6-24 months) in Day Care
Yogurt
(364)
Yogurt+
P-value
L. casei
(360)
Children with
diarrhea
Duration of
diarrhea (days)
Rotavirus
positive stool
87 (22%) 61 (16%)
3.95
3.53
2.2%
0.3%
0.029
0.24
CA Pedone, et al. Int J Clin Pract 54(9):568-71, 2000
Prevention of Diarrheal Illness
12 Week Therapy in Israeli Infants (4-10 months) in Day Care
Controls
(60)
B. lactis
L. reuteri
(73)
(68)
Days with
diarrhea
0.59
0.37
0.15
<0.001
Episodes of
diarrhea
0.31
0.13
0.02
<0.001
Clinic visits
0.55
0.51
0.23
0.002
Absences
0.43
0.41
0.14
0.015
P-value
Z Weizman, et al. Pediatrics 115:5-9, 2005
Treatment of Acute Diarrhea
5 Day Therapy in Danish Children (9 to 44 months) in Day Care with Acute Diarrhea
Whole Study Group
Control
(19)
L. reuteri/
L. rhamnosus
P-value
(24)
Duration of diarrhea
(hours)
115.7
75.9
0.05
Duration of watery
diarrhea
37
38.1
0.94
Duration of fever
(days)
1.1
1.4
0.59
7
2
0.03
Diarrhea after 120
hours
V Rosenfeldt, et al. Pediatr Infect Dis J 21:417-9, 2002
PROBIOTIC TREATMENT IN CASES OF
INFECTIOUS DIARRHEA
• Experiment conducted with children up to 2 years of age in chronic care
facility
• Subjects were randomized to receive B. bifidum and S. thermophilus or
placebo
• Probiotic supplement resulted in statistically less diarrhea (7% vs 31%)
• Statistically less rotavirus shedding (10% vs 39%) with probiotics
Saavedra et al, Lancet 1994
PROBIOTICS IN
ANTIBIOTIC ASSOCIATED DIARRHEA
• Diarrhea is a common side effect of antibiotic therapy
• Up to 40% of children receiving broad spectrum
antibiotic therapy
• Likely due to altered microbial flora
• Leads to altered metabolism of osmotically active
substances
PREBIOTICS AND SYNBIOTICS
• Prebiotics: Non-digestable food ingredients with positive effects on endogenous
microbiota
• Stimulate the growth and activity of one or more species of beneficial microbiota;
usually confer benefits to a range of beneficial microblora, especially
Bifidobacterium and LAB
• Prebiotic examples: Inulin (a dietary fiber found in some plants/roots),
oligosaccharides (polymers of simple sugars found in cell membranes)
• Synbiotics – a probiotic combined with its own, specific prebiotic food – improves
survival rate of probiotics through the GI tract
TOP 10 FOODS CONTAINING
PREBIOTICS
Food
Prebiotic Fiber Content by Weight
Raw Chicory Root
64.6%
Raw Jerusalem Artichoke
31.5%
Raw Dandelion Greens
24.3%
Raw Garlic
17.5%
Raw Leek
11.7%
Raw Onion
8.6%
Cooked Onion
5%
Raw Asparagus
5%
Raw Wheat bran
5%
Whole Wheat flour, Cooked
4.8%
Raw Banana
1%
PROBIOTICS
PRACTICAL ISSUES
• Correctly purified strains of bacteria?
• Must be selected for ability to:
• Survive acid/bile in upper GI tract
• Colonize
• Adhere
• Must have shelf viability
• Should have quality control
• Not FDA regulated
PROBIOTICS
PRACTICAL ISSUES
• Typically $1 to $3 per day
• VSL3: $56 for 20 day supply
• Culturelle (LGG): $55 for 30 day supply
• Custom Probiotics CP-1: $40 for 30 day supply
• May need several months of therapy to see an effect
• Likely stop working after discontinued
• Concentration (dose) highly variable
MICROBIOME AND PROBIOTICS
TAKE HOME MESSAGE
• All organisms form symbiotic relationships with microbial communities
• These “microbiomes” are more important to health/survival/behavior of
organisms than previously understood
• The adaptive traits conferred by the microbiome are coded as part of the
hologenome – the sum of organismal and microbial genes that are
transferred down through generations
EMERGING MICROBIAL DISEASES
• Hanta Virus - single-stranded, enveloped, RNA viruses. Passed to humans
through contact with rodent urine, saliva, or feces. Some strains may be
fatal, others are benign in humans.
