L4 Microbial Symbiosis

Microbiota vs Microbiome

• Microbiota

  • The microorganisms present in a particular habitat (like the skin)

  • “Who is there?” → what microbes are sitting in these diff. locations on our body

• Microbiome

  • The microbial community plus its collective genes and functional potential (like the human microbiome)

  • “Who is there- and what can they do?” → how are they functioning/contributing

• Different ecosystems in the body

  • Each body site selects for different microbes by:

    • O2 pH moisture nutrients temperature secretions host defenses

Overview of the Human Microbiome

• Why study the Human Microbiome?

  • development of biomarkers for predicting predisposition to diseases

  • designing targeted/personalized therapies

  • development of probiotics

• US National Institutes of Health - Human Microbiome Project, major source of knowledge and tools for microbiome studies

  • Moving toward precision medicine!

Key Questions in Microbiome Research

• Do individuals share a core microbiome?

• Is there a correlation between the composition of microbiota colonizing a body site and host genotype?

• Do differences in the microbiome correlate with differences in health?

• Are differences in the relative abundance of specific bacterial populations important to either health or disease?

Overview of the Human Microbiome - 1

• Barrier to microbiome research: Most Bacteria cannot be cultured

• Non-cultivable bacteria are detected by DNA sequencing (doesn’t tell you what cells are actually doing)

• Limitation: DNA does not prove the organism is alive or metabolically active

Gastrointestinal Microbiota: Dynamic ecosystem

• The GI tract is not one uniform habitat

  • Conditions change dramatically along the tract:

    • Stomach → Small Intestine → Colon (Acidic/more oxygen exposure → increasingly anaerobic)

• What do gut microbes do for us?

  • Digestion of dietary components

  • Vitamin production

  • Immune system maturation (help distinguish what’s commensal/pathogenic)

  • Metabolism of otherwise poorly digestible nutrients

  • Protection against invading pathogens

• Colonization begins at birth

  • Delivery mode feeding family contacts. diet. medications. environment

A Word About Animal Gut Systems

Rumen and the Ruminants

• Rumen microbes synthesize volatile fatty acids (VFAs), amino acids and vitamins for their hosts

• VFAs main source of energy in ruminants

• Rumen microbes - protein source to host when they are directly digested

• Anaerobic bacteria dominate in the rumen

Gastrointestinal Microbiota: Location matters!

Question: Does fecal microbiota perfectly represent every intestinal site or mucosal community? NO

Stomach and Small Intestine: Microbial survival in a harsh habitat

• The stomach is selective - not sterile

  • Low pH (~pH 2) is a strong ecological barrier

  • Acid-tolerant microbes and organisms protected within gastric mucus can persist

• Small intestine generally contains fewer microbes than the colon because of:

  • bile digestive enzymes motility greater oxygen exposure

• Spothlight: Helicobacter pylori

  • Colonizes the gastric mucosa in 50% of world’s population; persists chronically

  • Associated with gastritis and peptic ulcer disease

    • Yet many colonized individuals remain asymptomatic

Gastrointestinal Microbiota

• Intestinal microorganisms carry out a variety of essential metabolic reactions that produce various compounds

• Large Intestine: Colon is an in vivo fermentation vessel, with the microbiota using nutrients derived from the digestion of food

• Most organisms are restricted to the lumen of the large intestine, while others are in the mucosal layers

Gastrointestinal Microbiota: Composition & Immune Education

• Gut dominated by Firmicutes, Bacteroidetes, and Proteobacteria

• No single “ideal” gut microbiota- healthy individuals vary

• Microbial composition can affect energy harvest from diet

• Gut microbes help educate mucosal immunity (have to be selective w/ what bacteria you’re going to respond to)

  • tolerate commensals

  • respond to pathogens

• Disrupted host-microbe signaling may contribute to inflammation

Biochemical/Metabolic Contributions of Intestinal Microorganisms

• Gut microbes expand the host’s metabolic capacity!

• They synthesize vitamins, transform bile acids and steroids, metabolize amino acids, and ferment carbohydrates into organic acids

What about the oral cavity, airways, etc.?

