Microbiology Human Microbiome

Maternal exposures

Oral - pre-mastication of food, dental amalgam

Mammary - breastfeeding, bottle feeding

Cutaneous - contact with skin, early bathing

Vaginal - birth canal passage, cesarean, early antibiotics

Exposures that alter species composition

Genetics (prenatal) - antibiotics not best for mother, lactobacillus, bifidobacterium

Birth (c- section) - staphylococcus, corynebacterium

Treatments -

Probiotics - bifidobacterium, lactobacillus ( week 1 )

Feeding

- breast (Bifidobacterium )

- formula (Enterobacteriaceae)

Antibiotics - decreased Microbial diversity

Foods / weaning (1 year) development of adult like microbes

Breast milk bioactive molecule functions

HMO's : immune regulation

HMOs promote the growth of beneficial gut bacteria.

Immunoglobulins - antibodies : IgA , IgG

Protection: Cytokines, cell signaling molecules influencing inflammation and immune responses.

Bifidobacterium longum infantis

Breaks down HMOs into short chain fatty acids

SCFA (short chain fatty acids)

Seals gut

- signaling

- tells gut cells connect to each other- adhere or seal up (tight junctions)

"Leaky gut "

develop allergies

Sialic Acid

Brain growth

signaling molecule- expression of proteins - brain development

enhance neural connections

HMO's

Glycine mimic ( sugar molecule )

selectively stimulate growth of Bifidobacterium

dominate the gut of breastfed infants —> healthy immune and metabolic development

Breastmilk contains its own microbial community

variations in HMO composition correlate with changes in both milk microbiota and infant gut colonization (e.g., ↑Bifidobacterium, ↓Streptococcus/Staphylococcus)

HMOs contribute to immune protection and pathogen defense.

Rise in immune disease is linked to

Microbes

Vanishing Microbes: Human adapted

• weakens immune training

• poor development of regulatory pathways that normally prevent overreaction

Limited exposure: Hygiene hypothesis

• fewer infections and less contact with environmental microbes → immune system skews to hypersensitivity.

Microbiome depletion affects barrier tissues (gut, skin, airways), increasing susceptibility to inflammatory and autoimmune diseases.

The gut microbiota

largest mucosal surface with the greatest bacterial diversity

• 500 different species

• Firmicutes and Bacteroidetes phyla

Functions:

digestion, nutrient synthesis, immune system development and regulation, inflammation, neurological processes

Firmicutes/Bacteroidetes ratio dictates health status

increased ratio - associated with conditions like obesity, metabolic disorders, and inflammatory bowel diseases

The gut brain axis

Complex bidirectional network of communication between the central nervous system, the intestine, and intestinal microbiota

• vagus nerve

After the brain, the gut contains the most neurons

• Immunity, metabolism, activation of the vagus nerve, neurotransmission, neurotrophic factors and memory

• Transfer of the microbiome depressed-healthy rodent = depression

SCFA: Metabolites produced via anaerobic fermentation

Reinforce BBB, modulate neurotransmission

SCFA's act as signaling molecules - activate responses from cell

Manipulation of the Microbiome: Diet

Fermented Foods - Increase bacterial diversity

Increasing fiber uptake is not sufficient, need to replace vanished organisms that utilize that fiber

Manipulation of the Microbiome: Probiotics

Probiotic - Live microorganisms that benefit health if consistently consumed in large enough quantities

Bifidobacterium and Lactobacillus

Manipulation of the Microbiome: Prebiotics

Prebiotic - nondigestible food ingredient that benefits host by selectively stimulating growth/ activity of a limited number of bacteria in the colon, and thus improves host health

Enhance the activity or promote the growth of resident bacteria

Probiotics

Live microorganisms

Bacteria or yeast

Common probiotic organisms —> Bifidobacterium and Lactobacillus

supplements and certain foods containing live cultures such as yoghurt, kefir, kombucha, sauerkraut

support treatment of diarrhea, irritable bowel syndrome, intestinal infections, reduce severity of colds/ flu or aid digestion

Prebiotics

Non-living, non-digestible by human ingredient (carbohydrates)

Serve as food for friendly bacteria within the gut

food supplements and naturally occurring in certain foods

aid digestion and support treatment of several chronic digestive disorders or inflammatory bowel disease

Compounds must be resistant to host digestion and absorption

Enhance the activity or promote the growth of resident bacteria

Manipulation of the Microbiome: Antibiotics

Antibiotic – Any substance or compound that inhibits bacterial growth/survival • Administer to suppress or eliminate certain populations of microbial pathogens

Results in profound changes in the population:

• Diversity

• Total bacterial density

• Not always temporary

• Antibiotic use can result in disease as an off-target affect

• Combination therapy with probiotics

The host immune response

Innate immunity: only immune system at birth besides antibiotics is breast milk

- Present at birth

-Barriers to infection

-Nonspecific responses to destroy invading cells

Adaptive immunity: Reaction to specific antigens, specific to individual

-Parts of foreign proteins, sugars, chemicals

-Specific targeted reaction developed

-Retains "memory" of those antigens

- Faster response if exposed a second time

Dysbiosis

An imbalance in microbiome composition that can lead to disease

Skin

protective barrier by occupying niches and preventing pathogen attachment (competitive exclusion).

• Commensal bacteria produce antimicrobial compounds that inhibit pathogen growth.

• Support immune function by stimulating local immune cells and promoting proper inflammatory responses.

• Acidic pH (pH 4–6) owing to the secretion of organic acids by oil and sweat glands

  • Organic acids inhibit microbial growth by lowering bacterial cytoplasmic pH

• Epidermal secretions are also high in salt and low in water activity 

  •  Enzymes such as lysozyme → degrade bacterial peptidoglycan

When and how does a person develop a microbiome?

babies are exposed to microbes residing in the birth canal and the outside world

• The initial makeup shaped in part by the mode of delivery

  • Natural-birth babies → colonized by microbes acquired by passage through the mother’s vagina

  • Cesarean section → microbes donated by the delivery room and by contact with the mother’s skin