Microbiota: Its Evolution and Essence. Hsin-Jung Joyce Wu "Microbiota and man: the story about us

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1 Microbiota: Its Evolution and Essence

2 Overview q Define microbiota q Learn the tool q Ecological and evolutionary forces in shaping gut microbiota q Gut microbiota versus free-living microbe communities

3 Why study normal microbiota? 1. The Human/Microbiota Superorganism Learning all about us 2. Normal Microbiota: Control health and disease Dysbiosis (imbalance of gut microbiota)-related disease

4 Examples of associations of human diseases with particular microbiota dysbiosis

5 lactobacilli on honeybee crop

6 Gut microbiota regulate intestinal fatty acid absorption in zebrafish

7 Normal Microbiota: Who are they? q Also termed normal flora and indigenous microbiota q Refers Hsin-Jung to the Joyce organisms Wu "Microbiota and man: the that story about colonize us the hosts without normally causing disease

q In parasitism, one organism benefits at the expense of

8 Symbiosis q In commensalism, one organism benefits, and the other is unaffected q In mutualism, both organisms benefit q In parasitism, one organism benefits at the expense of the other q Some normal microbiota are opportunistic pathogens

9 Opportunistic pathogens q Normal microbiota can cause infection under certain circumstances q Conditions that provide opportunities for pathogen-like behavior Immune suppression Changes in the normal microbiota changes in relative abundance of normal microbiota may allow opportunity for a member to thrive and cause disease Introduction of normal microbiota into unusual site in the body It goes beyond infection!!!

10 Normal Microbiota: Where are they from? q Microbiota begins to develop during the birthing process q Much of ones resident microbiota established during the first 3 year of life

11 Acquisition of the microbiome in early life by vertical transmission and factors modifying mother-to-child microbial transmission

12 Normal Microbiota: Where are they?

13 Spatial aspects of the gut microbiota

14 Demilitarized zone lumen

15 Gut Microbiota: What do they do? " Gut microbiota help the host by " Occupying niches that pathogens might occupy " Aid in digestion " Supply essential nutrients " Promote angiogenesis and enteric nerve function " Facilitate the development of immune system both inside and outside the gut

16 The ERA of gut microbiota: Dark Ages q Gut Microbiota: Health and Disease Important but. Ø Complexity of gut microbial communities Ø Culturable gut bacteria: <10-20% of the total gut bacterial population

17 16S ribosomal RNA analysis, old dog with new tricks q Culture independent, thorough analysis Ø Phylochips (microarray for bacteria, up to 8700 phylotypes per chip) Ø 454 next generation sequencing 13 years for Human genomic project vs. 2 month to sequence James Watson s DNA

19 Method of analysis I Operational taxonomic unit (OTU) A group of organisms that is defined by its sequence similarity (for Bacteria and Archaea, typically using their 16S ribosomal RNA (rrna) genes). OTUs at the 97% level (all 16S rrna gene sequences are at least 97% identical) are often considered to define a species.

20 Method of analysis II UniFrac analysis A phylogenetic analysis technique that measures the distance between two community samples in terms of the amount of sequence divergence on a phylogenetic tree that is unique to each of the samples. UniFrac distance: In practice, a master phylogenetic tree is constructed from all biological samples. Pairwise comparisons of samples (communities) are then performed by dividing the non-shared to the total branches on the tree.

21 UniFrac

22 Method of analysis III Principal coordinate analysis (PCA) An analysis that is based on distances between samples, and detects a few dimensions to explain as much of the variation (usually up to 3) in the samples as possible.

23 Evolution of mutualism q q In ~1960, evolutionary biologists rejected the idea that natural selection would generally favor the good of the species (mutualism). No-cost mutualism Organisms can have traits that contribute directly to their own fitness and also incidentally benefit members of another species. Plant polysaccharides that are not digestible by humans are the main substrates for microbial growth in the colon, whereas butyrate and other products of microbial fermentation are important energy sources for the host.

24 Selection Pressures in the Human-Microbial Hierarchy q Host-driven ( top-down ) selection for functional redundancy would result in a community composed of widely divergent microbial lineages whose genomes contain functionally similar suites of genes. q Competition between members of the microbiota would exert bottom-up selection pressure that results in specialized genomes with functionally distinct suites of genes.

25 Low levels of deep diversity

26 q The Firmicutes and the Bacteroidetes dominated, together accounting for >98% of all bacteria in all mammalian host. q A marked excess of phylotype diversity at the species and strain level

27 Site-specific distributions of bacterial phyla in healthy humans

28 Factors that shape the mammalian gut microbiota 1. Diet 4. immune selection 2. Gut morphology 3. Outliers

29 Microbe communities: Vertebrate gut-associated vs. Free-living Microbes of herbivore or omnivore not only differs greatly from freeliving microbes but also differ from carnivore-gut microbes Invertebrate gut-communities clustered with free-living microbes with the exception of termite and beetle gut Gut-associated microbes was more than twice as much as the separation of saline and fresh water communities

30 Relative abundance of phyla in various samples

31 Microbe communities: Vertebrate gut-associated vs. Free-living *Clustering patterns are replicated in each bacteria phylum

32 Network analysis of bacterial communities from animal-associated and free-living communities

Conclusions q Normal microbiota are essential for the host s health q The power of next generation sequencing provides cultureindependent, thorough and systemic analysis of microbes q Low levels of

33 Conclusions q Normal microbiota are essential for the host s health q The power of next generation sequencing provides cultureindependent, thorough and systemic analysis of microbes q Low levels of deep diversity in gut microbiota with the Firmicutes and the Bacteroidetes dominated in all mammalian host q Lessons from Panda and Columbine monkey: gut morphology seems to be more important than host phylogeny and diet in determining fecal microbial community composition.

34 Daunting tasks lie ahead q Describe the composition of microbial communities in each habitat of the human body and how this varies over time, with respect to variables such as diet, host genotype and health status. Human Microbiome Project q Develop experimental models: They can highlight evolutionarily conserved features that are likely to be crucial for function. q Re-examination of immunology: intestinal microbiota shaping the local and systemic immune responses. q Think from microbial perspective.

35 Thank You and More Questions?

Outline Classes of diversity measures. Species Divergence and the Measurement of Microbial Diversity. How do we describe and compare diversity?

Species Divergence and the Measurement of Microbial Diversity Cathy Lozupone University of Colorado, Boulder. Washington University, St Louis. Outline Classes of diversity measures α vs β diversity Quantitative