• Distinct microhabitats: tongue, teeth, saliva, mucosa, gingival crevices

• Saliva provides nutrients but also contains antimicrobial defenses

• Teeth do not shed, allowing microbial biofilms/plaque to persist (very solid piece of tissue)

• Nutrient-rich and low-oxygen sites support dense microbial growth

• teeth consist of enamel, dentin, and pulp

Key takeaway: Oral health depends on microbial balance; frequent sugar exposure and plaque buildup can favor acid-producing microbes

Airways

• The upper respiratory tract is continually exposed to inhaled microbes

• Mucus traps microbes and particles before they reach the lower airways

• Cilia move mucus upward via the mucociliary escalator

• Trapped microbes are expelled, swallowed, or destroyed by host defenses

• Smoking and respiratory disease can impair clearance and increase infection risk

Key takeaway: The airways rely on continuous mechanical and immune defenses to limit microbial colonization

Urogenital Tracts and Their Microbes

• Changes in the urinary tract can allow resident or nearby microbes to cause opportunistic infection

  • E. coli and Proteus mirabilis are common causes of UTis in women

• Vaginal Lactobacillus (Gram positive rods) ferments glycogen → lactic acid → maintains a low pH; provides colonization resistance by inhibiting many potential pathogens

• Female anatomy increases UTI risk because the urethra is shorter and closer to intestinal microbial sources

  • Versus male urogenital microbiota are generally similar to skin microbiota

Key takeaway: Colonization ≠ disease- location, abundance, host defenses, and local conditions determine whether a microbe becomes pathogenic

The Skin and Its Microbes

• ~10⁶ bacteria/cm²; ~10¹⁰ microbes on an adult’s skin

• Skin contains distinct dry, moist, and sebaceous microenvironments

• Each niche selects for different microbial communities

• Resident microbes help provide colonization resistance

The Skin and Its Microbial Composition

• environmental factors (e.g., weather, clothing, occupation, etc.)

• host factors (age, reproductive status, personal hygiene

• each microenvironment shows a unique microbiota

• “Microbial biogeography” applies to the human body just as it does to geographic ecosystems

Mouse Model to Study Human Microbiome

• Mice allow tight control of diet, genetics, antibiotics, and microbial exposure

• Germ-free mice reveal effects of microbial colonization

• Microbiota can be manipulated using antibiotics or fecal transplant

• Major fermentation site: mouse = cecum | human = colon

• Fecal transfer can test whether a microbiome-associated trait is causal and transferable

Key limitation: Mouse findings inform human biology, but do not automatically translate to humans

Colonization, Succession, And Stability of the Gut Microbiota

• Colonization begins at birth and develops through ecological succession

• Facultative anaerobes establish first (consume O2) and help create conditions for later anaerobes

• Delivery mode (vaginal vs C-section), feeding, diet, antibiotics, and environment shape early communities

• Breast milk oligosaccharides support beneficial (commensal) microbes, especially bifidobacteria

• The microbiome becomes relatively stable with age, but can still shift with major disturbances

Key takeaway: Early microbiome development is dynamic- initial differnces do not necessarily persist for life

Disorders Attributed to the Gut Microbiota

• Inflammatory Bowel Disease (IBD)

• Chronic inflammation of the gut; and dysbiosis - disruption of microbiome homeostasis

• Antibiotic use increases the risk of developing IBD

• Individuals with IBD have lower gut microbiome diversity

Disorders Attributed to the Oral Microbiota

• Dental plaque = multispecies biofilm on tooth surfaces

• Fermentation of dietary sugars → acid production → enamel demineralization → dental caries

  • Repeated low pH favors acid-tolerant microbes

• Periodontitis involves dysbiosis + damaging host inflammation

• Periodontal disease is associated with systemic conditions, including cardiovascular disease and arthritis

Key takeaway: Oral disease reflects a shift in microbial ecology + host response, not simply infection by one organism

Antibiotics and the Human Microbiome

• Oral antibiotics reduce susceptible pathogens AND commensals (makes them more vulnerable to pathogenic bacteria, no longer have competition from commensals)

  • Loss of commensals can weaken colonization resistance

• Disruption may allow Clostridiodes difficile to expand

  • C. diff forms endospores and produces toxins that damage the colon

• Fecal microbiota-based therapy (i.e., fecal transplants) can restore microbial community function in recurrent infection

Key takeaway: Antibiotics can cause ecological “collateral damage”- another reason antibiotic stewardship matters!

Clostridioides difficile Infection

Probiotics and Prebiotics

• Probiotics = live microbes that provide a health benefit

  • Common examples: Lactobacillus and Bifidobacterium

  • Can support colonization resistance by competing with pathogens

• Prebiotics = nondigestible substrates that feed beneficial gut microbes

  • Often fermentable carbohydrates/fibers

  • Can promote production of short-chain fatty acids

Prebiotics vs Probiotics