Microbial Systems: The human microbiome and Probiotics

1. Microbial Systems: The human microbiome and Probiotics

2. 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

3. 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…

4. 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 microbiomeweighs 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

5. 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

6. 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 Bifodobacteriuminfantis 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

7. Hologenome theory of evolution • All animals and plants establish symbiotic relationships with microorganisms • Different host species contain different symbiontpopulations; individuals of the same species may contain different symbiontpopulations • Host organism +microbial community relationships affect both the host and its microbiota • Genetic info encoded by microorganisms can change under environmental demands more rapidlyand 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 holobiontwith 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

8. 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 a Technological “solutions”

9. “…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

10. Coevolution of the Holobiont • Holobiont = host + symbiotic microbiota • Coral reefs are examples of holobionts – Oculinapatagonia – Mediterranean coral infected by Vibrio bacteria – coral developed resistanceby 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

11. 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

12. 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

13. 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-positivefacultative anaerobic or microaerophilic rod-shaped bacteria • Streptococcus • Saccharomyces

14. 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

16. 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

17. 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

18. Treatment of Acute Diarrhea 5 Day Therapy in Danish Children (9 to 44 months) in Day Care with Acute Diarrhea Whole Study Group V Rosenfeldt, et al. Pediatr Infect Dis J 21:417-9, 2002

19. 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. thermophilusor 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

20. 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

21. 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

22. Top 10 Foods containing Prebiotics

23. 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

24. 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