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1. Overview
2. Structural & Functional Features
3. Taxonomy
4. Communities
Bacteria Outline
PHYLUM
Bacteria - Taxonomy
CLASS
ORDER
FAMILY
GENUS
SPECIES
SUB-SPECIES & STRAINS
FirmicutesBacteroidetes
ProteobacteriaActinobacteria
TenericutesVerrucomicrobia
FusobacteriaCyanobacteria
etc.
Bacteria - Phyla
90%
Do we really need to learn taxonomy?
Yes. (if you want to interpret
functional labs and understand the microbiome
in depth)
§ Interpreting functional microbiome test results (stool tests, organic acid tests, etc.)
§ Understanding probiotics and interaction with microbiome
§ Understanding importance / relevance of scientific and clinical microbiome research
Taxonomy + FunctionImportant for …
Be patient! Mastering technical terminology takes time and familiarity.
PHYLUM
CLASS
ORDER
FAMILY
GENUS
SPECIES
STRAIN
Firmicutes
Bacilli
Lactobacillales
Lactobacillaceae
Lactobacillus
L. acidophilus
DDS-1
Actinobacteria
Actinobacteria
Bifidobacteriales
Bifidobacteriaceae
Bifidobacterium
B. bifidum
ATCC 29521
1. Lactobacillus acidophilus 2. Bifidobacterium bifidum
§ Mostly gram-positive (“strong skin”)
§ Tend to be associated closely with intestinal mucosa (vs. lumenal)
§ Mostly coccus and bacillus forms
§ Many can produce endospores
§ Common groups:• Lactobacillus (commensal and probiotic)• Bacillus (commensal and probiotic)• Clostridia (commensal)
Firmicutes
§ Gram-negative & anaerobic
§ Tend to be located lumenally (vs. mucosal)
§ Rod-shaped
§ Do not form endospores
§ Common groups:• Bacteroides• Prevotella
Bacteroidetes
§ Gram-negative
§ Facultative & obligate anaerobes
§ Very diverse forms (“protean” = capable of assuming many forms)
§ Includes a variety of well-known pathogens / pathobionts
• Escherichia coli, Salmonella, Helicobacter pylori, Yersinia pestis (plague)
Proteobacteria
§ Actinobacteria• Gram-positive
• Long rods & filaments
• Example: Bifidobacteria
§ Verrucomicrobia• Verruca = “wart”
• Anaerobic, gram-negative
• Example: Akkermansia muciniphila
Other Phyla
A few notable groups and species …
(commensals, pathobionts, and pathogens)
Clostridia§ Firmicutes > Clostridia
§ Abundant (10-40% of total gut bacteria) and complex group
§ Very important group; some perform many beneficial functions
§ Strictly anaerobic, gram-positive
§ Colonizes near the epithelial barrier in the colon
Clostridia§ Major butyrate producers (feed colon epithelial
cells)
§ Also produce secondary bile acids from primary bile acids
§ Form endospores
§ Includes some pathogens: C. difficile, C. tetani, C. botulinum, etc.
COMMENSALS
§ Faecalibacterium prausnitzii
§ Roseburia intestinalis
§ Eubacterium rectale
§ Coprococcus eutactus
§ Clostridium scindens
§ Butyrivibrio crossotus
Clostridia Examples
PATHOGENS
§ Clostridium difficile (diarrhea, severe colitis)
§ Clostridium tetani (tetanus)
§ Clostridium botulinum (botulism, botox)
§ Clostridium perfringens (food poisoning, gangrene)
§ Phylum: Verrucomicrobia
§ Relatively abundant: up to 3.0% of gut bacterial population on average
§ Strictly anaerobic, gram-negative
§ Colonizes the mucus layer; produces propionate and acetate from mucus
§ SCFAs modulate gene expression via epigenetics
§ Improves epithelial barrier function
Akkermansia Muciniphila
Pathobionts & Pathogens
Dysbiosis & Pathobionts
Commensals (Symbionts)
Pathogens & Parasites
EXTERNAL (Transient)
Beneficial Microbes
INTERNAL (Long-term)
§ Bacteroidetes• Bacteroides fragilis
§ Proteobacteria• Helicobacter pylori: Can cause ulcers and stomach cancer
but may reduce esophageal cancer risk
• Bilophila wadsworthia: normal commensal but may contribute to colitis with high-fat diet
• Klebsiella: normal commensal but can cause infections (sometimes serious)
Pathobiont Examples
§ Obligate anaerobe, gram-negative
§ Polysaccharide A: stimulates anti-inflammatory response (induces Treg cells)
§ BUT, it can be a pathobiont• Can produce a capsule (virulence factor)• Common opportunistic pathogen in internal
abdominal infections (leaky gut)• Underscores importance of barrier integrity for both
commensals and pathogens
Bacteroides fragilis
§ Proteobacteria• Salmonella enterica (typhimurium)
• Escherichia coli (pathogenic strains)
• Vibrio cholerae
• Campylobacter jejuni
• Klebsiella pneumoniae
§ Firmicutes > Bacilli > Lactobaciallales• Enterococcus faecalis• Enterococcus faecium
Pathogenic Bacteria
§ Taxonomy important for working with microbiome
§ Commensals: some groups and species play a special positive role• Immune function, intestinal barrier, motility, many others …
• Keeping pathobionts and pathogens in check
§ Pathobionts & pathogens• Can cause disease
• Depends on context, including the health of the individual, the overall health of the microbiome, and environmental factors
Taxonomy: Take-Homes
1. Overview
2. Structural & Functional Features
3. Taxonomy
4. Communities
Bacteria Outline
§ Flexibility in using different substrates (depending on genes within each bacteria)
§ Ability to tolerate variable physiological factors (oxygen, pH, bile, etc.)
