- L23-LO1: We are partly made of microbes
1 trillion bacterial cells with around 1000 species but >90% of cells from just 2 phyla. The gut microbiota of most vertebrates is broadly similar to the human gut microbiota.
- L23-LO2: The distribution & composition of the normal microbiota reflects the gut anatomy and our environment (including our diet).
Microbes are not distributed uniformly.
Transit time, available nutrients, physico-chemical properties & antimicrobial secretions influence what microbe species can live in the gut and where.
The epithelium is a ‘privileged’ site.
- L23-LO3: Many gut functions involve microbes - we require microbes to be normal.
Germ free animals are not different morphologically, metabolically & immunologically.
The activities of our microbiome profoundly influences our health.
- L23-LO4: The gut is critically involved in many major diseases.
A site of pathology: Diarrhoeal disease, Gastric ulcers & Colorectal cancer.
Gut functions are a risk factor for other diseases: obesity, diabetes, cardiovascular disease.
- What are three ways that microbes can contribute to differences in humans?
- DRUG & IMMUNE RESPONSE vary in ways that aren’t accountable for by genetic differences
- WEIGHT gain/loss varies in people with comparable diet & exercise.
- Post-meal BLOOD GLUCOSE varies in ways that do NOT reflect food OR genetic differences.
- There are a range of functions that take place in a series of processes. Some of these functions are gut micro-dependent - explain.
MOLECULES absorbed from the gut lead to systemic effects:
- transport to the liver
- signals transduced to ENS -> brain
- signals transduced to enteroendocrine system -> hormone release
- immune surveillance of gut & cytokine signalling.
This includes molecules of microbial origin!
Large intestine particular involvement: Fermentation, absorption of short chain FAs.
- Chronic diseases with similar epidemiological change include:
What are all of these associated with?
Rheumatoid arthritis, cardiovascular disease, autism spectrum disorder, type 2 diabetes, food allergy.
All these are also associated with gut microbiome differences!
- To improve public health we targeted nutrition & infectious disease, and changed our ‘microbial self’.
What are example changes and how they impacted ‘normal microbes’ for our gut?
In the aim to decrease infectious diseases, improvements in public health led to decreases in host susceptibility and in disease transmission.
- Better nutrition -> changes gut microbe food too
- Better housing & safer food & water -> makes it harder for normal microbes to get to us
- Immunisations & improved hygiene & sanitation -> changes tolerance of normal microbes
- Antibiotics -> Kills normal gut microbes too
All essentially leads to a change in the microbial combined genome!
- Views of microbial diversity may be achieved by observation of culturing or sequencing. Explain the differences/pros/cons of these two meethods.
Culture only samples cells that remain live & viable after handling protocol, whilst sequencing only samples cells that yield DNA after extraction protocol.
Culture only samples what grows to detection limits under culture protocol, whilst sequencing only samples what is targeted by primers under PCR protocol.
Culture can potentially distinguish anything that has different physiology/biochemistry, whilst sequencing only distinguishes what has different rRNA sequence.
In culture, relative abundance of each type reflects colony-forming units, not individual cells. In sequencing, relative abundance of each type reflects amplification success & gene copy number, not individual cells.
Essentially, culture is a better way to characterise PHYSIOLOGY, but sequencing can characterise the community and determine which parts contribute to a problem.
- True or false?
a) Humans have the same phyla present: human microbiota has SIMILAR MEMBERSHIP at phylum level.
b) There are differences in phylum abundance: Human microbiota has DIFFERENT DISTRIBUTION at phylum level.
Both true!
People may have differing ‘strains’ within these phyla. All humans have distinct microbiomes (membership AND distribution) at strain level.
- Name a few factors which oppose microbe growth in the stomach, duodenum/jejunum and ileum as opposed to the large intestine?
acidity in the stomach (<10^4 cells/mL)
mild acidity, bile salts and fast transit in the duodenum/jejunum (10^3-10^5 cells/mL)
medium transit, lymphoid tissue, bile salts in the ileum (10^8 cells/mL)
The large intestine (10^11-10^12 cells/mL): lymhpoid tissue, slow transit, low bile salts, soluble nutrient depleted.
- What main four factors shape the gut microbiome?
