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MICROBIAL SYSTEMS: THE HUMAN MICROBIOME AND PROBIOTICS
SYSTEMS THEORY• From reductionism to synthesis: leaps in modern science and theory
• Evolution – the study of inherited phenotypic change in organisms over successive generations; Darwin noted: more offspring are produced than survive, traits vary among individual offspring = different rates of survival and reproduction, traits are inherited
• Evolution is not “progress,” it is change by
adaptation; natural selection drives adaptation
• Punctuated equilibrium – Gould
• Endosymbiosis – Lynn Margulis
• Gaia – Lovelock
• In short, modern scientific investigation increasingly reveals cooperation and symbiosis as adaptive in many circumstances
EMERGING SYSTEMS SCIENCE
• Modern environmental conditions lead us to recognize the interconnected nature of human and non-human communities, of ecology and economy, and of psychology and consciousness…
• Ecological and biological sciences have increasingly exposed the importance of systems, networks, and interconnected (often cooperative) relationships
• Are you a solitary organism or a feature of a great holistic network of living things?
• …the map “is” not the terrain…
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 400-500 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
SOCIETY AND SCIENCE
• The cultural significance of evolutionary theory
- most modern cultures have abandoned creationism/religious explanations for life; scientific theory often guides society
- If life is about “survival of the fittest” in terms of competitive behavior, what behaviors will individuals adopt? What are the social and systemic results?
Beijing, China 2014: Attempting to co-opt biophila with aTechnological “solutions”
• “…the hologenome theory of evolution focuses on the holobiont as a single dynamic entity in which a vast amount of the genetic information and variability is contributed by the microorganisms. Evolution of the holobiont can occur by changes in the host genome and/or in any of the associated microbial genomes, and relies on cooperation between the genomes within the holobiont, as much as on competition with other holobionts.” – Rosenberg et al
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 non-pathogenic 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 rod-shaped bacteria
• Streptococcus
• Saccharomyces
PROBIOTICSMANY 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
Yogurt (364)
Yogurt+L. casei
(360)
P-value
Children with diarrhea
87 (22%)
61 (16%) 0.029
Duration of diarrhea (days) 3.95 3.53 0.24Rotavirus positive stool 2.2% 0.3%
Prevention of Diarrheal Illness
18 Week Therapy in French Children (6-24 months) in Day Care
CA Pedone, et al. Int J Clin Pract 54(9):568-71, 2000
Controls (60)
B. lactis (73)
L. reuteri (68)
P-value
Days with diarrhea 0.59 0.37 0.15 <0.00
1Episodes of diarrhea
0.31 0.13 0.02 <0.001
Clinic visits 0.55 0.51 0.23 0.002Absences
0.43 0.41 0.14 0.015
Prevention of Diarrheal Illness
12 Week Therapy in Israeli Infants (4-10 months) in Day Care
Z Weizman, et al. Pediatrics 115:5-9, 2005
Control (19)
L. reuteri/L.
rhamnosus (24)
P-value
Duration of diarrhea (hours) 115.7 75.9 0.05Duration of watery diarrhea 37 38.1 0.94Duration of fever (days) 1.1 1.4 0.59Diarrhea after 120 hours 7 2 0.03
Treatment of Acute Diarrhea5 Day Therapy in Danish Children (9 to 44 months) in Day Care with
Acute Diarrhea
V Rosenfeldt, et al. Pediatr Infect Dis J 21:417-9, 2002
Whole Study Group
PROBIOTIC TREATMENT IN CASES OFINFECTIOUS 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%
PROBIOTICSPRACTICAL 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
PROBIOTICSPRACTICAL 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