Interphase förel 1-6 Flashcards
NCD
Non-communicable disease, medical condition/disease not caused by infectious agents. Can refer to chronic diseases.
Main types are cardiovascular diseases, cancer, chronic respiratory diseases and diabetes. Also allergic disorders such as food allergy and allergic rhinitis among others.
The probability of dying of a NCD is the highest in developing regions.
We’re expecting an increased cost of NCDs in upcoming years.
NCD triggers
Stress
vit D deficiency
global mobility
air pollution
alcohol & smoking
consumption of antibiotics and other pharma-products
increased sanitation and hygiene
C-section as birth mode
formula feeding
Direct health effects of human microbial residents (local)
- Further digestion; provides 10-15% of host energy
- Nutrients for the gut epithelium
- Colonization resistance against pathogens
- Formation of health-promoting metabolites
- Formation of (geno-)toxic compounds
Indirect health effects of human microbial residents (systemic)
- Interaction with gut-associated lymphoid tissue (GALT) = 60-70% of our immune system
- Gut microbiome is largest endocrine organ, producing >30 hormone-like compounds
- Interaction with brain through gut-brain axis.
Humoral response of gut-brain axis
Gut-brain:
- Gastrointestinal hormones
- Inflammatory mediators
Brain-gut:
- HPA axis
Neural response of gut-brain axis
- Autonomic nervous system
Enteric nervous system
Issues related to microbiota-gut-brain-axis
- Stress
- Metabolic disorder
- Obesity
- Diabetes
- Functional Gastrointestinal Disorders
- IBS
- Neurodegenerative Disorders
- Alzheimer’s
- Parkinson’s
- Neurodevelopmental disorders
- Autism
- Schizophrenia
- Addiction
- Alcohol dependence
Microbiology
monocultures in test tubes
Microbiome
totality of microbes, their genes and their interactions with the environment. An ecosystem inside the human, highly organized, interactive and dynamic ecological union.
Resident microbiome
symbiotic interactions with the host
Transient microbiome
passing through stimulating resident microbiome; supply metabolites for cross-feeding and growth factors etc., reducing/inhibiting pathogens, indirect impact through interaction with host epithelium
Two types of selective pressure
- Bottom up : due to competition between microbes, stimulating the developement fo new and specialized niches
- Top down: by the host resulting in functional redundancy to maintain itself
Multiple species that represent a variety of taxonomic groups can share similar, or even identical roles in the ecosystem
Functional niche
Not a physical location in the ecosystem. Has functional role of the microbe in the ecosystem.
Positive interactions between microbes create new niches. Occupation of all niches; all nutrients in the ecosystem are used.
Negative interaction: negative feedback to community. Balance of + and - results in a ‘climax community’. Dynamic stability.
Colonization resistance
Pre-emptive colonization. Fewer chances for pathogens. Comes from interaction processes between and with all microbial groups; not from a single organism. Every organism in the climax community has a specific role.
Quorum sensing
Regulating bacterial gene expression in function of the population density by production of signaling molecules, ‘auto-inducers’
Bacteria sense the population density. There is a critical cell population. Two/three types of auto-inducers. They are important for biofilms and microcolonies among others
Types of Quorum sensing
Type-1 or AI-1: Species-specific, intraspecies communication = AHL ring with carbon chain specific for the species (G-)
Type-2 or AI-2: Not specific, international language for interspecies communication and communication with other microorganisms (fungi, protozoa) = Furanosyl borate diester
Type-3 or AI-3: Found in EHEC, bacterium-human host communication (cross talk AI-3 and hormone epinephrine)
Quorum sensing gene regulation for:
Biofilm formation
Virulence and toxin production
Conjugation; exchange genetic material, e.g antibiotic resistance
Enzyme production and uptake of micronutrients
Bacteriocin production
Therapeutic potential of Quorum sensing (3)
Development of pharmaceuticals specifically inhibiting the QS system → avoiding virulence/toxicity
Quorum quenching = induce QS system at low cell density to stimulate a host response long before the pathogen population is large enough to sustain infection
Signals as a biosensor marker; e.g recognizing cancer microenvironments
Abilities of top-down host microbiome
Outgrow chemical and physical stresses such as pH, bile acids and peristalsis etc..
Fend off immune response from host
Tissue tropism
Tissue tropism
Choice of a specific species to adhere to a specific place
Different types of host cells; extracellular matrix, other microbes, excretion molecules
Mechanistic explanation: receptor on host tissue recognizes complementary adhesin from microbe.
Microbiome homeostasis
property of a microbial community to maintain their stability while adjusting to conditions optimal for survival. Stability attained is actually in a dynamic equilibrium, in which continuous change of the conditions occurs between pre-set limits (homeostatic range).
Dysbiosis
Term for microbial imbalance, when microbiome homeostasis on or inside the host is not successful. Tipping points; depending on resilience.
Rivet hypothesis
Removal of either type of species does not affect the structure of the community much and it is likely that the function of the community will be preserved. Only removing many species will give a functional change
Walker’s “drivers and passengers hypothesis”
Removal of a low-abundance species does not alter the structure significantly, but removal of a keystone species gives a major structural change, which is likely associated with loss of community function and major reorganization for the community.