FLOW RATE: sets growth rate
PHYSICO-CHEMICAL STRESS: oxygen, pH, antimicrobials
NUTRIENT AVAILABILITY: what compounds we eat & what we secrete
BIOLOGICAL PROCESSES: competition w other microbes, competition w host
- Microorganisms can contribute to ~10% of our energy. Explain
Organisms in the colon can efficiently utilise the fibre we cannot digest, i.e. ‘Digestion Resistant Carbohydrates’ (DRC). Microbial processes dominate polysaccharide fermentation, assisted by the high cell density (>10^10 cells/mL) and typical slow transit time of the colon (up to 30 hours).
- Describe some of the gradients associated with microbiota occupying physically, chemically and biologically distinct regions.
Longitudinal gradients from the stomach to the colon include:
- pH gradient: acidic to basic; main change in ileum
- Oxygen gradient: quick decrease from the stomach
- Total energy content gradient (caloric density)
- Bile gradient: absent in stomach, starts in duodenum
Also a cross-sectional gradient particularly in the colon; less at the epithelial surface and immediate mucous layer and more at the inner mucous layer (due to antimicrobial peptides, mucin secretions)
- Where is the highest density of microbes found in the human body?
The mid (ileum) and distal (colon) parts of the GIT have the highest concentrations of microbes - and these are overwhelmingly bacteria.
- In what ways do all people have similar gut bacteria and in what ways do they differ?
The vast majority of bacterial cells in mammalian guts belong to species with just 2 phyla - Bacteroidetes & Firmicutes. Proteobacteria, Verrucomicrobia, Actinobacteria & Fusobacteria are also nearly always represented but each with comparatively few species.
People vary in the relative numbers of all these phyla BUT MOSTLY people vary in which species & strains of Bacteroidetes & Firmicutes are present.
- So presence of certain bacteria in high numbers is normal - WHAT is the main FUNCTION of these bacteria?
The gut bacteria contribute the ability to digest non-starch polysaccharide - without them most plant-based foods are a poor source of energy.
- What do fecal microbe analyses tell us about our health?
Fecal microbe samples are a direct measure of your potential to degrade fibre. They are also a proxy measure of the ‘history’ of YOUR system biology.
- Microbe presence & activity profoundly changes how we interface with our environment, impacting our health. Explain
The chemical composition of intestinal contents is profoundly shaped by microbial metabolic activity.
Activity of microbes means:
- DIFFERENCES IN DIGESTION
- VITAMIN AVAILABILITY
- DRUG HALF-LIFE
Developmental influence of our microbes means:
> DIFFERENCES IN STRUCTURAL INTERFACE BW GUT & REST OF BODY SYSTEM
—- gut barrier
—- absorption efficiency
> DIFFERENCES IN HOW WE PERCEIVE & RESPOND TO OUR ENVIRONMENT
— regulation of IR
- metabolic regulation
- appetite regulation
- We require interaction with a consortium of microbes to be normal & live in the real world.
With regard to 1) nutrition & metabolism, 2) development, and 3) immune state, reliant factors include?
1) Nutrition & metabolism:
- energy balance
- detoxification
- vitamins
2) Development:
- intestinal tissue
- adipose tissue
3) Immune state:
- TC subtype ratio
- tolerance
> No single species is essential to a normal phenotype or can deliver it
Differences in microbiome composition can give different health outcomes
> > Diseases that have immunophenotype / energy balance as risk factors effectively have gut microbiome structure as a risk factor
- L24-LO1: Microbe-related disease of the gut encompasses intoxication, infection and dysbiosis.
Some infections are endogenous as a result of disturbance (C. difficile).
Some infections are acquired.
- L24-LO2: Acquired infection is when ‘foreign’ pathogens bypass host defenses to elicit disease.
The host defenses include normal flora, mucin, innate immunity, and adaptive immunity.
- L24-LO3: Pathogenesis of gastroenteritis encompasses a number of mechanisms.
Endotoxin, Exotoxin, Cytopathology.
- L23-LO4: Major acquired infections: Symptoms, mechanisms, epidemiology & treatment.
Viral gastroenteritis, E. coli/Shigella, Campylobacter, Staphyloccocus.
