MICB 211 Chapter 11 Notes

Human Microbiome

Microbiota

-ski, mucous membranes constantly in contact with microorganisms present in environment

ex: digestive tube from mouth through intestines and out the other end is constantly exposed to environmental microbes

-non-sterile areas of body are microenvironments colonized by certain microbial species

-in general, same bacterial species colonize the same anatomical sites in all people

• microbiota

-some organisms establish permanent residence within host while some are more transient and present for limited periods time

-microbiota of human body is very complex and consists of more than several hundred species of microorganisms

-bacteria are most numerous and obvious microbial components of microbiota

-archaea colonize the lower intestinal tract

Host and Microbiota interactions

-association between host and microbiota is dynamic

• relationship that benefits both host and bacteria

Bacteria Benefits

-bacteria in microbiome utilize host in number of ways

-host environment is a continuous source of nutrients — stable environment

-host plays a protective role against damaging conditions (desiccation, temperature extremes)

-utilize host as mode of transportation

Host Benefit

-minimizing hosts susceptibility to pathogens via microbial antagonism

-occurs when colonization of native microbiota inhibits colonization by pathogens

• occurs through occupying adherence sites, utilizing nutrients, chemical inhibition and modulating pH and oxygen availability

-nutritional synergism

• bacteria synthesize and excrete vitamins (vitamin K, B12)

  • can be absorbed as nutrients by host cells

• bacteria capable of converting bile acids to steroids

  • can be utilized by host

-microbiota stimulates immune system via induction of antibody response

• low levels of antibodies can cross react with certain related pathogens → prevent infection or invasion

Microorganisms of Microbiota are Adapted to their Host

-bacteria of microbiota have adapted to survive specifically within their host

-physical association between microbiota and host likely involves biochemical interactions between bacterial surface components (ligands/adhesins) and host cell molecular receptors

-bacteria of microbiota resist innate human defences

• don’t elicit strong adaptive immune responses that leads to their death

Harmful Aspects of Host-Microbiota Relationship

-not all host-microbiota interactions are beneficial

-translocation of bacteria from one niche to another can be harmful

ex: E.coli in GI tract is fine but can cause UTIs when in urinary tract

-certain normal residents of microenvironments in body may not be harmful when host is healthy but may become harmful or pathogenic under conditions when host is immunocompromised or suffers from external ailment

• opportunistic pathogens

• take advantage of host attenuated conditions to establish infections

Host-Microbiota Interactions that may Help or Harm Host

-intestinal microbiota can affect the brain (gut brain axis)

• bidirectional

-brain acts on GI and immune functions that help to shape gut’s microbial makeup

-gut microbes affect inflammatory responses and make neuroactive compounds

• including neurotransmitters and metabolites → both have effects on brain

-results in positive or negative effects on brain functions and disorders

• ex: prevention or development of anxiety and MS

Chronology and Source of Microbiota for Humans

-fetal environment is sterile and prior to birth → humans are free of microorganisms

-microbiota obtained from environment immediately after birth as a result of

• passage through birth canal

• exposure to other humans (and pets)

• ingestion of food and fluids

• inhalation of air-borne microorganisms

Factors that Affect Microbiota Composition

-diet is a major contributor to microbial makeup

• ex: infant’s diet of milk encourages establish of lactic acid bacteria as part of microbiota

-infection contributes to microbial diversity and composition

• infection results in temporary increase in pathogen numbers but antibiotic treatment is another major factor

-antibiotics result in decrease of microbiota

• in GI tract → leaves host susceptible to colonization by opportunistic bacteria

• microbiota eventually re-establishes itself after antibiotic therapy

Physiological Niches of Human Microbiome

Location of Microbiota

-microbiota bacteria are located at a particular anatomical site

1. certain species of bacteria are invariably in one locale and never in another

   • exhibits a tissue preference for colonization

     ex: production of stomach acids, bile salts, lysozyme, certain bacteria are unable to colonize regions of GI tract

2. at colonization sites, bacteria attaches to host receptors using specific bacterial ligands

   • these host receptors that interact with bacterial ligands are expressed only at certain locations in the host’s body

3. some members of microbiota are capable of constructing bacterial biofilms on surface of tissue