§ Rapid evolution of DNA
§ Horizontal gene transfer (via plasmids)
§ Replication rate, formation of endospores
§ Community interactions, biofilms
Adaptibility & Resilience
§ Complex ecological communities of microbes
§ Composition depends on local factors (physiological conditions, available substrates, other microbes, etc.)
§ Highly interdependent, complex functional relationships (with each other & with us)
§ Cooperate and compete
§ Relatively stable & resilient
Microbiome Communities
§ Location • Digestive tract region &
microenvironment / niche • Mucus layer vs. lumen
§ Available substrates § pH § Oxygen § Transit time / flow rate § Barriers & immune factors § Attachment sites § Others: Redox status, bile salts, etc.
Physiological Factors
§ Sources & types (diet, secretions, microbe metabolites)
§ Availability§ Competition with other microbes§ Digestion / absorption by GI tract§ Concentration, flow rate, etc.
§ Position in community “food chain”
Substrates (Nutrients)
Cross-Feeding & Competition
SPECIES 1
A Resistant starch
B SPECIES 3
C
Acetate
Butyrate
SPECIES 2
SPECIES 4
§ Direct§ Substrates (nutrients / metabolites)
§ Space / attachment sites (mucus / epithelial later)
§ Antimicrobial factors: organic acids, bacteriocins, lactocillin, etc.
§ Indirect§ Suppress immune response to themselves
§ Enhance immune response to competitors
§ Others, including possibly affecting eating behavior
Competition
§ Cross-feeding / food web (mutualism)• Metabolites produced by one species can be used as a
substrate for another
§ Coordination via “quorum sensing”• Molecules used to coordinate activities• Depends on density
§ Sharing DNA• e.g. - antibiotic resistance genes
§ Biofilms
Cooperation
§ Bacteria + EPS (extracellular polymeric substance – polysaccharides, proteins & nucleic acids)
§ Normal part of many communities, but can contribute to pathogenicity (resistance to treatments)
§ More stable, protected microenvironment
§ Enables greater synergy & cooperation within community
§ Contains extracellular enzymes – external “shared” digestion
Biofilms
§ Capacity of microbiome communities to resist new colonization by pathogens and other transients (e.g., probiotics, foodborne microbes)
§ Key to preventing GI infections: “First line of defense”
§ Main factors contributing:• Lack of niches (competition - space, available substrates)• Hostile environment (pH, antimicrobial factors, immune factors)• Biofilms• Coordination (quorum sensing)
Colonization Resistance
§ Above factors contribute to stability & resilience • Stability: resistance to change, ability to maintain homeostasis
• Resilience: capacity to return to homeostasis after disturbance
§ Diverse ecosystems are generally more stable & resilient
§ Microbiome stability, resilience, & functional capacity contribute to human health & resilience • Less prone to disruption of our homeostasis & health
• Contributes to tolerance of a wider range of foods and conditions • Makes it challenging to change the microbiome
• BUT less diverse (less stable) microbiomes may be easier to change
Stability & Resilience
1. Overview
2. Structural & Functional Features
3. Taxonomy
4. Communities
Bacteria Outline
1. Microbiome overview: getting a sense of the microbiome, research, what we know
2. Bacteria: features, functions, communities & taxonomy
3. Other microbes: archaea, fungi, viruses, parasites (protozoa & helminths)
Module 1 Overview