• Discovered in the 1950’s; symptoms include renal failure, generalized
hemorrhage, fever, and shock.
• More than eight states had reported 30 + cases of Hantavirus since 1993[ –
New Mexico (84), Colorado (70), Arizona (62), California (42), Washington
(41), Texas (37), Utah (31) and Montana (30). Other states reporting a
significant number of cases include Idaho (16), Kansas (15), South Dakota
(15), North Dakota (12) and Oregon (11).
• In late August and early September of 2012, eight new cases of Hantavirus
were confirmed, including three deaths, in Yosemite National Park.[19]
HANTA VIRUS CONTINUED
• No known antiviral treatment; natural recovery is possible with supportive
treatment.
• The virus can be transmitted by rodent saliva, excretia, and bites, control of
rats and mice in areas frequented by humans is key for disease prevention.
• Cases reported worldwide – Africa, Europe, Asia, South America
• Hanta virus likely originated in South Korea
WEST NILE VIRUS
• Likely from African tropics, found in warm climates, transferred by mosquito
vector
• Only 80% of infections in humans manifest clinical symptoms; symptoms
include fever, headaches, fatigue, muscle pain or aches, malaise, nausea,
anorexia, vomiting, myalgias and rash.
• There are no medications to treat or vaccines to prevent WNV infection.
About 1 in 5 people who are infected will develop a fever with other
symptoms. Less than 1% of infected people develop a serious, sometimes
fatal, neurologic illness.
FUKUSHIMA
• On 11 March 2011 the Fukushimi Daiici nuclear reactor suffered a
catastrophic failure
• The failure occurred when the plant was hit by the tsunami. The plant began
releasing substantial amounts of radioactive materials beginning on 12
March, becoming the largest nuclear incident since the 1986 Chernobyl
disaster and the second (with Chernobyl) to measure Level 7 on the
International Nuclear Event Scale.
• At least 300,000 people evacuated the area and as of August 2013 there
have been approximately 1,600 deaths were related to the evacuation
conditions, such as living in temporary housing and hospital closures
FUKUSHIMA HAPPENS…
• A 2013 WHO report predicts that for populations living in nearby areas there
is a 70% higher risk of developing thyroid cancer for girls exposed as infants, a
7% higher risk of leukemia in males exposed as infants, a 6% higher risk of
breast cancer in females exposed as infants and a 4% higher risk, overall, of
developing solid cancers for females
• On 22 July 2013 it was revealed that the plant is leaking radioactive water
into the Pacific Ocean. This had been denied by TEPCO.
• Fukushima Daiichi was central to a falsified-records scandal that led to the
departure of senior TEPCO executives. Dale Bridenbaugh, a lead GE
designer, claimed that GE was warned of major design flaws in 1976,
resulting in the resignations of several GE designers who protested GE's
negligence
FUKED-UPDATE
• Unexplained plumes of radioactive steam have been rising from Fukushima's
Reactor Building 3. TEPCO has confirmed the reports, adding that they were
not clear on the details of the sudden change at the reactor because of
"lethal radiation levels in that building."
• Fukushima's Reactor Building 3 exploded on 13th March 2011 as a result of a
hydrogen buildup, breaching the building's containment and emitting a
huge plume of radiation. The reactor itself is in meltdown.
• And now fresh plumes of steam have been seen coming out the structure.
These have now been confirmed by TEPCO, the owner of the nuclear plant,
from 19th December 2013 onwards.
• High levels of radiation are being recorded on the West Coast and
throughout the US