   • bacteria are also capable of growth on preexisting biofilms

   • biofilms are a mixture of microorganism

Microbiota of Gastrointestinal Tract

-majority of microbiota in human body resides in GI tract

• stomach, small intestine, large intestine

-intestinal microbiota is a complex ecosystem containing several hundred bacterial species

• majority of bacteria are anaerobes

  ex: E.coli, bacteroides, lactobacillus

-stomach is very acidic

• barrier to microbial growth

• bacterial count of stomach is very low → devoid of any significant microbiota

-only a few acid-tolerant bacteria can be cultured from stomach

ex: H.pylori is one of the few bacteria that can colonize stomach wall

• causative agent of gastric ulcers and gastric cancers

-bacteria occupy lumen, overlie the epithelial cells, adhere to mucosa of intestines

-in normal hosts, duodenal microbiota is sparse

• most organisms are derived from oral cavity and pass through gut with each meal

-last part of small intestine (ileum) contains a moderately mixed microbiota

-microbiota of large intestine is dense and contains a diverse population of bacteria

• viewed as anaerobic bacterial fermentation chamber

• any oxygen that may be present is quickly consumed by facultative anaerobes

-at birth, entire intestinal tract is sterile but bacteria enters with first feeding on infant

• initial colonizing bacteria varies with food source of infants

Essentiality of Microbiota

Gnotobiotic Organisms

-germ-free animals and birds

-colonies of gnotobiotic animals and birds established by isolating first-generation offspring using sterile techniques

-offspring raised in germ-free environments

-mammals

• delivering offspring via c-section

-birds

• exterior surface of egg is sterilized

-characteristics of gnotobiotic animals

• abnormal anatomical and physiological features

• underdeveloped lymphatic tissue and poorly developed immune systems

• thin intestinal walls

• low antibody titer

• higher susceptibility to pathogens

• reduced susceptibility to certain disease processes which are dependent on activity of microbes

Studying Microbiota

-measuring microbial diversity

Darwinian Tree of Life (TOL)

-displays evolutionary relationships between all forms of cellular life

-history of life is like a tree with multiple branches arising from a common trunk all the way to the tips of the youngest twigs, symbolic of present diversity of living organisms

-branch points present points of divergence or points at which diversity is generated from a common ancestor

-each fork of an evolutionary/phylogenetic tree is an ancestor common to all lines of decent branching from that fork

-2 organisms closely-related to each other share a common ancestor that represents a relatively recent branch point on the tree of life

-last common ancestor shared by all current life referred to as LUCA

Building a Tree of Life

-two closely-related organisms have to be similar with respect to structural characteristic while two distantly-related organisms have to be very different with respect to the same characteristic

-some essential attributes of an evolutionary indicator/chronometer:

1. structure should be found in all forms of life

   • so all organisms can be compared to each other using the same structure

2. structure should be able to accommodate variation over time without loss or change in function

   • variations should accumulate slowly so structure retains traces of ancestral patterns over billions of years of evolution

3. changes in structural feature should be measurable

-a good characteristic for tracing vertical evolutionary relationships might be sequence of nucleotides in RNA component of small ribosomal subunit (SSU rRNA)

1. all organisms must synthesize proteins, ribosomes are found in all forms of cellular life

2. structure of SSU rRNA already known to exhibit differences/variations between organisms without loss of ribosomal function

   • SSU rRNA only on component of complex translational machinery of a cell → has to interact with many other molecules involved in protein synthesis

   • SSU rRNA nucleotide sequences expected to vary slowly over evolutionary time

3. differences between nucleotide sequences of different SSU rRNA molecules could be measured in order to construct a phylogenetic tree

Woese Tree of Life

-using SSU rRNA as an evolutionary indicator/chronometer → data best represented as a TOL not with two major branches but with 3 branches

• prokaryotes → domains, bacteria, archaea

Determining Composition of Microbiota

-researchers use 16S rRNA gene sequence to measure microbial diversity

-different ways to define microbial diversity and dependent on parameters measured

-diversity can be a measure of

• richness

  • absolute number of different species in community

• abundance and evenness

  • relative prevalence of that species in community compared to other species

  • more proportional the distribution, the more more even the community is as well

• phylogenetic distance

  • how closely related the species are to each other on a phylogenetic tree

-higher the richness, evenness, phylogenetic distance → more diverse the community